5.monograph - Part I (J Z)

KP 9 539
Josamycin Propionate
O
H3C
CH3
H
OHC
CH3
H
CH3
H3C
CH3
OH
CH3
O
O
CH3
N CH3H
H O
H
H
O H
CH3
H
O
OH
O
CH3
H
CH3
C45H73NO16: 884.06
Josamycin Propionate is a derivative of josamycin.
Josamycin Propionate contains not less than 843 g
(potency) per mg of josamycin (C42H69NO15: 828.00),
calculated on the dried basis.
RS, dissolve in 10 mL of methanol, and add 0.06 mol/L

phosphate buffer solution, pH 5.6 to make solution so
that each mL contains 400.0 g (potency), and use this
solution as the standard stock solution. Keep the standard stock solution at not exceeding 5 C and use within 3 days. Take exactly a suitable amount of the standard stock solution before use, add 0.06 mol/L phosphate buffer solution, pH 5.6 to make solutions so that
each mL contains 80.0 g (potency) and 20.0 g (potency), and use these solutions as the high concentration standard solution and the low concentration standard solution, respectively. Perform the test with these
solutions according to the Cylinder-plate method (I 8)
as directed under Microbial Assay for Antibiotics.
Packaging and Storage Preserve in tight containers.
Kanamycin Monosulfate
Description Josamycin Propionate is a white to light

yellowish white crystalline powder, and is odorless and
tasteless.
Josamycin Propionate is very soluble in methanol or in
ethanol, soluble in ether, and practically insoluble in
water.
H2N
O
OH
OH
HO
Identification (1) Dissolve 2 mg of Josamycin Propionate in 5 mL of sulfuric acid: the solution turns to
red-brown.
(2) Determine the absorption spectrum of a solution
of Josamycin Propionate in methanol (1 in 100000) as
directed under Ultraviolet-visible Spectrophotometry, it
exhibits maximum between 230 nm and 233 nm.
Purity Heavy metalsProceed with 1.0 g of Josamycin Propionate according to Method 2 and perform the
test. Prepare the control solution with 3.0 mL of standard lead solution (not more than 30 ppm).
Loss on Drying Not more than 2.0 % (0.5 g, in vacuum, 60 C, 3 hours).
Residue on ignition Not more than 0.2 % (1 g).
Assay The Cylinder-plate method method (1) Agar
media for seed and base layer- Use the medium in I 2
1 under Microbial Assay for Antibiotics.
1) (1)
(2) Test organism- Bacillus subtilis ATCC 6633.
(3) Weigh accurately about 20 mg (potency) of Josamycin Propionate, dissolve in 10 mL of methanol,
and add 0.06 mol/L phosphate buffer solution, pH 5.6
to make solution so that each mL contains 400.0 g
(potency). Take exactly a suitable amount of this solution, add 0.06 mol/L phosphate buffer solution, pH 5.6
to make solutions so that each mL contains 80.0 g
(potency) and 20.0 g (potency), and use these solutions as the high concentration test solution and the low
concentration test solution, respectively. Separately,
weigh accurately about 20 mg of Josamycin Propionate
NH2
OH
O
HO
H2SO4
NH2
O
OH
OH
NH2
C18H36N4O11H2SO4: 582.58
Kanamycin Monosulfate is the sulfate of an aminoglycoside substance having antibacterial activity produced
by the growth of Streptomyces kanamyceticus.
Kanamycin Monosulfate contains not less than 750 g
(potency) per mg of kanamycin (C18H36N4O11: 484.50),
Description Kanamycin Monosulfate is a white to
yellowish white powder, is odorless or has a little bit of
odor, and has a little bit of bitter taste.
Kanamycin Monosulfate is freely soluble in water, and
practically insoluble in ethanol or in ether.
Identification (1) To 50 mg of Kanamycin Monosulfate add 3 mL of water and dissolve, and add 2 mL of
anthrone TS: a blue-purple color develops.
(2) To 20 mg of Kanamycin Monosulfate, add 2 mL
of 0.06 mol/L phosphate buffer solution, pH 5.6, dissolve, and add 1 mL of ninhydrin TS and boil: a bluepurple color develops.
(3) To 10 mg of Kanamycin Monosulfate add 1 mL
of water and dissolve, and add 1 mL of ninhydrin solution in n-butanol (1 in 500) and 0.5 mL of pyridine, and
heat in water bath for 5 minutes and add 1 mL of water:
a dark purple color develops.
(4) A solution of Kanamycin Monosulfate responds
540 Monographs, Part I

to Qualitative Tests for sulfate salt.
Kanamycin Sulfate
pH The pH of a solution obtained by dissolving 0.1 g

of Kanamycin Monosulfate in 10 mL of water is between 6.5 and 8.5.
H2N
O
OH
Sterility Test It meets the requirement, when Kanamycin Monosulfate is used in a sterile preparation.
OH
HO
Bacterial Endotoxins Less than 0.50 EU per mg of

kanamycin, when Kanamycin Monosulfate is used in a
sterile preparation.
HO
Residue on Ignition Not more than 1.0 % (1 g).

Assay The Cylinder-plate method method (1) Agar
media for seed and base layer- Use the medium in I 2
1) (1)
(3) Weigh accurately about 20 mg (potency) of Kanamycin Monosulfate, dissolve in sterile purified water,
to make a solution so that each mL contains 400.0 g
(potency), and use this solution as the test stock solution. Take exactly a suitable amount of this solution,
add 0.1 mol/L phosphate buffer solution, pH 8.0 to
make solutions so that each mL contains 20.0 g (potency) and 5.0 g (potency), and use these solutions as
the high concentration test solution and the low concentration test solution, respectively. Separately, weigh accurately about 20 mg of Kanamycin Sulfate RS, previously dried, dissolve in 0.05 mol/L phosphate buffer
solution, pH 6.0 to make solution so that each mL contains 400.0 g (potency), and use this solution as the
standard stock solution. Keep the standard stock solution between 5 C and 15 C, and use within 30 days.
Take exactly a suitable amount of the standard stock
solution before use, add 0.1 mol/L phosphate buffer solution, pH 8.0 to make solutions so that each mL contains 20.0 g (potency) and 5.0 g (potency), and use
these solutions as the high concentration standard solution and the low concentration standard solution, respectively. Perform the test with these solutions according to the Cylinder-plate method (I 8) as directed under
Microbial Assay for Antibiotics.
xH2SO4
NH2
O
OH
NH2
OH
OH
NH2
C18H36N4O11xH2SO4
Kanamycin Sulfate is the sulfate of an aminoglycoside
substance having antibacterial activity produced by the
growth of Streptomyces kanamyceticus.
Kanamycin Sulfate is prepared by adding not more than
1 mol of sulfuric acid to 1 mol of kanamycin monosulfate.
Kanamycin Sulfate contains not less than 600 g (potency) per mg of kanamycin (C18H36N4O11: 484.50),
Description Kanamycin Sulfate is a white to yellowish white powder, is odorless or has a little bit of odor,
and has a little bit of bitter taste.
Kanamycin Sulfate is very soluble in water, and practically insoluble in ethanol, in acetone, or in ether.
Identification Perform the test according to Identification in Kanamycin Monosulfate.
of Kanamycin Monosulfate in 10 mL of water is between 6.0 and 8.5.
Sterility Test It meets the requirement, when Kanamycin Sulfate is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Kanamycin Sulfate is used in a sterile preparation,. Weigh an
appropriate amount of Kanamycin Sulfate, dissolve in
water, make the solution so that each mL contains 10.0
mg, and use the solution as the test solution. The
amount of injection is 1.0 mL of the test solution per kg
of body weight of rabbit.
Assay Perform the test according to Assay in Kanamycin Monosulfate. Weigh accurately about 20 mg
(potency) of Kanamycin Sulfate, dissolve in sterile purified water to make a solution so that each mL contains 400.0 g (potency), and use this solution as the
test stock solution. Take exactly a suitable amount of
KP 9 541
this solution, add 0.1 mol/L phosphate buffer solution,
pH 8.0 to make solutions so that each mL contains 20.0
g (potency) and 5.0 g (potency), and use these solutions as the high concentration test solution and the low
concentration test solution, respectively.
Perform the test (not more than 0.021%).
(3) SulfateDissolve 0.5 g of Kainic Acid in 40

mL of water by warming. Cool, add 1 mL of dilute hydrochloric acid and water to make 50 mL and perform
the test. Prepare the control solution with 0.30 mL of
0.005 mol/L sulfuric acid VS (not more than 0.028%).
(4) AmmoniumTake 0.25 g of Kainic Acid and
perform the test. Prepare the control solution with 5.0
mL of standard ammonium solution (not more than
0.02%).
(5) Heavy metalsProceed with 1.0 g of Kainic
Acid according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
solution (not more than 20 ppm).
(6) ArsenicDissolve 1.0 g of Kainic Acid in 5 mL
of dilute hydrochloric acid and perform the test (not
more than 2 ppm).
(7) Related substancesDissolve 0.10 g of Kainic
Acid in 10 mL of water and use this solution as the test
solution. Pipet 2.0 mL of this solution and add water to
make exactly 100 mL. Pipet 1.0 mL of this solution,
add water to make exactly 20 mL and use this solution
as the standard solution. Perform the test as directed
under the Thin-layer Chromatography with these solutions. Spot 10 L each of the test solution and the standard solution on a plate of silica gel for thin-layer
chromatography. Develop the plate with the supernatant liquid of a mixture of water, n-butanol and glacial
acetic acid (5 : 4 : 1) to a distance of about 10 cm and
air-dry the plate. Spray evenly a solution of ninhydrin
in acetone (1 in 50) on the plate and dry the plate at 80
C for 5 minutes: the spots other than the principal spot
from the test solution are not more intense than the spot
obtained form the standard solution.
Kainic Acid
H
N
CO2H
H
CH2CO2H
H
H2C
H2O
CH3
C10H15NO4H2O: 231.25
Kainic Acid, previously dried, contains not less than
99.0% and not more than 101.0% of kainic acid
(C10H15NO4: 213.23).
Description Kainic Acid is white crystals or crystalline powder, is odorless and has an acid taste.
Kainic Acid is sparingly soluble in water or in warm
water, very slightly soluble in glacial acetic acid or in
ethanol and practically insoluble in ether.
Kainic acid dissolves in dilute hydrochloric acid or in
sodium hydroxide TS.
Melting pointAbout 252 C (with decomposition).
pHThe pH of a solution of Kainic Acid (1 in 100)
is between 2.8 and 3.5.
Identification (1) To 5 mL of a solution of Kainic
Acid (1 in 5000), add 1 mL of ninhydrin TS and warm
in a water-bath at a temperature between 60 C and 70
C for 5 minutes: a yellow color is produced.
(2) Dissolve 50 mg of Kainic Acid in 5 mL of glacial acetic acid and add 0.5 mL of bromine TS: the color of bromine disappears immediately.
Specific Optical Rotation [ ]20
D : Between -13 and 17 (0.5 g, water, 50 mL, 200 mm).
Purity (1) Clarity and color of solutionDissolve
0.10 g of Kainic Acid in 10 mL of water: the solution is
clear and colorless.
(2) ChlorideTake 0.5 g of Kainic Acid in a platinum crucible, dissolve in 5 mL of sodium carbonate TS
and evaporate In a water-bath to dryness. Heat the crucible slowly at first and then ignite until the sample is
almost incinerated. After cooling, add 12 mL of dilute
nitric acid to the residue, dissolve by warming and filter.
Wash the residue with 15 mL of water, combine the
washings and the filtrate and add water to make 50 mL.
Control solutionAdd 5 mL of sodium carbonate

TS to 0.30 mL of 0.01 mol/L hydrochloric acid VS and
proceed as directed above.
Loss on Drying Between 6.5% and 8.5% (1 g, 105

C , 4 hours).
Residue on Ignition Not more than 0.1% (0.5 g).
Assay Weigh accurately about 0.4 g of Kainic Acid,
previously dried and dissolve in 50 mL of warm water,
cool and titrate with 0.1 mol/L sodium hydroxide VS
(indicator: 10 drops of bromothymol blue TS).
Each mL of 0.1 mol/L sodium hydroxide VS
= 21.323 mg of C10H15NO4
Kallidinogenase
Kallidinogenase is an enzyme obtained from healthy
porcine pancreas, and has kinin-releasing activity based
on vleavage of kininogen.
Kallidinogenase contains not less than 25 Kallidinogenase Units per mg.
Usually, Kallidinogenase is diluted with Lactose Hydrate or the like.
Kallidinogenase contains not less than 90.0% and not
more than 110.0% of the labeled Units.
Kallidinogenase is a white to light
brown powder. Kallidinogenase is odorless or has a
faint, characteristic odor.
Kallidinogenase is freely soluble in water, and practically insoluble in ethanol and in ether.
pHThe pH of a solution of Kallidinogenase (1 in
300) is between 5.5 and 7.5.
Description
Identification (1) Weigh accurately an appropriate

amount of Kallidinogenase according to the labeled
Units, and dissolve in 0.05 mol/L phosphate buffer solution, pH 7.0 to prepare a solution containing 10 Kallidinogenase Units per mL. Pipet 5 mL of this solution,
and add exactly 1 mL of trypsin inhibitor TS and 0.05
mol/L phosphate buffer solution, pH 7.0 to make exactly 10 mL. Pipet 4 mL each of this solution into two
separate test tubes, add exactly 1 mL each of aprotinin
TS and 0.05 mol/L phosphate buffer solution, pH 7.0
separately to each test tube, allow them to stand at
room temperature for 20 minutes, and use these solutions as the test solutions (1) and (2). Separately, pipet
1 mL of trypsininhibitor TS, and 0.05 mol/L phosphate
buffer solution, pH 7.0 to mke exactly 10 mL. Pipet 4
mL each of this solution into two separate test tubes,
add exactly 1 mL each of aprotinin TS and 0.05 mol/L
phosphate buffer solution, pH 7.0 separately to each
tube, allow them to stand at room temperature for 20
minutes, and use these solutions as the test solutions (3)
and (4). Then, pipet 2.5 mL of substrate TS for Kallidinogenase assay (1), previously warmed at 30.0 0.5
for 5 minutes, place in a 10-mm cell, add exactly 0.5
mL of the test solution (1) warmed at 30.0 0.5 for
5 minutes, and start simultaneously a chronograph. Perform the test at 30.0 0.5 as directed under Ultraviolet-visible Spectrophotometry using water as the
blank, and determine the absorbances at 405 nm, A1 2
and A1 6 , of this solution, after having allowed it to
stand for exactly 2 and 6 minutes. Perform the same
test with the test solutions (2), (3) and (4), and determine the absorbances, A2 2 , A26 , A3 2 , A36 ,
A4 2 and A46 , of these solutions. Calculate I by using the following equation: the value of I does not exceed 0.2.
I=
( A1 6 A1 2 ) ( A3 6 A3 2 )
( A2 6 A2 2 ) ( A4 6 A4 2 )
(2) Pipet 2.9 mL of substrate TS for Kallidinogenase assay (2), previously warmed at 30.0 0.5 C for
5 minutes, place in a 10-mm cell, add exactly 0.1 mL of
the test solution obtained in the Assay, and start simultaneously a chromatograph. Perform the test at 30.0
0.5 C as directed under Ultraviolet-visible Spectrophotometry, and determine the change of the absorbance at
253nm for to inhibitor TS, and add 0.05 mol/L phosphate buffer solution, pH 7.0 to make exactly 10 mL.
Add exactly 0.1 mL of this solution to exactly 2.9 mL
of substrate TS for Kallidinogenase assay (2), previously warmed at 30.0 0.5 C for 5 minutes, and use this
solution as the blank. If the rate of change in the absorbance remains constant, determine the change of absorbance per 1 minute, A , and calculate R by using the
following equation: the value of R is between 0.12 and
0.16.
R=
A
1
0.0383 a b
a: Amount (mg) of Kallidinogenase in 1 mL of the

test solution.
b: Amount (unit) of Kallidinogenase in 1 mg of Kallidinogenase obtained in the Assay.
Specific Activity Perform the test with Kallidinogenase as directed under Nitrogen Determination to determine the nitrogen content, convert 1 mg of nitrogen
(N:14.01) into 6.25 mg of protein, and calculate the
specific activity using the amount (Units) of Kallidinogenase obtained in the Assay: it is not less than 100
Kallidinogenase Units per 1 mg of protein.
Purity (1) FatTo 1.0 g of Kallidinogenase add 20
mL of ether, extract with occasional shaking for 30 minutes, and filter. Wash the residue with 10 mL of ether,
combine the washing with the filtrate, evaporate the
ether, and dry the residue at 105 C for 2 hours: the
mass of the residue is not more than 1 mg.
(2) Kininase(i) Bradykinin solution: Weigh
an appropriate amount of bradykinin, and dissolve in
gelatin-phosphate buffer solution, pH 7.4 to prepare a
solution containing 0.200 g of bradykinin per mL.
(ii) Kallidinogenase solution: Weigh accurately a
suitable amount of Kallidinogenase according to the labeled unit, dissolve in gelatin-phosphate buffer solution,
pH 7.4 to make a solution containing 1 unit of Kallidinogenase per mL.
(iii) Test solution: Pipet 0.5 mL of bradykinin solution, warm at 30.0 0.5 C for 5 minutes, then add exactly 0.5 mL of Kallidinogenase solution previously
warmed at 30.0 0.5 C for 5 minutes, and mix immediately. After allow this solution to stand at 30.0 0.5
KP 9 543
C for exactly 150 seconds, add exactly 0.2 mL of a solution of a solution of trichloroacetic acid (1 in 5), and
shake. Boil for 3 minutes, then cool in ice immediately,
centrifuge, and allow to stand at a room temperature for
15 minutes. Pipet 0.5 mL of the supernatant liquid, add
exactly 0.5 mL of gelatin-tris buffer solution, pH 8.0,
and mix. Pipet 0.1 mL of this solution, add exactly 0.9
mL of trichloroacetic acid gelatin-tris buffer solution,
and mix. Pipet 0.2 mL of this solution, add exactly 0.6
mL of trichloroacetic acid- gelatin-tris buffer solution,
shake, and use this solution as the test solution.
(iv) Control solution: Proceed with 0.5 mL of gelatinphosphate buffer solution, pH 7.4 as described in (iii),
and use the solution so obtained as the control solution.
(v) Procedure: Add 0.1 mL of anti-bradykinin antibody TS to anti-rabbit antibody-coated wells of a 96-well
microplate, shake, and allow to stand at a constant temperature of about 25 C for 1 hour. Remove the antibradykinin antibody TS, add 0.3 mL of phosphate buffer solution for microplate washing to the wells, then
remove. Repeat this procedure 3 times, take off the
washings thoroughly, then add 100 L each of the test
solution and the control solution, and 50 L of gelatinphosphate buffer solution, pH 7.0, shake, and allow to
stand at a constant temperature of about 25 C for 1
hour. Then add 50 L of peroxidase-labeled bradykinin
TS, shake, and allow to stand in a cold place for a night.
Take off the solution, add 0.3 mL of phosphate buffer
solution for microplate washing, and remove. Repeat
this procedure more 4 times, take off the washings thoroughly, add 100 L of substrate solution for peroxidase determination, and allow to stand as a constant
temperature of about 25 C for exactly 30 minutes
while protecting from light. Then add 100 L of diluted
surfuric acid (23 in 500), shake, and determine the absorbance at 490 ~ 492 nm. Separately, dissolve a suitable amount of bradykinin in gelatin-phosphate buffer
solution, pH 7.0 to make solution containing exactly
100 ng, 25 ng, 6.25 ng, 1.56 ng, 0.39 ng and 0.098 ng
of bradykinin per mL, and use these solutions as the
standard solution (1), the standard solution (2), the
standard solution (3), the standard solution (4), the
standard solution (5), the standard solution (6), respectively. Use 1 mL of gelatin-phosphate buffer solution,
pH 7.0 as the standard solution (7). To each of the well
add 50 L each of the standard solutions and 100 L of
trichloroacetic acid-gelatin-tris buffer solution, and
proceed in the same manner as for the test solution and
for the control solution. Prepare the standard curve
from the amounts of bradykinin in the standard solutions and their absorbances, and determine the amount
of bradykinin, BT (pg) and B S (pg), of the test solution and the control solution. The absorbance is usually
determined by using a spectrophotometer for microplate. Since the wells are used as the cell for absorbance determination, take care for dirt and scratch of
the well. Light pass length of the well is changeable by
the amount of the liquid, exact addition of the liquid is
necessary.
(vi) Judgement: The value R calculated by the following equation is not less than 0.8.
R = ( BT / B S )
(3) Trypsin-like substancesPipet 4 mL of the test
stock solution prepared for the Assay, add exactly 1 mL
of trypsin inhibitor TS and 0.05 mol/L phosphate buffer
solution , pH 7.0 to make exactly 10 mL, and use this
solution as the test solution. Pipet 2.5 mL of substrate
TS for kallidinogenase assay (1), previously warmed at
30.0 0.5 for 5 minutes, place in a 10-mm cell, add
exactly 0.5 mL of the test solution, warmed at 30.0
0.5 C for 5 minutes, and start simultaneously a chronograph. Perform the test at 30.0 0.5 C as directed
under Ultraviolet-visible Spectrophotometry using water as the blank, and determine the absorbances at 405
nm, A 2 and A6 , of this solution after having allowed it to stand for exactly 2 and 6 minutes. Seperately, pipet 4 mL of the test stock solution prepared for the
Assay, add 0.05 mol/L phosphate buffer solution, pH
7.0 to make exactly 10 mL, and use this solution as the
control solution. Perform the same test with the control
solution, and determine the absorbances, A' 2 and
A' 6 . Calculate T by using the following equation: the
value of T does not exceed 0.05.
T = {( A' 6 A' 2 ) ( A6 A2 ) /( A' 6 A' 2 )}
(4) ProteaseWeigh accurately an appropriate

amount of kallidinogenase according to the labeled
Units, dissolve in 0.05 mol/L phosphate buffer solution,
pH 7.0 to prepare a solution containing 1 Kallidinogenase Unit per mL, and use this solution as the test solution. Pipet 1 mL of the test solution, place in a test tube,
and allow to stand at 35 0.5 C for 5 minutes. Then,
pipet 5 mL of substrate TS for kallidinogenase assay
(3), previously warmed to 35 0.5 C add quickly to
the test solution in the test tube, and allow to stand at
35 0.5 C for exactly 20 minutes. Then add exactly 5
mL of trichloroacetic acid TS, shake well, allow to
stand at room temperature for 1 hour, and filter through
a membrane filter (5 m in pore size). Discard the first
3 mL of the filtrate, and determine the absorbance, A .
of the subsequent filtrate at 289 nm within 2 hours as
directed under Ultraviolet-visible Spetrophotometry,
using water as the blank. Separately, pipet 1 mL of the
test solution, add exactly 5 mL of trichloroacetic acid
TS, shake well, and add exactly 5 mL of the substrate
TS for kallidinogenase assay (3). Proceed in the same
manner as described for the test solution, and determine
the absorbance, A0 , of this solution. Calculate the
value of ( A A0 ): it is not more than 0.2.
Loss on Drying Not more than 2.0% (0.5g, in vacuum, phosphorus (V) oxide, 4 hours).
Residue on Ignition
650~750 C).
Not more than 3.0% (0.5g,
Kinin-Releasing Activity (i) Kallidinogenase solution: Weigh accurately a suitable amount of Kallidinogenase, according to the labeled unit, dissolve in 0.02
mol/L phosphate buffer solution, pH 8.0 to make a solution containing 0.1 unit of Kallidinogenase per mL.
Perform this procedure by using glassware.
(ii) Test solution: Pipet 0.5 mL of kininogen TS, warm
at 30 0.5 C for 5 minutes, then add exactly 0.5 mL
of Kallidinogenase solution previously warmed at 30
0.5 C for 5 minutes, and mix immediately. After allow
this solution to stand at 30 0.5 C for exactly 2 minutes, add exactly 0.2 mL of a solution of trichloroacetic acid (1 in 5), and shake. Boil for 3 minutes, then cool
in ice immediately, centrifuge, and allow to stand at a
temperature for 15 minutes. Pipet 0.5 mL of the supernant liquid, addd exactly 0.5 mL of gelatin-tris buffer
solution, pH 8.0, and shake. Pipet 0.1 mL of this solution, add exactly 1.9 mL of trichloroacetic acid-gelatintris buffer solution, shake, and use this solution as the
test solution.
(iii) Procedure: Perform the test with the test solution
as directed in the Purity (2), and determine the amount,
B (pg), of kinin per well. The kinin-releasing activity
per 1 unit of Kallidinogenase calculated by the following equation is not less than 500 ng bradykinin equivalent/min/unit.
Kinin-releasing activity (ng bradykinin equivalent/min/unit) per 1 unit of Kallidinogenase
= B 4.8
Assay Weigh accurately an appropriate amount of
Kallidinogenase according to the labeled units, dissolve
in 0.05 mol/L phosphate buffer solution, pH 7.0 to prepare a solution containing about 10 Kallidinogenase
Units per mL, and use this solution as the test stock solution. Pipet 4 mL of the test stock solution, add exactly 1 mL of trypsin inhibitor TS and 0.05 mol/L phosphate buffer solution, pH 7.0 to make exactly 10 mL,
and use this solution as the test solution. Pipet 2.5 mL
of substrate TS for Kallidinogenase assay (1), previously warmed at 30 0.5 C for 5 minutes, place in a 1-cm
cell, add exactly 0.5 mL of the test solution, warmed at
30 0.5 C for 5 minutes, and start simultaneously a
chronograph. Perform the test at 30 0.5 C as directed
under the Ultraviolet-visible Spetrophotometry using
water as the blank, and determine the absorbances at
405 nm, AT 2 and AT 6 , of this solution after allowing
to stand for exactly 2 and 6 minutes. Separately, dissolve Kallidinogenase reference standard in 0.05 mol/L
phosphate buffer solution, pH 7.0 to make a solution so
that each mL contains exactly 10 Units, and use this solution as the standard stock solution. Pipet 4 mL of the
stock solution, add exactly 1 mL of trypsin inhibitor TS
and 0.05 mol/L phosphate buffer solution, pH 7.0 to

make exactly 10 mL, and use this solution as the standard solution. Take exactly 0.5 mL of the standard solution, perform the test in the same manner as described
for the test solution, and determine the absorbances,
AS 2 and AS 6 , of the solution after allowing to stand
for exactly 2 and 6 minutes. Separately, take exactly 1
mL of the trypsin inhibitor TS, and add 0.05 mol/L
phosphate buffer solution, pH 7.0 to make exactly 10
mL. Pipet 0.5 mL of this solution, perform the test in
the same manner as described for the test solution, and
determine the absorbances, A02 and A06 , of the solution after allowing to stand for exactly 2 and 6 minutes.
Units per 1 mg of Kallidinogenase =
( A AT2 ) ( A06 A02 ) WS 1
= T6
( AS6 AS2 ) ( A06 A02 ) a b
W S : Amount (Units) of Kallidinogenase Reference Standard

a: Volume (mL) of the standard stock solution
b: Amount (mg) of Kallidinogenase in 1 mL of the
test stock solution
Packaging and Storage Preserve in tight containers
Ketamine Hydrochloride
Cl
O
HCl
NHCH3
and enantiomer
C13H16ClNOHCl: 274.19
Ketamine Hydrochloride, when dried, contains not less
than 99.0% and not more than 101.0% of ketamine hydrochloride (C13H16ClNOHCl).
Description Ketamine Hydrochloride is a white crystal or crystalline powder.
Ketamine Hydrochloride is very soluble in formic acid,
freely soluble in water or in methanol, sparingly soluble in ethanol or in glacial acetic acid and practically
insoluble in acetic anhydride or in ether.
A solution of Ketamine Hydrochloride (1 in 10) shows
no optical rotation.
Melting point258 C (with decomposition).
Identification (1) Determine the absorption spectra
of solutions of Ketamine Hydrochloride and Ketamine
Hydrochloride RS in 0.1 mol/L hydrochloric acid TS (1
in 3000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities
KP 9 545
of absorption at the same waveleng.
(2) Determine the infrared spectra of Ketamine Hydrochloride and Ketamine Hydrochloride RS as directed in the potassium bromide disk method under the
Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) A solution of Ketamine Hydrochloride (1 in 10)
responds to the Qualitative Tests (2) for chloride.
Ketoconazole
N
%
Absorbance E11cm
(269 nm): Between 22.0 and 24.5
(after drying, 30 mg, 0.1 mol/L hydrochloric acid TS,
100 mL).
O
O
N
O
O
H3C
H
pH Dissolve 1.0 g of Ketamine Hydrochloride in 10

mL of freshly boiled and cool water: the pH of this solution is between 3.5 and 4.5.
1.0 g of Ketamine Hydrochloride in 5 mL of water: the
solution is clear and colorless.
(2) Heavy metalsProceed with 1.0 g of Ketamine
Hydrochloride according to Method 1 and perform the
(3) ArsenicPrepare the test solution with 1.0 g of
Ketamine Hydrochloride, according to Method 1 and
perform the test (not more than 2 ppm).
(4) Related substancesDissolve 0.5 g of Ketamine Hydrochloride in 10 mL of methanol and use this
solution as the test solution. Pipet 1.0 mL of the test solution, add methanol to make exactly 200 mL and use
this solution as the standard solution. Perform the test
with the test solution and the standard solution as directed under the Thin-layer Chromatography. Spot 2 L
each of the test solution and the standard solution on a
plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of cyclohexane and isopropylamine (49 : 1) to a distance of about 10 cm and
air-dry the plate. Spray evenly Dragendorffs TS for
spraying on the plate, dry the plate and then spray
evenly hydrogen peroxide TS: the spots other than the
principal spot from the test solution are not more intense than the spot from the standard solution.
Loss on Drying Not more than 0.5% (1 g, 105 C, 3
hours).
Residue on Ignition Not more than 0.1% (1 g).
Assay Weigh accurately about 0.5 g of Ketamine Hydrochloride, previously dried, dissolve in 1 mL of formic acid, add 70 mL of a mixture of acetic anhydride
and glacial acetic acid (6 : 1) and titrate with 0.1 mol/L
perchloric acid VS (potentiometric titration, Endpoint
Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
Each mL of 0.1 mol/L perchloric acid VS
= 27.419 mg of C13H16ClNOHCl
Cl
Cl
and enantiomer
C26H28Cl2N4O4: 531.43
Ketoconazole contains not less than 98.0% and not
more than 102.0% of ketoconazole (C26H28Cl2N4O4),
Description Ketoconazole is a white powder.
Ketoconazole is soluble in methanol, sparingly soluble
in ethanol, and practically insoluble in water.
Identification Determine the infrared spectra of Ketoconazole and Ketoconazole RS, as directed in the potassium bromide disk method under the Infrared spectrophotometry: both spectra exhibit similar intensities
of absorption at the same wavenumbers.
Melting Point
Between 148 C and 152 C .

D : Between -1 and +1
(0.4 g, methanol, 10 mL, 100 mm).
Purity (1) Heavy metalsProceed with 1.0 g of Ketoconazole according to Method 2, and perform the test.
Prepare the control solution with 2.0 mL of standard
lead solution (not more than 20 ppm).
(2) Related substancesDissolve 30 mg of Ketoconazole in 3.0 mL of chloroform and use this solution
as the test solution. Separately, weigh accurately a suitable quantity of Ketoconazole RS, dissolve it in chloroform to make a solution containing 10 mg per mL, and
use this solution as the standard solution. Pipet a suitable volume of this solution, add chloroform to make a
solution containing 1.0 mg per mL and use this solution
as a diluted standard solution. Perform the test with the
test solution, standard solution and the diluted standard
solution as directed under the Thin-layer Chromatography. Spot 10 L each of the test solution and the standard solution, and spot 2 L of the diluted standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of n-hexane,
ethyl acetate, methanol, water and glacial acetic acid
(42 : 40 : 15 : 2 : 1) to a distance of about 15 cm and
air-dry. Allow the plate to stand in iodine vapor: the

Rf value and the size of the principal spot from the
test solution corresponds to the Rf value and size of
the principal spot from the standard solution. The sum
of the spots other than the principal spot from the test
solution is not more intense than the principal spot
from the diluted standard solution.
Loss on Drying Not more than 0.5% (1 g, in vacuum,

80 C , 4 hours).
Assay Weigh accurately about 0.2 g of Ketoconazole,
dissolve in 40 mL of glacial acetic acid, and titrate with
0.1 mol/L perchloric acid VS (potentiometric titration,
Endpoint Detection Method in Titrimetry). Perform a
blank determination and make any necessary correction.
= 26.572 mg of C26H28Cl2N4O4
Ketoconazole Tablets
Ketoconazole Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of ketoconazole (C26H28Cl2N4O4: 531.43).
Method of Preparation Prepare as directed under
Tablets, with Ketoconazole.
Identification Weigh accurately and powder a quantity of Ketoconazole Tablets equivalent to about 50 mg
of Ketoconazole, add 50 mL of chloroform, shake for 2
minutes, filter, and use the filtrate as the test solution.
Separately, dissolve a suitable quantity of Ketoconazole
RS in chloroform to make a solution containing 1 mg
per mL and use this solution as the standard solution.
Perform the test with the test solution and the standard
solution as directed under the Thin-layer Chromatography. Spot 10 L each of the test solution and the standard solution on a plate of silica gel for thin-layer
chromatography. Develop the plate with a mixture of nhexane, ethyl acetate, methanol, water and glacial acetic acid (42 : 40 : 15 : 2 : 1) to a distance of about 15 cm,
and air-dry. And examine the plate under ultraviolet
light (main wavelength: 254 nm): the Rf value of the
principal spot obtained from the test solution corresponds to that obtained from the standard solution.
Disintegration Test It meets the requirement provided that the time limit of the test is 10 minutes.
Uniformity of Dosage Units
ment.
It meets the require-
Assay Weigh accurately and powder not less than 20

Ketoconazole Tablets. Weigh accurately a portion of
the powder, equivalent to about 0.2 g of Ketoconazole,
transfer to a glass-stoppered centrifuge tube and add
exactly 50 mL of a mixture of methanol and dichloromethane (1 : 1). Shake for 30 minutes with a shaker and
centrifuge. Pipet 5.0 mL of the supernatant, add 5.0 mL
of the internal standard solution and add a mixture of
methanol and dichloromethane (1 : 1) to make exactly
50 mL. Use this solution as the test solution. Separately,
weigh accurately about 20 mg of Ketoconazole RS, add
5.0 mL of the internal standard solution and add a mixture of methanol and dichloromethane (1 : 1) to make
exactly 50 mL. Use this solution as the standard solution. Perform the test with 20 L each of the test solution and the standard solution as directed under the
Liquid Chromatography according to the following
conditions and calculate the ratios, QT and QS , of
the peak area of Ketoconazole to that of the internal
standard for the test solution and the standard solution,
respectively.
Amount (mg) of Ketoconazole (C26H28Cl2N4O4)
Q
= amount (mg) of Ketoconazole RS T 10
QS
Internal standard solutionWeigh a suitable quantity of Terconazole RS and dissolve in a mixture of methanol and dichloromethane (1 : 1) to make a solution
containing 5 mg per mL.
Operating conditions
Detector: An ultraviolet absorption photometer
(wavelength: 225 nm).
Column: A stainless steel column, about 3.9 mm in
inside diameter and about 30 cm in length, packed with
octadecylsilanized silica gel for liquid chromatography
(3 m to 10 m in particle diameter).
Column temperature: A room temperature.
Mobile phase: A mixture of diisopropylamine in
methanol (1 in 500) and ammonium acetate in water (1
in 200) (7 : 3).
Flow rate: 3 mL/minute.
System suitability
System performance: When the procedure is run
with 20 L of the standard solution under the above
operating conditions, ketoconazole and the internal
standard are eluted in this order with a resolution between their peaks being not less than 2.0.
System repeatability: When the test is repeated 6
times with 20 L of the standard solution under the
above operating conditions, the relative standard deviation of the ratios of the peak area of Ketoconazole to
that of the internal standard is not more than 2.0%.
KP 9 547
Ketoprofen
H
H3C CCO2H
CO
and enantiomer
Cl6H14O3: 254.28
Ketoprofen, when dried, contains not less than 99.0%
and not more than 100.5% of ketoprofen (Cl6H14O3).
Description Ketoprofen occurs as a white, crystalline
powder.
Ketoprofen is very soluble in methanol, freely soluble
in ethanol or in acetone and practically insoluble in water.
A solution of Ketoprofen in dehydrated ethanol(1 in
100) shows no optical rotation.
Ketoprofen is colored to pale yellow by light.
of solutions of Ketoprofen and Ketoprofen RS in methanol (1 in 200000) as directed under the Ultravioletvisible Spectrophotomtry: both spectra exhibit similar
intensities of absorption at the same wavelength.
(2) Determine the infrared spectra of Ketoprofen
and Ketoprofen RS, previously dried, as directed in the
potassium bromide disk method under the Infrared
Spectrophotometry: both spectra exhibit similar intensities of absorption at the wavenumbers.
Melting Point
Between 94 C and 97 C

1.0 g of Ketoprofen in 10 mL of acetone: the solution is
clear and has no more color than the following control
solution.
Control solutionTo a mixture of 0.6 mL of
cobalt() chloride colorimetric stock solution and 2.4
mL of Iron() chloride colorimetric stock solution add
the diluted hydrochloric acid (1 in 10) to make 10 mL.
To 5.0 mL of this solution add diluted hydrochloric acid(1 in 10) to make 100 mL.
(2) Heavy metalsProceed with about 2.0 g of Ketoprofen according to Method 2 and perform the test.
(3) Related substances Perform this procedure
with a minimum of exposure to light, using lightresistant vessels.. Dissolve 20 mg of Ketoprofen in 20
mL of the mobile phase and use this solution as the test
solution. Pipet exactly 1 mL of the test solution and add

the mobile phase to make exactly 50 mL. Pipet exactly
1 mL of this solution, add the mobile phase to make
exactly 10 mL and use this solution as the standard solution. Perform the test with exactly 20 L each of the
test solution and the standard solution as directed under
the Liquid Chromatography according to the following
conditions. Determine each peak area by the automatic
integration method: the areas of the peaks from the test
solution, having the relative retention time of about 1.5
and about 0.3 with respect to Ketoprofen are not greater
than 2 times and 4.5 times peak area of ketoprofen
from the standard solution, respectively, the area of the
peak other than Ketoprofen and the peaks mentioned
above is not larger than the peak area of Ketoproren
from the standard solution, and total area of these peaks
is not larger than 2 times peak area of Ketoprofen from
the standard solution.
Operating conditins
Detector: An ultraviolet absorption photometrer
(wavelength : 233 nm)
Column: A stainlenn steel column, about 4.6 mm in
octadecylsilanized silica gel for Liquid Chromatography (5 m in particle diameter).
Column temperature: A constant temperature of
about 25 C
Mobile phase: Dissolve 68 g of potassium dihydro
phosphate in water to make 1000mL, and adjust the pH
to 3.5 with phosphoric acid, To 20 mL of this solution
add 430 mL of acetonitrile and 550 mL of water.
Flow rate: Adjust the flow rate so that the retention
time of ketoprofen is about 7minutes.
System suitability
Test for required detectability: To exactly 1 mL of
the standard solution, add the mobile phase to make exactly 10 mL. Confirm that the peak area of Ketoprofen
obtained with 20 L of this solution is equivalent to 9
to 11% of that with 20 L of the standard solution.
operation conditions, the number of the theoretical
plates and symmertrical factor the peak of Ketoprofen
is not less than 8000 and not more than 1.5 respectively.
above operating conditions, the relative standard deviation of the peak area of Ketoprofen is not more than
2.0%.
Time spar of measurement: About 7 times as long as
the retention time of ketoprofen.
Loss on Drying Not more than 0.5% (0.5 g, in vacuum, 60 C, 24 hours).
Assay Weigh accurately about 0.3 g of Ketoprofen,
previously dried, dissolve in 25 mL of ethanol, add 25

mL of water and titrate with 0.1 mol/L sodium hydroxide VS (indicator: 3 drops of phenolphthalein TS). Perform a blank determination and make any necessary
correction.
= 25.428 mg of Cl6H14O3
Packaging and Storage
tight containers.
Preserve in light-resistant,
Ketorolac Tromethamine
OH
OH
OH
HO
N
NH2
O
C15H13NO3C4H11NO3: 376.40
Ketorolac Tromethamine contains not less than 98.5%
and not more than 101.5% of ketorolac tromethamine
with a mixture of dichloromethane, acetone and glacial

acetic acid (95:5:2) to a distance of about 15 cm, and
air-dry the plate. Sprlay evenly a solution of ninhydrin
in ethanol (0.3 in 10) on the plate and heat the plate at
about 150 C for 2 to 5 minutes: yellow spots with pink
to purple borders is shown.
pH Dissolve 1 g of Ketorolac Tromethamine in 100
mL of water: the pH of this solution is between 5.7 and
6.7.
Purity (1) Heavy metals Proceed with 1.0 g of Ketorolac Tromethamine according to the method 2 and
mL of standard lead solution (not more than 20 ppm).
(2) Related substances Perform the test with 10
L of the test solution as directed under the Liquid
Chromatography according to following operating conditions. Determine each peak area by the automatic integration method, and calculate the amount of each related substances: the ketorolac 1-keto analog or the ketorolac 1-hydroxy analog is not more than 0.1% and
any other impurity is not more than 0.5% and the sum
of all impurities is not more than 1.0%.
Amount(%) of related substances = 100 rf1
(C15H13NO3C4H11NO3), calculated on the dried basis.

Description Ketorolac Tromethamine is a white,
crystalline powder.
Ketorolac Tromethamine is freely soluble in water or in
methanol, sparingly soluble in ethanol, in dehydrated
ethanol or in tetrahydrofuran, and practically insoluble
in acetone, in dichloromethane, in toluene, in ethylacetate, in dioxane, in hexane, in butanol or in acetonitrile.
Melting pointBetween 165 C and 170 C (decomposition).
of solutions of Ketorolac Tromethamine and Ketorolac
Tromethamine RS in methanol (1 in 100000) as directed under Ultraviolet-visible Spectrophotometry:
both spectra exhibit similar intensities of absorption at
the same wavelength.
(2) Determine the infrared spectra of Ketorolac
Tromethamine and Ketorolac Tromethamine RS as directed in the potassium bromide disk method under the
Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumber.
(3) Dissolve each 50 mg each of Ketorolac Tromethamine and Ketorolac Tromethamine RS in a mixture
of dichloromethane and methanol (2:1) to make 10 mL,
and use these solutions as the test solution and the
standard solution. Perform the test with the test solution
and the standard solution as directed under the Thinlayer Chromatography. Spots each 40 L of the test solution and the standard solution on a plate of silica gel
for the thinlayer chromatography. Develop the plate
Ai
AS
rf1 : Response factor of each individual related substance peak relative to that of ketorolac; the rf1
values are 0.52 for the ketorolac 1- to analog, 0.67
for the ketorolac 1-hydroxy analog,
2.2 for the related substance peak having a retention
time of 0.54 relative to that of ketorolac, and
0.91 for the related substance peak at a relative retention time of 0.66.
Ai : Peak response for each related substance.
AS : Sum of all the peak responses of the related
substance peaks and the principal ketorolac peak.
Test solution, mobile phase, detector, column, injection volume are the same in the Assay.
Time span of measurement: About three times as long
as the retention time of ketorolac.
Loss on Drying not more than 0.5%.
Residue on Ignition not more than 0.1%.
Assay Weigh accurately about 20 mg each of Ketorolac
Tromethamine and Ketorolac Tromethamine RS, dissolve in a mixture of water and tetrahydrofuran (70:30)
to make exactly 50 mL, and use these solutions as the
test solution and the standard solution. The test solution
and the standard solution are protected from light. Perform the test with 10 L each of the test solution and
the standard solution as directed under the Liquid
Chromatography according to the following operating
KP 9 549
conditions. Calculate the area of the principal peak of
each solutions, AT and AS , by the automatic integration method.
Amount(mg) of ketorolac tromethamine
tight containers.
Lacidipine
H 3C
H
N
CH3
(C15H13NO3C4H11NO3)
= amount (mg) of Ketorolac Tromethamine RS
AT
AS
Dtector: An ultraviolet absortion photometer (wavelength: 313 nm).
inside diameter and 25 cm in length, packed with octylsilanized silica gel for liquid chromatography (5 m in
particle diameter).
about 40 C.
Mobile phase: A mixture of ammonium phosphate
buffer and tetrahydrofuran (70:30).
Flow rate: 1.5 mL/minute.
System suitability
System performance: In a 250-mL separator, mix
100 mL of water, 100 mL of dichloromethane, 30 mg
of Ketorolac Tromethamine RS and 1 mL of 1 mol/L
hydrochloric acid, shake, and allow the layers to separate. Tasfer the lower dichloromethane to a flask, and
discard the upper layer. Expose the dichloromethane
solution to direct sunlight 10 to 15 minutes. Transfer
1.0 mL of this solution to a vial, evaporate in a current
of air or in a stream of nitrogen to dryness, add 1.0 mL
of a mixture of water and tetrahydrofuran (70 : 30), and
dissolve. This solution may be stored under refrigeration, and used as long as the chromatogram obtained as
directed in Assay is suitable for identifying the peaks
due to the ketorolac 1-keto analog and ketorolac 1hydroxy analog, and for the measurement of the resolution. When the procedure is run with 10 L of this solution according to the above operating conditions, the
relative retention time of ketorolac 1-hydroxy analog
and ketorolac 1-keto analog to the ketorolac peak are
about 0.63 and 0.89, respectively, with the resolutions
of these peaks being not less than 1.5. Perform the test
with 10 L of standard solution: the theoretical plate
numbers are not less than 5500.
above operating conditions, the relative standard deviation of the peak area of Ketorolac is not more than
1.5%.
Ammonium phosphate bufferDissolve 5.75 g of
ammonium dihydrogen phosphoric acid in water to
make 1000 mL, add phosphoric acid, and adjust to pH
3.0. Make adjustments, if necessary, to achieve a retention time for ketorolac of about 8 to 12 minutes.
C2H5OOC
COOC2H5
COOC4H9
C26H33NO6: 455.54
Lacidipine contains not less 97.5% and not more than
102.0% of lacidipine (C26H33NO6), calculated on the
anhydrous and solvent-free basis.
Description Lacidipine is a white to pale yellow
crystalline powder.
Lacidipine is freely soluble in dichloromethane or in
acetone, sparingly soluble in dehydrated ethanol, and
practically insoluble in water.
Melting pointAbout 178 C.
Identification (1) Determine the infrared spectra of
Lacidipine and Lacidipine RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
absorption at the same wavenumbers.
(2) When proceed as directed in the Assay, the retention time of the principal peak in the test solution
corresponds to that in the standard solution.
Purity (1) IsopropanolWeigh accurately 1.0 g of
Lacidipine, add the internal standard solution to make
exactly 50 mL and use this solution as the test solution.
Pipet accurately 2 L of isopropanol, add the internal
standard solution to make exactly 100 mL and use this
solution as the standard solution. Perform the test with
1 L each of the test solution and the standard solution
as directed under the Gas Chromatography according to
the following operating conditions and calculate the
content (%) of isopropanol in the test solution (not
more than 0.5%).
Internal standard solutionPipet accurately 2 L
of dioxane and add dimethylacetamide to make exactly
100 mL.
Detector: A hydrogen flame-ionization detector.
Column: A glass column, about 0.32 mm in inside
diameter and about 60 cm in length, coated inside surface with polymethylsiloxane for gas chromatography 5
m in thickness.
Column temperature: Maintain the initial tempera-

ture of 60 C for 1 minute, up to 110 C at the rate of 3
C per minute, then up to 200 C at the rate of 50 C
per minute and hold at 200 C for 7 minutes.
Carrier gas: Nitrogen.
System suitability
with 1 L of the standard solution as directed under the
above operating conditions, two peaks are clearly separated with each other and the retention time for isopropanol and dioxin is about 6.2 minutes and about 15 minutes, respectively.
(2) Related substancesWeigh accurately 10 mg
of Lacidipine, add dehydrated ethanol to make exactly
10 mL, pipet 1.0 mL of this solution, add the mobile
phase to make exactly 5 mL and use this solution as the
test solution. Pipet 1.0 mL of the test solution, add mobile phase to make exactly 500 mL and use this solution as the standard solution. Perform the test with 20
L of the test solution and the standard solution as directed under the Liquid Chromatography according to
the following operating conditions and determine the
area of the peaks in the test solution and the standard
solution the area of the peak corresponding to lacidipine related substance I obtained from the test solution
is not more than twice the area of the principal peak obtained from the standard solution (0.2%, the relative response factor: 2), the area of any other related substance from the test solution is not more than the area
of the principal peak from the standard solution (0.2%).
Calculate the content of lacidipine related substance I
using the response factor and the content of any other
related substance using the standard solution: total
amount of impurities is not greater than 0.5%.
Column: A stainless steel column about 4.6 mm in
cyanosilyl silica gel for liquid chromatography (5 m
in particle diameter).
Mobile phase: A mixture of n-hexane and dehydrated ethanol (97:3). Adjust the composition so that
the retention time of lacidipine is about 10 min.
Flow rate: About 2.0 mL/minute.
Water Not more than 0.2% (0.5 g, coulometric titration).
Assay Weigh accurately 10 mg each of Lacidipine
and Lacidipine RS, add dehydrated ethanol to make exactly 10 mL each, pipet 5.0 mL each, add the mobile
phase to make exactly 100 mL each and use these solutions as the test solution and the standard solution, respectively. Perform the test with 20 L of the test solution and the standard solution as directed under the
Liquid Chromatography according to the following operating conditions and determine the area of lacidipine
peak in the test solution, AT , and the standard solution, A S .

Amount (mg) of lacidipine (C26H33NO6)
A
= amount (mg) of Lacidipine RS T
AS
Proceed as directed in the operating conditions of
the Related Substances under the Purity.
Packaging and Storage Preserve in well-closed containers.
Lactulose
HOH2C
OH
O
H
HO
H
CH2OH
OH
CH2OH
O
H
OH
OH
C12H22O11: 342.30
Lactulose is a solution of Lactulose prepared by isomerizing lactose under the existing of alkaline and purified
by ion-exchange resin.
Lactulose contains not less than 50.0% and not more
than 56.0% of lactulose (C12H22O11).
Description Lactulose is a clear, colorless of pale
yellow, viscous liquid, is odorless and has a sweet taste.
Lactulose is miscible with water and with formamide.
Identification (1) To 0.7 g of Lactulose, add 10 mL
of water, 10 mL of ammonium molybdate (1 in 25) and
0.2 mL of glacial acetic acid and heat in a water-bath
for 5 minutes to 10 minutes: a blue color is observed.
(2) Mix 0.3 g of Lactulose and 30 mL of water, add
16 mL of 0.5 mol/L iodine TS, then immediately add
2.5 mL of 8 mol/L sodium hydroxide TS, allow to stand
for 7 minutes and add 2.5 mL of diluted sulfuric acid (3
in 20). To this solution, add a saturated solution of sodium sulfite until the solution turns pale yellow, then
add 3 drops of methyl orange TS, neutralize with a solution of sodium hydroxide (4 in 25) and add water to
make 100 mL. To 10 mL of this solution, add 5 mL of
Fehlings TS and boil for 5 minutes: a red precipitate is
produced.
Specific gravity
20
: Between 1.320 and 1.360.
d 20
KP 9 551
pH Dissolve 2.0g of Lactulose in 15 mL of water: the
pH of this solution is between 3.5 and 5.5.
Purity (1) Heavy metalsProceed with 5.0 g of
Lactulose according to Method 4 and perform the test.
Lactulose according to Method 1 and perform the test
(not more than 2 ppm).
(3) Other saccharidesDetermine the heights of
the peaks corresponding to D-galactose and Lactose,
respectively, on the chromatogram obtained in Assay
from the test solution and the standard solution and calculate the ratios of the peak heights of D-galactose and
Lactose to that of the internal standard from the test solution, QTa and QTb and then from the standard solution, QSa and QSb : it contains D-galactose of not
more than 11.0% and lactose monohydrate of not more
than 6.0%.
Amount (mg) of galactose (C6H12O6)
Q
= amount (mg) of D-galactose Ta
QSa
Detector: A differential refractometer.
Column: A stainless steel column, about 8 mm in
gel type strong acid ion-exchange resin for liquid
chromatography (degree of crosslinkage: 6%) (11 m
about 75 C.
Mobile phase: Water.
time of lactulose is about 18 minutes.
System suitability
operating conditions, lactulose and internal standard are
eluted in this order with the resolution between their
peaks being not less than 8.0.
times with 20L of the standard solution under the
above operating conditions, the relative standard deviation of the ratios of the peak heights of lactulose, galactose and lactose to that of the internal standard are not
more than 2.0% respectively.
Amount (mg) of lactose monohydrate (C12H22O11H2O)

Q
= amount (mg) of lactose monohydrate Tb
QSb
Assay Weigh accurately about 1 g of Lactulose, add
10.0 mL of the internal standard solution and water to
make exactly 50 mL and use this solution as the test solution. Separately, weigh accurately about 0.5 g of Lactulose RS, accurately about 80 mg of D-galactose and
accurately about 40 mg of lactose monosaccharide, add
10.0 mL of the internal standard solution and water to
make exactly 50 mL and use this solution as the standard solution. Perform the test with 20 L each of the
the peak height of lactulose to that of the internal standard, for the test solution and the standard solution respectively.
Amount (mg) of lactulose (C12H22O11)
Q
= amount (mg) of Lactulose RS T
QS
Internal standard solutionA solution of Dmannitol (1 in 20).
Lamivudine
O
N
HO
NH2
O
N
S
C8H11N3O3S: 229.26
Lamivudine contains not less than 98.0% and not more
than 102.0% of lamivudine (C8H11N3O3S), calculated
on the anhydrous and solvent-free basis.
Description Lamivudine is a white solid.
Lamivudine is soluble in water.
Lamivudine and Lamivudine RS as directed in the
paste method under the Infrared Spectrophotometry:
the same wavenumbers.
(2) When proceed as directed in the Lamivudine
enantiomer under the Purity, the retention time of the
principal peak from the test solution corresponds to that
from the standard solution.
Purity (1) Clarity and color of solutionProceed
with a solution of Lamivudine (1 in 20) as directed under the Infrared Spectrophotometry and measure the

absorbance of this solution at 440 nm in 4 cm: not more
than 0.0015.
(2) Lamivudine enantiomerWeigh accurately
about 25 mg of Lamivudine, add water to make 100 mL
and use this solution as the test solution. Perform the
test with 10 L of the test solution as directed under the
Liquid Chromatography according to the following operating conditions, determine the areas of the principal
peaks and calculate the content of lamivudine enantiomer: not more than 0.3%.
Content (%) of lamivudine enantiomer
Ai
= 100
Ai + AS
Ai : Peak area of lamivudine enantiomer

AS : Peak area of lamivudine
beta-cyclodextrin bonded to silica gel for liquid chromatography (5-10 m in particle diameter).
Mobile phase: A mixture of 0.1 mol/L ammonium
acetate solution and methanol (95:5).
System suitability
System performance: Dissolve the content of one
vial of lamivudine resolution mixture I RS in 5 mL of
water, wash the inner side of the vial with 2 mL each of
water, combine the washings and the dissolved content,
and add water to make exactly 10 mL. Perform the test
with 10 L of this solution as directed under the Liquid
Chromatography according to the above operating conditions, the relative retention times for lamivudine peak
and lamivudine enantiomer peak are about 1.0 and 1.2,
respectively, with the resolution between lamivudine
peak and lamivudine enantiomer peak being not less
than 1.5.
0.1 mol/L Ammonium acetate solutionDissolve
about 7.7 g of ammonium acetate in water and dilute
with water to make 1000 mL.
(3) Residual solventsWeigh accurately 5 g of
Lamivudine, add 10 mL of the internal standard solution, add a mixture of dimethylsulfoxide and water
(1:1) to make exactly 100 mL and use this solution as
the test solution. To 10 mL of the internal standard solution, add accurately 100 L each of dehydrate ethanol,
isopropyl acetate, methanol and triethylamine, add a
mixture of dimethyl sulfoxide and water (1:1) to make
exactly 100 mL and use this solution as the standard solution. Perform the test with 0.5 L each of the test solution and the standard solution as directed under the
Gas Chromatography according to the following operating conditions, determine the areas of peaks in these
solutions and calculate the content of residual solvents

in Lamivudine: not more than 0.2% of ethanol, not
more than 0.2% of isopropyl acetate, not more than
0.1% of triethylamine and not more than 0.3% of total
residual solvents.
Content (%) of each residual solvent
C Q
= 10 i
W QS
C: Concentration (mg/mL) of the respective analyte
in the standard solution
W: Weight (g) of Lamivudine taken
Qi : Peak area ratio of the respective analyte to the
internal standard in the test solution
QS : Peak area ratio of the respective analyte to the
internal standard in the standard solution
Internal standard solutionPipet 1 mL of 2pentanone and add a mixture of dimethylsulfoxide and
water (1:1) to make exactly 100 mL.
Column: A fused silica tube, about 0.53 mm in inside diameter and about 50 m in length, coated inside
surface with dimethylpolysiloxane for gas chromatography 5 m in thickness.
Column temperature: Maintain the initial temperature of 70 C for 3 minute, up to 200 C at the rate of
30 C per minute and hold at 200 C for 6.5 minutes.
Carrier gas: Helium.
Injection port temperature: 150 C.
Detector temperature: 250 C.
(4) Related substancesWeigh accurately about
25 mg of Lamivudine, dissolve in the mobile phase as
directed in the Assay to make exactly 100 mL and use
this solution as the test solution. Weigh accurately a
portion of salicylic acid, add the mobile phase as directed in the Assay to render the concentration of 0.625
g per mL and use this solution as the salicylic acid solution. Perform the test with 10 L each of the test solution and the salicylic acid solution as directed under
the Liquid Chromatography according to the operating
conditions directed in the Assay, determine the area of
salicylic acid peak in these solutions and calculate the
content of salicylic acid according to the equation (1):
not more than 0.1%. Calculate the content of other related substances according to the equation (2): not more
than 0.3% for the related substance having the relative
retention time of about 0.4, not more than 0.2% for the
related substance having the relative retention time of
about 0.9 and not more than 0.6% for total related substances.
KP 9 553
Content (%) of salicylic acid = 10
C AT
W AS
(1)
C: Concentration (g/mL) of salicylic acid in the

salicylic acid solution
W: Weight (mg) of Lamivudine taken
AT : Peak area of salicylic acid obtained from the
test solution
AS : Peak area of salicylic acid obtained from the
salicylic acid solution
Content (%) of other related substance = 100
Ai
(2)
AS
Ai : Peak area of related substance other than salicylic acid obtained from the test solution
AS : Total area of peaks obtained from the test solution
respectively, with the resolution between lamivudine

peak and lamivudine enantiomer peak being not less
than 1.5.
above operating conditions, the relative standard deviation of the areas of lamivudine peak is not more than
2.0%.
0.025 mol/L Ammonium acetate bufferWeigh
about 1.9 g of ammonium acetate, dissolve in 900 mL
of water and adjust the pH to 3.8 0.2 with acetic acid
and add water to make 1000 mL.

well-closed containers.
Lanatoside C
Water Not more than 0.2% (1 g, coulometric titration).
O
O
OH
H
Assay Weigh accurately about 25 mg each of Lamivudine and Lamivudine RS, add a mixture of 0.025
mol/L ammonium acetate buffer and methanol (95:5) to
make exactly 100 mL each and use these solutions as
the test solution and the standard solution, respectively.
Perform the test with 10 L each of the test solution
and the standard solution as directed under the Liquid
conditions and determine the area of the principal peak
in the test solution, AT , and in the standard solution,
AS .
CH3
(3-10 m in particle diameter).
Mobile phase: A mixture of 0.025 mol/L ammonium acetate buffer and methanol (95:5).
about 35 C.
System suitability
System performance: Dissolve the content of one
vial of lamivudine resolution mixture II RS in 5 mL of
the mobile phase. Perform the test with 10 L of this
solution as directed under the above operating conditions, the relative retention times for lamivudine peak
and lamivudine enantiomer peak are about 1.0 and 0.9,
OH
O
H
H
H
CH3
O
O
OH
H
H
CH3
O
H
CH2OH
Amount (mg) of lamivudine (C8H11N3O3S)

A
= amount (mg) of Lamivudine RS T
AS
H
H
CH3
CH3
O
OH
H
H
H
O
O
H
OH
OH
C CH3
O
HO
C49H76O20: 985.12
Lanatoside C, when dried, contains not less than 90.0%
and not more than 102.0% of lanatoside C (C49H76O20).
Description Lanatoside C is a colorless or white
crystal or a white, crystalline powder and is odorless.
Lanatoside C is soluble in methanol, slightly soluble in
ethanol and practically insoluble in water or in ether.
Lanatoside C is hygroscopic.
Identification Place 1 mg of Lanatoside C to a small
test tube having an internal diameter of about 10 mm,
dissolve in 1 mL of a solution of ferric chloride in glacial acetic acid (1 in 10000) and underlay gently with 1
mL of sulfuric acid: at the zone of contact of the two
liquids, a brown ring is produced and the color of the
upper layer near the contact zone gradually changes to

blue through purple. Finally the color of the entire acetic acid layer changes to blue-green through deep blue.
D : Between + 32 and
+ 35 (after drying, 0.5 g, methanol, 25 mL, 100 mm).
Purity Related substancesDissolve 10 mg of Lanatoside C in exactly 5 mL of methanol and use this solution as the test solution. Separately, dissolve 1.0 mg
of Lanatoside C RS in exactly 5 mL of methanol and
use this solution as the standard solution. Perform the
test with the test solution and the standard solution, as
directed under Thin-layer Chromatography. Spot 20 L
plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of dichloromethane, methanol and water (84 : 15 : 1) to a distance of about 13
cm and air-dry the plate. Spray evenly dilute sulfuric
acid on the plate and heat the plate at 110 C for 10 minutes: no spot other than the principal spot from the test
solution is larger nor darker than the standard solution.
Loss on Drying Not more than 7.5% (0.5 g, in vacuum, P2O5, 60 C, 4 hours).
Assay Weigh accurately about 50 mg each of Lanatoside C and Lanatoside C RS, previously dried, dissolve
separately in methanol to make exactly 25 mL each, pipet 5.0 mL of each solution, add methanol to make 100
mL each and use these solution as the test solution and
the standard solution, respectively. Pipet 5.0 mL each
of the test solution and the standard solution into lightresistant, volumetric flasks and add 5 mL each of picric
acid TS and 0.5 mL each of a solution of sodium hydroxide (1 in 10), shake well and add methanol to make
25 mL each. Allow these solutions to stand between 18
C and 22 C for 25 minutes. Separately pipet 5.0 mL
of methanol, proceed in the same manner and use this
solution as the blank solution. Determine the absorbances, AT and AS , of the solutions at 485 nm as directed under the Ultraviolet-visible spectrophotometry
for the test solution and the standard solution, respectively.
Amount (mg) of lanatoside C (C49H76O20)
A
= amount (mg) of Lanatoside C RS T
AS
tight containers.
Lanatoside C Tablets
Lanatoside C Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of lanato-
side C (C49H76O20: 985.12).

Tablets, with Lanatoside C.
Identification (1) Shake a portion of powdered Lanatoside C Tablets, equivalent to 1 mg of Lanatoside C
according to the labeled amount with 3 mL of ether and
filter. Wash the residue with two 3 mL volumes of ether
and air-dry. To the remaining residue, add 10 mL of a
mixture of chloroform and methanol (9 : 1), shake and
filter. Wash the residue with two 5 mL volumes of a
mixture of chloroform and methanol (9 : 1), combine
the filtrate and washings and evaporate on a water-bath
to a smaller volume. Transfer the solution to a small
test tube having an internal diameter of about 10 mm,
further evaporate on a water-bath to dryness and proceed as directed in the Identification under Lanatoside
C.
(2) Perform the test with the test solution and the
standard solution obtained in the Assay as directed under the Thin-layer Chromatography. Spot 25 L each of
the test solution and the standard solution on a plate of
silica gel for thin-layer chromatography. Develop the
plate with a mixture of dichloromethane, methanol and
water (84 : 15 : 1) of a distance of about 13 cm and airdry the plate. Spray evenly dilute sulfuric acid on the
plate and heat the plate at 110 C for 10 minutes: the
spots obtained from the test solution and the standard
solution show a black color and have the same Rf values.
Dissolution Test Take 1 tablet of Lanatoside C Tablets and perform the test with 500 mL of diluted hydrochloric acid (3 in 500), degassed by a suitable method, at 100 revolutions per minute as directed in Method 2 under the Dissolution Test. Take 20.0 mL of the
dissolved solution at 60 minutes after starting the test
and filter through a membrane filter (not more than 0.8
m). Discard the first 10 mL of the filtrate and use the
subsequent filtrate as the test solution. Separately,
weigh accurately a portion of Lanatoside C RS, dried in
vacuum over P2O5 at 60 C for 4 hours, equivalent to
100 times an amount of the labeled amount of Lanatoside C (C49H76O20), dissolve in methanol to make exactly 100 mL. Pipet 1 mL of this solution, add the test
solution to make exactly 500 mL, warm at 37 C for 60
minutes and use this solution as the standard solution.
Pipet 3.0 mL each of the test solution, the standard solution and the dissolution solution and transfer to glassstoppered brown test tubes, T, S and B, respectively. To
these solutions, add exactly 10 mL each of 12 mg/dL
ascorbic acid-hydrochloric acid TS and shake. Immediately, add exactly 0.2 mL each of diluted hydrogen
peroxide TS (1 in 100), shake well and allow to stand at
a constant temperature between 30 C and 37 C for 45
minutes. Determine immediately the fluorescence intensities, FT , FS and FB , of the test solution, the
standard solution and the dissolution solution, respec-
KP 9 555
tively, at 355 nm of the excitation wavelength and at
490 nm of the fluorescence wavelength as directed under the Fluorometry.
Individual dissolution rate of Lanatoside C Tablets for
the six tablets after 60 minutes is not less than 65%.
Requirement of retest is not applied to Lanatoside C
Tablets.
Dissolution rate (%) to labeled amount of lanatoside C
F FB 1
(C49H76O20) = W S T
FS F B C
WS: Amount (mg) of Lanatoside C RS,
C: Labeled amount (mg) of lanatoside
(C49H76O20) in each tablet.
Uniformity of Dosage Units It meets the requirement when the content uniformity test is performed according to the following procedure. Warm 1 tablet of
Lanatoside C Tablets with 5 mL of water until the tablet
is disintegrated, add 30 mL of ethanol, disperse finely
the particles with the aid of ultrasonic wave, add ethanol to make exactly V mL of a solution containing
about 5 g of lanatoside C (C49H76O20) per mL and filter. Discard the first 10 mL of the filtrate and use the
weigh accurately about 25 mg of Lanatoside C RS,
previously dried in vacuum over P2O5 at 60 C for 4
hours and dissolve in ethanol to make exactly 100 mL.
Pipet 2.0 mL of this solution, add 10 mL of water, add
ethanol to make exactly 100 mL and use this solution
as the standard solution. Pipet 2.0 mL each of the test
solution, the standard solution and diluted ethanol (17
in 20) into three brown glass-stoppered test tubes, T, S
and B, previously containing exactly 10 ml of 12
mg/dL ascorbic acid-hydrochloric acid TS, add exactly
1 mL each of dilute hydrogen peroxide TS immediately,
shake vigorously and allow to stand at a constant temperature between 25 C and 30 C for 40 minutes. Determine the fluorescence intensities, FT , FS and FB ,
of the test solution, the standard solution and the diluted ethanol (17 in 20), respectively, at 355 nm of the
excitation wavelength and at 490 nm of the fluorescence wavelength as directed under the Fluorometry.
= amount (mg) of lanatoside C RS
FT F B
V
F S F B 5000
Lanatoside C Tablets. Weigh accurately a portion of the
powder, equivalent to about 5 mg of lanatoside C
(C49H76O20), into a light-resistant volumetric flask, add
50 mL of ethanol and shake for 15 minutes. Then dilute
with ethanol to make exactly 100 mL. Filter this solution, discard the first 20 mL of the filtrate and use the
weigh accurately about 5.0 mg of Lanatoside C RS,

hours, dissolve in ethanol to make exactly 100 mL and
use this solution as the standard solution. Pipet 5.0 mL
each of the test solution and the standard solution into
light-resistant, glass-stoppered test tubes, add 3.0 mL
each of alkaline picric acid TS, shake well and allow to
stand between 22 C and 28 C for 25 minutes. Determine the absorbances, AT and AS , of the subsequent
test solution and the standard solution, respectively, at
490 nm as directed under the Ultraviolet-visible Spectrophotometry, using a solution, prepared by the same
manner with 5 mL of ethanol, as the blank.
A
= amount (mg) of Lanatoside C RS T
AS

tight containers.
Lansoprazole
H
N
O
S
N
N
CH3
O
CF3
C16H14F3N3O2S: 369.36
Lansoprazole contains not less than 99.0% and not
more than 101.1% of lansoprazole (C16H14F3N3O2S),
calculated on the anhydrous basis.
Description Lansoprazole is a white or brown crystalline powder.
Lansoprazole is freely soluble in dimethylformamide,
soluble in methanol, sparingly soluble in dehydrated
ethanol, very slightly soluble in ether and practically
insoluble in water.
Melting pointAbout 166 C (with decomposition)
of solutions of Lansoprazole and Lansoprazole RS in
methanol (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Lansoprazole
and Lansoprazole RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorp-

tion at the same wavenumbers.
Purity Related substancesWeigh accurately about
0.125 g of Lansoprazole, dissolve in methanol to make
exactly 50 mL, pipet 1.0 mL of this solution, add a
mixture of the mobile phase A and the mobile phase B
(9:1) to make exactly 10 mL and use this solution as the
test solution. Prepare the test solution immediately before use. Separately, weigh accurately about 25 mg of
Lansoprazole RS, dissolve in methanol to make exactly
100 mL, pipet 5.0 mL of this solution, add methanol to
make exactly 50 mL. To 1.0 mL of this solution, add a
(9:1) to make exactly 10 mL and use this solution as the
standard solution. To 9 mL of a mixture of the mobile
phase A and the mobile phase B (9:1), add 1 mL of methanol and use this solution as the blank solution. Perform the test with 40 L each of the test solution, the
standard solution and the blank solution as directed in
the peak area percentage method under the Liquid
Chromatography. Disregard the peaks obtained from
the test solution corresponding to the peaks obtained
from the blank solution and determined the peak area
of each related substance other than the principal peak
from the test solution, Ai , and the peak area of the
principal peak from the standard solution, AS : total
content of related substances is not more than 0.1%.
Content (%) of each related substance
C A
= 50 i
W AS
C: Concentration (g/mL) of lansoprazole in the
standard solution
W: Weight (mg) of Lansoprazole taken
(5 m in particle diameter).
Mobile phase: Control the step or concentration
gradient by mixing the mobile phases A and B as directed in the following table.
Mobile phase A: Water
Mobile phase B: A mixture of acetonitrile, water
and triethylamine (160:40:1). Adjust the pH of the solution to 7.0 by the addition of phosphoric acid.
Time
(min)
Mobile
phase A
(vol%)
Mobile
phase B
(vol%)
0-40
9020
1080
40-50
20
80
50-51
2090
8010
51-60
90
10
Elution
condition
Linear
gradient
Isocratic
Linear
gradient
Isocratic
Flow rate: 0.8 mL/min.

System suitability
System performance: Weigh 5 mg each of Lansoprazole RS and lansoprazole related substance I {2[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]
sulfonyl]benzimidazole} RS, dissolve in methanol to
make 200 mL, pipet 1.0 mL of this solution and add a
(9:1) to make exactly 10 mL. When the procedure is
run with 40 L of this solution under the above operating conditions, the resolution between lansoprazole
peak and the related substance I peak is not less than 6.
System repeatability: Weigh 2.5 mg of lansoprazole related substance I RS, dissolve in methanol to
(9:1) to make exactly 10 mL. When the test is repeated
6 times with 40 L each of this solution under the
above operating conditions, the relative standard deviation of the areas of lansoprazole related substance I
peak is not more than 3%.
Water Not more than 0.1% (1.0 g, volumetric titration, direct titration).
Use 50 mL of a mixture of pyridine and ethylene glycol
(9:1 or 8:2) as the solvent in this test.
Assay Weigh accurately about 50 mg each of Lansoprazol and Lansoprazole RS, dissolve in the internal
standard solution to make 10 mL each, pipet 1 mL each
of these solution, add a mixture, prepared by mixing
water, acetonitrile and triethylamine (60:40:1) and by
adjusting the pH of the solution to 10 with phosphoric
acid, to make exactly 50 mL each and use these solutions as the test solution and the standard solution, respectively. Perform the test with 10 L each of the test
solution and the standard solution as directed under the
Liquid Chromatography according to the following operating conditions and determined the ratios of the peak
area of lansoprazole to that of the internal standard
from the test solution, QT , and from the standard solution, QS .
Amount (mg) of lansoprazole (C16H14F3N3O2S)
Q
= amount (mg) of Lansoprazole RS T
QS
Internal standard solutionWeigh about 25 mg of
4-ethoxyacetophenone and dissolve in a mixture, prepared by mixing water, acetonitrile and triethylamine
(60:40:1) and by adjusting the pH of the solution to 10
with phosphoric acid, to make 10 mL.
KP 9 557
Mobile phase: A mixture of water, acetonitrile and
triethylamine (60:40:1). Adjust the pH of the solution
to 7.0 by the addition of phosphoric acid.
Flow rate: 1 mL/min.
System suitability
System performance: Weigh 5 mg each of Lansoprazole RS and lansoprazole related substance I RS,
and dissolve in a mixture, prepared by mixing water,
acetonitrile and triethylamine (60:40:1) and by adjusting the pH of the solution to 10 with phosphoric acid,
to make exactly 50 mL. When the procedure is run with
10 L of this solution under the above operating conditions, the resolution between lansoprazole peak and the
related substance I peak is not less than 5.
times with 10 L each of the standard solution under
the above operating conditions, the relative standard
deviation of the areas of lansoprazole peak is not more
than 0.5%.
corresponds to that from the standard solution.

Purity (1) Heavy metalsProceed with 1.0 g of Letrozole according to Method 2, and perform the test.
(2) Related substancesWeigh accurately about 25
mg of Letrozole, dissolve in 75 mL of acetonitrile, add
water to make exactly 250 mL and use this solution as
the test solution. Separately, to 5.0 mL of the test solution, add a mixture of water and acetonitrile (7:3) to
make exactly 50 mL, pipet 5.0 mL of this solution, add
a mixture of water and acetonitrile (7:3) to make exactly 50 mL and use this solution as the standard solution.
conditions and determine the areas of peaks from these
solutions: not more than 0.3% for letrozole related substance I (4,4-(1H-1,3,4-triazol-1-ylmethylene) dibenzonitrile), not more than 0.2% for 4,4,4methylidenetrisbenzonitrile, not more than 0.1% for
any other related substance and not more than 0.3% for
total related substances (the relative retention time for
4,4,4-methylidenetrisbenzonitrile is about 1.9).
Content (%) of each related substance=
Letrozole
Ai
AS
Ai : Area of each related substance peak obtained

from the test solution
AS : Area of the principal peak obtained from the
standard solution
N
N
N
NC
CN
C17H11N5 : 285.30
Letrozole contains not less than 98.0% and not more
than 102.0% of letrozole (C17H11N5), calculated on the
anhydrous basis.
Description Letrozole is a white to yellowish-white
crystal or crystalline powder.
Letrozole is freely soluble in dichloromethane, slightly
soluble in ethanol and practically insoluble in water.
Letrozole and Letrozole RS as directed in the paste method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same
wavenumbers.
(2) When proceed as directed in the Assay, the retention time of the principal peak from the test solution
Detector, column, mobile phase and flow rate: proceed as directed in the operating conditions under Assay
System suitability
System performance: Weigh 2 mg of letrozole
related substance I RS and 10 mg of Letrozole RS, dissolve in a mixture of water and acetonitrile (7:3) to
mixture of water and acetonitrile (7:3) to make 50 mL.
When the procedure is run with 15 L of this solution
under the above operating conditions, the relative retention times are about 0.68 and 1.0 for letrozole related
substance I and letrozole, respectively, with the resolution between the two peaks being not less than 1.5.
deviation of the areas of letrozole peak is not more than
10.0%.
Water Not more than 0.3% (1 g, volumetric titration,
direct titration).

Assay Weigh accurately about 20 mg each of Letrozole and Letrozole RS, dissolve in a mixture of water
and acetonitrile (7:3) to make exactly 100 mL each, pipet 5.0 mL each of these solutions, add a mixture of
water and acetonitrile (7:3) to make exactly 100 mL
each and use these solution as the test solution and the
standard solutions, respectively. Perform the test with
20 L each with the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions and determine the area of letrozole peak in the test solution,
AT , and in the standard solution, AS .
Amount (mg) of letrozole (C17H11N5)
A
= amount (mg) of Letrozole RS T
AS
inside diameter and about 12.5 cm in length, packed
with octadecylsilanized silica gel for liquid chromatography (5 m in particle diameter).
Mobile phase A: Water
Mobile phase B: Acetonitrile
Time
(min)
0
Mobile
phase A
(vol%)
70
Mobile
phase B
(vol%)
30
0-25
7030
3070
Elution
condition
Isocratic
Linear
gradient

System suitability
operating conditions, the symmetry factor for letrozole
peak is between 0.8 and 1.5.
deviation of the areas of letrozole peak is not more than
2.0%.
L-Leucine
H
(CH3)2CHCH2
C
NH2
CO2H
C6H13NO2: 131.17
L-Leucine, when dried, contains not less than 98.5%
and not more than 101.0% of L-leucine (C6H13NO2).
Description L-Leucine is a white crystal or crystalline powder, is odorless or has a faint characteristic
odor and has a slightly bitter taste.
L-Leucine is freely soluble in formic acid, sparingly soluble in water and practically insoluble in ethanol.
L-Leucine dissolves in dilute hydrochloric acid.
Identification Determine the infrared spectra of LLeucine and L-Leucine RS, previously dried, as directed in the potassium bromide disk method under the
D : Between +14.5
and +16.0 (after drying, 1 g, 6 mol/L hydrochloric acid
TS, 25 mL, 100 mm).
pH Dissolve 1.0 g of L-Leucine in 100 mL of water:
the pH of this solution is between 5.5 and 6.5.
0.5 g of L-Leucine in 10 mL of 1 mol/L hydrochloric
acid TS: the solution is clear and colorless.
(2) ChlorideDissolve 0.5 g of L-Leucine in 40
mL of water and 6 mL of dilute nitric acid, add water to
make 50 mL, and perform the test. Prepare the control
solution with 0.30 mL of 0.01 mol/L hydrochloric acid
VS (not more than 0.021%).
(3) SulfateDissolve 0.6 g of L-Leucine in 40 mL
of water and 1 mL of dilute hydrochloric acid, add water to make 50 mL, and perform the test. Prepare the
control solution with 0.35 mL of 0.005 mol/L sulfuric
acid VS (not more than 0.028%).
(4) AmmoniumPerform the test with 0.25 g of LLeucine. Prepare the control solution with 5.0 mL of
standard ammonium solution (not more than 0.02%).
(5) Heavy metalsProceed with 1.0 g of L-Leucine
according to Method 4 and perform the test. Prepare the
control solution with 2.0 mL of standard lead solution
L-Leucine according to Method 2 and perform the test
(7) Related substancesDissolve 0.1 g of LLeucine by warming, after cooling, add water to make
25 mL and use this solution as the test solution. Proceed as directed in the Purity (7) under L-Isoleucine.
hours).
KP 9 559
Assay Weigh accurately about 0.13 g L-Leucine, previously dried and dissolve in 3 mL of formic acid, add
50 mL of glacial acetic acid and titrate with 0.1 mol/L
= 13.117 mg of C6H13NO2
Levallorphan Tartrate
CH2CH
H
CH2
CO2H
CHOH
CHOH
CO2H

D : Between -37.0
and -39.2 (0.2 g, previously dried, water, 10 mL, 100
mm)
Purity (1) Clarity and Color of SolutionWhen 0.2
g of Levallorphan Tartrate in 10 mL of water: the solution is colorless and clear.
(2) Heavy metalsProceed with 1.0 g of Levallorphan Tartrate according to Method 4 and prepare the
(3) Related compoundsDissolve 0.20 g of Levallorphan Tartrate in 10 mL of water and use this solution
as the test solution. Pipet 1.0 mL of the test solution,
as the standard solution. Proceed with the test solution
and the standard solution as directed under the Thinlayer Chromatography. Spot 20 L each of the test solution and the standard solution on a plate of silica gel
for thin-layer chromatography. Develop the plate with a
mixture of methanol and ammonia TS (200 : 3) to a
distance of about 10 cm and air-dry. Spray evenly Dragendorffs TS on the plate: principal spot from the test
solution are not more intense than the spot from the
standard solution.
HO
C19H25NOC4H6O6: 433.50
Levallorphan Tartrate, when dried, contains not less
than 98.5% and not more than 101.0% of levallorphan
tartrate (C19H25NOC4H6O6).
Description Levallorphan Tartrate is a white to pale
yellow crystalline powder and is odorless.
Levallorphan Tartrate is soluble in water or in glacial
acetic acid, slightly soluble in ethanol and insoluble in
ether.
of solutions of Levallorphan Tartarate and Levallorphan Tartrate RS in 0.01 mol/L hydrochloric acid TS (1
in 10000) as directed under the Ultraviolet-visible
Spectrometry: both spectra exhibit similar intensities of
absorption at the same wavelengths.
(2) Determine the infrared spectra of Levallorphan
Tartrate and Levallorphan Tartrate RS, both previously
dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same
wavenumbers.
(3) A solution of Levallorphan Tartrate (1 in 30) responds to Qualitative Tests (1) and (2) for the tartrate.
Melting Point Between 174 C and 178 C.
pH Dissolve 0.2 g of Levallorphan Tartarte in 20 mL
of water: the pH of this solution is between 3.3 and 3.8.
Loss on Drying Not less than 0.5% (1 g, in vacuum,

P2O5, 80 C, 4 hours).
Assay Weigh accurately about 0.5 g of Levallorphan
Tartrate, previously dried, dissolve in 30 mL of glacial
acetic acid and titrate with 0.1 mol/L perchloric acid
VS (indicator: 2 drops of methyllosanilin chloride TS).
Perform a blank determination and make any necessary
correction.
= 43.35 mg of C19H25NOC4H6O6
Levallorphan Tartrate Injection

Levallorphan Tartrate Injection is an aqueous solution
for injection. Levallorphan Tartrate Injection contains
not less than 93.0% and not more than 107.0% of levallorphan tartrate (C19H25NOC4H6O6: 433.50).
Method of Preparation Prepare as directed under Injections, with Levallorphan Tartrate.
Description Levallorphan Tartrate Injection is a clear,
colorless liquid.
pHBetween 3.0 and 4.5
Identification Take a volume of Levallorphan Tartrate Injection, equivalent to 3 mg of Levallorphan Tartrate according to the labeled amount, and add 5 mL of
water and 2 drops of dilute hydrochloric acid. Wash
with five 15 mL volumes of ether by shaking thoroughly and separate. Take water layer and heat on a waterbath to evaporate ether and cool it. Add 50 mL of 0.01
mol/L hydrochloric acid TS. Determine the absorption
spectrum of this solution as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum
between 277 nm and 281 nm.
Sterility Test It meets the requirement.
Foreign Insoluble Matter Ttest
quirement.
It meets the re-
Insoluble Particulate Matter Test for Injections It

meets the requirement.
Determination of Volume of Injection in Containers
It meets the requirement.
Assay Take a volume of Levallorphan Tartrate Injection, equivalent to about 2 mg of levallorphan tartrate
(C19H25NOC4H6O6) according to the labeled amount,
add 10.0 mL of internal standard solution and use this
solution as the test solution. Separately weigh accurately about 0.1 g of levallorphan Tartrate RS, previously
dried in vacuum for 4 hours at 80 C in the presence of
P2O5 and dissolve in water to make exactly 100 mL.
Pipet 2.0 mL of this solution, add 10.0 mL of internal
standard solution and use this solution as the standard
solution. Perform the test with 10 L each of the test
solution and the standard solution according to the following operating conditions as directed under the Liquid Chromatography and calculate the ratios of the
peak areas of levallorphan to that of the internal standard, QT and QS , for the test solution and the standard solution, respectively.
Amount (mg) of levallorphan tartrate
(C19H25NOC4H6O6) = amount (mg) of Levallorphan
Q
1
Tartrate RS T
QS 50
Internal standard solutionDissolve 40 mg of isobutyl paraoxybenzoate in 10 mL of ethanol and add water to make 100 mL. Take 10 mL of this solution and
add water to make 100 mL.
Column: A stainless steal column, about 4 mm in
internal diameter and 15cm in length, packed with octadecylsilylated silica gel for liquid chromatography (5
m in particle diameter).
Column Temperature: A constant temperature at
about 40 C.
Mobile phase: Dissolve 1.0 g of lauryl sodium sulfate in 500 mL of diluted phosphoric acid (1 in 1000)
and adjust the pH with sodium hydroxide TS to 3.0.
Mix 300 mL of this solution and 200 mL of acetonitrile.
time of levallorphan is approximately 12 minutes.
System suitability
operating conditions, the internal standard and levallorphan are eluted in this order with the resolution between their peaks being not less than 5.0.
times with the 10 L of the standard solution under the
above operating conditions, the relative standard deviation of the ratios of the peak area of levallorphan to that
of the internal standard is not more than 1.0%.
tainers.
Preserve in hermetic con-
Levodopa
H
HO
CH 2
CO 2H
NH 2
HO
C9H11NO4: 197.19
Levodopa, when dried, contains not less than 98.5%
and not more than 101.0% of levodopa (C9H11NO4).
Description Levodopa is a white or pale grayish
white crystal or crystalline powder and is odorless.
Levodopa is freely soluble in formic acid, slightly soluble in water and practically insoluble in ethanol or in
ether.
Levodopa dissolves in dilute hydrochloric acid.
pHThe pH of a saturated solution of Levodopa is
between 5.0 and 6.5.
Identification (1) Take 5 mL of a solution of Levodopa (1 in 1000), add 1 mL of ninhydrin TS and heat
for 3 minutes in a water-bath: a purple color is observed.
(2) Take 2 mL of a solution of Levodopa (1 in
5000), add 10 mL of 4-aminoantipyrine TS and shake:
a red color is observed.
(3) Dissolve separately 3 mg each of Levodopa and
Levodopa RS in 0.001 mol/L hydrochloric acid TS to
make 100 mL each and determine the absorption spectra of these solutions as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
KP 9 561
intensities of absorption at the same wavelengths.
D : Between -11.5
and -13.0 (after drying, 2.5 g, 1 mol/L hydrochloric
acid TS, 50 mL, 100 mm).
%
E11cm
Absorbance
(280 nm): Between 136 and 146
(after drying, 30 mg, 0.001 mol/L hydrochloric acid TS,
1000 mL).
1.0 g of Levodopa in 20 mL of 1 mol/L hydrochloric
acid TS: the solution is clear and colorless.
(2) ChlorideDissolve 0.5 g of Levodopa in 6 mL
of dilute nitric acid and add water to make 50 mL. Perform the test. Prepare the control solution with 0.30 mL
of 0.01 mol/L hydrochloric acid VS (not more than
0.021%).
(3) SulfateDissolve 0.40 g of Levodopa in 1 mL
of dilute hydrochloric acid and add water to make 50
mL. Perform the test. Prepare the control solution with
0.25 mL of 0.005 mol/L sulfuric acid VS (not more
than 0.030%).
(4) Heavy metalsProceed with 1.0 g of Levodopa
(5) ArsenicDissolve 1.0 g of Levodopa in 5 mL
of dilute hydrochloric acid and perform the test (not
more than 2 ppm).
(6) Related substancesDissolve 0.10 g of Levodopa in 10 mL of sodium metabisulfite TS and use this
solution as the test solution. Pipet 1.0 mL of the test solution, add sodium metabisulfite TS to make exactly 25
mL. Pipet 1.0 mL of this solution, add sodium metabisulfite TS to make exactly 20 mL and use this solution
as the standard solution. Perform the test with the test
Thin-layer Chromatography. Spot 5 L each of the test
solution and the standard solution on a plate of cellulose for thin-layer chromatography. Develop the plate
with a mixture of n-butanol, water, glacial acetic acid
and methanol (10 : 5 : 5 : 1) to a distance of about 10
cm and air-dry the plate. Spray evenly a solution of
ninhydrin in acetone (1 in 50) on the plate and heat at
90 o C for 10 minutes: the spots other than the principal spot from the test solution are not more intense than
the spot from the standard solution.
hours).
Assay Weigh accurately about 0.3 g Levodopa, previously dried and dissolve in 3 mL of formic acid, add
perchloric acid VS until the color of the solution
changes from purple through blue-green to green (indicator: 3 drops of methylrosaniline chloride TS). Perform a blank determination and make any necessary
correction.
= 19.719 mg of C9H11NO4
tight containers.
Levodropropizine
N
N
OH
H
OH
C13H20N2O2: 236.31
Levodropropizine, when dried, contains not less than
98.5% and not more than 101.0% of levodropropizine
(C13H20N2O2).
Description Levodropropizine is a white powder.
Levodropropizine is freely soluble in dilute glacial
acetic acid or in methanol, and slightly soluble in water
or in ethanol.
Identification Determine the infrared spectra of Levodropropizine and Levodropropizine RS as directed in
the potassium bromide disk method under the Infrared
Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
pH To 2.5 g of Levodropropizine, add 100 mL of water, heat to dissolve and cool: the pH of this solution is
D : Between -30.0
and 33.5 (1.5 g, after drying, 21 mg/mL, hydrochloric acid 50 mL, 100 mm).
Purity (1) Related substance I and related substancesDissolve 24.0 mg of Leveodropropizine in
the mobile phase to make exactly 100 mL and use this
solution as the test solution. Separately, dissolve 12.0
mg of levodropropizine related substance I (1phenylpiperazine) in methanol to make exactly 100 mL,
pipet 1.0 mL of this solution, add the mobile phase to
make exactly 100 mL and use this solution as the standard solution (1). Pipet 0.5 mL of the test solution and
1.0 mL of the standard solution (1), mix, add the mobile phase to make exactly 100 mL and use this solution as the standard solution (2). Perform the test with

20 L each of the test solution, the standard solutions
(1) and (2) as directed under the Liquid Chromatography according to the following operating condition, and
determine the area of the peaks in the test solution and
the standard solutions: the area of the peak corresponding to the related substance I obtained from the test solution is not more than the area of the corresponding
peak obtained from the standard solution (1) (0.5%)
and the individual area of any other peak from the test
solution is not more than 0.2 times the area of the related substance I peak from the standard solution (1)
(0.1%). Disregard any peaks having not more than 0.02
times the area of the related substance I peak from the
standard solution.
base-deactivated octylsilanized silica gel for liquid
chromatography (5 m in particle diameter).
Mobile phase: A mixture of phosphate buffer and
methanol (88:12).
System suitability
with 20 L of the standard solution (2) under the above
operating conditions, the resolution between levodropropizine peak and the related substance I peak is not
less than 2.0.
Phosphate bufferDissolve 6.81 g of potassium
dihydrogen phosphate in water to make 1000 mL and
adjust the pH to 3.0 by the addition of phosphoric acid.
(2) Related substance IIPrepare immediately before use. Dissolve 0.50 g of Levodropropizine in dichloromethane to make exactly 2.5 mL and use this solution as the test solution. Separately, dissolve 0.20 g of
levodropropizine related substance II {(2RS)-oxiran-2yl]methanol (glycidol)} in dichloromethane to make
exactly 100 mL, pipet 0.5 mL of this solution, add dichloromethane to make exactly 100 mL and use this solution as the standard solution (1). Dissolve 0.50 g of Levodropropizine in a volume of dichloromethane, add
0.5 mL of the standard solution (1), add dichloromethane to make exactly 2.5 mL and use this solution as
the standard solution (2). Perform the test with 1 L of
the test solution and the standard solution (2) as directed under the Gas Chromatography according to the
following operating conditions, and determine the area
of the peaks from the test solution and the standard solution (2): the area of the peak corresponding to the related substance II obtained from the test solution is not
more than 0.5 times the area of the peak corresponding
to the related substance II obtained from the standard
solution (2) (0.001%).

diameter and about 30 m in length, coated inside surface with poly[(cyanopropyl) (phenyl)] [dimethyl] siloxane for gas chromatography 3 m in thickness.
Injection port temperature: 170 C.
Split ratio: About 1 : 8
(3) EnantiomerDissolve 10.0 mg of Levodropropizine in 10.0 mL of a mixture of hexane and ethanol (6:4), pipet 1.0 mL of this solution, add a mixture
of hexane and ethanol (6:4) to make exactly 50 mL,
and use this solution as the test solution. Separately,
dissolve 10.0 mg of Levodropropizine RS in 10.0 mL
of a mixture of hexane and ethanol (6:4), pipet 1.0 mL
of this solution, add a mixture of hexane and ethanol
(6:4) to make exactly 50 mL, and use this solution as
the standard solution (1). Dissolve 10.0 mg of levodropropizine related substance III [(2R)-3-(4-phenyl piperazin-1-yl)propane-1,2-diol (dextrodropropizine)] RS in
10.0 mL of hexane and ethanol (6:4), pipet 1 mL of this
solution, add a mixture of hexane and ethanol (6:4) to
make exactly 50 mL and use this solution as the standard solution (2). Pipet 1.0 mL of the standard solution
(2), add a mixture of hexane and ethanol (6:4) to make
exactly 50 mL and use this solution as the standard solution (3). Mix 1 mL of the standard solution (1) and 1
mL of the standard solution (2), and use this mixture as
the standard solution (4). Perform the test with 20 L
each of the test solution, the standard solution (1), (3)
and (4) as directed under the Liquid Chromatography
according to the following operating conditions and determine the area of the peaks in the solutions: the area
of the peak corresponding to the related substance III
obtained from the test solution is not more than the area
of the corresponding peak obtained from the standard
solution (3) (not more than 2%).
silica gel OD for chiral separations for liquid chromatography.
Mobile phase: A mixture of hexane, ethanol and diethylamine (95:5:0.2).
System suitability
operating conditions, the related substance III and levodropropizine are eluted in this order with the resolution between these two peaks being not less than 2.0.
Loss on Drying Not more than 0.5% (0.5 g, 0.150.25 kPa, 60 C, P2O5, 4 hours).
KP 9 563
Assay Weigh accurately about 0.2 g of Levodropropizine, add 50 mL of glacial acetic acid to dissolve and
titrate with 0.1 mol/L of perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Read the volume added at the second point of
inflexion. Perform a blank determination and make any
necessary correction.
= 11.82 mg of C13H20N2O2
Levomepromazine Maleate
H3C
H
C
CH2
N
CH2N(CH 3)2
OCH 3
CO 2H
C
C
CO 2H
C19H24N2OSC4H4O4: 444.54
Levomepromazine Maleate, when dried, contains not
less than 98.0% and not more than 101.0% of levomepromazine maleate (C19H24N2OSC4H4O4).
Description Levopromazine Maleate is a white crystal or crystalline powder, is odorless and has a slightly
bitter taste.
Levopromazine Maleate is freely soluble in glacial
acetic acid, soluble in chloroform, sparingly soluble in
methanol, slightly soluble in ethanol or in acetone, very
slightly soluble in water and practically insoluble in
ether.
Melting pointBetween 184 C and 190 C (with
decomposition).
Identification (1) Dissolve 5 mg of Levopromazine
Maleate in 5 mL of sulfuric acid: a red-purple color is
observed, which slowly becomes deep red-purple. To
this solution, add 1 drop of potassium dichromate TS: a
brownish yellow-red color is observed.
(2) Take 0.2 g of Levopromazine Maleate, add 5
mL of sodium hydroxide TS and 20 mL of ether and
shake well. Separate the ether layer, wash twice with 10
mL volumes of water, add 0.5 g of anhydrous sodium
sulfate, filter, evaporate the ether solution on a waterbath and dry the residue at 105 C for 2 hours: the residue melts between 124 C and 128 C.
(3) Take 0.5 g of Levopromazine Maleate, add 5
mL of water and 2 mL of strong ammonia water, ex-
tract with three 5 mL volumes of chloroform, separate

and evaporate the water layer to dryness. To the residue,
add 2 to 3 drops of dilute sulfuric acid and 5 mL of water and extract with four 25 mL volumes of ether. Combine all the ether extracts, evaporate the ether on a water-bath at a temperature of about 35 C with the aid of
a current of air: the residue melts between 128 C and
136 C.
D : Between -13.5
and -16.5 (after drying, 0.5 g, chloroform, 20 mL, 200
mm).
Purity (1) Clarity and color of solutionTake 0.5 g
of Levopromazine Maleate, add 10 mL of methanol and
dissolve by warming: the solution is clear and colorless
to pale yellow.
(2) ChlorideDissolve 0.5 g of Levopromazine
Maleate in 40 mL of methanol and add 6 mL of dilute
nitric acid and water to make 50 mL. Perform the test.
Prepare the control solution with 0.40 mL of 0.01
mol/L hydrochloric acid VS, 40 mL of methanol, 6 mL
of dilute nitric acid and water to make 50 mL (not more
than 0.028%).
(3) Heavy metalsProceed with 2.0 g of Levopromazine Maleate according to Method 2 and perform
standard lead solution (not more than 10 ppm).
hours).
Assay Weigh accurately about 1.0 g of Levopromazine Maleate, previously dried and dissolve in a mixture of 40 mL of glacial acetic acid and 20 mL of acetone for nonaqueous titration. Titrate with 0.1 mol/L
changes from red-purple through blue-purple to blue
(indicator: 5 drops of bromocresol green-methyl rosaniline chloride TS). Perform a blank determination and
make any necessary correction.
= 44.45 mg of C19H24N2OSC4H4O4
tight containers.
Levothyroxine Sodium Hydrate

I
H
OH
CH 2
C
NH2
CO 2Na
H 2O

C15H10I4NNaO4xH2O
Levothyroxine Sodium Hydrate contains not less than
97.0% of levothyroxine sodium (C15H10I4NNaO4:
798.85), calculated on the dried basis.
Description Levothyroxine Sodium Hydrate is a pale
yellowish white to pale yellow-brown powder and is
odorless.
Levothyroxine Sodium Hydrate is slightly soluble in
ethanol and practically insoluble in water or in ether.
Levothyroxine Sodium dissolves Hydrate in sodium
hydroxide TS.
Levothyroxine Sodium Hydrate is gradually affected by
light.
Identification (1) Heat 0.1 g of Levothyroxine Sodium Hydrate over a flame: a purple gas evolves.
(2) Take 0.5 mg of Levothyroxine Sodium Hydrate,
add 8 mL of a mixture of water, ethanol, hydrochloric
acid and sodium hydroxide TS (6 : 5 : 2 : 2), warm in a
water-bath for 2 minutes, cool and add 0.1 mL of sodium nitrite TS. Allow to stand in a dark place for 20
minutes and add 1.5 mL of strong ammonia water: a
yellowish red color is observed.
(3) Determine the absorption spectra of solutions of
Levothyroxine Sodium Hydrate and Levothyroxine Sodium Hydrate RS in dilute sodium hydroxide TS (1 in
10000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities
of absorption at the same wavelengths.
(4) Moisten Levothyroxine Sodium Hydrate with
sulfuric acid and ignite: the residue responds to the Qualitative Tests (1) and (2) for sodium salt.
D : Between -5 and 6 (0.3 g, calculated on the dried basis, a mixture of
ethanol and sodium hydroxide TS (2 : 1), 10 mL, 100
mm).
0.3 g of Levothyroxine Sodium Hydrate in 10 mL of a
mixture of ethanol and sodium hydroxide TS (2 : 1) by
warming: the solution is clear and pale yellow to pale
yellow-brown in color.
(2) Soluble halidesDissolve 10 mg of Levothyroxine Sodium Hydrate in 10 mL of water and 1 drop
of dilute nitric acid, shake for 5 minutes and filter. To
the filtrate, add water to make 10 mL, then add 3 drops
of silver nitrate TS and mix: the solution has no more
opalescence than the following control solution.
Control solutionTo 0.20 mL of 0.01 mol/L hydrochloride VS, add 10 mL of water and 1 drop of dilute nitric acid and proceed as directed above.
(3) Related substancesDissolve 20 mg of Levothyroxine Sodium Hydrate in 2 mL of a mixture of
ethanol and strong ammonia water (14 : 1) and use this

solution as the test solution. Pipet 1.0 mL of this solution, add a mixture of ethanol and strong ammonia water (14 : 1) to make exactly 50 mL and use this solution
solution and the standard solution on a plate of silica
gel for thin-layer chromatography. Develop the plate
with a mixture of tert-butanol, tert-amyl alcohol, water,
strong ammonia water and methyl ethyl ketone (59 :
32 : 17 : 15 : 7) to a distance of about 12 cm and air-dry
the plate. Spray evenly a solution of 0.3 g of ninhydrin
in 100 mL of a mixture of n-butanol and glacial acetic
acid (97 : 3) on the plate and heat at 100 C for 3 minutes: the red-purple spots other than the principal spot
Loss on Drying Between 7.0% and 11.0% (0.5 g, in
vacuum, P2O5, 60 C, 4 hours).
Assay Weigh accurately about 25 mg of Levothyroxine Sodium Hydrate and proceed as directed in the Assay under Liothyronine Sodium.
Each mL of 0.02 mol/L sodium thiosulfate VS
= 0.6657 mg of C15H10I4NNaO4
tight containers.
Levothyroxine Sodium Tablets

Levothyroxine Sodium Tablets contain not less than
90.0% and not more than 110.0% of the labeled amount
of levothyroxine sodium (C15H10I4NNaO4: 798.85).
Tablets, with Levothyroxine Sodium Hydrate.
Identification (1) Weigh a portion of powdered Levothyroxine Sodium Tablets, equivalent to 0.5 mg of
Levothyroxine Sodium according to the labeled amount,
add 8 mL of a mixture of water, ethanol, hydrochloric
acid and sodium hydroxide TS (6 : 5 : 2 : 2), warm in a
water-bath for 2 minutes, cool and filter. To the filtrate,
add 0.1 mL of sodium nitrate TS and allow to stand in a
dark place for 20 minutes. Add 1.5 mL of strong ammonia water: a yellowish red color is observed.
(2) To a portion of powdered Levothyroxine Sodium Tablets, equivalent to 1 mg of Levothyroxine Sodium according to the labeled amount, add 10 mL of
ethanol, shake, filter and use the filtrate as the test solution. Dissolve 10 mg of Levothyroxine Sodium RS in
100 mL of ethanol and use this solution as the standard
solution. Perform the test with the test solution and the
KP 9 565
standard solution as directed under the Thin-layer
Chromatography. Spot 20 L each of the test solution
and the standard solution on a plate of silica gel for
thin-layer chromatography. Develop the plate with a
mixture of tert-butanol, tert-amyl alcohol, water, strong
ammonia water and methyl ethyl ketone (59 : 32 : 17 :
15 : 7) to a distance of about 12 cm and air-dry the
plate. Spray a solution of 0.3 g of ninhydrin in 100 mL
of a mixture of n-butanol and glacial acetic acid (97 : 3)
on the plate and heat at 100 C for 3 minutes: the spots
obtained from the test solution and the standard solution show a red-purple color and has the same Rf value.
Purity Soluble halidesWeigh a portion of powdered Levothyroxine Sodium Tablets, equivalent to 2.5
mg of Levothyroxine Sodium according to the labeled
amount, add 25 mL of water, warm to 40 o C , shake for
5 minutes, add 3 drops of dilute nitric acid and filter. To
the filtrate, add 3 drops of silver nitrate TS and mix: the
solution has no more opalescence than the following
control solution.
Control solutionTo 0.25 mL of 0.01 mol/L hydrochloride VS, add 25 mL of water and 3 drops of dilute nitric acid and proceed as directed above.
Disintegration Test It meets the requirement.
Uniformity of Dosage Units It meets the requirement when the content uniformity test is performed according to the following procedure. Place 1 tablet of
Levothyroxine Sodium Tablets in a glass-stoppered
centrifuge tube, add exactly 10 mL of 0.01 mol/L sodium hydroxide TS, warm at 50 C for 15 minutes and
shake vigorously for 20 minutes. Centrifuge this solution, pipet 5.0 mL of the supernatant liquid, add 1.0 mL
of the internal standard solution and use this solution as
the test solution. Perform the test with 20 L of the test
solution as directed under the Liquid Chromatography
according to the following conditions and calculate the
ratio of the peak area of levothyroxine sodium to that of
the internal standard.

time of levothyroxine sodium is about 9 minutes.
System suitability
System performance: To 5 mL of a solution of
Levothyroxine Sodium in 0.01 mol/L sodium hydroxide TS (1 in 200000) and add 1 mL of the internal standard solution. When the procedure is run with 20 L of
this solution under the above operating conditions, levothyroxine sodium and the internal standard are eluted
in this order with a resolution between their peaks being not less than 2.0.
Levothyroxine Sodium Tablets. Weigh accurately a
portion of the powder, equivalent to about 3 mg of levothyroxine sodium (C15H10I4NNaO4) into a crucible
and add potassium carbonate amounting to twice the
weight of the powder. In the case that the weighed
powder is less than 4 g, add 8 g of potassium carbonate
to the crucible. Mix well and gently tap the crucible on
the bench to compact the mixture. Overlay with 10 g of
potassium carbonate and compact again by tapping.
Heat the crucible strongly at a temperature between 675
C and 700 C for 25 minutes. Cool, add 30 mL of water, heat gently to boiling and filter into a flask. To the
residue, add 30 mL of water, boil and filter into the
same flask. Rinse the crucible and the char on the funnel with hot water until the filtrate measures 300 mL.
Add slowly 7 mL of freshly prepared bromine TS and
diluted phosphoric acid (1 in 2) in the ratio of 3.5 mL to
1 g of the added potassium carbonate and boil until
starch-potassium iodide paper is no longer colored blue
by the evolved gas. Wash the inside of the flask with
water and continue boiling for 5 minutes. During the
boiling, add water from time to time to maintain a volume of not less than 250 mL. Cool, add 5 mL of a solution of phenol (1 in 20), rinse again the inside of the
flask with water and allow to stand for 5 minutes. Add
2 mL of diluted phosphoric acid (1 in 2) and 5 mL of
potassium iodide TS and titrate immediately the liberated iodine with 0.01 mol/L sodium thiosulfate VS
(indicator: 3 mL of starch TS). Perform a blank determination and make any necessary correction.
Internal standard solutionA solution of Ethinylestradiol in a mixture of acetonitrile and diluted phosphoric acid (1 in 10) (9 : 1) (3 in 40000).

= 0.33286 mg of C15H10I9NNaO4
(wavelength: a constant wavelength between 220 nm
and 230 nm).
Column: A stainless steel column, 4 mm to 6 mm in
inside diameter and 10 cm to 25 cm in length, packed
Column temperature: A constant temperature at
about 25 o C .
Mobile phase: A mixture of methanol, water and
phosphoric acid (6700 : 3300 : 5).
Packaging and Storage Preserve in light- resistant,

tight containers.
Lidocaine
CH3
O
NH
CH3
CH2N(CH 2CH 3)2

C14H22N2O: 234.34
Lidocaine, when dried, contains not less than 99.0%
and not more than 101.0% of lidocaine (C14H22N2O).
Description Lidocaine is a white to pale yellow crystal or crystalline powder.
Lidocaine is very soluble in methanol or in ethanol, soluble in ether or in glacial acetic acid and practically insoluble in water.
Lidocaine dissolves in dilute hydrochloric acid.
Identification (1) Dissolve 40 mg each of Lidocaine
and Lidocaine RS in 10 mL each of 1 mol/L hydrochloric acid TS and add water to make 100 mL each. Determine the absorption spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry:
the same wavelengths.
(2) Determine the infrared spectra of Lidocaine and
Lidocaine RS, as directed in the potassium bromide
disk method under the Infrared Spectrophotometry:
3 : 1 : 1) to a distance of about 10 cm and air-dry the

plate and dry at 80 o C for 30 minutes. After cooling,
examine under ultraviolet light (main wavelength: 254
nm): the spots other than the principal spot from the
test solution are not more intense than the spot from the
standard solution.
silica gel, 24 hours).
Assay Dissolve 0.5 g of Lidocaine, previously dried
and accurately weighed, in 20 mL of glacial acetic acid
and titrate with 0.1 mol/L perchloric acid VS (indicator:
1 drop of methylrosaniline chloride TS) until the color
of the solution changes from purple through blue to
blue-green. Perform a blank determination and make
any necessary correction.
= 23.434 mg of C14H22N2O
Melting Point Between 66 C and 69 C

Purity (1) Clarity and color of solution Dissolve
1.0 g of Lidocaine in 2 mL of dilute hydrochloric acid
and add water to make 10 mL: the solution is clear and
colorless to pale yellow.
(2) ChlorideDissolve 0.6 g of Lidocaine in 6 mL
of dilute nitric acid, add water to make 50 mL and perform the test. Prepare the control solution with 0.70 mL
0.041%).
(3) SulfateDissolve 0.5 g of Lidocaine in 5 mL
of dilute hydrochloric acid, add water to make 50 mL
and perform the test. Prepare the control solution with
1.0 mL of 0.005 mol/L sulfuric acid VS, 5 mL of dilute
hydrochloric acid and water to make 50 mL (not more
than 0.096%).
(4) Heavy metalsCarbonize 2.0 g of Lidocaine by
gentle ignition. After cooling, add 10 mL of a solution
of magnesium nitrate in ethanol (1 in 10) and burn the
ethanol. After cooling, add 1 mL of sulfuric acid, proceed according to Method 4 and perform the test. Prepare the control solution with 2.0 mL of standard lead
(5) Related substancesDissolve 0.10 g of Lidocaine in 2 mL of methanol and use this solution as the
test solution. Pipet 1.0 mL of the test solution, add methanol to make exactly 100 mL and use this solution as
the standard solution. Perform the test with the test solution and the standard solution as directed under the
Thin-layer Chromatography. Spot 10 L each of the
test solution and the standard solution on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethylacetate, methyl ethyl ketone, water and formic acid (5 :
Lidocaine Injection
Lidocaine Injection is an aqueous solution for injection.
Lidocaine Injection contains not less than 95.0% and
not more than 105.0% of the labeled amount of lidocaine hydrochloride (C14H22N2OHCl: 270.80).
Lidocaine Injection does not apply to the Pyrogen Test.
Method of Preparation Prepare as directed under Injections, with Lidocaine and an equivalent amount of
hydrochloric acid.
No preservative is added in the case of intravenous injections.
Description Lidocaine Injection is a colorless, clear
liquid.
pHBetween 5.0 and 7.0.
Identification To a volume of Lidocaine Injection,
equivalent to 20 mg of lidocaine hydrochloride
(C14H22N2OHCl) according to the labeled amount, add
1 mL of sodium hydroxide TS and extract with 20 mL
of hexane. To 10 mL of the hexane extract, add 20 mL
of 1 mol/L hydrochloric acid TS and shake vigorously.
Determine the absorption spectrum of the water layer
as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 261 nm and 265
nm.
Foreign Insoluble Matter Test It meets the require-
KP 9 567
ment.
internal standard is not more than 1.0%.


tainers.

Assay Take an exactly measured volume of Lidocaine Injection, equivalent to about 0.1 g of lidocaine
hydrochloride (C14H22N2OHCl), add 10.0 mL of the internal standard solution and 0.001 mol/L hydrochloric
acid TS to make exactly 50 mL and use this solution as
the test solution. Separately, weigh accurately about 85
mg of Lidocaine RS, previously dried in a desiccator
(in vacuum, silica gel) for 24 hours, dissolve in 0.5 mL
of 1 mol/L hydrochloric acid TS and a suitable volume
of 0.001 mol/L hydrochloric acid TS and add 10.0 mL
of the internal standard solution. Then add 0.001 mol/L
hydrochloric acid TS to make exactly 50 mL and use
with 5 L each of the test solution and the standard solution as directed under the Liquid Chromatography
ratios, QT and QS , of the peak area of lidocaine to
that of the internal standard for the test solution and the
standard solution, respectively.
Amount (mg) of lidocaine hydrochloride
(C14H22N2OHCl) = amount (mg) of Lidocaine RS
QT
1.1556
QS
Internal standard solutionA solution of benzophenone in methanol (1 in 4000).

inside diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10
about 25 C.
Mobile phase: Dissolve 2.88 g of sodium lauryl sulfate in 1000 mL of a mixture of 0.02 mol/L phosphate
buffer solution, pH 3.0 and acetonitrile (11 : 9).
time of lidocaine is about 6 minutes.
System suitability
with 5 L of a standard solution under the above operating conditions, lidocaine and the internal standard are
above operating conditions, the relative standard deviation of the ratios of peak area of lidocaine to that of the
Lidocaine Hydrochloride
Hydrate
CH3
H
N
CH3
HCl
H2 O
O
CH3
CH3
C14H22N2OHClH2O : 288.81
Lidocaine Hydrochloride Hydrate contains not less than
97.5% and not more than 102.5% of lidocaine hydrochloride (C14H22 N2OHCl), calculated on the anhydrous
basis.
Description Lidocaine Hydrochloride Hydrate is a
white, crystalline powder, is ordorless and has a
slightly bitter taste.
Lidocaine Hydrochloride Hydrate is very soluble in
water or in ethanol, soluble in chloroform, and practically insoluble in ether.
Identification (1) Dissolve about 0.3 g in 5 to 10 mL
of water in a separator, add 4 mL of 6 mol/L ammonium hydroxide TS, and extract with four 15-mL portions of chloroform. Combine the chloroform extracts,
evaporate chloroform, and dry the residue in vacuum
over silica gel for 24 hours. Determine the infrared absorption spectra of the crystalline precipitate so obtained and Lidocaine Hydrochloride Hydrate RS as directed in the potassium bromide disk method under the
(2) Dissolve about 0.1 g of the crystalline precipitate obtained in the procedure (1) in 1 mL of ethanol,
add 10 drops of cobalt chloride TS, and shake about 2
minutes. A bright green color appears and fine precipitates are formed.
Purity (1) Sulfate Dissolve about 200 mg of Lidocaine Hydrochloride Hydrate in 20 mL of water, add 2
mL of 3 mol/L hydrochloric acid, mix, and divide into
two parts. To one part of the solution, add 1 mL of barium chloride TS: no more turbidity is produced than is
present in the remaining portion of the solution to
which nothing has been added.
(2) Heavy metalsProceed with 1.0 g of Lidocaine

Hydrochloride Hydrate according to Method 1 and perform the test. Prepare the control solution with 2.0 mL
of standard lead solution (not more than 20 ppm).
Water Between 5.0% and 7.0% (0.2 g, volumetric titration, direct titration).
Residue on Ignition Not more than 0.1%.
Lincomycin Hydrochloride
Hydrate
CH3
N
OH
H
H
N
H3C
CH3
Assay Weigh accurately about 0.1 g of Lidocaine

Hydrochloride Hydrate, dissolve in the mobile phase to
make 50 mL, and use this solution as the test solution.
Separately, dissolve about 85 mg of Lidocaine RS in
0.5 mL of 1 mol/L hydrochloric acid, with warming if
necessary, dilute with the mobile phase to 50 mL, and
test with 20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions. Determine the peak area ( AT ) of lidocaine hydrochloride
from the test solution and that ( AT ) from the standard
solution.
Amount (mg) of lidocaine hydrochloride
(C14H22N2OHCl)
A
270.80
= amount (mg) of Lidocaine RS T
AS 234.34
Column: A stainless steel 3.9 mm inside diameter
and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 m in particle diameter).
Column temperature: 20 C 25 C.
Mobile phase: Mix 50 mL of glacial acetic acid and
930 mL of water, and adjust with 1 mol/L sodium hydroxide to a pH of 3.40. Mix about 4 parts of this solution with 1 part of acetonitrile, so that the retention
time of lidocaine is about 4 to 6 minutes.
System suitability
System performance: Dissolve 22 mg of methyl
parahydroxybenzoate in the mobile phase. Mix 2 mL of
this solution and 20 mL of the standard solution. When
the procedure is run with 20 L of this solution, the
resolution between lidocaine and methyl parahydroxybenzoate is not less than 3.0.
times with the standard solution according to the above
conditions, the relative standard deviation of the peak
area of lidocaine is not more than 1.5%.
H2O
CH3
OH
O
HO
HCl
S
OH
C18H34N2O6SHClH2O: 461.01
Lincomycin Hydrochloride Hydrate is the hydrochloride of a substance having antibacterial activity produced by the growth of Streptomyces licolnensis var. licolnensis.
Lincomycin Hydrochloride Hydrate contains not less
than 790 g (potency) per mg of lincomycin
(C18H34N2O6S: 406.54), calculated on the anhydrous basis
Description Lincomycin Hydrochloride Hydrate is
white crystal or crystalline powder, is odorless, and has
a bitter taste.
Lincomycin Hydrochloride Hydrate is very soluble in
water, freely soluble in methanol or in etnanol, and
practically insoluble in ether.
Lincomycin Hydrochloride Hydrate and Lincomycin
Hydrochloride Hydrate RS, as directed in the paste method under the Infrared spectrophotometry: both spectra
exhibit similar intensities of absorption at the same wavenumbers.
(2) Weigh about 50 mg each of Lincomycin Hydrochloride Hydrate and Lincomycin Hydrochloride
Hydrate RS, dissolve in 10 mL of methanol, and use
these solutions as the test solution and the standard solution. Perform the test with these solutions as directed
under Thin-layer Chromatography. Spot 10 L each of
plate with the developing solvent which is a mixture of
methylethylketone, acetone and water (8:4:1) to a distance of about 10 cm, and air-dry the plate. Then spray
0.5 % potassium permanganate solution on the plate,
and after 10 minutes spray 0.2 % bromphenol blue solution: the blue spots obtained from the test solution
and the standard solution are the same in the Rf value.
(3) A solution of Lincomycin Hydrochloride Hydrate responds to the Qualitative Tests for chloride.
(4) Determine the retention times according to the
procedure of Assay: the retention time of the principal
peak in the chromatogram obtained with test solution is
the same as that of the principal peak in the chromatogram obtained with the standard solution.
KP 9 569
25
Specific Optical Rotation [ ]D :

(0.5 g, water, 25 mL, 200 mm).
Liothyronine Sodium
+135 ~ +150
pH The pH of a solution obtained by dissolving 1 g

of Lincomycin Hydrochloride Hydrate in 10 mL of water is between 3.0 and 5.5.
lincomycin hydrochloride hydrate, when Lincomycin
Hydrochloride Hydrate is used in a sterile preparation.
Histamine It meets the requirement, When Lincomycin Hydrochloride Hydrate is used in a sterile preparation. Weigh appropriate amount of Lincomycin Hydrochloride Hydrate, dissolve in Isotonic sodium chloride Injection solution, make the solution so that each
mL contains 3.0 mg, and use the solution as the test solution.
Water Not less than 3.0 % and not more than 6.0%
(0.3 g, volumetric titration, direct titration).
Assay Weigh accurately about 10 mg (potency) each
of Lincomycin Hydrochloride Hydrate and Lincomycin
Hydrochloride Hydrate RS, dissolve each in a suitable
amount of the mobile phase, add the mobile phase to
make exactly 100 mL, and use these solutions as the
test solution and the standard solution, respectively.
Perform the test with 20 L of each of the test solution
conditions, and determine the peak areas, AT and AS, of
lincomycin.
Amount [g (potency)] of lincomycin (C18H34N2O6S)
A
= Amount [g (potency)] of Lincomycin RS T
AS
(wavelength: 210 nm)
inside diameter and about 150 ~ 300 mm in length,
packed with octadecylsilanized silica gel for liquid
chromatography (5 ~ 10 m in particle diameter).
Mobile phase: The mixture of phosphoric acid solution (13.5 in 1000), acetonitrile and methanol
(78:15:15).
H
HO
CH2
CO2Na
NH 2
I
C15H11I3NNaO4: 672.96
Liothyronine Sodium contains not less than 95.0% and
not more than 101.0% of liothyronine sodium
(C15H11I3NNaO4), calculated on the dried basis.
Description Liothyronine Sodium is a white to pale
brown powder and is odorless.
Liothyronine Sodium is slightly soluble in ethanol and
practically insoluble in water or in ether.
Liothyronine Sodium dissolves in sodium hydroxide
TS or in ammonia TS.
Identification (1) Take 5 mL of a solution of Liothyronine Sodium in ethanol (1 in 1000), add 1 mL of ninhydrin TS and warm in a water-bath for 5 minutes: a
purple color is observed.
(2) Heat 20 mg of Liothryonine Sodium with a few
drops of sulfuric acid over a flame: a purple gas is
evolved.
Liothyronine Sodium and Liothyronine Sodium RS in
ethanol (1 in 10000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(4) Ignite 20 mg of Liothyronine Sodium until thoroughly charred. After cooling, add 5 mL of water to
residue, shake and filter: the filtrate responds to the
Qualitative Tests (1) for sodium salt.
D : Between +18 and
+22 (0.2 g, calculated on the dried basis, a mixture of
ethanol and 1 mol/L hydrochloric acid TS (4 : 1), 10
mL, 100 mm).
Purity (1) Soluble halideTake 10 mg of Liothyronine Sodium, add 10 mL of water and 1 drop of dilute
nitric acid, shake for 5 minutes and filter. Add water to
the filtrate to make 10 mL and mix with 3 drops of silver nitrate TS: the solution shows no more turbidity
than the following control solution.
Control solutionTo 0.35 mL of 0.01 mol/L hydrochloric acid VS, add 1 drop of dilute nitric acid and
water to make 10 mL and add 3 drops of silver nitrate
TS.
(2) Iodine and iodideDissolve 0.10 g of Liothryonine Sodium in 10 mL of dilute sodium hydroxide

TS and 15 mL of water, add 5 mL of dilute sulfuric acid
and allow to stand for 10 minutes with occasional shaking. Filter the mixture into a Nessler tube, add 10 mL of
chloroform and 3 drops of a solution of potassium
iodide (1 in 100) to the filtrate, mix for 30 seconds and
allow to stand: the chloroform layer has no more color
Control solutionWeigh exactly about 0.111g of
potassium iodide and dissolve in water to make 1000
mL. Pipet 1.0 mL of this solution, add 10 mL of dilute
sodium hydroxide TS, 14 mL of water and 5 mL of dilute sulfuric acid and mix. Filter the mixture into a
Nessler tube and perform the test with the filtrate in the
same manner as for the sample.
(3) Related substancesDissolve 0.15 g of Liothyronine Sodium in 5 mL of diluted ammonia TS (1 in 3)
of this solution, add diluted ammonia TS (1 in 3) to
make exactly 50 mL and use this solution as the standard solution. Perform the test with the test solution
and the standard solution as directed under the Thinlayer Chromatography. Spot 1 L each of the test solution and the standard solution on a plate of silica gel for
mixture of tert-butanol, tert-amyl alcohol, strong ammonia water and methyl ethyl ketone (59 : 32 : 17 : 15 :
7) to a distance of about 12 cm and air-dry the plate.
Spray evenly solution of 0.3 g of ninhydrin in 100 mL
of a mixture n-butanol and glacial acetic acid (97 : 3)
on the plate and dry the plate at 100 C for 3 minutes:
the spots other than the principal spot from the test solution are not more intense than the spot from the standard solution.
Loss on Drying Not more than 4.0% (0.2 g, 105 C,
2 hours).
Assay Weigh accurately about 25 mg of Liothyronine
Sodium and proceed as directed under the Oxygen
Flask Combustion Method, using a mixture of 10 mL
of a solution of sodium hydroxide (1 in 100) and 1 mL
of a freshly prepared solution of sodium bisulfate (1 in
100) as the absorbing liquid and prepare the test solution. Apply a small amount of water to the upper part of
apparatus A, pull out C carefully and wash C, B and the
inner wall of A with 40 mL of water. To the test solution, add 1 mL of bromine-acetic acid TS, insert the
stopper C and shake vigorously for 1 minute. Wash C,
B and the inner wall of A with 40 mL of water and add
0.5 mL of formic acid. Stopper the flask with C and
shake vigorously for 1 minute again. Wash C, B and the
inner wall of A with 40 mL of water again. Bubble the
solution with enough nitrogen gas in the flask to remove the oxygen and excess bromine, add 0.5 g of potassium iodide to the solution and dissolve. Add immediately 3 mL of dilute sulfuric acid, mix and allow to
stand for 2 minutes. Titrate the solution with 0.02
mol/L sodium thiosulfate VS (indicator: 3 mL of starch
TS). Perform a blank determination and make any necessary correction.

= 0.7477 mg of C15H11I3NNaO4
tight containers.
Liothyronine Sodium Tablets

Liothyronine Sodium Tablets contain not less than
of liothyronine sodium (C15H11I3NNaO4: 672.96).
Tablets, with Liothyronine Sodium.
Identification (1) To a glass-stoppered centrifuge
tube, add a portion of finely powdered Liothyronine
Sodium Tablets, equivalent to 0.1 mg of Liothyronine
Sodium according to the labeled amount, add 30 mL of
dilute sodium hydroxide TS, shake vigorously and centrifuge. Transfer the supernatant to a separatory funnel,
add 10 mL of dilute hydrochloric acid and extract with
two 20 mL volumes of ethyl acetate. Filter each extract
successively through absorbent cotton, previously overlaid with 8 g of anhydrous sodium sulfate. Evaporate
the filtrate on a water-bath to dryness with the aid of a
current of nitrogen. Dissolve the residue in 0.5 mL of
methanol and use this solution as the test solution. Separately, dissolve 10 mg of Liothyronine Sodium RS in
methanol to make 50 mL and use this solution as the
mixture of tert-butanol, tert-amyl alcohol, water, strong
ammonia water and methyl ethyl ketone (59 : 32 : 17 :
plate. Spray evenly a solution of 0.3 g of ninhydrin in
100 mL of a mixture of n-butanol and glacial acetic acid(97 : 3) on the plate and dry the plate at 100 C for 3
minutes: the spots obtained from the test solution and
the standard solution show a red-purple color and has
the same Rf value.
(2) The colored solution obtained in the Assay is
blue in color.
Uniformity of Dosage Units It meets the requirement when the content uniformity test is performed according to the following method.
Place 1 tablet of Liothyronine Sodium Tablets in a
glass-stoppered centrifuge tube and exactly 10 mL of
0.01 mol/L sodium hydroxide TS, warm at 50 o C for
KP 9 571
15 minutes and shake vigorously for 20 minutes. Centrifuge for 5 minutes and filter the supernatant liquid, if
necessary. Pipet a definite volume of this solution and
add a volume of 0.01 mol/L sodium hydroxide VS to
prepare a definite volume of a solution containing
about 0.5 g of liothyronine sodium (C15H11I3NNaO4)
per mL. Pipet 5.0 mL of this solution, add 1.0 mL of
the internal standard solution and use this solution as
the test solution. Perform the test with 200 L of the
test solution as directed under the Liquid Chromatography according to the following conditions and calculate
the ratio of the peak area of the Liothyronine to that of
Internal standard solutionA solution of propylparahydroxybenzoate in a mixture of methanol and diluted phosphoric acid (1 in 10) (9 : 1) (1 in 250000).
(wavelength: a constant wavelength between 220 nm
and 230 nm).
Column: A stainless steel column, 4 mm to 6 mm in
with octadecylsilanized silica gel (5 m in particle diameter).
about 25 C.
Mobile phase: A mixture of methanol and water
(57 : 43).
time of Liothyronine is about 9 minutes.
System suitability
System performance: Take 5 mL of a solution of
Liothyronine Sodium in 0.01 mol/L sodium hydroxide
TS (1 in 2000000) and add 1.0 mL of the internal standard solution. When the procedure is run with 200 L
of this solution under the above operating conditions,
internal standard and liothyronine are eluted in this order with a resolution between their peaks being not less
than 2.0.
System repeatability: When the test is repeated
6 times with 200 L of the solution for system suitability test under the above operating conditions, the relative standard deviation of the ratios of the peak area of
liothyronine to that of the internal standard is not more
than 1.0%.
in the same manner. Ignite the combined mixture in the

crucible between 675 C and 700 C for 30 minutes.
Cool, add a few mL of water to the crucible, heat gently
to boil and filter the contents of the crucible through a
glass filter (G4) into a volumetric flask. Wash the residue with water and combine the washings with the filtrate. Cool, add water to make 20 mL and use this solution as the test solution. Separately, weigh accurately
about 75 mg of Potassium Iodide RS, previously dried
at 105 C for 4 hours and dissolve in water to make exactly 200 mL. Measure exactly 5 mL of the solution
and add a solution of potassium carbonate (1 in 8) to
make exactly 100 mL. Take 2.0 mL of this solution,
add a solution of potassium carbonate (1 in 8) to make
exactly 20 mL and use this solution as the standard solution. Pipet 5.0 mL each of the test solution and the
standard solution into glass-stoppered test tubes, add
3.0 mL of diluted sulfuric acid (4 in 25) and 2.0 mL of
potassium permanganate TS and heat in a water-bath
for 15 minutes. Cool, add 1.0 mL of diluted sodium nitrite TS (1 in 10), swirl to mix and add 1.0 mL of a
freshly prepared diluted potassium iodide TS (1 in 40),
swirl to mix and transfer each solution to a volumetric
flask. Rinse the test tube with water, collect the washings in the volumetric flask, add water to make 20 mL
and allow to stand for 10 minutes. Perform the test with
these solutions as directed under the Ultraviolet-visible
Spectrophotometry, using a solution prepared with 5
mL of potassium carbonate (1 in 8) in the same manner
as the test solution as the blank. Determine the absorbances, AT and AS , of the test solution and the standard solution at the wavelength of a maximum absorption at about 600 nm, respectively.
Amount (mg) of lithothyronine sodium
(C15H11I3NNaO4) = amount (mg) of Potassium
1
A
Iodide RS T
1.3513
AS 2000
tight containers.
Lisinopril Hydrate
NH2
Assay Weigh accurately not less than 20 Liothyronine Sodium Tablets and finely powder. Place a portion
of the powder accurately weighed, equivalent to about
50 mg of liothyronine sodium (C15H11I3NNaO4), in an
agate mortar and add 1 g of powdered potassium carbonate and mix well. Transfer the mixture cautiously to
a porcelain crucible and compact the contents by gently
tapping the crucible on a table. Add an additional 1.5 g
of powdered potassium carbonate to the same agate
mortar, mix well with any content adhering to the mortar, cautiously overlay the mixture on the top of the
same porcelain crucible and compact the contents again
OH
O
2H2O
N
N
H
OH
O
C21H31N3O52H2O: 441.52

Lisinopril Hydrate contains not less than 98.5% and not
more than 101.0% of lisinopril (C21H31N3O5: 405.49),
Description Lisinopril Hydrate is a white crystalline
powder and has a slight, characteristic odor .
It is soluble in water, sparingly soluble in methanol,
and practically insoluble in dehydrated ethanol.
Identification (1) Determine the absorption spectra of
solutions of Lisinopril Hydrate and Lisinopril Hydrate
RS in methanol (1 in 1000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit
similar intensities of absorption at the same wavelengths.
(2) Determine the infrared absorption spectra of Lisinopril Hydrate and Lisinopril Hydrate RS as directed
in the paste method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
D : Between -43.0
and -47.0 (0.25 g calculated on the anhydrous basis,
0.25 ml/L zinc acetate buffer solution, pH 6.4, 25 mL,
100 mm).
0.25 mol/L zinc acetate buffer solutionTo 600
mL of water, add 150 mL of glacial acetic acid and
54.9 g of zinc acetate. Mix to dissolve by stirring, add
150 mL of strong ammonia water to cool to room temperature. Add strong ammonia water to adjust the pH to
6.4 and water to make 1000 mL.
Purity (1) Heavy metalsProceed with 2.0 g of Lisinopril Hydrate according to Method 4, and perform
(2) Related substancesDissolve 0.10 g of Lisinopril Hydrate in 50 mL of water, and use this solution as
the test solution. Pipet 3 mL of the test solution, add
water to make exactly 200 mL, and use this solution as
the standard solution. Perform the test with exactly 15
L each of the test solution and the standard solution as
directed under the Liquid Chromatography according to
the following conditions, and determine each peak area
by the automatic integration method: the area of the
peak, having the relative retention time of about 1.2
with respect to lisinopril, is not larger than 1/5 times
the peak area of lisinopril from the standard solution,
and the area of the peak other than lisinopril and the
peak mentioned above is not larger than 2/15 times the
peak area of lisinopril from the standard solution.

about 60 C.
Mobile phase: Control the gradient by mixing the
mobile phases A and B as directed in the following table.
Mobile phase A: Diluted 0.05 mol/L sodium dihydrogen phosphate TS (1 in 2).
Mobile phase B: A mixture of diluted 0.05 mol/L
sodium dihydrogen phosphate TS (1 in 2) and acetonitrile for liquid chromatography (3:2).
Time after injection
of sample (min)
0-10
10-25
Mobile
phaseA (vol%)
Mobile
phaseB (vol%)
9050
50
1050
50
Flow rate: 1.5 mL per minute.

System suitability
Test for required detectability: Measure exactly
2.5 mL of the standard solution, and add water to make
exactly 50 mL. Confirm that the peak area of lisinopril
obtained with 15 L of this solution is equivalent to 3.5
to 6.5% of that with 15 L of the standard solution.
System performance: To 10 mg of Lisinopril
Hydrate, add 2 mL of a solution of anhydrous caffeine
(1 in 1000) and water to make 200 mL. When the procedure is run with 15 L of this solution under the
above operating conditions, lisinopril and caffeine are
eluted in this order with the resolution between these
peaks being not less than 6.
deviation of the peak area of lisinopril is not more than
2.0%.
Time span of measurement: About 2.5 times as
long as the retention time of lisinopril beginning after
the solvent peak.
Water Not less than 8.0% and not more than 9.5%
(0.3 g, volumetric titration, back titration).
Residue on Ignition
Not more than 0.1% (1 g).
Assay Weigh accurately about 0.66 g of Lisinopril

Hydrate, dissolve in 80 mL of water, and titrate with
0.1 mol/L sodium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination in the same manner, and
= 40.55 mg of C21H31N3O5
KP 9 573
Lithium Carbonate
Li2CO3: 73.89
Lithium Carbonate, when dried, contains not less than
99.5% and not more than 101.0% of lithium carbonate
(Li2CO3).
Description Lithium Carbonate is a white, crystalline
powder and is odorless.
Lithium Carbonate is sparingly soluble in water,
slightly soluble in hot water and practically insoluble in
ethanol or in ether.
Lithium Carbonate dissolves in dilute acetic acid.
pHThe pH of a solution of Lithium Carbonate (1
in 100) is between 10.9 and 11.5.
Identification (1) Dissolve 0.2 g of Lithium Carbonate in 3 mL of dilute hydrochloric acid and add 4 mL
of sodium hydroxide TS and 2 mL of dibasic sodium
phosphate TS: a white precipitate is produced. To the
precipitate, add 2 mL of hydrochloric acid: it dissolves.
(2) A solution of Lithium Carbonate (1 in 100) responds to the Qualitative Tests for carbonate.
(3) Perform the test as directed under the Flame Coloration Test (1) with Lithium Carbonate: a persistent
red color appears.
0.10 g of Lithium Carbonate in 10 mL of water by
warming: the solution is clear and colorless.
(2) Acetic acid insoluble substancesTake 1.0 g
of Lithium Carbonate, dissolve in 40 mL of dilute acetic acid, filter the insoluble substances using filter paper
for assay, wash with five 10 mL volumes of water and
ignite the insoluble substances together with the filter
paper to incinerate: the weight of the residue is not
more than 1.5 mg.
(3) ChlorideTo 0.40 g of Lithium Carbonate, add
10 mL of water and 7 mL of dilute nitric acid and dissolve by heating to boil. After cooling, add 6 mL of dilute nitric acid and dilute with water to make 50 mL.
Perform the test. Prepare the control solution with 0.25
mL of 0.01 mol/L hydrochloric acid VS (not more than
0.022%).
(4) SulfateTo 0.40 g of Lithium Carbonate, add
10 mL of water and 4 mL of dilute hydrochloric acid
and dissolve by heating to boil. After cooling, add 1 mL
of dilute hydrochloric acid and dilute with water to
make 50 mL. Perform the test. Prepare the control solution with 0.40 mL of 0.005 mol/L sulfuric acid VS (not
more than 0.048%).
(5) Heavy metalsTo 4.0 g of Lithium Carbonate,
add 5 mL of water, gradually add 10 mL of hydrochloric acid while mixing and dissolve. Evaporate the solution on a water-bath to dryness. To the residue, add 10
mL of water and dissolve. Place this solution in a Nessler tube, add 1 drop of phenolphthalein TS, add ammo-
nia TS until the soultion shows a spale red color, then

add 2 mL of dilute acetic acid and dilute with water to
make 50 mL. Perform the test. Prepare the control solution as follows: evaporate 10 mL of hydrochloric acid
on a water-bath to dryness, to this residue, add 10 mL
of water and dissolve. Place the solution in a Nessler
tube, add 1 drop of phenolphthalein TS, add ammonia
TS until the solution shows a pale red color, then add
2.0 mL of standard lead solution and 2 mL of dilute
acetic acid and dilute with water to make 50 mL (not
more than 5 ppm).
(6) IronPrepare the test solution with 1.0 g of Lithium Carbonate according to Method 2 using 11 mL of
dilute hydrochloric acid and perform the test according
to Method B. Prepare the control solution with 1.0 mL
of standard iron solution (not more than 10 ppm).
(7) AluminumWeigh 5.0 g of Lithium Carbonate,
add 20 mL of water, mix, add slowly 15 mL of hydrochloric acid to dissolve and evaporate on a waterbath. Dissolve the residue to 50 mL of water and if necessary and use filter, this solution as solution A. Separately, evaporate 15 mL of hydrochloric acid on a water-bath. Prepare solution B as the same method. To 10
mL of solution A, add 10 mL of water and 5 mL of
acetic acid-sodium acetate buffer solution, pH 4.5 and
shake. Add 1 mL of a solution of ascorbic acid (1 in
100), 2 mL of aluminon TS and water to make 50 mL,
shake well and allow to stand for 10 minutes: the solution has no more color than the following control solution.
Control solutionDissolve 0.1758 g of potassium
aluminum sulfate in water to make 1000 mL. To 1.0
mL of this solotion, add 10 mL of solution B and water
to make 20 mL, add 5 mL of acetic acid-sodium acetate
buffer solution, pH 4.5 and proceed in the same manner.
(8) BariumTo 20 mL of solution A obtained in
(7), add 6 mL of water, 0.5 mL of dilute hydrochloric
acid, 3 mL of ethano1 and 2 mL of potassium sulfate
TS and allow to stand for 1 hour: the solution has no
more turbidity than the following control solution.
Control solutionDissolve 0.0178 g of barium
chloride in water to make 1000 mL. To 6 mL of this solution, add 20 mL of solution B obtained in (7), 0.5 mL
of dilute hydrochloric acid and 3 mL of ethanol and
proceed in the same manner.
(9) CalciumWeigh accurately about 5.0 g of Lithium Carbonate, add 50 mL of water and 15 mL of
hydrochloric acid and dissolve. Remove carbon dioxide
from the solution by boiling, add 5 mL of ammonium
oxalate TS, then make alkaline with ammonia TS and
allow to stand for 4 hours. Filter the produced precipitate through a glass filler (G4), wash with warm water
until the turbidity of the washing is not produced with
calcium chloride TS within 1 minute. Transfer the precipitate and the glass filter into a beaker, add water until the glass filter is covered with water, then add 3 mL

of sulfuric acid, heat between 70 C and 80 C and titrate with 0.02 mol/L potassium permanganate VS until
a pale red color persists for 30 seconds: the amount of
calcium (Ca: 40.08) is not more than 0.05%.
Each mL of 0.02 mol/L potassium permanganate VS
= 2.0039 mg of Ca
(10) MagnesiumTo 3.0 mL of solution A obtained in (7), add 0.2 mL of a solution of titan yellow (1
in 1000) and water to make 20 mL, then add 5 mL of
sodium hydroxide (3 in 20) and allow to stand for 10
minutes: the solution has no more color than the following control solution.
Control solutionDissolve 49.5 mg of magnesium
sulfate, previously dried at 105 C for 2 hours and
heated at 450 C for 3 hours, in water to make 1000 mL.
Take 6 mL of this solution, add 3 mL of solution B obtained in (7), 0.2 mL of a solution of titan yellow (1 in
1000) and water to make 20 mL and proceed in the
same manner.
(11) PotassiumDissolve 1.0 g of Lithium Carbonate in water to make 100 mL and use this solution as
the test solution. To 5 mL of the test solution, add 1.0
mL of dilute acetic acid, shake, add 5 mL of a solution
of sodium tetraphenylborate (1 in 30), shake immediately and allow to stand for 10 minutes: the solution
has no more turbidity than the following control solution.
Control solutionDissolve 9.5 mg of potassium
chloride in water to make 1000 mL. To 5 mL of this solution, add 1.0 mL of dilute acetic acid, shake and proceed in the same manner.
(12) SodiumWeigh accurately about 0.8 g of Lithium Carbonate, dissolve in water to make exactly 100
mL and use this solution as the test stock solution.
Measure exactly 25 mL of the test stock solution, add
the test solution (1). Separately, weigh accurately 25.4
mg of sodium chloride, dissolve in water to make exactly 1000 mL and use this solution as the standard solution. Measure exactly 25 mL of the test stock solution,
add exactly 20 mL of the standard solution, then add
the test solution (2). Determine emission intensities of
sodium using a flame photometer with the test solutions (1) and (2) under the following conditions. Adjust
the wavelength dial to 589 nm, atomize the test solution
(2) into the flame, then adjust the sensitivity so that the
emission intensity, LS , shows 100 adjustment and determine emission intensity, LT , of the test solution (1).
Then, make the other conditions identical, change the
wavelength dial to 580 nm, determine emission intensity, LB , of the test solution (1): the amount of sodium,
calculated from the following equation, is not more
than 0.05% .
Amount (%) of sodium (Na) =
LT LB W '
100
LS LT W
W : Amount (mg) of the sample in 25 mL of the test

stock solution,
W ': Amount (mg) of sodium in 20 mL of the standard solution.
(13) ArsenicPrepare the test solution with 1.0 g
of Lithium Carbonate, add 2 mL of water and 3 mL of
hydrochloric acid and perform the test (not more than 2
ppm).
hours).
Assay Weigh accurately about 1.0 g of Lithium Carbonate, previously dried, add 100 mL of water and exactly 50 mL of 0.5 mol/L sulfuric acid VS, remove carbon dioxide by boiling gently, cool and titrate the
excess sulfuric acid with 0.5 mol/L sodium hydroxide
VS until the color of the solution changes from red to
yellow (indicator: 3 drops of methyl red TS). Perform a
Each mL of 0.5 mol/L sulfuric acid VS
= 36.945 mg of Li2CO3
Lithium Carbonate Capsules

Lithium Carbonate Capsules contain not less than
95.0% and not more than 105.0% of the labelled
amount of lithium carbonate (Li2CO3: 73.89).
Capsules, with Lithium Carbonate.
Identification A portion of the contents of the capsule responds to the Identification under Lithium Carbonate.
Dissolution Test Perform the test with 1 capsule of
Lithium Carbonate Capsules at 100 revolutions per
minute according to Method 1 under the Dissolution
Test, using 900 mL of water. Add water to the dissolved
solution to make exactly 1000 mL after 30 minutes
from the start of the test and filter. Transfer 20 mL of
the filtrates to a volumetric flask, add 500 mL of water,
1 drop of hydrochlroric acid and 20 mL of a suitable
surfactant solution and mix. Add water to this solution
to make exactly 1000 mL and use this solution as the
test solution. Perform the test as directed in the Assay.
KP 9 575
Assay Weigh accurately the content of not less than

20 Lithium Carbonate Capsules. Weigh accurately a
portion of the content, equivalent to about 0.6 g of lithium carbonate (Li2CO3) in a volumetric flask, add 40
mL of water and 5 mL of hydrochloric acid and shake
until the solid is well disintegrated. Dilute with water to
make exactly 1000 mL and filter. Pipet exactly 10 mL
of the filtrates, add 800 mL of water, 20 mL of the surfactant solution, and water to make exactly 1000 mL,
test as directed in the Assay under Lithium Carbonate
Tablets.
nate (Li2CO3), add 40 mL of water and 5 mL of hydrochloric acid and shake until the solid is well disintegrated. Add water to make exactly 1000 mL and filter.
Pipet exactly 10 mL of the filtrates, add 800 mL of water and 20 mL of a suitable surfactant solution, add water to make exactly 1000 mL and use this solution as
mg of Lithium Carbonate RS, previously dried at 200
C for 4 hours, add about 20 mL of water and 0.5 mL
of hydrochloric acid, shake to dissolve and add water to
make exactly 100 mL. Pipet exactly 20 mL of this solution, add 800 mL of water and 20 mL of a suitable surfactant solution, add water to make exactly 1000 mL
and use this solution as the standard solution. Perform
the test with the test solution and the standard solution
using a flame photometer and determine emission intensity, PT and PS for the test solution and the standard
solution, respectively, at 671 nm.
Amount (mg) of lithium carbonate (Li2CO3)

PT
= amount (mg) of Lithium Carbonate RS P 20
S
Amount (mg) of lithium carbonate (Li2CO3)

PT
= amount (mg) of Lithium Carbonate RS P 20
S
The dissolution rate of Lithium Carbonate Capsules in

30 minutes is not less than 80.0%.
ment.
Lithium Carbonate Tablets
Loperamide Hydrochloride
Lithium Carbonate Tablets contain not less than 95.0%

and not more than 105.0% of the labeled amount of lithium carbonate (Li2CO3: 73.89).
Tablets, with Lithium Carbonate.
Identification A portion of the powered tablets reponds to the Identification under Lithium Carbonate.
Dissolution Test Perform the test with 1 tablet of Lithium Carbonate Tablets at 100 revolutions per minute
according to Method 1 under the dissolution test, using
900 mL of water. Add water to the dissolved solution to
make exactly 1000 mL after 30 minutes of the test and
filter. Take exactly 20 mL of the filtrates, add 500 mL
of water, 1 drop of hydrochlroric acid and 20 mL of a
suitable surfactant solution and mix, add water to make
exactly 1000 mL and use this solution as the test solution. Perform the test with the test solution as directed
in the Assay.
The dissolution rate of Lithium Carbonate Tablets in 30
minutes is not less than 80%.
ment.

Lithium Carbonate Tablets. Weigh accurately a portion
of powder, equivalent to about 0.6 g of lithium carbo-
HO
N
HCl
Cl
H3C
N
CH3
C29H33ClN2O2HCl: 513.50
Loperamide Hydrochloride, contains not less than
98.0% and not more than 102.0% of loperamide hydrochloride (C29H33ClN2O2HCl), calculated on the
dried basis.
Description Loperamide Hydrochloride is a white
and pale yellowish powder.
Loperamide Hydrochloride is freely soluble in methanol, in isopropanol or in chloroform and practically insoluble in water or in dilute acid solution.
Identification (1) Weigh accurately about 40 mg
each of Loperamide Hydrochloride and Loperamide
Hydrochloride RS, transfer each to 100 mL volumetric
flasks, dissolve by the addition of about 50 mL of isopropanol each, add 0.1 mol/L hydrochloric acid TS to
make exactly 100 mL. Determine the absorption spec-

tra of these solutions as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared spectra of Loperamide
Hydrochloride and Loperamide Hydrochloride RS,
previously dried, as directed in the potassium bromide

= 51.35 mg of C29H33ClN2O2HCl
Neutralized acetic acidDissolve 10 mg of
naphtholbenzein in 100 mL of glacial acetic acid, titrate
with 0.1 mol/L perchloric acid to a green endpoint and
use this solution as the neutralized acetic acid. In this
preparation, disregard the amount of titrant consumed.
Purity
(1) Chloride contentWeigh accurately
about 13 mg of Loperamide Hydrochloride and perform the test as directed under the Oxygen Flask Combustion Method. In particular, use a mixture of 10 mL
of 0.02 mol/L sodium hydroxide TS and 2 drops of
30% hydrogen peroxide TS as the adsorbing liquid of
the test. When the combustion is complete, rinse the
stopper, sample holder and the inner wall with 50 mL
of isopropanol. Add 4 mL of 0.1 mol/L nitric acid TS
and titrate with 0.01 mol/L mercuric nitrate VS using
diphenylcarbazone TS as the indicator. The chloride
content is not less than 13.52% and not more than
14.20%.
Each mL of 0.01 mol/L mercuric nitrate
= 0.3545 mg of Cl
(2) Related SubstancesDissolve Loperamide
Hydrochloride and Loperamide Hydrochloride RS in
chloroform to make 10 mg per mL and use these solutions as the test solution and the standard solution, respectively. Perform the test with the test solution and
the standard solution as directed under the Thin-layer
Chromatography. Spot 10 L each of these solutions to
a plate of silica gel for thin-layer chromatography and
develop the plate using a mixture of chloroform, methanol and formic acid (85 : 10 : 5) to a distance of
about 15 cm, air-dry the plate and expose the plate to
fumes of iodine: the principal spot obtained from the
test solution corresponds in Rf value, color and intensity to that from the standard solution and no other
spots are observed.
(3) Heavy metalsProceed with 1.0 g of Loperamide Hydrochloride according to Method 2 and perform the test. Prepare the control solution with 2.0 ml
Loss on Drying Not more than 0.5% (1 g, in vacuum
drying, 80 C, 4 hours).
Assay Dissolve about 0.375 g, accurately weighed, of
Loperamide Hydrochloride in 25 mL of neutralized
acetic acid, add 10 mL of mercuric acetate solution
(prepared by dissolving 1 g of mercuric acetate in 33
mL of neutralized acetic acid) and titrate with 0.1
mol/L perchloric acid VS to the original green color.
Loperamide Hydrochloride
Capsules
Loperamide Hydrochloride Capsules contain not less
than 90.0% and not more than 110.0% of the labeled
amount of loperamide hydrochloride (C29H33ClN2O2
HCl: 513.51).
Capsules, with Loperamide Hydrochloride.
Identification (1) Transfer a portion of the contents
of Loperamide Hydrochloride Capsules, equivalent to
about 10 mg of Loperamide Hydrochloride, to a stoppered vial, add 10 mL of methanol, shake for 5 minutes
and filter. Use this solution as the test solution. Separately dissolve a portion of Loperamide Hydrochloride
RS in methanol to render the concentration of 10 mg
Spot 10 L of the test solution and 1 L of the standard
solution on a plate of silica gel for thin-layer chromatography. Develop the plate using a mixture of chloroform, methanol and formic acid (85 : 10 : 5) to a distance of about 15 cm, dry the plate between 40 C and
60 C and expose the plate to fumes of iodine: the Rf
value of the spot obtained from the test solution corresponds to that obtained from the standard solution.
(2) The retention time of the major peak in the
chromatogram of the test solution corresponds to that
of the standard solution, as obtained in the Assay.
Loperamide Hydrochloride Capsules at 100 revolutions
per minute according to Method 1 under the Dissolution Test. Mix 200 mL of 1 mol/L acetic acid TS and
600 mL of water, adjust pH to 4.70 0.05 with 1 mol/L
sodium hydroxide TS and dilute with water to make
1000 mL. Use 500 mL of this solution as a dissolution
solution. Filter the dissolved solution after 30 minutes
from the start of the test. Use the filtrate as the test solution. Separately, weigh Loperamide Hydrochloride
RS, previously dried at 80 C for 4 hours in vacuum
and dissolve at the same concentration as the test solution and use this solution as the standard solution. Assay 50 L each of the test solution and the standard solution as directed in the Assay under Loperamide Hy-
KP 9 577
drochloride.
The dissolution rate of Loperamide Hydrochloride
Capsules in 30 minutes is not less than 80%.
are eluted in this order with the resolution of between

their peaks being not less than 3.0.
Uniformity of Dosage Units It meets the requirement when the content uniformity test is performed as
directed under the Assay.
Assay Transfer, as completely as possible, the contents of not less than 20 Loperamide Hydrochloride
Capsules and determine the average weight per capsule.
Transfer a portion of the powder, accurately weighed,
equivalent to about 10 mg of Loperamide Hydrochloride in diluted methanol (7 in 10) to make exactly 50
mL and treat under the supersonic wave for 15 minutes
and filter. Discard first 10 mL of the filtered solution
and pipet 10.0 mL of the filtrate, add 4.0 mL of internal
standard solution and diluted methanol (7 in 10) to
make exactly 50 mL and use this solution as the test solution. Separately, take accurately about 10 mg Loperamide Hydrochloride RS, previously dried for 4 hours
at 80 C in vacuum and dissolve in diluted methanol (7
in 10) to make exactly 50 mL. Pipet 10.0 mL of this solution, add 4.0 mL of internal standard solution and diluted methanol (7 in 10) to make exactly 50 mL and use
this solution as the standard solution. Test with 10 L
each of the test solution and the standard solution as directed under the Liquid Chromatography. Calculate the
ratios, QT and QS , of the peak areas of loperamide
to that of the internal standard for the test solution and
the standard solution, respectively.
Amount (mg) of loperamide hydrochloride
(C29H33ClN2O2HCl) = amount (mg) Loperamide
Q
Hydrochloride RS T
QS
penoxypropyl benzoic acid and dissolve in diluted methanol (7 in 10) in a volume of 50 mL.
with octadecylsilanized silica gel for liquid chromatography (5 m to 10 m in particle diameter).
Mobile phase: Dissolve about 1.8 g of anhydrous
monosodium phosphate in 300 mL of water, add 700
mL of methanol and titrate with phosphoric acid (1 in
100) to pH 7.0.
time of loperamide is about 9 minutes.
System suitability
with 10 L each of the standard solution according to
the above conditions internal standard and loperamide
Lorazepam
O
H
N
OH
Cl
N
Cl
and enantiomer
C15H10Cl2N2O2: 321.16
Lorazepam, when dried, contains not less than 98.5%
and not more than 101.0% of lorazepam
(C15H10Cl2N2O2).
Description Lorazepam is a white, crystalline powder and is odorless.
Lorazepam is sparingly soluble in ethanol or in acetone,
slightly soluble in ether and practically insoluble in water.
Lorazepam is gradually affected by light.
Identification (1) Take 20 mg of Lorazepam, add 15
mL of dilute hydrochloric acid, boil for 5 minutes and
cool: the solution responds to the Qualitative Tests for
primary aromatic amines.
Lorazepam and Lorazepam RS in ethanol (1 in 200000)
as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(3) Determine the infrared spectra of Lorazepam
and Lorazepam RS, previously dried, as directed in the
(4) Perform the test with Lorazepam as directed under Flame Coloration Test (2): a green color is observed.
%
Absorbance E11cm
(229 nm): Between 1080 and
1126 (after drying, 1 mg, ethanol, 200 mL).
Purity (1) ChlorideTake 1.0 g of Lorazepam, add

50 mL of water, allow to stand for 1 hour with occasional shaking and filter. To 25 mL of the filtrate, add 6
mL of dilute nitric acid and water to make 50 mL. Perform the test. Prepare the control solution with 0.20 mL
0.014%).
(2) Heavy metalsProceed with 1.0 g of Lorazepam according to Method 2 and perform the test. Pre-

pare the control solution with 2.0 mL of standard lead
Lorazepam according to Method 3 and perform the test
(4) Related substancesDissolve 0.10 g of Lorazepam in 20 mL of ethanol and use this solution as the
test solution. Pipet 1.0 mL of the test solution, add
ethanol to make exactly 100 mL and use this solution
test solution and the standard solution on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform, dioxane and glacial acetic acid (91 : 51 : 4) to a
distance of about 15 cm and air-dry the plate. Examine
under ultraviolet light (main wavelength: 254 nm): the
spots other than the principal spot from the test solution
are not more intense than the spot from the standard solution.
Loss on Drying Not more than 0.5% (1g, in vacuum,
105 C, 3 hours).
Assay Weigh accurately about 0.4 g of Lorazepam,
previously dried, dissolve in 50 mL of acetone and titrate with 0.1 mol/L tetrabutylammonium hydroxide
VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and
Each mL of 0.1 mol/L tetrabutylammonium hydroxide
VS = 32.116 mg of C15H10Cl2N2O2
tight containers.
Lormetazepam
Me
O
N
OH
Cl
N
Cl
and enantiomer
C16H12Cl2N2O2: 335.19
Lormetazepam contains not less than 99.0% and not
more than 101.0% of lometrazepam (C16H12Cl2N2O2),
Description Lormetazepam is a white crystalline

powder.
Lormetazepam is soluble in methanol or in ethanol and
Lormetazepam and Lormetazepam RS as directed in
(2) When proceed as directed in the Related substances under the Purity, the retention time of the Lormetazepam peak from the test solution corresponds to
that from the standard solution (2).
Purity Related substancesWeigh accurately 0.250
g of Lormetazepam, add 70% methanol to make exactly 100 mL and use this solution as the test solution
(1). Pipet accurately 1 mL of this solution, add 70%
methanol to make exactly 100 mL, pipet 10 mL of this
solution, add 70% methanol to make exactly 50 mL and
use this solution as the test solution (2). Pipet accurately 25 mL of the test solution (2), add 70% methanol to
make exactly 50 mL and use this solution as the test solution (3). Separately, weigh accurately 5 mg of Lormetazepam RS and add 70% methanol to make exactly
100 mL. Pipet 5 mL of this solution, add 70% methanol
to make 50 mL and use this solution as the standard solution. Perform the test with 10 L each of the test solutions (1), (2) and (3), and the standard solution as directed under the Liquid Chromatography according to
area of the peaks from these solutions by the automatic
integration method: the area of each peak other than
the principal peak obtained from the test solution (1) is
not more than the area of the principal peak obtained
from the test solution (2) (0.2%), the number of peaks
having the area greater than the area of the principal
peak from the test solution (3) is not more than 2 from
the test solution (1) and total area of these peaks from
the test solution (1) is not more than 2.5 times the area
of the principal peak from the test solution (2) (0.5%).
Mobile phase: A mixture of methanol and phosphate buffer (48:52).
System suitability
System performance: Weigh 5 mg of Lormetazepam RS, add 70% methanol to make 100 mL, pipet 5
mL of this solution and add 70% methanol to make 50
mL. Mix 25 mL of this solution and 25 mL of a solution containing 5 g Lorazepam per mL, prepared by
KP 9 579
dissolving Lorazepam RS in 70% methanol. When the
procedure is run with 20 L of this solution under the
above operating conditions, the resolution between two
principal peaks is not less than 4.
Phosphate bufferDissolve 4.91 g of sodium dihydrogen phosphate and 0.633 g of disodium hydrogen
phosphate in water to make 1000 mL.
Not more than 1.0% (1 g, 105 C, 3
Loss on Drying
hours).

Assay Weigh accurately about 0.5 g of Lormetazepam, dissolve in 50 mL of nitroethane and titrate with
= 33.52 mg of C16H12Cl2N2O2
tight containers.
Lovastatin
H
HO
H3C
H3 C
O H
O
H
H
CH3
H3C
H
C24H36O5 : 404.54
Lovastatin contains not less than 98.5% and not more
than 101.0% of lovastatin (C24H36O5), calculated on the
dried basis.
Description Lovastatin is a white, crystalline powder.
Lovastatin is soluble in acetone, sparingly soluble in
ethanol and practically insoluble in water.
Identification (1) Dissolve 10 mg each of Lovastatin
and Lovastatin RS in acetone to make 100 mL. Pipet 5
mL of the solutions, add acetonitrile to make exactly
100 mL, and use these solutions as the test solution and
the standard solution. Determine the absorption spectra
of the solutions as directed under the Ultraviolet-visible
Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared absorption spectra of
Lovastatin and Lovastatin RS as directed in the paste
method under the Infrared Spectrophotometry: both
spectra exhibit similar intensities of absorption at the
same wavenumbers.
D : Between +324
and +338 (0.125 g previously dried, acetonitrile, 25
mL, 100 mm).
Purity (1) Heavy metalsProceed the test with 1.0 g
of Lovastatin according to Method 2. Prepare the control solution with 2.0 mL of standard lead solution (not
more than 20 ppm).
(2) Lovastatin related substance IWeigh accurately about 25 mg, dissolve in acetonitrile to make exactly 25 mL, and use this solution as the test solution.
Separately, weigh accurately about 10.0 mg of Lovastatin RS, and dissolve in acetonitrile to make 100 mL.
Pipet 2.0 mL of this solution, dilute with acetonitrile to
100 mL, and use this solution as the standard solution.
Perform the test with exactly 10 L each of the test solution and the standard solution as directed under the
conditions. Based on the peak areas of Lovastatin and
lovastatin related substance I (dihydrolovastatin), calculate the percentage of the related compound I in Lovastatin according to the following the formula:
Amount (%) of lovastatin related substance I =
C A
2 .5 F T
W AS
F is the response factor for the related compound A
(1.6);
C is the concentration of Lovastatin RS (g/mL) in
the standard solution
W is the amount (mg) of Lovastatin in the test solution
AT is the peak response for lovastatin related compound I from the test solution
AS is the peak response for Lovastatin obtained
from the standard solution
Column: A stainless steel column 4.6 mm in inside
diameter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 m in
particle diameter).
about 40 C.
Mobile phase: a mixture of acetonitrile and 0.01
mol/L phosphoric acid (13:7).
System suitability
System performance: Dissolve 10 mg each of
Lovastatin RS and lovastatin related substance RS in
acetonitrile to make 100 mL. Pipet 2.0 mL of this solution, and add acetonitrile to make 100 mL. When the

above operating conditions, the relative retention times
are about 1.0 for lovastatin and 1.3 for lovastatin related compound I with the resolution between these
System repeatability: When the test is run 6 times
with 10 L of the standard solution, the relative standard deviation of the peak area of lovastatin is not more
than 5.0%.
(3) Other related substancesWeigh accurately
about 25 mg of Lovastatin, dissolve in acetonitrile to
make exactly 25 mL, and use this solution as the test
solution. Separately, weigh accurately about 10 mg of
Lovastatin RS and dissolve in acetonitrile to make exactly 100 mL. Pipet 2 mL of this solution, add acetonitrile to make 100 mL, and use this solution as the standard solution. Perform the test with 10 L each of the
conditions, measure all the peak areas by automatic integration, and calculate the percentages of related substances by the below formula. The percentage of each
related substance is not more than 2.0%, and the total
percentage of all related substances is not more than
1.0%. For this calculation, it is allowed to exclude any
related substances with less than 0.04%.
Amount (%) of related substances = 2.5 F
C AT
W AS
F is the response factor for each related substance

(1.4 for a related substance with the relative retention
time of 0.73; 1.0 for any other related substances).
C is the concentration of Lovastatin RS (g/mL) in
W is the amount (mg) of Lovastatin in the test solution.
AT is the peak response for each related substance
from the test solution.
AS is the peak response for Lovastatin obtained
diameter and 12.5 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (4 m in
particle diameter).
about 40 C.
Flow rate: 1.5 mL/min
Mobile phase: Use variable mixtures of solution A
and solution B, and program the chromatograph as follows.
Mobile phase A Adjust the pH of 0.001 mol/L
phosphoric acid solution to 4.0 with 1 mol/L sodium
hydroxide.
Mobile phase B Acetonitrile.
Time
(minutes)
02
25
58
816
1625
2527
2735
Mobile
phase A
(%)
Mobile
phase B
(%)
60
40
60 45
45
40 55
55
45 10
10
55 90
90
10 60
60
90 40
40
Elution
isocratic
linear gradient
isocratic
linear gradient
isocratic
linear gradient
isocratic
System suitability
Lovastatin RS and compactin in acetonitrile to make
100 mL. Pipet 2.0 mL of this solution, and add acetonitrile to make 100 mL. When the procedure is run with
10 L of this solution under the above operating conditions, the relative retention times are about 1.0 for lovastatin and 0.85 for compactin with the resolution between these peaks being not less than 3.5.
System repeatability: When the test is run 6 times
with 10 L of the standard solution, the relative standard deviation of the peak area of lovastatin is not more
than 5.0%.
Loss on Drying Not more than 0.3% (1 g, vacuum,
60 C, 6 hours).
Assay Weigh accurately about 30 mg each of Lovastatin and Lovastatin RS, dissolve in acetonitrile to
test solution and the standard solution. Perform the test
with 10 L each of the test solution and the standard
according to the following conditions, and calculate the
ratios, AT and AS , of the peak area of lovastatin
from the test solution to that from the standard solution.
Amount (mg) of lovastatin (C24H36O5)
A
= amount (mg) of Lovastatin RS T
AS
particle diameter).
Mobile phase: a mixture of acetonitrile and 0.1%
phosphoric acid (65:35).
System suitability
KP 9 581
System performance: Perform the test with 10 L
of the standard solution under the above operating conditions, the column efficiency is not less than 3000
theoretical plates, and the symmetry factor is not more
than 1.4.
above operating conditions, the relative standard deviation of the peak area is not more than 1.0%.
under nitrogen in a cold place.
Loxoprofen Sodium Hydrate

CH3
CO2Na
2H2O
The color is not darker than that of diluted Matching

Fluid for Color A (1 in 2).
(2) Heavy metalsProceed with 2.0 g of Loxoprofen Sodium Hydrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL
(3) Related substancesDissolve 1.0 g of Loxoprofen Sodium Hydrate in 10 mL of methanol, and use
this solution as the test solution. Pipet 1 mL of the test
solution, add methanol to make exactly 200 mL, and
test with these solutions as directed under the Thinlayer Chromatography. Spot 10 L each of the test solution and the standard solution on a plate of silica gel
with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of 1,2dichloroethane and glacial acetic acid (9:1) to a distance of about 15 cm, and air-dry the plate. Examine
C15H17NaO3.2H2O: 304.31
Loxoprofen Sodium Hydrate contains not less than
98.5% and not more than 101.0% of loxoprofen sodium
(C15H17NaO3: 268.28), calculated on the anhydrous basis.
Description Loxoprofen Sodium Hydrate is a white
to yellowish-white crystal or crystalline powder.
Loxoprofen Sodium Hydrate is very soluble in water or
in methanol, and practically insoluble in ether.
A solution of Loxoprofen Sodium Hydrate (1 in 20)
shows no optical rotation.
pHThe pH of a solution of Loxoprofen Sodium
Hydrate in freshly boiled and cooled water (1 in 20) is
Identification Determine the absorption spectra of
solutions of Loxoprofen Sodium Hydrate and Loxoprofen Sodium Hydrate RS (1 in 55000) as directed under
the Ultraviolet-visible Spectrophotometry: both spectra
exhibit similar intensities of absorption at the same wavelengths.
Loxoprofen Sodium Hydrate and Loxoprofen Sodium
Hydrate as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same
wavenumbers.
(3) A solution of Loxoprofen Sodium Hydrate (1 in
10) responds to the Qualitative Tests for sodium salt.
1.0 g of Loxoprofen Sodium Hydrate in 10 mL of water: the solution is clear and colorless or pale yellow.
Water Not less than 11.0% and not more than 13.0%
Assay Weigh accurately about 60 mg of Loxoprofen
Sodium Hydrate, and dissolve in diluted methanol (3 in
5) to make exactly 100 mL. Pipet 5 mL of this solution,
add exactly 10 mL of the internal standard solution, add
diluted methanol (3 in 5) to make 100 mL, and use this
solution as the test solution. Separately, weigh accurately about 50 mg of Loxoprofen RS, previously dried
in a desiccator (in vacuum, 60 C) for 3 hours, and dissolve in diluted methanol (3 in 5) to make exactly 100
mL. Pipet 5 mL of this solution, proceed in the same
manner as directed for the preparation of the test solution, and use so obtained solution as the standard solution. Perform the test with 10 L each of the test solution and standard solution as directed under the Liquid
Chromatography according to the following conditions,
and calculate the ratios, QT and QS , of the peak area
of loxoprofen to that of the internal standard for the test
solution and the standard solution, respectively.
Amount (mg) of loxoprofen sodium (C15H17NaO3)
Q
= amount (mg) of Loxoprofen RS T 1.0892
QS
Internal Standard SolutionA solution of ethyl
benzoate in diluted methanol (3 in 5) (1 in 50000).

about 40 C.
Mobile phase: A mixture of methanol, water, glacial acetic acid and triethylamine (600:400:1:1).
time of loxoprofen is about 7 minutes.
System suitability
operating conditions, loxoprofen and the internal standard are eluted in this order with the resolution between
these peaks being not less than 10.
deviation of the ratios of the peak area of loxoprofen to
Lysine Hydrochloride
H
H 2NCH 2CH 2CH 2CH 2
CO 2H
HCl
NH 2
L-Lysine
Hydrochloride
C6H14N2O2 HCl: 182.65
Lysine Hydrochloride, when dried, contains not less

than 98.5% and not more than 101.0% of lysine hydrochloride (C6H14N2O2HCl).
Description Lysine Hydrochloride is a white powder,
is odorless and has a slight, characteristic taste.
Lysine Hydrochloride is freely soluble in water or in
formic acid, very slightly soluble in ethanol and practically insoluble in ether.
Identification (1) Determine the infrared absorption
spectra of Lysine Hydrochloride and Lysine Hydrochloride RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
absorption at the same wavenumbers. If any difference
appears between the spectra, dissolve Lysine Hydrochloride in water, evaporate the water to dryness at 60 C,
and repeat the test with the residue.
(2) A solution of Lysine Hydrochloride (1 in 10) responds to the Qualitative Tests for chloride.
[ ]20
D
Specific Optical Rotation

: Between +19.0
and +21.5 (after drying, 2 g, 6 mol/L hydrochloric acid
TS, 25 mL, 100 mm).
pH Dissolve 1.0 g of Lysine Hydrochloride in 10 mL

1.0 g of Lysine Hydrochloride in 10 mL of water: the
(2) SulfatePerform the test with 0.6 g of Lysine
Hydrochloride. Prepare the control solution with 0.35
mL of 0.005 mol/L sulfuric acid VS (not more than
0.028%).
(3) AmmoniumPerform the test with 0.25 g of
Lysine Hydrochloride. Prepare the control solution with
5.0 mL of standard ammonium solution (not more than
0.02%).
(4) Heavy metalsProceed with 2.0 g of Lysine
Lysine Hydrochloride according to Method 1 and perform the test (not more than 2 ppm).
(6) Related substancesDissolve 0.10 g of Lysine
Hydrochloride in 25 mL of water and use this solution
add water to make exactly 50 mL, pipet 5.0 mL of this
solution, add water to make exactly 20 mL and use this
the test solution and the standard solution as directed
under the Thin-layer Chromatography. Spot 5 L each
of the test solution and the standard solution on a plate
of silica gel for thin-layer chromatography. Develop the
plate with a mixture of n-propanolol and strong ammonia water (67 : 33) to a distance of about 10 cm and dry
the plate at 100 C for 30 minutes. Spray evenly the
plate with a solution of ninhydrin in acetone (1 in 50)
and heat at 80 C for 5 minutes: the spots other than the
hours).
Assay Weigh accurately 0.1 g of Lysine Hydrochloride, previously dried, dissolve in 2 mL of formic acid,
add exactly 25 mL of 0.1 mol/L perchloric acid VS and
heat in a water-bath for 30 minutes. After cooling, add
45 mL of glacial acetic acid and titrate the excess perchloric acid with 0.1 mol/L sodium acetate VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any
= 9.132 mg of C6H14N2O2HCl
KP 9 583
Magnesium Aspartate
Hydrate
H
2+
Mg
NH2
. 2H2O
HOOC
-
COO
C8H12O8N2Mg2H2O : 324.53
Magnesium Aspartate Hydrate contains not less than
98.0% and not more than 102.0% of magnesium aspartate (C8H12O8N2Mg : 288.49), calculated on the anhydrous basis.
Description Magnesium Aspartate Hydrate is a white
crystalline powder or colorless crystals.
Magnesium Aspartate Hydrate is freely soluble in water.
Identification (1) Ignite about 15 mg of Magnesium
Aspartate Hydrate until a white residue is obtained, dissolve the residue in 1 mL of dilute hydrochloric acid,
neutralize to red litmus paper by the addition of dilute
sodium hydroxide TS and filter if necessary. Upon the
addition of 6 mol/L ammonia water to this solution,
white precipitate is formed and the precipitate is dissolved with the addition of 10.7w/v% ammonium chloride solution, and the addition of 9w/v% disodium hydrogen phosphate solution form a white crystalline precipitate.
(2) Dissolve 0.10 g of the Magnesium Aspartate
Hydrate in water to make 10 mL, dilute 1 mL of this
solution with water to make 50 mL, and use this solution as the test solution. Separately, dissolve 10 mg of
Magnesium Aspartate Hydrate RS in water to make 50
mL, and use this solution as the standard solution. Perform the test with the test solution and the standard solution as directed under the Thin-layer Chromatography.
Spot 5 L each of the test solution and the standard solution on a plate of silica gel with fluorescent indicator
for thin-layer chromatography. Develop the plate with
the upper layer of the mixture of n-butanol, water and
glacial acetic acid (60 : 20 : 20) to a distance of about
15 cm and air-dry the plate. Spray evenly ninhydrin TS
on the plate and heat at 105 C for 15 minutes: the color and Rf value of both the principal spots from the test
solution and the standard solution are the same.
D : Between +20.5 and
+23.0 (0.50 g, a solution prepared by mixing 51.5 g of
hydrochloric acid and water to make 100 mL, 25 mL,
100 mm).
pH The pH of a solution of Magnesium Aspartate
Hydrate in water (25 in 100) is between 6.0 and 8.0.
Purity (1) Clarity and color of solutionA 100 mL

solution of 2.5 g Magnesium Aspartate Hydrate in water is colorless and clear.
(2) ChloridesPerform the test with 1.0 g of Magnesium Aspartate Hydrate. Prepare the control solution
with 0.564 mL of 0.01 mol/L hydrochloric acid VS (not
more than 0.02%).
(3) SulfatesPerform the test with 0.5 g of Magnesium Aspartate Hydrate. Prepare the control solution
with 0.52 mL of 0.005 mol/L sulfuric acid VS (not
more than 0.05%).
(4) AmmoniumPerform the test with 0.25 g of
Magnesium Aspartate Hydrate. Prepare the control solution with 5 mL of ammonium standard solution (not
more than 0.02%).
(5) Heavy metalsProceed with 2.0 g of Magnesium Aspartate Hydrate according to Method 1. and
(6) IronIn a separatory funnel, dissolve 0.20 g of
Magnesium Aspartate Hydrate in 10 mL of dilute hydrochloric acid. Extract three quantities, each of 10 mL,
of methyl isobutyl ketone, shaking for 3 minutes each
time. To the combined organic layers add 10 mL of water and shake for 3 minutes. Put the aqueous layer in a
Nessler tube, add 2 mL of 20 w/v% citric acid solution
and 0.1 mL of mercaptoacetic acid, alkalinize with 10
mol/L ammonia water, then add water to 20 mL, and
allow to stand for 5 minutes: the color appeared is not
darker than the color of the standard solution obtained
from the same process with 10 mL of the standard iron
solution (1 in 10) (not more than 50 ppm).
(7) Ninhydrin-positive substancesDissolve 0.10 g
of Magnesium Aspartate Hydrate in water to make 10
ml. Dilute 1 mL of this solution with water to make 50
mL and use this solution as the test solution (1). Dilute
1 mL of the test solution (1) with water to make 50 mL
and use this solution as the test solution (2). Dilute 5
mL of the test solution (2) with water to make 20 mL
and use this solution as the standard solution (1). Separately, dissolve 10 mg of Magnesium Aspartate Hydrate
RS and 10 mg of Glutamic Acid RS in water to make
25 mL and use this solution as the standard solution (2).
Perform the test with the test solutions and the standard
solutions as directed under the Thin-layer Chromatography. Spot 5 L each of the test solution (1) and the
standard solutions (1) and (2) on a plate of silica gel
with fluorescent indicator for thin-layer chromatography. Develop the plate with the upper layer of the
mixture of n-butanol, water and glacial acetic acid (60 :
plate. Spray evenly ninhydrin TS on the plate and heat
at 105 C for 15 minutes: Any spot from the test solution (1), other than the principal spot, is not more intense than the spot from the standard solution (1)
(0.5%). The test is not valid unless the chromatogram
obtained with the standard solution (2) shows two
clearly separated principal spots.

Water Between 10.0% and 14.0% (0.1 g, volumetric
titration, direct titration).
Assay Weigh accurately about 0.26 g of Magnesium
Aspartate Hydrate, dissolve in 10 mL of water, add 10
mL of ammoniaammonium chloride buffer solution
(pH 10.0), and titrate with 0.1 mol/L disodium ethylenediaminetetraacetate VS until the color of the solution
changes from violet to blue (indicator : about 50 mg of
eriochrome black Tsodium chloride indicator). Perform a blank determination and make any necessary
correction.
Each mL of 0.1 mol/L disodium ethylenediaminetetraacetate VS
= 28.853 mg of C8H12MgN2O8.
Magnesium Carbonate
Magnesium Carbonate is a basic hydrated magnesium
carbonate or a normal hydrated magnesium carbonate.
Magnesium Carbonate contains not less than 40.0%
and not more than 44.0% of magnesium oxide (MgO:
40.30).
Heavy Magnesium Carbonate may be used as a commonly used name for Magnesium Carbonate which
shows the height of the precipitate below the 12.0 mL
graduation line in the Precipitation Test.
Description Magnesium Carbonate is a white, friable
masses or powder and is odorless.
Magnesium Carbonate is practically insoluble in water,
in ethanol, in ether or in n-propanol.
Magnesium Carbonate dissolves in dilute hydrochloric
acid with effervescence.
Saturated solution of Magnesium Carbonate is alkaline.
Identification (1) Dissolve 1 g of Magnesium Carbonate in 10 mL of dilute hydrochloric acid, boil, then
cool, neutralize with sodium hydroxide TS and filter, if
necessary: the solution responds to the Qualitative Tests
for magnesium salt.
(2) Magnesium Carbonate responds to the Qualitative Tests (1) for carbonate.
Purity (1) Soluble saltsTo 2.0 g of Magnesium
Carbonate, add 40 mL of n-propanol and 40 mL of water, heat to boil with constant stirring, cool and filter.
Wash the residue with water, combine the washings
with the filtrate and add water to make exactly 100 mL.
Evaporate 50 mL of the solution on a water-bath to
dryness and dry at 105 C for 1 hour: the residue is not
more than 10.0 mg.
(2) Heavy metalsMoisten 1.0 g of Magnesium
Carbonate with 4 mL of water, dissolve by addition of
10 mL of dilute hydrochloric acid and evaporate on a

water-bath to dryness. Dissolve the residue in 35 mL of
water, 2 mL of dilute acetic acid, 1 drop of ammonia
TS, filter, if necessary, wash the filter paper with water,
combine the washings with the filtrate and add water to
make 50 mL and perform the test. Prepare the control
solution as follows: Evaporate 10 mL of dilute hydrochloric acid on a water-bath to dryness, add 2 mL of
dilute acetic acid and 3.0 mL of standard lead solution
and dilute with water to make 50 mL (not more than 30
ppm).
(3) IronPrepare the test solution with 0.10 g of
Magnesium Carbonate according to Method 1 and perform the test according to Method A. Prepare the control solution with 2.0 mL of standard iron solution (not
more than 200 ppm).
of Magnesium Carbonate, previously moistened with
1.5 mL of water, add 3.5 mL of dilute hydrochloric acid
and perform the test (not more than 5 ppm).
(5) Calcium oxideWeigh accurately about 0.6 g
of Magnesium Carbonate and dissolve in 35 mL of water and 6 mL of dilute hydrochloric acid. Add 250 mL
of water and 5 mL of a solution of tartaric acid (1 in 5),
then add 10 mL of a solution of 2,2,2nitryltriethanolamine (3 in 10) and 10 mL of 8 mol/L
potassium hydroxide TS, allow to stand for 5 minutes
and titrate with 0.01 mol/L disodium ethylenediaminetetraacetate VS until the color of the solution changes
from red-purple to blue (indicator: 0.1 g of NN indicator). Perform a blank determination and make any necessary correction.
The content of calcium oxide (CaO: 56.08) is not more
than 0.6%.
Each mL of 0.01 mol/L disodium ethylenediaminetetraacetate VS = 0.5608 mg of CaO
(6) Acid-insoluble substancesMix 5.0 g of Magnesium Carbonate and 75 mL of water, add 10 mL of
hydrochloric acid drop-wise while stirring, boil for 5
minutes and cool. Collect the insoluble residue using
filter paper for Assay, wash well with water until the
last washing shows no turbidity with silver nitrate TS
and ignite the residue together with the filter paper: the
residue is not more than 2.5 mg.
Precipitation Transfer 1.0 g of Magnesium Carbonate, previously sifted through a No. 100 sieve to a
glass-stoppered measuring cylinder with a 50 mL graduation line at 150 mm from the bottom and add water
to make 50 mL, Shake vigorously for exactly 1 minute,
allow to stand for 15 minutes and measure the height of
the precipitate (in graduation in mL).
Carbonate, dissolve in 10 mL of water and 3.5 mL of
dilute hydrochloric acid and add water to make exactly
100 mL. Pipet 25.0 mL of the solution, add 50 mL of
water and 5 mL of ammonia-ammonium chloride buf-
KP 9 585
fer solution, pH 10.7 and titrate with 0.05 mo1/L disodium ethylenediaminetetraacetate VS (indicator: 40
mg of eriochrome black T-sodium chloride indicator).
correction. From the volume of 0.05 mo1/L disodium
ethylenediaminetetraacetate VS consumed deduct the
volume of 0.05 mol/L disodium ethylenediaminetetraacetate VS corresponding to the content of Calcium
Oxide (CaO) obtained in the Purity (5).
Each mL of 0.05 mol/L disodium ethylenediaminetetraacetate VS = 2.0152 mg of MgO
Each mg of calcium oxide (CaO) = 0.36 mL of 0.05
mol/L disodium ethylenediaminetetraacetate VS
Magnesium Glycerophosphate
O
Mg
OP
2+
O- HO
2+
OH
Mg
O
P
HO
OH
and enantiomer
C3H7MgO6P: 194.36
Magnesium Glycerophosphate contains not less than
11.0 % and not more than 12.5 % of Mg, calculated on
the dried basis.
Description Magnesium Glycerophosphate is a white
powder.
Magnesium Glycerophosphate is practically insoluble
in ethanol.
Magnesium Glycerophosphate is soluble in dilute solutions of acids.
Magnesium Glycerophosphate is hygroscopic.
Identification (1) Mix 1 g of Magnesium Glycerophosphate with 1 g of potassium hydrogen sulfate in a
test tube fitted with a glass tube. Heat strongly and direct the white vapor towards a piece of filter paper impregnated with a freshly prepared 1 w/v% sodium nitroprusside solution: the filter paper develops a blue
color in contact with piperidine.
(2) Ignite 0.1 g of Magnesium Glycerophosphate in
a crucible, add 5 mL of nitric acid to the residue, heat
in a water-bath for 1 min and filter. To 1 mL of the filtrate, add 2 mL of molybdovanadic TS: a yellow color
develops.
(3) Magnesium Glycerophosphate responds to the
Qualitative Tests for magnesium.
2.5 of Magnesium Glycerophosphate in 50 mL of water: this solution is not more opalescent than the reference suspension
Reference suspensionTo 30 mL of standard suspension, add 70 mL of water. Prepare when use and
shake well before use.
Standard suspensionPrepare as directed in the
reagent under the Test Methods for Plastic Containers.
(2) AcidDissolve 1.0 g of Magnesium Glycerophosphate in 100 mL of water and titrate with 0.1
mol/L sodium hydroxide VS (indicator: 2 drops of
phenolphthalein TS): less than 1.5 mL of 0.1 mol/L sodium hydroxide VS consumed.
(3) ChlorideProceed with 0.20 g Magnesium
Glycerophosphate and perform the test. Prepare the
control solution with 0.84 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.015%).
(4) SulfateProceed with 0.20 g of Magnesium
Glycerophosphate and perform the test. Prepare the
(5) PhosphateDissolve 2.5 g of Magnesium Glycerophosphate in 50 mL of water. Pipet 4.0 mL of this
solution and add water to make 100 mL. Pipet 1.0 mL
of this solution, add water to make 100 mL and use this
solution as the test solution. To 100 mL of the test solution, add 4 mL of sulfomolybdic TS and 0.1 mL of
stannous chloride TS and allow the mixture to stand for
10 minutes: the color from this solution is not more intense than that from a solution containing 2 mL of
standard phosphate solution and 98 mL of water (not
more than 0.5%).
(6) Heavy metalsDissolve 1.0 g of Magnesium
Glycerophosphate in 20 mL of water, add 15 mL of
hydrochloric acid and 25 mL of methyl isobutyl ketone,
and mix by shaking for 1 minute. After standing, take
the aqueous layer and evaporate to dryness. Dissolve
the residue in 2 mL of dilute acetic acid, add 50 mL of
water and perform the test using this solution as the test
solution. Prepare the control solution with 2.0 mL of
(7) IronPlace 67 mg of Magnesium Glycerophosphate to a Nessler tube, add water to make 10 mL,
add 2 mL of 20w/v% citric acid solution and 0.1 mL of
mercaptoacetic acid to mix, make the solution alkaline
by the addition of 10 mol/L ammonia water, add water
to make 20 mL and allow this solution to stand for 5
minutes: the color from this solution is not more intense than that from diluted standard iron solution (1 in
10) (not more than 150 ppm).
(8) Glycerol and alcohol-soluble substancesTo
1.0 g of Magnesium Glycerophosphate, add 25 ml of
ethanol, mix by shaking for 2 min, filter and wash the
residue with 5 ml of ethanol. Combine the filtrate and
the washings, evaporate to dryness in a water-bath, dry
the residue at 70 o C for 1 h and weigh (not more than

1.5%).
hours).
Assay Weigh accurately 0.2 g of Magnesium Glycerophosphate, add 40 mL of water to dissolve, add 10
mL of ammonia-ammonium chloride buffer solution,
pH 10 and titrate with 0.1 mol/L disodium ethylenediaminetetraacetate VS (indicator: 50 mg of eriochrome
black T-sodium chloride TS) until the color of the solution changes from purple to blue.
Each mL of 0.1 mol/L disodium ethylenediaminetetraacetate VS = 2.431 mg of Mg
Magnesium Hydroxide
Mg(OH)2 : 58.32
Magnesium Hydroxide, when dried, contains not less
than 95.0% and not more than 100.5% of magnesium
hydroxide [Mg(OH)2].
Description Magnesium Hydroxide is a white bulky
powder.
Magnesium Hydroxide is practically insoluble in water
or ethanol.
Magnesium Hydroxide is soluble in dilute hydrochloric
acid.
Identification A 3 mol/L solution of Magnesium
Hydroxide in hydrochloric acid TS (1 in 20) responds
to the Qualitative Tests (1) for magnesium.
Purity (1) Soluble saltsBoil 2.0 g of Magnesium
Hydroxide with 100 mL of water for 5 minutes in a
covered beaker, filter while hot, cool, and dilute the filtrate with water to 100 mL. Titrate 50 mL of the diluted
filtrate with 0.1 mol/L sulfuric acid, using methyl red
TS as the indicator: not more than 2.0 mL of acid is
consumed. Evaporate 25 mL of the diluted filtrate to
dryness, and dry at 105 C for 3 hours: not more than
10 mg of residue remains.
(2) CarbonateBoil a mixture of 0.10 g of Magnesium Hydroxide with 5 mL of water, cool, and add 5
mL of 6 mol/L acetic acid: not more than a slight effervescence is observed.
(3) CalciumTransfer 0.25 g of Magnesium Hydroxide, previously dried, to a beaker, add 30 mL of dilute hydrochloric acid, and stir until dissolved, heating
if necessary. Transfer this solution to a 200 mL volumetric flask containing 4 mL of Lanthanum TS, dilute
with water to volume, mix, and use this solution as the
test solution. Separately, Weigh accurately 249.7 mg of
calcium chloride, previously dried at 300 C for 3
hours and cooled in a silica gel desiccator for 2 hours,

dissolve in small quantities of hydrochloric acid, dilute
with water to exactly 100 mL. Pipet each 5.0, 10.0,
15.0 mL of this solution, put each in 1000 mL volumetric flasks, add each 20 mL of Lanthanum TS and 40
mL of diluted hydrochloric acid (1 in 10), dilute with
water to volume and use these solutions as the standard
solutions. 1 mL of each standard solution contains 5.0,
10.0, 15.0 g of calcium, respectively. Transfer 4 mL
of Lanthanum TS and 10 mL of diluted hydrochloric
acid (1 in 10) in a 200 mL volumetric flask and dilute
with water to volume and use this solution as the balnk
solution. Perform the test with the blank, the test, and
the standard solutions as directed under the Atomic Absorption Spectrophotometry according to the following
conditions and calculate the calcium content of the test
solution from the calibration curve obtained from the
absorbance of the standard solution.( not more than
1.5%.)
Gas: Combustible gas- Acetylene.
Supporting gas- Air.
Lamp: A calcium hollow cathode lamp.
Wavelength: 422.7 nm.
Hydroxide in 15 mL of 3 mol/L hydrochloric acid TS,
and evaporate the solution on a steam bath to dryness.
Dissolve the residue in 20 mL of water, and filter. To
the filtrate, which should be neutral to litmus, add 2 mL
of 1 mol/L acetic acid, dilute with water to 50 mL, and
perform the test, Prepare the control solution with 15
mL of 3 mol/L hydrochloric acid as and 2.0 mL of
standard lead solution (not more than 20 ppm) directed
for the preparation of the test solution..
(5) LeadDissolve 1.0 g of Magnesium Hydroxide
in 20 mL of 3 mol/L hydrochloric acid TS and use this
solution as the test solution. Transfer the test solution
into a separatory funnel, wash with 10 mL of water,
and combine the washings into the separatory funnel.
Add 6 mL of ammonium citrate and 2 mL of hydroxylamine hydrochloride TS and 2 drops of phenolred,
and alkalinize with strong ammonia water. Allow to
cool if necessary, add 2 mL of potassium cyanide solution, extract with each 5 mL of dithizone solution for
extraction until the extract become green, and combine
the extracts in a separatory funnel. To the combined extracts add 20 mL of diluted nitric acid (1 in 100), shake
for 30 second to mix, and discard the chloroform layer.
To the nitric acid layer add 5.0 mL of standard dithizone solution and 4 mL of ammoniacyanide solution,
shake for 30 second, and compare the color of the solution with that of the control solution obtained from the
same procedure with 10 mL of diluted standard lead solution (1 in 10): the color obtained from the test solution is not darker than that from the control solution
Ammoniacyanide solutionDissolve 2 g of potassium cyanide in 15 mL of strong ammonia water and
dilute with water to 100 mL.
KP 9 587
Microbial Limit Test It meets the requirement(no E.
coli detected).
hours).
Loss on Ignition
C).
Between 30.0% to 33.0% (1 g, 800
Assay Weigh accurately about 75 mg of Magnesium

Hydroxide, previously dried, and transfer to a conical
flask. Add 2 mL of 3 mol/L hydrochloride TS and swirl
to dissolve. Add 100 mL of water and adjust the reaction of the solution to a pH of 7 with 1 mol/L sodium
hydroxide TS, add 5 mL of ammoniaammonium chloride buffer solution, pH 10.7, and titrate with 0.05
mol/L disodium ethylenediaminetetraacetate VS until
the color of the solution changes to blue (indicator :
0.15 mL of eriochrome black T TS)
Each mL of 0.05 mol/L disodium ethylenediaminetetraacetate VS = 2.916 mg Mg(OH)2
Magnesium Oxide
MgO: 40.30
Magnesium Oxide, when ignited, contains not less than
96.0% and not more than 101.0% of magnesium oxide
(MgO). When 5 g of Magnesium Oxide has a volume
of not more than 30 mL, it may be labeled Heavy
Magnesium Oxide.
Description Magnesium Oxide is a white powder or
granules and is odorless.
Magnesium Oxide is practically insoluble in water, in
Magnesium Oxide dissolves in dilute hydrochloric acid.
Magnesium Oxide absorbs moisture and carbon dioxide
in air.
Identification A solution of Magnesium Oxide in dilute hydrochloric acid (1 in 50) responds to the Qualitative Tests for magnesium salt.
Purity (1) Alkali and soluble saltsTransfer 2.0 g
of Magnesium Oxide to a beaker, add 100 mL of water,
cover the beaker with a watch-glass, heat in a waterbath for 5 minutes and filter immediately. After cooling,
to 50 mL of the filtrate, add 2 drops of methyl red TS
and 2.0 mL of 0.05 mol/L sulfuric acid VS: a red color
develops. Evaporate 25 mL of the remaining filtrate to
dryness and dry the residue at 105 o C for 1 hour: the
residue is not more than 10 mg.
(2) CarbonateBoil 0.10 g of Magnesium Oxide

with 5 mL of water, cool and add 5 mL of acetic acid:
almost no effervescence occurs.
Oxide in 20 mL of dilute hydrochloric acid and evaporate on a water-bath to dryness. Dissolve the residue in
35 mL of water, add 1 drop of phenolphthalein TS, neutralize with ammonia TS, add 2 mL of dilute acetic acid
and filter, if necessary. Wash the filter paper with water,
add water to the combined washing and the filtrate to
solution as follows: to 20 mL of dilute hydrochloric acid, add 1 drop of phenolphthalein TS, neutralize with
ammonia TS and add 2 mL of dilute acetic acid, 4.0 mL
of standard lead solution and water to make 50 mL (not
more than 40 ppm).
(4) IronPrepare the test solution with 40 mg of
Magnesium Oxide according to Method 1 and perform
the test according to Method A. Prepare the control solution with 2.0 mL of standard iron solution (not more
than 500 ppm).
(5) Calcium oxideWeigh accurately 0.25 g of
Magnesium Oxide, previously ignited, dissolve in 6 mL
of dilute hydrochloric acid by heating. Cool, add 300
mL of water and 3 mL of a solution of tartaric acid (1
in 5), then add 10 mL of a solution of triethanolamine
(3 in 10) and 10 mL of 8 mol/L potassium hydroxide
TS, allow to stand for 5 minutes and titrate with 0.01
mol/L disodium ethylenediaminetetraacetate VS until
the color of the solution changes from red-purple to
blue (indicator: 0.1 g of NN indicator). Perform a blank
determination and make any necessary correction,
The mass of calcium oxide (CaO: 56.08) is not more
than 1.5%.
Each mL of 0.01 mol/L disodium ethylenediaminetetraacetate VS = 0.5608 mg of CaO
(6) ArsenicDissolve 0.20 g of Magnesium Oxide
in 5 mL of dilute hydrochloric acid and perform the test
with this solution as the test solution (not more than 10
ppm).
(7) Acid-insoluble substancesMix 2.0 g of Magnesium Oxide with 75 mL of water, add 12 mL of hydrochloric acid drop-wise, while shaking and boil for 5
minutes. Collect the insoluble residue using filter paper
for Assay, wash well with water until the last washing
shows no turbidity with silver nitrate TS and ignite the
residue together with the filter paper: the residue is not
more than 2.0 mg.
(8) FluoridePerform the test under the conditions
of Purity (7) of Natural Aluminium Silicate. The
amount of fluoride (F: 19.00) is not more than 0.08%.
Loss on Ignition Not more than 10.0 %(0.25 g, 900
C, constant mass).

Assay Ignite Magnesium Oxide to constant mass at
900 o C , weigh accurately about 0.2 g of the residue,
dissolve in 10 mL of water to make exactly 100 mL.
Pipet 25.0 mL of this solution, add 50 mL of water and
5 mL of ammonia-ammonium chloride buffer solution,
pH 10.7 and titrate with 0.05 mol/L disodium ethylenediaminetetraacetate VS (indicator: 40 mg of eriochrome
black T-sodium chloride indicator). Perform a blank determination and make any necessary correction. From
the volume of 0.05 mol/L disodium ethylenediaminetetraacetate VS consumed, deduct the volume of 0.05
mol/L disodium ethylene-diaminetetraacetate VS corresponding to the content of calcium oxide(CaO) obtained in the Purity(5).
Each mL of 0.05 mol/L disodium Ethylenediaminetetraacetate VS = 2.0152 mg of MgO
Each mL of calcium oxide(CaO) = 0.36 mL of 0.05
mol/L disodium ethylenediaminetetraacetate VS
Magnesium Silicate
Magnesium Silicate contains not less than 45.0% of silicon dioxide (SiO2: 60.08) and not less than 20.0% of
magnesium oxide (MgO: 40.30) and the ratio of percentage (%) of magnesium oxide to silicon dioxide is
not less than 2.2 and not more than 2.5.
Description Magnesium Silicate is a white, fine
powder, is odorless and tasteless.
Magnesium Silicate is practically insoluble in water, in
Identification (1) Mix 0.5 g of Magnesium Silicate
with 10 mL of dilute hydrochloric acid, filter and neutralize the filtrate with ammonia TS: the solution responds to the Qualitative Tests for magnesium salt.
(2) Prepare a bead by fusing dibasic sodium ammonium phosphate on a platinum loop. Place the bead in
contact with Magnesium Silicate and fuse again: an infusible matter appears in the bead, which changes to an
opaque bead with a web-like structure upon cooling.
Purity (1) Soluble saltsAdd 150 mL of water to
10.0 g of Magnesium Silicate, heat on a water-bath for
60 minutes with occasional shakings, then cool, dilute
with water to make 150 mL and centrifuge. Dilute 75
mL of the resultant transparent liquid with water to
make 100 mL and use this solution as the test solution.
Evaporate 25 mL of the test solution on a water-bath to
dryness and ignite the residue at 700 o C for 2 hours:
the residue is not more than 20 mg.
(2) AlkaliTake 20 mL of the test solution obtained in (1) and add 2 drops of phenolphthalein TS and
1.0 mL of 0.1 mol/L hydrochloric acid VS: no color is

observed.
(3) ChlorideTake 10 mL of the test solution obtained in (1), add 6 mL of dilute nitric acid, dilute with
water to make 50 mL and perform the test. Prepare the
(4) SulfateTo residue obtained in (1), add 3 mL
of hydrochloric acid and heat on a water-bath for 10
minutes. Add 30 mL of water, combine the washing
with the filtrate and dilute with water to make 50 mL
with water. To 4 mL of the solution, add 1 mL of dilute
hydrochloric acid and water to make 50 mL, and perform the test. Prepare the control solution with 1.0 mL
of 0.005 mol/L sulfuric acid VS (not more than
0.480%).
(5) Heavy metalsTo 1.0 g of Magnesium Silicate,
add 20 mL of water and 3 mL of hydrochloric acid and
boil for 2 minutes. Filter and wash the residue on the
filter with two 5-mL volumes of water. Evaporate the
combined filtrate and washing on a water-bath to dryness, add 2 mL of dilute acetic acid to the residue,
warm until it dissolves, filter, if necessary, add water to
solution with 3.0 mL of standard lead solution, 2 mL of
dilute acetic acid and water to make 50 mL (not more
than 30 ppm).
(6) ArsenicWeigh accurately 0.40 g of Magnesium Silicate and proceed in the Purity (5) under Natural Magnesium Silicate (not more than 5 ppm).
Loss on Ignition Not more than 34.0% (0.5 g, 850 ,
3 hours).
Test for Acid-Neutralizing Capacity Weigh accurately about 0.2 g of Magnesium Silicate and transfer in
a glass-stoppered flask. Add exactly 30 mL of 0.1
mol/L hydrochloric acid VS and 20 mL of water, shake
at 37 2 C for 1 hour, and cool. Pipet 25 mL of the
supernatant liquid, and titrate the excess hydrochloric
acid, while stirring well, with 0.1 mol/L sodium hydroxide VS until the pH becomes 3.5. 1 g of Magnesium Silicate, calculated on the anhydrous basis by
making allowance for the observed loss on ignition determined as directed under the Loss on Ignition, consumes not less than 140 mL and not more than 160 mL
of 0.1 mol/L hydrochloric acid.VS.
Assay (1) Silicon dioxideWeigh accurately about
0.7 g of Magnesium Silicate, add 10 mL of 0.5 mol/L
sulfuric acid TS, evaporate on a water-bath to dryness,
add 25 mL of water to the residue and heat on a waterbath for 15 minutes with occasional stirring. Filter the
supernatant liquid through filter paper for Assay, add
25 mL of hot water to the residue, stir and decant the
supernatant liquid on the filter paper to filter. Wash the
residue in the same manner with two 25 mL volumes of
hot water, transfer the residue onto the filter paper and
wash with hot water until the last washing does not respond to the Qualitative Tests (1) for sulfate. Place the
KP 9 589
residue and the filter paper in a platinum crucible, incinerate with strong heating and ignite between 775 C
and 825 C for 30 minutes, then cool and weigh the residue as a (g). Moisten the residue with water and add 6
mL of hydrofluoric acid and 3 drops of sulfuric acid.
Evaporate to dryness, ignite for 5 minutes, cool and
weigh the residue as b (g).
Content (%) of silicon dioxide (SiO2)
a-b
= amount (g) of the sample 100
(2) Magnesium oxideWeigh accurately about 0.3
g of Magnesium Silicate, transfer to an Erlenmeyer
flask, add 10 mL of 0.5 mol/L sulfuric acid TS and heat
on a water-bath for 15 minutes. Cool, transfer to a volumetric flask, wash the Erlenmeyer flask with water,
add the washing to the volumetric flask, dilute with water to make 100 mL and filter. Pipet 50.0 mL of the filtrate, shake with 50 mL of water and 5 mL of diluted
triethanolamine (1 in 2), add 2.0 mL of ammonia TS
and 10 mL of ammonia-ammonium chloride buffer solution, pH 10.7 and titrate with 0.05 mol/L disodium
ethylenediaminetetraacetate VS (indicator: 40 mg of
eriochrome black T-sodium chloride indicator).
Each mL of 0.05 mol/L disodium ethylenediaminetetraacetate VS = 2.0152 mg of MgO
(3) Ratio of percentages (%) of magnesium oxide
(MgO) to silicon dioxide (SiO2)Calculate the quotient from the percentages obtained in (1) and (2).
Magnesium Sulfate Hydrate

MgSO47H2O: 246.48
Magnesium Sulfate Hydrate, when ignited, contains not
less than 99.0% and not more than 101.0% of magnesium sulfate (MgSO4: 120.37).
Description Magnesium Sulfate Hydrate is a colorless or white crystal, has a cooling, saline and bitter
taste.
Magnesium Sulfate Hydrate is very soluble in water
and practically insoluble in ethanol or in ether.
Identification A solution of Magnesium Sulfate Hydrate (1 in 40) responds to the Qualitative Tests for
magnesium salt and for sulfate.
pH Dissolve 1.0 g of Magnesium Sulfate Hydrate in
20 mL of water: the pH of this solution is between 5.0
and 8.2.

1.0 g of Magnesium Sulfate Hydrate in 20 mL of water:
the solution is clear and colorless.
(2) ChloridePerform the test with 1.0 g of Magnesium Sulfate Hydrate. Prepare the control solution
more than 0.014%).
(3) Heavy metalsProceed with 2.0 g of Magnesium Sulfate Hydrate according to Method 1 and perform the test. Prepare the control solution with 2.0 mL
(4) ZincDissolve 2.0 g of Magnesium Sulfate
Hydrate in 20 mL of water and add 1 mL of acetic acid
and 5 drops of potassium ferrocyanide TS: no turbidity
is produced.
(5) CalciumDissolve 1.0 g of Magnesium Sulfate
Hydrate in 5.0 mL of dilute hydrochloric acid, add water to make 100 mL and use this solution as the test solution. Separately, dissolve 1.0 g of Magnesium Sulfate
Hydrate in 2.0 mL of standard calcium solution and 5.0
mL of dilute hydrochloric acid, add water to make exactly 100 mL and use this solution as the standard solution. Perform the test with the test solution and the
standard solution as directed under Atomic Absorption
Spectrophotometry according to the following conditions and determine the absorbances, AT and AS , respectively: AT is not more than AS - AT (not
more than 0.02 %)
Gas: Combustible gasAcetylene or hydrogen
Supporting gasAir
Lamp: Calcium hollow-cathode lamp
Wavelength: 422.7 nm
Magnesium Sulfate according to Method 1 and perform
the test (not more than 2 ppm).
Loss on Ignition Between 45.0% and 52.0% (1 g, after drying at 105 C for 2 hours, ignite at 450 C for 3
hours).
Sulfate, previously ignited at 450 C for 3 hours after
drying at 105 C for 2 hours and dissolve in 2 mL of dilute hydrochloric acid and water to make exactly 100
mL. Pipet exactly 25 mL of this solution and perform
the test as directed in the Assay under Magnesium
Oxide.
Each mL of 0.05 mol/L disodium ethylenediaminetetraacetate VS = 6.018 mg of MgSO4
Magnesium Sulfate Injection

Magnesium Sulfate Injection is an aqueous solution for
injection. Magnesium Sulfate Injection contains not
less than 95.0% and not more than 105.0% of the labeled amount of magnesium sulfate hydrate
(MgSO47H2O: 246.48).
Method of Preparation Prepare as directed under Injections, with Magnesium Sulfate Hydrate.
Description Magnesium Sulfate Injection is a clear
and colorless liquid.
Magnesium Sulfate Injection is neutral.
Identification Measure a volume of Magnesium Sulfate Injection, equivalent to 0.5 g of Magnesium Sulfate
Hydrate according to the labeled amount and add water
to make 20 mL: the solution responds to the Qualitative
Tests for magnesium salt and for sulfate.
pH Between 5.5 to 7.0. When the labeled concentration excceeds 5 w/v%, prepare a solution of 5 w/v%
with water, and perform the test.
Bacterial Endotoxins Less than 0.90 EU per 1 mg of
Magnesium Sulfate Hydrate. Perform the test after diluting with water for the test of endotoxin to 5 w/v%.
Foreign Insoluble Matter Test It meets the requirement.
Assay Measure exactly a volume of Magnesium Sulfate Injection, equivalent to about 0.3 g of magnesium
sulfate Hydrate (MgSO47H2O) and add water to make
25 mL. Proceed as directed in the Assay under Magnesium Oxide.
= 12.324 mg of MgSO47H2O
tainers.
Maltose Hydrate
CH2OH
CH2OH
O
H
H
OH
maltose
OH
OH
H
H
OH
OH
H2O
H
H
OH
C12H22O11H2O: 360.31
Maltose Hydrate, when dried, contains not less than

98.0% and not more than 101.0% of maltose hydrate
(C12H22O11H2O).
Description Maltose Hydrate is a white, crystal or
crystalline powder and has a sweet taste.
Maltose Hydrate is freely soluble in water, very slightly
soluble in ethanol and practically insoluble in ether.
Identification (1) Dissolve 0.5 g of Maltose Hydrate
in 5 mL of water, add 5 mL of ammonia TS and heat
for 5 minutes in a water-bath: an orange-red color is
observed.
(2) Add 2 to 3 drops of a solution of Maltose Hydrate (1 in 50) to 5 mL of boiling Fehling TS: a red
precipitate is produced.
D : Between +126
and +131. Weigh accurately about 10 g of Maltose
Hydrate, previously dried, dissolve in 0.2 mL of ammonia TS and water to make exactly 100 mL and determine the specific rotation of this solution in a 100mm cell.
pH The pH of a solution of Maltose Hydrate (1 in 10)
Purity (1) Clarity and color of solutionPut 10 g of
Maltose Hydrate in 30 mL of water in a Nessler tube,
warm at 60 C on a water-bath to dissolve, cool and
add water to make 50 mL: the solution is clear and has
no more than the following control solution.
Control solutionAdd water to a mixture of 1.0
mL of cobaltous chloride stock CS, 3.0 mL of ferric
chloride stock CS and 2.0 mL of cupric sulfate stock
CS to make 10.0 mL. To 1.0 mL of this solution, add
water to make 50 mL.
(2) ChloridePerform the test with 2.0 g of Maltose Hydrate. Prepare the control solution with 1.0 mL
0.018%).
(3) SulfatePerform the test with 2.0 g of Maltose
Hydrate. Prepare the control solution with 1.0 mL of
(4) Heavy metalsProceed with 5.0 g of Maltose
Hydrate according to Method 1 and perform the test.
KP 9 591
(5) ArsenicDissolve 1.5 g of Maltose Hydrate in
5 mL of water, add 5 mL of dilute sulfuric acid and 1
mL of bromine TS, heat on a water-bath for 5 minutes,
then heat to concentrate to 5 mL and use this solution
as the test solution after cooling. Perform the test (not
more than 1.3 ppm).
(6) Dextrin, soluble starch and sulfiteDissolve
1.0 g of Maltose Hydrate in 10 mL of water and add 1
drop of iodine TS: a yellow color appears and the color
changes to a blue by adding 1 drop of starch TS.
(7) NitrogenWeigh accurately about 2.0 g of
Maltose Hydrate and perform the test as directed under
the Nitrogen Determination using 10 mL of sulfuric acid for the decomposition and 45 mL of a solution of sodium hydroxide (2 in 5) for the addition: the amount of
nitrogen (N: 14.01) is not more than 0.01%.
(8) Related substancesDissolve 0.5 g of Maltose
Hydrate in 10 mL of water and use this solution as the
test solution. Pipet 1.0 mL of the test solution, add water to make exactly 100 mL and use this solution as the
standard solution. Perform the test with 20 L each of
under the Liquid Chromatography according to the following operating conditions. Determine the peak areas
from the test solution and the standard solution by the
automatic integration method: the total area of the
peaks which appear before the peak of Maltose Hydrate
from the test solution is not larger than 1.5 times of the
peak area of Maltose Hydrate from the standard solution. The total area of the peaks which appear after the
peaks of Maltose Hydrate from the test solution is not
larger than 0.5 times of the peak area of Maltose Hydrate from the standard solution.
Detector, column, temperature, mobile phase, flow
rate and system performance: Proceed as directed in the
Assay.
Detection sensitivity: Adjust the sensitivity so that
the peak height of Maltose Hydrate obtained from 20
L of the standard solution is about 30 mm.
Time span of measurement: About 2 times as long
as the retention time of Maltose Hydrate.
hours).
Assay Weigh accurately about 0.1 g each of Maltose
Hydrate and Maltose Hydrate RS, previously dried and
dissolve in 10.0 mL each of the internal standard solution and use these solutions as the test solution and the
standard solution, respectively. Perform the test with 20
ratios, QT and QS , of the peak area of maltose to

that of the internal standard, for the test solution and
Amount (mg) of maltose hydrate (C12H22O11H2O)
Q
= amount (mg) of Maltose Hydrate RS T
QS
Internal standard solutionA solution of ethylene
glycol (1 in 50).
gel-typed strong acid cation-exchange resin for liquid
about 50 C.
time of maltose is about 18 minutes.
System suitability
System peformance: Dissolve 0.25 g of maltose,
0.25 g of Glucose and 0.4 g of ethylene glycol in water
to make 100 mL. When the procedure is run with 20 L
of this solution according to the above operating conditions, maltose, glucose and ethylene glycol are eluted in
this order with the resolution of between the peaks of
maltose and glucose being not less than 4.0.
D-Mannitol
HOH2C
OH
OH
OH
OH
CH2OH
C6H14O6: 182.17
D-Mannitol, when dried, contains not less than 98.0%
and not more than 101.0% of D-mannitol (C6H14O6).
Description D-Mannitol is a white, crystalline powder, is odorless and has a sweet taste with a cold sensation.
D-Mannitol is freely soluble in water and practically insoluble in ethanol or in ether.
D-Mannitol dissolves in sodium hydroxide TS.
Identification (1) Take 5 drops of a saturated solution of D-Mannitol and add 1 mL of ferric chloride TS
and 5 drops of a solution of sodium hydroxide (1 in 5):
a yellow precipitate is produced. Shake this solution
vigorously: a clear solution is produced. On addition of
a solution of sodium hydroxide (1 in 5), no precipitate

is produced.
(2) Determine the infrared spectra of D-Mannitol
and D-Mannitol RS as directed in the potassium Bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
If any difference appears between the spectra, dissolve
1 g of D-Mannitol in 3 mL of warm water, then allow to
stand at 5 C for 24 hours or until crystals appear, and
filter. Wash the crystals so obtained with a few amount
of cold water, dry at 105 C for 4 hours, and perform
the test with the crystals.
[ ]20
D

: Between +137
and +145. Weigh accurately 1.0 g of D-Mannitol, previously dried, dissolve in 80 mL of a solution of ammonium molybdate (1 in 20) and add diluted sulfuric
acid (1 in 35) to make exactly 100 mL. Measure the
optical rotation of this solution in a 100-mm cell.
2.0 g of D-Mannitol in 10 mL of water by warming: the
(2) AcidDissolve 5.0 g of D-Mannitol in 50 mL of
freshly boiled and cooled water and add 1 drop of phenolphthalein TS and 0.50 mL of 0.01 mol/L sodium hydroxide VS: a red color is observed.
(3) ChloridePerform the test with 2.0 g of DMannitol. Prepare the control solution with 0.40 mL of
0.01 mol/L hydrochloric acid VS (not more than
0.007%).
(4) SulfatePerform the test with 2.0 g of DMannitol. Prepare the control solution with 0.40 mL of
(5) Heavy metalsProceed with 5.0 g of DMannitol according to Method 1 and perform the test.
(6) NikelDissolve 0.5 g of D-Mannitol in 5 mL
of water, add 3 drops of dimethylglyoxime TS and 3
drops of ammonia TS and allow to stand for 5 minuets:
no red color is observed.
D-Mannitol according to Method 1 and perform the test
(not more than 1.3 ppm).
(8) SugarsTake 5.0 g of D-Mannitol, add 15 mL
of water and 4.0 mL of dilute hydrochloric acid and
heat under a reflux condenser on a water-bath for 3
hours. After cooling, neutralize with sodium hydroxide
TS (indicator: 2 drops of methyl orange TS) and add
water to make exactly 50 mL. Pipet 10.0 mL of this solution into a flask, boil gently with 10 mL of water and
40 mL of Fehling' TS for 3 minutes and allow to stand
to precipitate cuprous oxide. Filter the supernatant liquid through a glass filter (G4), wash the precipitate
with hot water until the last washing no longer shows
an alkaline reaction and filter the washings through the
glass filter described above. Dissolve the precipitate in

20 mL of ferric sulfate TS in the flask filter through the
glass filter described above and wash the filter with water. Combine the washings and the filtrate, heat to 80
C and titrate with 0.02 mol/L potassium permanganate
VS: the consumed volume is not more than 1.0 mL.
hours).
Assay Weigh accurately about 0.2 g of D-Mannitol,
previously dried and dissolve in water to make exactly
100 mL. Pipet 10.0 mL of the solution into an iodine
flask, add exactly 50 mL of potassium periodate TS and
heat for 15 minutes in a water-bath. After cooling, add
2.5 g of potassium iodide, stopper tightly and shake
well. Allow to stand for 5 minutes in a dark place and
titrate the produced iodine with 0.1 mol/L sodium thiosulfate VS (indicator: 1 mL of starch TS). Perform a
= 1.8217 mg of C6H14O6
D-Mannitol
Injection
D-Mannitol Injection is an aqueous solution for injection. D-Mannitol Injection contains not less than 95.0%
and not more than 105.0% of the labeled amount of Dmannitol (C6H14O6: 182.17).
Method of Preparation Prepare as directed under Injections, with D-Mannitol. No preservative is added.
Description D-Mannitol Injection is a clear, colorless
liquid and has a sweet taste.
pH
Between 4.5 and 7.0.
Identification Concentrate D-Mannitol Injection on a

water-bath to make saturated solution. Proceed with 5
drops of this solution as directed in the Identification
(1) under D-Mannitol.
Residue on Ignition Evaporate exactly measured volume of D-Mannitol Injection, equivalent to 1.0 g of DMannitol, on a water-bath to dryness and perform the
test: the residue is not more than 1.0 mg.
Pyrogen Test
Perform the test with D-Mannitol Injec-
KP 9 593
tion stored in a container of a volume exceeding 10
mL: it meets the requirement of the Pyrogen Test.
Determination of Volume of Injection in Container
Assay Measure exactly a volume of D-Mannitol Injection, equivalent to about 5 g of D-mannitol
(C6H14O6), add water to make exactly 250 mL. To exactly 10 mL of this solution, add water to make exactly
100 mL. Measure exactly 10 mL of this solution into an
idodine flask, and proceed as directed in the Assay under D-Mannitol
= 1.822 mg of C6H14O6
tainers.
Maprotiline Hydrochloride
H
N
HCl
C20H23NHCl: 313.86
Maprotiline Hydrochloride, when dried, contains not
less than 99.0% and not more than 101.0% of
maprotiline hydrochloride (C20H23NHCl).
Description Maprotiline Hydrochloride is a white
crystalline powder.
Maprotiline Hydrochloride is soluble in methanol or in
glacial acetic acid, sparingly soluble in dehydrated
ethanol and slightly soluble in water.
Melting pointabout 244 C (with decomposition).
of the solutions of Maprotiline Hydrochloride and Maprotiline Hydrochloride RS in methanol (1 in 10000) as
directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Maprotiline
Hydrochloride and Maprotiline Hydrochloride RS, previously dried, as directed in the potassium bromide disk

same wavenumbers. If any difference appears between
the spectra, dissolve Maprotiline Hydrochloride and
Maprotiline Hydrochloride RS in anhydrous ethanol,
evaporate anhydrous ethanol to dryness and perform
the test with the residues.
(3) Take 5 mL of a solution of Maprotiline Hydrochloride (1 in 200) add 2 mL of ammonia TS, heat
on a water bath for 5 minutes, cool and filter. Acidify
the filtrate with dilute nitric acid: the solution responds
to Qualitative Test for chloride.
Purity (1) Heavy metalsProceed with 2.0 g of Maprotiline Hydrochloride according to Method 2 and perform the test. Prepare the control solution with 2.0 mL
(2) Related substancesDissolve 0.10 g of Maprotiline Hydrochloride in 5 mL of methanol and use this
solution as the test solution. Pipet 1.0 mL of the test solution, add methanol to make exactly 200 mL and use
with these solutions as directed under the Thin-layer
and the standard solution on a plate of silica gel with a
fluorescent indicator for thin-layer chromatography.
Develop with a mixture of 2-butanol, diluted ammonia
solution (1 in 3) and ethyl acetate (14 : 5 : 4) to a distance of about 10 cm and air-dry the plate. Examine
number of the spot other than the principal spot from
the test solution is not more than 2 and they are not
more intense than the spot from the standard solution.
hours).
Residue on Ignition
Assay Weigh accurately about 0.25 g of Maprotiline

Hydrochloride, previously dried, dissolve in 180 mL of
glacial acetic acid, add 8 mL of a solution of bismuth
nitrate pentahydrate in glacial acetic acid (1 in 50) and
titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Methods in Titrimetry). Perform a blank determination and make any necessary correction.
= 31.386 mg of C20H23NHCl

solution.
Mebendazole
H
O
H
N

hours).
C
CH3
C16H13N3O3: 295.29
Mebendazole, when dried, contains not less than 98.0%
and not more than 102.0% of mebendazole
(C16H13N3O3).

Assay Weigh accurately about 0.225 g of Mebendazole, dissolve in 30 mL of glacial acetic acid and titrate
with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary
correction.
= 29.53 mg of C16H13N3O3
Description Mebendazole is a white to pale yellow

powder.
Mebendazole is freely soluble in formic acid and practically insoluble in water, in dilute sulfuric acid, in
ethanol, in ether or in chloroform.
Melting pointAbout 290 C
Identification Determine the infrared spectra of Mebendazole and Mebendazole RS, previously dried, as
directed in the potassium bromide disk method under
the Infrared Spectrophotometry: both spectra exhibit
the similar intensities of absorption at the same wavenumbers.
Mebendazole, when dried, contains not less than 98.0%

and not more than 102.0% of mebendazole
(C16H13N3O3 : 295.29).
Purity (1) Heavy metalsProceed with 1.0 g of Mebendazole according to Method 2 and perform the test.
Prepare the control solution with 2.0 mL standard lead
(2) Related substancesDissolve 50 mg of Mebendazole in 1 mL of 96% formic acid, add chloroform
to make exactly 10 mL and use this solution as the test
solution. Weigh accurately Mebendazole RS, prepare to
make the solution containing 5 mg per mL similarly as
the test solution and use this solution as the standard
stock solution. Transfer 1 mL of this standard stock solution to a volumetric flask, add a mixture of chloroform and 96.0% formic acid (9 : 1) to make 200 mL,
mix and use this solution as the standard solution. Perform the test with the test solution and the standard solution as directed under the Thin-layer Chromatography.
Spot 10 L each of the test solution and the standard
solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chloroform,
methanol and 96.0% formic acid (90 : 5 : 5) to a distance of about 15 cm and air-dry. Examine the plate
Rf value of the principal spot from the test solution
corresponds to the Rf value of the principal spot from
the dilute standard solution. The spot other than the
principal spot from the test solution is not larger and
not more intense than the spot from the dilute standard
Mebendazole Tablets

Tablets, with Mebendazole.
Identification Finely powder a quantity of Tablets,
equivalent to about 200 mg of Mebendazole and mix
the powder with 20 mL of a mixture of chloroform and
96.0% formic acid (19 : 1). Warm the suspension on a
water-bath for a few minutes, cool and filter through a
glass filter (G4) and use this solution as the test solution. Dissolve Mebendazole RS in a mixture of chloroform and 96.0% formic acid (19 : 1) containing 10 mg
chromatography and develop the plate in a mixture of
chloroform, methanol and 96.0% formic acid (90 : 5 :
Examine the plate under ultraviolet light (main wavelength: 254 nm): the Rf value of the principal spot
obtained from the test solution corresponds to that obtained from the standard solution.
Dissolution Test Perform the test with 1 tablet of
Mebendazole Tablets at 75 revolutions per minute according to the Method 2 under the Dissolution Test, using 900 mL of 0.1 mol/L hydrochloric acid containing
1.0 % sodium lauryl sulfate. Take the dissolved solution after 120 minutes from the start of the test and filter. Use this solution as the test solution. Separately,
KP 9 595
weigh accurately about 25 mg of Mebendazole RS, add
10.0 mL of formic acid and add methanol to make exactly 50 ml. Take this solution, make the same concentration of the test solution and use this solution as the
standard solution. Perform the test as directed under the
conditions.
The dissolution rate of Menbendazole Tablets in 120
Mobile phase: A mixture of acetonitrile and buffer
solution (3 : 7)
System suitability
above operating conditions, the relative standard deviation of the peak area of Mebendazole is not more than
2.0%.
Mix 1 Tablet with 20 mL of 96% formic acid in a 100mL volumetric flask, and heat on a steam bath for 15
minutes. Cool, add isopropyl alcohol to volume, mix,
and filter. Transfer an accurately measured portion of
the filtrate, equivalent to 1 mg of mebendazole, to a
100-mL volumetric flask, dilute with isopropyl alcohol
to volume, and mix. This solution is used as a test solution. Separately, transfer about 20 mg of Mebendazole
RS, accurately weighed, to a 10-mL volumetric flask,
add 4 mL of 96% formic acid, and mix to dissolve. Add
isopropyl alcohol to volume, and mix. Pipet 0.5 mL of
this solution into a 100-mL volumetric flask, dilute
with isopropyl alcohol to volume, and mix. This solution is used as a standard solution. As directed under
the Ultraviolet-visible Spectrophotometry, concomitantly determine the absorbance ( AS ) of the standard
solution and that ( AT ) of the test solution at the wavelength of maximum absorbance at about 310 nm, using
a 1 in 500 solution of 96% formic acid in isopropyl alcohol as the blank.
The quantity (mg) of mebendazole (C16H13N3O3) in the
TC AT
Tablet =
D AS
T: the labeled quantity (mg) of mebendazole in the
Tablet
C: the concentration (g/mL) of Mebendazole RS
in the standard solution

D: the concentration (g/mL) of mebendazole in
the test solution, based on the labeled quantity per Tablet and the extent of dilution
Mebendazole Tablets. Weigh accurately a portion of the
powder, equivalent to about 500 mg of Mebendazole,
add 50 mL of formic acid and heat at 50 o C for 15 minutes in a water-bath. Shake for 1 hour with a shaker,
add water to make exactly 100 mL and filter. Pipet 5.0
mL of this solution and add a mixture of formic acid
and methanol (1 : 9) to make exactly 100 mL. Pipet 5.0
mL of this solution, add 25.0 mL of mobile phase,
shake well and filter. Use this solution as the test solution. Separately, weigh accurately about 25 mg of Mebendazole RS, add 10 mL of formic acid and warm at
50 C for 15 minutes in a water-bath. Shake for 5 minutes with a shaker and add methanol to make exactly
100 mL. Pipet 5.0 mL of this solution, add mobile
phase to make exactly 25 mL, shake well and filter. Use
with 15 L each of the test solution and standard solution as directed under the Liquid Chromatography according to the following conditions. Measure the peak
areas, AT and AS , of Mebendazole, for the test solution and the standard solution, respectively.
Amount (mg) of mebendazole (C16H13N3O3)
A
1
= amount (mg) of Mebendazole RS T
AS 20
about 30 C.
Mobile phase: Titrate a mixture of methanol and
0.05 mol/L of monobasic potassium phosphate TS (60 :
40) with 0.1 mol/L phosphoric acid TS or 1 mol/L sodium hydroxide TS to pH 5.5.
System suitability
operating conditions, the symmetry factor of Mebendazole peak is not more than 2.0.
above operating conditions, the relative standard deviation of the peak areas of mebendazole is not more than
1.0%.
Preserve well-closed con-

tainers.
Mebeverin Hydrochloride
O
OCH3
H3CH2C
N
HCl
H
H3CO
H3C
OCH3
and enantiomer
C25H35NO5HCl : 466.01
Mebeverin Hydrochloride contains not less than 99.0%
and not more than 101.0% of mebeverin hydrochloride
(C25H35NO5HCl), calculated on the dried basis.
Description Mebeverin Hydrochloride is a white
crystalline powder.
Mebeverin Hydrochloride is very soluble in water, freely soluble in ethanol, and practically insoluble in ether.
Mebeverin Hydrochloride and Mebeverin Hydrochloride RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same
wavenumbers.
(2) Dissolve 25 mg of Mebeverin Hydrochloride in
25 mL of water, acidify by the addition of 2 mol/L nitric acid and centrifuge: the supernatant liquid responds
to the Qualitative Tests (2) for chloride.
pH Dissolve 2.0 g of Mebeverin Hydrochloride in
and 6.5.
Purity (1) Ether extractDissolve 40 mg of Mebeverin Hydrochloride in 25 mL of 2 mol/L hydrochloric
acid TS, add 50 mL of ether, mix by shaking for 1
minute, wash the ether layer three times each with 25
mL of water, evaporate the ether layer to dryness, add a
portion of methanol to residue to make 20 mL and determine the absorbance of the solution at 260 nm as directed under the Ultraviolet-visible Spectrophotometry
using methanol as the reference: the absorbance is not
more than 0.23.
(2) Non-tertiary amineDissolve 0.5 g of Mebeverin Hydrochloride in 5 mL of pyridine, add 5 mL of
cupric chloride-pyridine TS, heat at 50 C for 30 minutes, cool, add acetone to make 50 mL and use this solution as the test solution. Separately, proceed with a
solution of 0.0060w/v% di-n-butylamine in 5 mL of pyridine in a manner similar to the preparation of the test
solution and use this solution as the control solution.
Prepare a solution with 5 mL of pyridine in a manner

similar to the preparation of the test solution and use
this solution as the blank solution. Perform the test with
the test solution and the control solution as directed under the Ultraviolet-visible Spectrophotometry and determine the absorbance of these solutions as 405 nm using the blank solution as the reference: the absorbance
of the test solution is not more than that of the control
solution.
(3) Related substanceWeigh 20 mg of Mebeverin
Hydrochloride, add acetone to make exactly 10 mL and
use this solution as the test solution. Separately, weigh
10 mg of Mebeverin Hydrochloride, add acetone to
make exactly 100 mL and use this solution as the standard solution (1). Weigh 2.0 mg of veratric acid, add
acetone to make exactly 100 mL and use this solution
as the standard solution (2). Perform the test with the
test solution, the standard solutions (1) and (2) as directed under the Thin-layer Chromatography. Spot 10
L each of the test solution, the standard solution (1)
and (2) on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate
with a mixture of dehydrated ethanol, chloroform and
strong ammonia water (50:50:1) to a distance of about
15 cm and air-dry the plate. Expose the plate under ultraviolet light (main wavelength 254 nm) and allow the
plate to stand in iodine vapor for 1 hour: the spot corresponding to the veratric acid from the test solution is
not more intense than that from the standard solution
(2) and the spots other than the principal spot are not
more intense than the principal spot from the test solution (1).
Loss on Drying
hour).
Not more than 0.5% (1 g, 105 C, 1

Assay Weigh accurately about 0.4 g of Mebeverin
Hydrochloride in 50 mL of glacial acetic acid, add 7
mL of mercury (II) acetate TS and titrate with 0.1
mol/L perchloric acid VS (potentiometric titration,
= 46.60 mg of C25H35NO5HCl
Packaging and Storage Preserve in light-resistant,
tight containers and store in a temperature not more
than 30 C.
KP 9 597
tions: total area of the peaks other than the peak of
meclizine hydrochloride from the test solution is not
more than 2 times of the peak area of meclizine hydrochloride from the standard solution (not more than
1.0%) and each peak area of the peaks is not larger than
the peak area of meclizine hydrochloride from the standard solution (not more than 0.5%).
Meclizine Hydrochloride
Hydrate
2 HCl
H2O
N
N
Cl
CH3
and enantiomer
Meclizine Hydrochloride
C25H27ClN22HClH2O: 481.89
Meclizine Hydrochloride Hydrate contains not less than
97.0% and not more than 100.5% of meclizine hydrochloride (C25H27ClN22HCl: 463.87), calculated on
the anhydrous basis.
Description Meclizine Hydrochloride Hydrate is a
white to pale yellow crystalline powder, has a slight
odor and has no taste.
Meclizine Hydrochloride Hydrate is freely soluble in
chloroform, in pyridine or in a mixture of acid, ethanol
and water and slightly soluble in dilute acid or in ethanol and practically insoluble in water or in ether.
of solutions of Meclizine Hydrochloride Hydrate and
Meclizine Hydrochloride Hydrate RS in a diluted hydrochloric acid TS (1 in 100) (1 in 100000), as directed
under the Ultraviolet-visible Spectrophotometry: both
same wavelengths.
(2) Determine the infrared spectra of Meclizine
Hydrochloride Hydrate and Meclizine Hydrochloride
Hydrate RS as directed in the potassium bromide disk
method under the Infrared Spectrometry: both spectra
(3) Dissolve 25 mg of Meclizine Hydrochloride
Hydrate in a mixture of 2 mol/L nitric acid and ethanol
(3 : 5): it responds to the Qualitative Tests for chloride.
Purity Related substancesWeigh accurately a portion of Meclizine Hydrochloride Hydrate, dissolve in
the mobile phase to make a solution containing 0.5 mg
per mL and use this solution as the test solution. Separately, weigh accurately a portion of Meclizine Hydrochloride Hydrate RS (previously determine the content of water), add mobile phase to make a solution
containing 2.5 g per mL and use this solution as the
under the Liquid Chromatography according to the following conditions. Determine peak areas of both solu-
Mobile phase: Dissolve 1.5 g of l-heptansulfonic
acid in 300 mL of water, add 700 mL of acetonitrile and
mix. Titrate the solution to pH 4 with 0.05 mol/L of sulfuric acid.
System suitability
System performance: Weigh a volume of Meclizine Hydrochloride Hydrate and 4-chlorobenzophenone, dissolve in mobile phase to make the solution
containing 10 g per mL. When the procedure is run
with 20 L of this solution according to the above operating conditions, meclizine hydrochloride and 4chlorobenzophenone are eluted in this order, with the
resolution between the peaks of meclizine hydrochloride and 4-chlorobenzophenone being not less than 2.0.
times with 20 L of the standard solution according to
deviation of the peak areas of meclizine hydrochloride
is not more than 1.5%.
Assay Weigh accurately about 0.35 g of Meclizine
Hydrochloride Hydrate, dissolve in 50 mL of chloroform, add 50 mL of glacial acetic acid, 5 mL of acetic
anhydride and 10 mL of mercuric acetate TS, mix and
titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry).
correction.
= 23.195 mg of C25H27ClN22HCl
Meclofenoxate Hydrochloride
O
OCH2
OCH2CH2N(CH3)2
HCl
Cl
C12H16ClNO3HCl: 294.17
Meclofenoxate Hydrochloride contains not less than
98.0% and not more than 101.0% of meclofenoxate hydrochloride (C12H16ClNO3HCl), calculated on the anhydrous basis.
Description Meclofenoxate Hydrochloride is a white
crystal or crystalline powder. Meclofenoxate Hydrochloride has a pale, characteristic odor and a bitter taste.
Meclofenoxate Hydrochloride is freely soluble in water
or in ethanol, sparingly soluble in acetic anhydride and
pHThe pH of a solution of Meclofenoxate Hydrochloride (1 in 20) is between 3.5 and 4.5.
Identification (1) To 10 mg of Meclofenoxate Hydrochloride, add 2 mL of ethanol, dissolve by warming,
if necessary, cool, add 2 drops of a saturated solution of
hydroxylamine hydrochloride in ethanol and 2 drops of
a saturated solution of potassium hydroxide in ethanol
and heat on a water-bath for 2 minutes. After cooling,
render the solution slightly acidic with dilute hydrochloric acid and add 3 drops of ferric chloride TS: a redpurple to dark purple color is observed.
(2) Dissolve 50 mg of Meclofenoxate Hydrochloride in 5 mL of water and add 2 drops of Reinecke salt
TS: a pale red precipitate is produced.
(3) Determine the absorption spectra of the solutions of Meclofenoxate Hydrochloride and Meclofenoxate Hydrochloride RS (1 in 10000) as directed under the Ultraviolet-visible Spectrophotometry: both
same wavelengths.
(4) A solution of Meclofenoxate Hydrochloride (1
in 100) responds to the Qualitative Tests for chloride.
0.5 g of Meclofenoxate Hydrochloride in 10 mL of water: the solution is clear and colorless.
(2) SulfatePerform the test with 1.0 g of Meclofenoxate Hydrochloride. Prepare the control solution
with 1.0 mL of 0.005 mol/L sulfuric acid VS (not more
than 0.048%).
(3) Heavy metalsProceed with 1.0 g of Meclofenoxate Hydrochloride according to Method 1 and per-
form the test. Prepare the control solution with 2.0 mL

Meclofenoxate Hydrochloride according to Method 3
(5) Organic acidsTake 2.0 g of Meclofenoxate
Hydrochloride, add 50 mL of ether, shake for 10 minutes, filter through a glass filter (G3), wash the residue
with two 5 mL volumes of ether and combine the washings with the filtrate. To this solution, add 50 mL of
neutralized ethanol and 5 drops of phenolphthalein TS
and neutralize with 0.1 mol/L sodium hydroxide VS:
the volume of 0.1 mol/L sodium hydroxide VS consumed is not more than 0.54 mL.
direct titration).
Assay Weigh accurately about 0.4 g of Meclofenoxate Hydrochloride, dissolve in 70 mL of acetic anhydride and titrate with 0.1 mol/L perchloric acid VS until
the color of the solution changes from blue-green
through yellow-green to pale greenish yellow [indicator: 3 drops of a solution of malachite green in glacial
acetic acid (1 in 100)]. Perform a blank determination
and make any necessary correction.
= 29.417 mg of C12H16ClNO3HCl
Mecobalamin
KP 9 599
red color does not disappear.
20 mg of Mecobalamin in 10 mL of water: the solution
is clear and red color.
(2) Related substancesPerform the test with 10
L of the test solution obtained in the Assay as directed
under the Liquid Chromatography according to the following conditions. Determine the peak area of mecobalamin and others of the test solution by the automatic
integration method: each area of the peaks other than
mecobalamin is not larger than 0.5% of the peak area of
mecobalamin, and the total area of the peaks other than
mecobalamin is not larger than 2.0%.
C63H91CoN13O14P : 1344.38
Mecobalamin contains not less than 98.0% and not
more than 101.0% of mecobalamin (C63H91CoN13O14P).
Description Mecobalamin occurs as dark red crystals
or crystalline powder.
Mecobalamin is sparingly soluble in water, slightly soluble in dehydrated ethanol, and practically insoluble in
acetonitrile.
Mecobalamin is affected by light.
Identification (1) Perform this procedure without
exposure to light, using light-resistant vessels. Determine the absorption spectra of the solutions of Mecobalamin and Mecobalamin RS in hydrochloric acidpotassium chloride buffer solution, pH 2.0 (1 in 20000)
as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths. Separately, determine the absorption spectra of the solutions of Mecobalamin and Mecobalamin RS in phosphate buffer solution, pH 7.0 (1 in 20000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit
(2) Mix 1 mg of Mecobalamin with 50 mg of potassium bisulfate, and fuse by igniting. Cool, break up the
mass with a glass rod, add 3 mL of water, and dissolve
by boiling. Add 1 drop of phenolphthalein TS, then add
dropwise sodium hydroxide TS until a light red color
just develops. Add 0.5 g of sodium acetate, 0.5 mL of
dilute acetic acid and 0.5 mL of a solution of disodium
1-nitroso-2-naphthol-3,6-disulfonate (1 in 500): a red to
orange-red color is immediately produced. Then add
0.5 mL of hydrochloric acid, and boil for 1 minute: the
Detector, column, column temperature, mobile
phase, and flow rate: Proceed as directed in the operating conditions in the Assay.
System suitability
Test for required detectability: To exactly 1 mL
of the test solution, add the mobile phase to make exactly 100 mL, and use this solution as the test solution
for system suitability. Pipet 1 mL of the test solution for
system suitability, add the mobile phase to make exactly 100 mL. Confirm that the peak area of mecobalamin
from 10 L of this solution is equivalent to 7 to 13% of
that of mecobalamin from 10 L of the test solution for
system suitability.
System performance: Proceed as directed in the
system suitability in the Assay.
System repeatability: When the testis repeated 6
times with 10 L of the test solution for system suitability under the above operating conditions, the relative
standard deviation of the peak areas of mecobalamin is
not more than 3.0%.
long as the retention time of mecobalamin.
Water Not more than 12% (0.1 g, volumetric titration,
direct titration).
Assay Perform this procedure without exposure to
light, using light-resistant vessels. Weigh accurately
about 50 mg of Mecobalamin and Mecobalamin RS
(separately, determine the water in the same manner as
Mecobalmin), dissolve each in the mobile phase to
make exactly 50 mL, and use these solutions as the test
solution and the standard solution, respectively. Perform the test with exactly 10 L of each of the test solution and the standard solution as directed under the
conditions, and determine the peak areas, AT and AS ,
of mecobalamin in each solution.
Amount (mg) of C63H91CoN13O14P
= Amount (mg) of Mecobalamin RS calculated on the
A
anhydrous basis T
AS

particle diameter).
about 40 C.
Mobile phase: To 200 mL of acetonitrile, add 800
mL of 0.02 mol/L phosphate buffer solution, pH 3.5,
then add 3.76 g of sodium 1-hexane sulfonate to dissolve.
time of mecobalamin is about 12 minutes.
System suitability
System performance: Dissolve 5 mg each of cyanocobalamin and hydroxocobalamin acetate in the mobile phase to make 100 mL. When the procedure is run
with 10 L of this solution under the above operating
conditions, cyanocobalamin and hydroxocobalamin are
peaks being not less than 3. In addition, when the procedure is run with 10 L of the standard solution under
the above operating conditions, the number of theoretical plates of the peak of mecobalamin is not less than
6000.
above operating conditions, the relative standard deviation of the peak areas of mecobalamin is not more than
1.0%.
tight containers.
Medazepam
CH3
N
Cl
C16H15ClN2: 270.76
Medazepam, when dried, contains not less than 98.5%
and not more than 101.0% of medazepam (C16H15ClN2).
Description Medazepam is a white to pale yellow
crystal or crystalline powder and is odorless.
Medazepam is freely soluble in methanol, in ethanol, in
glacial acetic acid or in ether and practically insoluble
in water.
Medazepam is gradually colored by light.
Identification (1) Dissolve 10 mg of Medazepam in
3 mL of citric acid-acetic acid TS: a deep orange color
is observed. Heat on a water-bath for 3 minutes: the
color changes to dark red.
(2) Determine the absorption spectra of the solutions of Medazepam and Medazepam RS in methanol
(1 in 100000) as directed under the Ultraviolet-visible
(3) Perform the test with Medazepam as directed
under the Flame Coloration Test (2): a green color is
observed.
1.0 g of Medazepam in 10 mL of methanol: the solution
is clear and pale yellow to yellow in color.
(2) ChlorideDissolve 1.5 g of Medazepam in 50
mL of ether, add 46 mL of water and 4 mL of sodium
carbonate TS, shake and collect the water layer. Wash
the water layer with two 20-mL volumes of ether and
filter. To 20 mL of the filtrate, add diluted nitric acid to
neutralize, add 6 mL of diluted nitric acid and water to
(3) Heavy metalsProceed with 1.0 g of Medazepam according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
Medazepam according to Method 3 and perform the
test (not more than 2 ppm).
(5) Related substancesDissolve 0.25 g of Medazepam in 10 mL of methanol and use this solution as
the test solution. Pipet 1.0 mL of the test solution and
add methanol to make exactly 20 mL. Pipet 2.0 mL of
this solution, add methanol to make exactly 50 mL and
test with the test solution and standard solution as directed under the Thin-layer Chromatography. Spot 10
L each of the test solution and the standard solution
on a plate of silica gel with a fluorescent indicator for
mixture of cyclohexane, acetone and strong ammonia
water (60 : 40 : 1) to a distance of about 10 cm and airdry the plate. Examine under ultraviolet light (main
wavelength: 254 nm): the spots other than the principal
spot from the test solution are not more intense than the
spot from the standard solution.
60 C, 4 hours).
KP 9 601
Assay Weigh accurately about 0.4 g of Medazepam,
previously dried, dissolve in 50 mL of glacial acetic acid and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Methods in Titrimetry). Perform a blank determination and make any
= 27.076 mg of C16H15ClN2
tight containers.
Medicinal Carbon
Description Medicinal Carbon is a black, odorless
and tasteless powder.
Identification Place 0.5 g of Medicinal Carbon in a
test tube and heat by direct application of flame with
the aid of a current of air: it burns without any flame.
Pass the evolved gas through calcium hydroxide TS: a
white turbidity is produced.
Purity (1) Acid or alkaliBoil 3.0 g of Medicinal
Carbon with 60 mL of water for 5 minutes, allow to
cool, dilute to 60 mL with water and filter: the filtrate is
colorless and neutral.
(2) ChlorideTake 4.0 mL of the filtrate obtained
in (1) in a Nessler tube, add 6 mL of dilute nitric acid
and sufficient water to make 50 mL and perform the
test. Prepare the control solution with 0.80 mL of 0.01
mol/L hydrochloric acid VS (not more than 0.142%).
(3) SulfateTake 5 mL of the filtrate obtained in
(1) in a Nessler tube, add 1 mL of dilute hydrochloric
acid and sufficient water to make 50 mL and perform
0.005 mol/L sulfuric aicd VS (not more than 0.192%).
(4) SulfideBoil 0.5 g of Medicinal Carbon with a
mixture of 15 mL of dilute hydrochloric acid and 10
mL of water: lead acetate paper does not become brown
when held in the evolved gas within 5 minutes.
(5) Cyanogen compoundsPlace a mixture of 5 g
of Medicinal Carbon, 2 g of tartaric acid and 50 mL of
water in a distilling flask connected to a condenser provided with a tightly fitting adapter, the end of which
dips below the surface of a mixture of 2 mL of sodium
hydroxide TS and 10 mL of water, contained in a small
flask surrounded by ice. Heat the mixture in the distilling flask to boiling and distil to 25 mL. Dilute the distillate with water to make 50 mL. To 25 mL of the diluted distillate, add 1 mL of ferrous sulfate solution (1
in 20), heat the mixture almost to boiling, cool and filter. To the filtrate, add 1 mL of hydrochloric acid and
0.5 mL of dilute ferric chloride TS: no blue color is

produced.
(6) Acid soluble substancesTake about 1 g of
Medicinal Carbon, accurately weighed, add 20 mL of
water and 5 mL of hydrochloric acid, boil for 5 minutes,
filter, wash the residue with 10 mL of hot water and
add the washings to the filtrate. Add 5 drops of sulfuric
acid to the filtrate, evaporate to dryness and ignite the
residue strongly: the residue is not more than 3.0%.
(7) Heavy metalsProceed with 0.5 g of Medicinal
Carbon according to Method 2 and perform the test.
(8) ZincIgnite 0.5 g of Medicinal Carbon to ash,
add 5 mL of dilute nitric acid to the residue, boil gently
for 5 minutes, filter, wash with 10 mL of water and
combine the washings and the filtrate. Add 3 mL of
ammonia TS to the solution, filter again, wash with water, combine the washings and the filtrate, add another
washing to make 25 mL, add 1 drop of sodium sulfide
TS and allow to stand for 3 minutes: the liquid produces no turbidity.
Medicinal Carbon according to Method 3 and perform
Loss on Drying Not mort than 15.0% (1 g, 105 C, 4
hours).
Adsorptive power (1) Add 1.0 g of Medicinal Carbon, previously dried, to 100 mL of water containing
120 mg of Quinine Sulfate, shake the mixture vigorously for 5 minutes, filter immediately and discard the first
20 mL of the filtrate. Add 5 drops of iodine TS to 10
mL of the subsequent filtrate: no turbidity is produced.
(2) Dissolve 0.25 g of methylene blue, exactly
weighed, in water to make exactly 250 mL. Measure
two 50 mL volumes of this solution into each of two
glass-stoppered flasks, To one flask, add exactly 0.25 g
of Medicinal Carbon, previously dried and weighed accurately, and shake vigorously for 5 minutes. Filter the
contents of each flask, discard the first 20 mL of each
filtrate. Pipet exactly 25 mL of the subsequent filtrate
into two 250 mL volumetric flasks. To each volumetric
flask, add 50 mL of a solution of sodium acetate (1 in
10), then add exactly 35 mL of 0.05 mol/L iodine VS
with swirling. Allow them to stand for 50 minutes,
shaking vigorously from time to time. Dilute each mixture to exactly 250 mL with water, allow to stand for 10
minutes and filter each solution at a temperature not
exceeding 20 C, discard the first 30 mL of each filtrate.
Titrate the excess iodine in 100 mL of each filtrate with
0.1 mol/L sodium thiosulfate VS. The difference between the two titrations is not less than 1.2 mL.
Packaging and Storage Preserve in well-closed con-

tainers.
Medroxyprogesterone Acetate
O
H3C
H3C
CH3
O
CH3
O
H
O
H
CH3
C24H34O4: 386.52
Medroxyprogesterone Acetate, contains not less than
97.0% and not more than 103.0% of medroxyprogesterone acetate (C24H34O4), calculated on the dried basis.
Description Medroxyprogesterone Acetate is a white
crystalline powder and is odorless.
Medroxyprogesterone Acetate is freely soluble in chloroform and soluble in acetone or in dioxane and sparingly soluble in ethanol or in methanol and slightly soluble in ether and practically insoluble in water.
Medroxyprogesterone Acetate is stable in air.
Melting PointAbout 205 C
of ethanol solutions (1 in 100000) of Medroxyprogesterone Acetate and Medroxyprogesterone Acetate RS as
directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths. And the difference in absorption at 241 nm, calculated on the dried basis, is not
more than 2.0%.
(2) Determine the infrared spectra of Medroxyprogesterone Acetate and Medroxyprogesterone Acetate RS, previously dried, as directed in the potassium
bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
D : Between +45 and
+51 (after drying, 0.1 g, dioxane, 10 mL, 100 mm)
Purity (1) Related substance IWeigh accurately
about 0.20 g of Medroxyprogesterone Acetate, dissolve
in dichloromethane to make exactly 10 mL and use this
solution as the test solution. Separately, weigh accurately 0.20 g of Medroxyprogesterone Acetate RS and
1.0 mg of medroxyprogesterone acetate related substance I RS, dissolve in dichloromethane to make 10
mL and use this solution as the standard solution. Proceed with these solutions as directed under the Thinlayer Chromatography. Apply 10 L each of the test solution and the standard solution on a plate of silica gel
for thin-layer chromatography. Develop the plate using

a mixture of hexane, tert-butylmethyl ether and tetrahydrofuran (45 : 45 : 10) to a distance of about 10 cm
and air-dry the plate. Heat the plate to dry at 120 C for
10 minutes, spray evenly the plate with a solution of ptoluenesulfonic acid in ethanol (1 in 5), heat the plate at
120 C for 10 minutes and examine the plate under UV
light (main wavelength: 365 nm). A large blue fluorescent spot with an Rf value higher than that of the principal spot from the test solution is not more intense that
the corresponding blue fluorescent spot obtained from
the standard solution (not more than 0.5%).
(2) Related substances IIDissolve about 62.5 mg
of Medroxyprogesterone Acetate, accurately weighed,
in 25 mL of the mobile phase and use this solution as
the test solution. Separately, weigh accurately a portion
of Medroxyprogesterone Acetate RS and dissolve in
mobile phase so that each mL contains 1 mg of Medroxyprogesterone Acetate RS and use this solution as
the standard solution. Perform the test with 20 L each
of the test solution and the standard solution as directed
under the Liquid Chromatography according to the following operating conditions. Determine peak area of
each peak from the test solution and the standard solution: the area of each peak other than the principal peak
is not more than 1% and the total area of the peaks other than the principal peak is not more than 1.5%.
inside diameter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography
(about 3m to 10 m in particle diameter)
Mobile phase: A mixture of acetonitrile and water
(3 : 2).
System suitability
System performance: Weigh a suitable portion of
megesterol acetate RS and Medroxyprogesterone Acetate RS and dissolve in the mobile phase to render the
concentration of 40 g in 1 mL each. When the procedure is run with 20 L of this solution according to the
above operating conditions, the resolution between
megesterol acetate and medroxyprogesterone acetate is
not less than 1.5.
times with 20 L each of the standard solution according to the above operating conditions, the relative standard deviation of the peak areas of medroxyprogesterone acetate is not more than 3.0%.
hours)
Assay Weigh accurately about 25 mg of Medroxyprogesterone Acetate, dissolve in acetonitrile to make
KP 9 603
Separately, weigh accurately about 25 mg of Medroxyprogesterone Acetate RS, previously dried at 105 C for
3 hours, dissolve in acetonitrile to make exactly 25 mL
the test with 10 L each of the test solution and the
standard solution as directed under the Liquid Chromatography according to the following operating conditions. Determine the peak areas, AT and AS , of medroxyprogesterone acetate for the test solution and the
amount, to a centrifuge tube and centrifuge. Decant the

supernatant liquid and wash the solids with two 15 mL
volumes of water (discard the water washings). Dissolve the residue in 10 mL of chloroform and transfer
in a small beaker and heat at 105 C for 3 hours to dryness. Proceed with the residue as directed in the Identification (2) under Medroxyprogesterone Acetate.
Amount (mg) of medroxyprogesterone

acetate (C24H34O4) = Amount (mg) of
A
Medroxyprogesterone Acetate RS T
AS

(3 m to 10 m in particle diameter)
Column temperature: A room temperture.
Mobile phase: A mixture of water and acetonitrile
(60 : 40).
System suitability
operating conditions, the symmetry factor for the peak
of medroxyprogesterone acetate is not more than 2.0.
times with the standard solution under the above operating conditions, the relative standard deviation of the
peak areas is not more than 2.0%.
tight containers.
Medroxyprogesterone Acetate
Injection (Aqueous Suspension)
Medroxyprogesterone Acetate Injection is an aqueous
solution for injection. Medroxyprogesterone Acetate Injection contains not less than 90.0% and not more than
110.0% of medroxyprogesterone acetate (C24H34O4 :
386.52).
Method of Preparation Prepare as directed under Injections, with Medroxyprogesterone Acetate.
Identification Transfer a volume of Medroxyprogesterone Acetate Injection, equivalent to 50 mg of Medroxyprogesterone Acetate according to the labeled
pH
Assay Take accurately a volume of Medroxyprogesterone Acetate Injection, equivalent to about 50 mg of

medroxyprogesterone acetate (C24H34O4), mix with
25.0 mL of chloroform for 20 minutes and centrifuge.
Evaporate 4.0 mL of chloroform layer to dryness, dissolve the residue in 20.0 mL of internal standard solution and use this solution as the test solution. Separately,
weigh accurately about 8 mg of Medroxyprogesterone
Acetate RS, previously dried at 105 C for 3 hours, dissolve in the internal standard solution to make exactly
20 mL and use this solution as the standard solution.
conditions. Determine the ratios, QT and QS , of
peak areas of Medroxyprogesterone Acetate to that of
the internal standard, of the test solution and the standard solution, respectively.
Amount (mg) of medroxyprogesterone
acetate (C24H34O4) = amount (mg) of
Q
50
Medroxyprogesterone Acetate RS T
QS 8
Internal standard solutiona solution of Progesterone RS in mobile phase (1 in 4000)
inside diameter and about 25 cm length, packed with
porous silica gel for liquid chromatography (5 m in
particle diameter).
Mobile phase: A mixture of butyl acetate saturated
with water, hexane saturated with water and acetonitrile
(70 : 30 : 8).
System suitability
with 10 L of the standard solution according to the
above operating conditions, Progesterone and Medroxyprogesterone Acetate are eluted in this order with the

resolution between their peaks being not less than 5.0.
deviation of the ratios of peak area of Medroxyprogesterone Acetate to that of the internal standard is not
more than 2.0%.

tainers.
Mefenamic Acid
CO 2H
H
N
H3C
CH3
C15H15NO2: 241.29
Mefenamic Acid, when dried, contains not less than
99.0% and not more than 101.0% of mefenamic acid
(C15H15NO2).
Description Mefenamic Acid is a white to pale yellow powder, is odorless and tasteless at first, but leaves
a slightly bitter aftertaste.
Mefenamic Acid is sparingly soluble in ether, slightly
soluble in methanol, in ethanol or in chloroform and
Mefenamic Acid dissolves in sodium hydroxide TS.
Identification (1) Dissolve 10 mg of Mefenamic Acid in 1 mL of methanol by warming, cool, add 1 mL of
a solution of p-nitrobenzenediazonium fluoroborate (1
in 1000) and 1 mL of sodium hydroxide TS and mix
thoroughly: an orange-red color is observed.
(2) Dissolve 10 mg of Mefenamic Acid in 2 mL of
sulfuric acid and heat: a yellow color and green fluorescence is observed.
(3) Dissolve 7 mg of Mefenamic Acid in a solution
of hydrochloric acid in methanol (1 in 1000) to make
500 mL. Separately, dissolve 7 mg of Mefenamic Acid
RS in the same solution. Determine the absorption
spectra of both solutions as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
Purity (1) ChlorideTake 1.0 g of Mefenamic Acid,
add 20 mL of sodium hydroxide TS and dissolve by
warming. Cool, add 2 mL of glacial acetic acid and water to make exactly 100 mL, mix well and filter. Discard the first 10 mL of the filtrate, take subsequent 25
mL of the filtrate and add 6 mL of dilute nitric acid and
water to make 50 mL. Perform the test. Prepare the
control solution as follows: take 0.50 mL of 0.01 mol/L
hydrochloric acid VS, add 5 mL of sodium hydroxide

TS, 0.5 mL of glacial acetic acid, 6 mL of dilute nitric
acid and water to make 50 mL (not more than 0.071%).
(2) Heavy metalsProceed with 2.0 g of Mefenamic Acid according to Method 2 and perform the test.
Mefenamic Acid according to Method 3 and perform
(4) Related substancesDissolve 0.10 g of Mefenamic Acid in 5 mL of a mixture of chloroform and
methanol (3 : 1) and use this solution as the test solution. Pipet 1.0 mL of the test solution, add a mixture of
chloroform and methanol (3 : 1) to make exactly 200
mL. Pipet 10.0 mL of this solution, add a mixture of
chloroform and methanol (3 : 1) to make exactly 50 mL
as directed under the Thin-layer Chromatography. Spot
25 L each of the test solution and the standard solution on a plate of silica gel with a fluorescent indicator
mixture of isobutanol and strong ammonia water (3 : 1)
to a distance of about 10 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254
standard solution.
P2O5, 4 hours).
Assay Weigh accurately about 0.5 g of Mefenamic
Acid, previously dried, dissolve in 100 mL of neutralized ethanol by warming gently. Cool and titrate with
0.1 mol/L sodium hydroxide VS until the color of the
solution changes from yellow through yellow-red to
red-purple (indicator: 2 to 3 drops of phenol red TS).
correction.
= 24.129 mg of C15H15NO2
Mefenamic Acid Capsules

Mefenamic Acid Capsules contain not less than 90.0%
and not more than 110.0% of the labeled amount of mefenamic acid (C15H15NO2: 241.29).
Capsules, with Mefenamic Acid.
KP 9 605
Identification (1) Take out contents of Mefenamic
Acid Capsules and mix well, weigh a portion of the
contents equivalent to 0.25 g of Mefenamic Acid according to the labeled amount, dissolve in 100 mL of a
mixture of chloroform and methanol (3 : 1), shaking
vigorously and add a mixture of chloroform and methanol (3 : 1) to make 250 mL and filter. Use this filtrate as the test solution. Separately, weigh 25 mg of
Mefenamic Acid RS, dissolve in a mixture of chloroform and methanol (3 : 1) to make 25 mL and use this
under the Thin-layer Chromatograhy. Spot 10 L each
plate with a mixture of chloroform, ethyl acetate and
glacial acetic acid (75 : 25 : 1) to a distance of about 10
cm and air-dry the plate. Expose the plate to fume of
iodine vapor: the Rf values and the intensities of the
spots obtained from the test solution correspond to
those from the standard solution.
(2) Proceed as directed in the Assay, both spectra of
the test solution and the standard solution exhibit similar peaks at the same retention time.
Mefenamic Acid Capsules at 100 revolutions per
Test, using 900 mL of 0.05 mol/L tris buffer as the dissolution solution. Take the dissolved solution after 45
minutes from the start of the test and filter. Pipet a suitable portion of the filtrate, dilute with the dissolution
solution to make the concentration of about 0.2 mg per
mL and use this solution as the test solution. Separately,
weigh a suitable amount of Mefenamic Acid RS, dissolve in the dissolution solution to give the same concentration as the test solution and use this solution as
Assay.
The dissolution rate of Mefenamic Acid Capsules in 45
use the filtrate as the test solution. Separately, weigh

accurately about 50 mg of Mefenamic Acid RS, dissolve in 5 mL of tetrahydrofuran by shaking, add the
mobile phase to make exactly 250 mL and use this solution as the standard solution. Perform the test with 10
the following operating conditions and measure the
peak areas, AT and AS , of Mefenamic Acid for the
Amount (mg) of mefenamic acid (C15H15NO2)
A
= amount (mg) of Mefenamic Acid RS T
AS
Mobile phase: A mixture of acetonitrile, buffer solution and tetrahydrofuran (23: 20: 7)
System suitability
above operating conditions, the symmetry factor for the
peak of Mefenamic Acid is not more than 1.6.
deviation of the peak areas of Mefenamic Acid is not
more than 1.0%.
Buffer solutionDissolve 5.7 g of monobasic ammonium phosphate in 1000 mL of water. Adjust the pH
with ammonia TS to 5.0.
0.05 mol/L tris bufferWeigh 60.5 g of 2-amino-2hydroxymethyl-1,3-propane-diol dissolve in 6 L of water and add water to make 10 L. Adjust the pH with
phosphoric acid to 9.0 0.05. Dissolve 100 g of soium
lauryl sulfate in 6 L of the solution and mix this solution with the first solution.
ment.
Mefruside
O
O
O
NH2
CH3
CH2N
Cl
CH3 O
Assay Weigh accurately the contents of not less than

20 Mefenamic Acid Capsules. Weigh accurately a portion of the contents equivalent to about 50 mg of mefenamic acid (C15H15NO2), add 5 mL of tetrahydrofuran
and dissolve using an ultrasonic wave for 5 minutes,
add mobile phase to make exactly 250 mL, filter and
and enantiomer
Cl3H19ClN2O5S2: 382.88
Mefruside, when dried, contains not less than 98.5%
and not more than 101.0% of mefruside

(C13H19ClN2O5S2).
Description Mefruside is a white, crystalline powder
and is odorless.
Mefruside is very soluble in dimethylformamide, freely
soluble in acetone, soluble in methanol, sparingly soluble in ethanol, slightly soluble in ether and practically
insoluble in water.
A solution of Mefruside in dimethylformamide (1 in
of the solutions of Mefruside and Mefruside RS in methanol (1 in 40000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
intensities at the same wavelengths
(2) Determine the infrared spectra of Mefruside and
Mefruside RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
at the same wavenumbers.
(3) Perform the test with Mefruside as directed under the Flame Coloration Test (2): a green color appears.
Purity (1) Heavy metalsDissolve 1.0 g of Mefruside in 30 mL of acetone and add 2 mL of dilute acetic
acid and water to make 50 mL. Perform the test. Prepare the control solution as follows: to 2.0 mL of standard lead solution, add 30 mL of acetone, 2 mL of dilute acetic acid and water to make 50 mL (not more
than 20 ppm).
Mefruside according to Method 3 and perform the test
(3) Related substancesDissolve 0.20 g of Mefruside in 10 mL of acetone and use this solution as the
test solution. Pipet 1.0 mL of the test solution, add acetone to make exactly 200 mL and use this solution as
the standard solution. Perform the test with the test solution and the standard solutions as directed under the
test solution and the standard solution on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform and acetone (5 : 2) to a distance of about 10 cm
and air-dry the plate. Examine under ultraviolet light
(main wavelength: 254 nm): the spots other than the
mide and titrate with 0.1 mol/L tetramethylammonium

hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Separately, perform a
blank determination with a solution prepared by adding
13 mL of water to 80 mL of dimethylformamide and
Each mL of 0.1 mol/L tetramethylammonium
hydroxide VS = 38.288 mg of Cl3H19ClN2O5S2
Meglumine
HOH 2C
OH
OH
OH
OH
CH 2NHCH 3
C7H17NO5: 195.21
Meglumine, when dried, contains not less than 99.0%
and not more than 101.0% of meglumine (C7H17NO5).
Description Meglumine is a white, crystalline powder, is odorless and has a slightly bitter taste.
Meglumine is freely soluble in water and slightly soluble in ethanol and practically insoluble in ether.
pHThe pH of a solution of Meglumine (1 to 10)
Identification (1) Take 1 mL of a solution of Meglumine (1 in 10) and add 1 mL of potassium naphthoquinone sulfonate TS: a deep red color is observed.
(2) Take 2 mL of a solution of Meglumine (1 in 10),
add 1 drop of methyl red TS and add 0.5 mL of dilute
sodium hydroxide TS and 0.5 g of boric acid after neutralizing with 0.5 mol/L sulfuric acid TS: a deep red
color is observed.
(3) Dissolve 0.5 g of Meglumine in 1 mL of diluted
hydrochloric acid (1 in 3) and add 10 mL of dehydrated
ethanol: a white precipitate is produced. Then, rubbing
the inside wall with a glass rod, cool with ice and produce more precipitate. Filter the precipitate by suction
through a glass filter (G3), wash the precipitate with a
small volume of dehydrated ethanol and dry at 105 C
for 1 hour: the residue thus obtained melts between 149
C and 152 C.

hours).

D : Between -16.0
and -17.0 (after drying, 1 g, water, 10 mL, 100 mm).
Assay Weigh accurately about 0.5 g of Mefruside,

previously dried, dissolve in 80 mL of dimethylforma-

1.0 g of Meglumine in 10 mL of water: the solution is
KP 9 607
(2) ChlorideDissolve 1.0 g of Meglumine in 30
mL of water and add 10 mL of dilute nitric acid and
(3) SulfateDissolve 1.0 g of Meglumine in 30
mL of water and add 5 mL of dilute hydrochloric acid
and water to make 50 mL. Perform the test. Prepare the
(4) Heavy metalsProceed with 2.0 g of Meglumine according to Method 4 and perform the test. Prepare the control solution with 2.0 mL of standard lead
Meglumine according to Method 3 and perform the test
(6) Reducing substancesTake 5 mL of a solution
of Meglumine (1 in 20), add 5 mL of Fehlings TS and
boil for 2 minutes: no red-brown precipitate is produced.
hours).
Assay Weigh accurately about 0.4 g of Meglumine,
previously dried, dissolve in 25 mL of water and titrate
with 0.1 mol/L hydrochloric acid VS (indicator: 2 drops
of methyl red TS).
Each mL of 0.1 mol/L hydrochloric acid VS
= 19.521 mg of C7H17NO5
Meglumine Amidotrizoate
Injection
Meglumine Amidotrizoate Injection is an aqueous solution for injection. Meglumine Amidotrizoate Injection
contains not less than 46.9w/v% and not more than
51.8w/v% of amidotrizoic acid (C11H9I3N2O4: 613.91).
Method of Preparation
Amidotrizoic acid (anhydrous)
493.2 g
Meglumine
156.8 g
Water for injection
a sufficient quantity
To make 1000 mL
Prepare as directed under Injections, with the above ingredients.
Description Meglumine Amidotrizoate Injection is a
clear, colorless to pale yellow, slightly viscous liquid.

Meglumine Amidotrizoate Injection is gradually colored by light.
Identification (1) Take 2 mL of Meglumine Amidotrizoate Injection, add 25 mL of water and add 2.5 mL
of dilute hydrochloric acid with stirring: a white precipitate is produced. Filter the precipitate by suction
through a glass filter (G4), wash with two 10 mL volumes of water and dry at 105 C for 1 hour. Proceed
with the precipitate so obtained as directed in the Identification (2) under Amidotrizoic Acid.
(2) Take 1 mL of Meglumine Amidotrizoate Injection and add 1 mL of potassium naphthoquinone sulfonate TS and 0.2 mL of sodium hydroxide TS: a deep
red color develops.
and -4.20 (100 mm).
pH
[ ]20
D : Between -3.63
Purity (1) Primary aromatic aminesMix 0.40 mL

of Meglumine Amidotrizoate Injection with 6 mL of
water, add 4 mL of a solution of sodium nitrite (1 in
100) and 10 mL of 1 mol/L hydrochloric acid TS and
shake. Proceed as directed in the Purity (2) under Amidotrizoic Acid: the absorbance is not more than 0.19.
(2) Iodine and iodideTake 0.50 mL of Meglumine Amidotrizoate Injection, add water to make 20
mL, shake with 5 mL of dilute nitric acid and filter by
suction through a glass filter (G4). Add 5 mL of chloroform to the filtrate and shake vigorously: no color develops in the chloroform layer. Then add 1 mL of
strong hydrogen peroxide water and shake vigorously:
the chloroform layer is not more intense in color than
the following control solution.
Control solutionDissolve 0.10 g of potassium iodide
in water to make 100 mL. Add 20 mL of water to 0.10
mL of this solution, add 5 mL of dilute nitric acid, 5
mL of chloroform and 1 mL of strong hydrogen peroxide water and shake vigorously.
Pyrogen Prepare a solution with Isotonic Sodium
Chloride Injection so as to contain 0.20 g of amidotrizoic acid (C11H9I3N2O4) per mL and perform the test: it
meets the requirement of the Pyrogen Test.

Assay Take an exactly measured volume of Meglumine Amidotrizoate Injection, equvalent to about 0.5 g
of amidotrizoic acid (C11H9I3N2O4), add water to make
exactly 200 mL, pipet exactly 2 mL of this solution,
add exactly 10 mL of the internal standard solution and
water to make 100 mL and use this solution as the test
solution. Separately, weigh accurately about 0.25 g of
amidotrizoic acid RS (previously determine its loss on
drying at 105 C, 4 hours), dissolve in a solution of
meglumine (3 in 1000) to make exactly 100 mL. Pipet
exactly 2 mL of this solution, add exactly 10 mL of the
internal standard solution and water to make 100 mL,
standard solution as directed under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS , of the peak area of
amidotrizoic acid to that of the internal standard for the
Amount (mg) of amidotrizoic acid (C11H9I3N2O4)
= amount (mg) of Amidotrizoic Acid RS,
Q
calculated on the dried basis T 2
QS
Internal standard solutionDissolve 60 mg of acetrizoic acid in a solution of meglumine (3 in 1000) to
make 100 mL.
about 25 C.
Mobile phase: Dissolve 1.7 g of tetrabutylammonium phosphate and 7.0 g of dipotassium hydrogen
phosphate in 750 mL of water, adjust the pH to 7.0 with
diluted phosphoric acid (1 in 10), add water to make
800 mL, then add 210 mL of acetonitrile, and mix.
time of amidotrizoic acid is about 5 minutes.
System suitability
with 5 L of the standard solution under the above operating conditions, amidotrizoic acid and the internal
standard are eluted in this order with the resolution between their peaks being not less than 6.
above operating conditions, the relative standard deviation of the ratios of the peak area of amidotrizoic acid
to that of the internal standard is not more than 1.0%.
hermetic containers.
Meglumine Iotalamate Injection

Meglumine Iotalamate Injection is an aqueous solution
for injection. Meglumine Iotalamate Injection contains
not less than 95.0% and not more than 105.0% of the
labeled amount of iotalamic acid (C11H9I3N2O4:
613.92).
Method of preparation
(1) Iotalamic acid
227.59 g
Meglumine
72.41 g
Water for injection
To make 1000 mL
(2) Iotalamic acid
455 g
Meglumine
145 g
Water for injection
To make 1000 mL
Prepare as directed under Injections, with the above ingredients (1) or (2).
Description Meglumine Iotalamate Injection is a
clear, colorless to pale yellow, slightly viscous liquid.
Meglumine Iotalamate Injection is gradually colored by
light.
Identification (1) Take 1 mL of Meglumine Iotalamate Injection and add 1 mL of potassium naphthoquinone sulfonate TS and 0.2 mL of sodium hydroxide TS:
a deep red color develops.
(2) Take a volume of Meglumine Iotalamate Injection, equivalent to 1 g of Iotalamic Acid according to
the labeled amount, add 25 mL of water and add 2.5
mL of dilute hydrochloric acid with thorough shaking:
a white precipitate is produced. Filter the precipitate by
suction through a glass filter (G4), wash the precipitate
with two 10 mL volumes of water and dry at 105 o C
for 4 hours. Proceed with the precipitate so obtained as
directed in the Identification (2) under Iotalamic Acid.
Method of preparation (1)
[ ]20
D : Between -1.67 and -1.93 (100 mm).
[ ]20
D : Between -3.35 and -3.86 (100 mm).
pH Between 6.5 and 7.7.
Purity (1) Primary aromatic aminesTake a volume
of Meglumine Iotalamate Injection, equivalent to 0.20
g of Iotalamic Acid according to the labeled amount,
add 15 mL of water, shake, add 4 mL of a solution of
sodium nitrite (1 in 100) under ice-cooling and proceed
KP 9 609
as directed in the Purity (2) under Iotalamic Acid: the
absorbance is not more than 0.17.
(2) Iodine and iodideTake a volume of Meglumine Iotalamate Injection, equivalent to 1.5 g of Iotalamic Acid according to the labeled amount, add 20 mL
of water and 5 mL of dilute sulfuric acid, shake well
and filter the precipitate by suction through a glass filter (G4). To the filtrate, add 5 mL of toluene and shake
vigorously: the toluene layer is colorless. Then add 2
mL of a solution of sodium nitrite (1 in 100) and shake
vigorously: the toluene layer has no more color than the
following control solution.
iodide in water to make 1000 mL. To 2.0 mL of this solution, add 20 mL of water, 5 mL of dilute sulfuric acid,
5 mL of toluene and 2 mL of a solution of sodium nitrite (1 in 100) and shake vigorously.
Bacterial Endotoxins Less than 0.90 EU / mL
Foreign Insoluble Matter Test It meets the requirement
meets the requirement
Internal standard solutionDissolve 20 mg of

Acetaminophen in the mobile phase to make
100 mL.
Mobile phase: A mixture of acetonitrile and diluted
acetic acid (1 in 100) (10 : 90).
System suitability
operating conditions, Iotalamic Acid and the internal
above operating conditions, relative standard deviation
of the ratios of the peak area of Iotalamic Acid to that

Assay Take an accurately measured volume of Meglumin Iotalamate Injection, equivalent to about 0.89 g
of iotalamic acid (C11H9I3N2O4), add 10 mL of 0.1
mol/L sodium hydroxide TS, shake well and add mobile phase to make exactly 200 mL. Pipet 2.0 mL of
this solution, add mobile phase to make exactly 100 mL.
Pipet 5.0 mL of this solution, add 20.0 mL of the internal standard solution and the mobile phase to make 20
weigh accurately about 25 mg of Meglumine Iotalamate RS, previously dried 105 o C for 4 hours, dissolve
in 10 mL of 0.1 mol/L sodium hydroxide TS and add
mobile phase to make exactly 100 mL. Pipet 2.0 mL of
this solution, add 2.0 mL of the internal standard solution and the mobile phase to make exactly 20 mL and
test with 10 L each of the test solution and standard
solution as directed under the Liquid Chromatograophy
according to the following operating conditions and
calculate the ratios, QT and QS of the peak area of
Iotalamic Acid to that of the internal standard for the
Amount (mg) of iotalamic acid (C11H9I3N2O4)
Q
= amount (mg) of iothalamic acid RS T 40
QS
Meglumine Sodium
Amidotrizoate Injection
Meglumine Sodium Amidotrizoate Injection is an
aqueous solution for injection. Meglumine Sodium
Amidotrizoate Injection contains not less than 95.0%
and not more than 105.0% of the labeled amount of
amidotrizoic acid (C11H9I3N2O4: 613.91).
(1) Amidotrizoic Acid (anhydrous)
522.77 g
Sodium Hydroxide
25.16 g
Meglumine
43.43 g
Water for Injection
To make 1000 mL
471.78 g
Sodium Hydroxide
5.03 g
Meglumine
125.46 g
Water for Injection
To make 1000 mL
Sodium Hydroxide
Meglumine
597.30 g
6.29 g
159.24 g

Water for Injection
To make 1000 mL
Prepare as directed under Injections, with the above ingredients (1), (2) or (3).
Description Meglumine Sodium Amidotrizoate Injection is a clear, colorless to pale yellow, slightly viscous liquid.
Meglumine Sodium Amidotrizoate Injection is gradually colored by light.
Identification (1) Take a volume of Meglumine Sodium Amidotrizoate Injection, equivalent to 1 g of
Amidotrizoic Acid according to the labeled amount,
add 25 mL of water and add 2.5 mL of dilute hydrochloric acid with stirring: a white precipitate is produced.
Filter the precipitate by suction through a glass filter
(G4), wash with two 10 mL volumes of water and dry
at 105 o C for 1 hour. Proceed with the precipitate so
obtained as directed in the Identification (2) under
Amidotrizoic Acid.
(2) Take 1 mL of Meglumine Sodium Amidotrizoate Injection and add 1 mL of potassium naphthoquinone sulfonate TS and 0.2 mL of sodium hydroxide TS:
a deep red color develops.
(3) Meglumine Sodium Amidotrizoate Injection responds to the Qualitative Tests (1) for sodium salt.
[ ]20
D : Between -1.01 and -1.17 (100 mm).
[ ]20
D : Between -2.91 and -3.36 (100 mm).
[ ]20
D : Between -3.69 and -4.27 (100 mm).
pH
Purity (1) Primary aromatic aminesTake a volume

of Meglumine Sodium Amidotrizoate Injection, equivalent to 0.20 g of Amidotrizoic Acid according to the labeled amount, add 6 mL of water, mix, add 4 mL of a
solution of sodium nitrite (1 in 100) and 10 mL of 1
mol/L hydrochloric acid TS and shake. Proceed as directed in the Purity (2) under Amidotrizoic Acid: the
absorbance is not more than 0.19.
(2) Iodine and iodideTake a volume of Meglumine Sodium Amidotrizoate Injection, equivalent to
0.25 g of Amidotrizoic Acid according to the labeled
amount, add water to make 20 mL, add 5 mL of dilute
nitric acid, shake well and filter by suction through a
glass filter (G4). Add 5 mL of chloroform to the filtrate
and shake vigorously: no color develops in the chloroform layer. Then add 1 mL of strong hydrogen peroxide
water and shake vigorously: the chloroform layer has
no more color than the following control solution.

in water to make 100 mL. Add 20 mL of water to 0.10
mL of this solution, add 5 mL of dilute nitric acid, 5
mL of chloroform and 1 mL of strong hydrogen peroxide water and shake vigorously.
Pyrogen Test Dilute Meglumine Sodium Amidotrizoate Injection with Isotonic Sodium Chloride Injection
so as to contain 0.20 g of amidotrizoic acid
(C11H9I3N2O4) per mL according to the labeled amount
and perform the test: it meets the requirement of the
Pyrogen Test.
Assay Take an exactly measured volume of Meglumine Sodium Amidotrizoate Injection, equivalent to
about 0.5 g of amidotrizoic acid (C11H9I3N2O4), add
water to make exactly 200 mL. Pipet exactly 2 mL of
this solution, add exactly 10 mL of the internal standard
solution and water to make exactly 100 mL and use this
solution as the test solution. Separately, weigh accurately about 0.25 g of amidotrizoic acid RS (separately
determine its loss on drying at 105 o C for 4 hours),
dissolve in a solution of Meglumine (3 in 1000) to
make exactly 100 mL, then pipet exactly 2 mL of this
solution, add exactly 10 mL of the internal standard solution and water to make exactly 100 mL and use this
as directed under the Liquid Chromatography according to the following operating conditions and calculate
the ratios, QT and QS , of the peak area of Amidotrizoic Acid to that of the internal standard for the test solution and the standard solution, respectively.
Amount (mg) of amidotrizoic acid (C11H9I3N2O4)
= amount (mg) of amidotrizoic acid RS,
Q
QS
Internal standard solutionDissolve 60 mg of acetrizoic acid in a solution of Meglumine (3 in 1000) to
make 100 mL.
(wavelength 254 nm).
KP 9 611
octadecylsilanized silica gel for liquid chromatograhy
about 25 C.
Mobile phase: Dissolve 1.7 g of tetrabutylammonium
phosphate and 7.0 g of dibasic potassium phosphate in
750 mL of water, adjust the pH to 7.0 with diluted
phosphoric acid (1 in 10), add water to make 800 mL,
then add 210 mL of acetonitrile and mix.
time of Amidotrizoic Acid is about 5 minutes.
System suitability
with 5 L of the standard solution under the above operating conditions, Amidotrizoic Acid and the internal
standard are eluted in this order with the resolution between their peaks being not less than 6.0.
above operating conditions, the relative standard deviation of the ratios of the peak area of amidotrizoic acid
Meglumine Sodium Iodamide

Injection
Meglumine Sodium Iodamide Injection is an aqueous
solution for injection. Meglumine Sodium Iodamide Injection contains not less than 59.7w/v% and not more
than 65.9w/v% of iodamide (C12H11I3N2O4: 627.94).
Iodamide
627.9 g
Sodium hydroxide
6.0 g
Meglumine
165.9 g
Water for Injection
To make 1000 mL
Description Meglumine Sodium Iodamide Injection
is a clear, colorless to pale yellow, slightly viscous liquid.
Meglumine Sodium Iodamide Injection is gradually colored by light.
Identification (1) Take 2 mL of Meglumine Sodium
Iodamide Injection, add 25 mL of water and 3 mL of
dilute hydrochloric acid with thorough stirring: a white
precipitate is produced. Filter the precipitate by suction
through a glass filter (G3) and wash with two 10 mL
volumes of water. Transfer the precipitate to a suitable

flask, add 100 mL of water, dissolve by heating and
boil gently until the volume becomes about 30 mL. After cooling, collect the separated crystals by filtration,
dry at 105 C for 1 hour and obtain the crystals by filtration. Dry at 105 C` for 1 hour and proceed with the
crystals so obtained as directed in the Identification (1)
and (2) under Iodamide.
(2) Determine the infrared spectrum of the dried
crystals obtained in (1) as directed in the potassium
bromide disk method under the Infrared Spectrophotometry: it exhibits absorptions at the wavenumbers of
about 3390 cm-1, 1369 cm-1,1296 cm-1, 1210 cm-1 and
1194 cm-1. If the absorption wavenumbers are different
from these, dissolve 1 g of the dried crystal in 100 mL
of water by heating, repeat Identification (1) and repeat
above process.
(3) Take 1 mL of Meglumine Sodium Iodamide Injection and add 1 mL of potassium naphthoquinone sulfonate TS and 0.2 mL of sodium hydroxide TS: a deep
red color is observed.
(4) Meglumine Sodium Iodamide Injection responds to the Qualitative Tests (1) for sodium salt.
and -4.42 (100 mm).
[ ]20
D : Between -3.84

Purity (1) Primary aromatic aminesMix 0.30 mL
of Meglumine Sodium Iodamide Injection and 6 mL of
water, then add 4 mL of a solution of sodium nitrite (1
in 100) and 10 mL of 1 mol/L hydrochloric acid TS,
shake well and proceed as directed in the Purity (2) under Iodamide: the absorbance is not more than 0.22.
(2) Iodine and iodideTake 0.40 mL of Meglumine Sodium Iodamide Injection, add water to make 20
mL, then add 5 mL of dilute nitric acid, shake well and
filter by suction through a glass filter (G3). To the filtrate, add 5 mL of chloroform and shake vigorously: no
color is observed in the chloroform layer. Then add 1
mL of strong hydrogen peroxide solution and shake vigorously: the chloroform layer is not more intense in
color than the control solution.
in water to make 100 mL. To 0.10 mL of this solution,
add 20 mL of water, 5 mL of dilute nitric acid, 5 mL of
chloroform and 1 mL of strong hydrogen peroxide solution and shake vigorously.
Pyrogen Test Dilute Meglumine Sodium Iodamide
Injection with Isotonic Sodium Chloride Injection to
make the solution containing 0.30 mL of Meglumine
Sodium Iodamide Injection per mL according to the labeled amount and perform the test: it meets the requirement of the Pyrogen Test.

Assay Take exactly 8 mL of Meglumine Sodium
Iodamide Injection, add sodium hydroxide TS to make
Pipet exactly 10 mL of the test solution into a flask, add
30 mL of sodium hydroxide TS and 1 g of zinc powder
and proceed as directed in the Assay under Iodamide.
Each mL of 0.1 mol/L silver nitrate VS
= 20.931 of Iodamide (C12H11I3N2O4 )
Meloxicam
O
O
S
NCH3
H
N
OH
S
CH3
C14H13N3O4S2 : 351.40
Meloxicam contains not less than 99.0% and not more
than 100.5% of meloxicam (C14H13N3O4S2), calculated
on a dried basis.
Description Meloxicam is a pale yellow powder.
Meloxicam is soluble in dimethylformamide, slightly
soluble in acetone, very slightly soluble in ethanol or in
methanol, and practically insoluble in water.
of the solutions of Meloxicam and Meloxicam RS in
methanol (1.5 in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit
Meloxicam and Meloxicam RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
Purity (1) Clarity and color of solutionThe solution obtained by dissolving 0.5 g of Meloxicam in 10
mL of dimethylformamide is clear.
(2) Heavy metalsProceed with 2.0 g of Melox-
icam according to Method 2and perform the test. Prepare the control solution with 2.0 mL of standard lead
(3) Related substancesDissolve 40.0 mg of Meloxicam in a mixture of 40% methanol and 0.4 mol/L
sodium hydroxide (50:3) to make exactly 10 mL. Add
to this solution 10 mL of 40% methanol, and use this
solution as the test solution. Pipet 1.0 mL of the test solution, and dilute with 40% methanol to 100 mL. Pipet
1.0 mL of this solution, dilute with 40% methanol, and
use this solution as the standard solution (1). Separately,
dissolve 40.0 mg of Meloxicam Related Substances RS
in a mixture of 40% methanol and 0.4 mol/L sodium
hydroxide (50:3) to make exactly 10 mL. Add to this
solution 10 mL of 40% methanol, and use this solution
as the standard solution (2). Perform the test with 10
L each of the test solution, the standard solution (1),
and the standard solution (2) as directed under the Liquid Chromatography according to the following conditions, and determine the peak areas by the automatic integration method. In the chromatogram obtained with
the test solution at 350 nm, any peak areas corresponding to the related substances I (ethyl 4-hydroxy-2methyl-2H-1,2-benzothiazine-3-carboxylate1,1dioxide) and the related substance III [4-hydroxy-2methyl-N-ethyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2benzothia zine-3-carboxamide1,1-dioxide] are not
greater than half the peak area obtained with the standard solution (1) at 350 nm (0.1% of the related substance I assuming a correction factor of 2.0, and 0.05%
for the related substance III). In the chromatogram obtained with the test solution at 260 nm, any peak area
corresponding to the related substance II (5-methyl 1,3thiazol-2-amine) is not greater than the peak area obtained with the standard solution (1) at 350 nm (0.1%).
In both the chromatograms obtained with the test solution at 350 nm and at 260 nm, the area of any other
secondary peak is not greater than the area of the peak
in the chromatogram obtained with the standard solution (1) at 350 nm (0.1%). Calculate the percentage
content of the related substances I and III at 350 nm,
the percentage content of the related substance II at 260
nm and the percentage content of any other secondary
peaks at the wavelength of higher response. The nominal total content of any such related substances is not
greater than 0.3%.
(wavelength: 260 nm and 350 nm)
Column: A stainless steel column about 4.6 mm inside diameter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 m
Mobile phase: Use variable mixtures of mobile A
and mobile phase B, and program the chromatograph as
follows.
Mobile phase A Dissolve 1 g of potassium
dihydrogen orthophosphate in 1000 mL of water, and
adjust the solution pH to 6.0 with dilute sodium hy-
KP 9 613
droxide solution.
Mobile phase Bmethanol.
Time
(min)
Mobile
phase A (%)
Mobile
phase B (%)
Elution
0
2.5
12
60
60
30
40
40
70
isocratic
isocratic
isocratic

Time span of measurement: 20 minutes or until the
elution of the related substance III is complete.
Loss on Drying Not more than 0.5% (3 g, 105 C,
constant weight)
Assay Dissolve 0.25 g of Meloxicam, accurately
weighed, in a mixture of 50 mL of glacial acetic acid
and 5 mL of anhydrous formic acid, and titrate with 0.1
Endpoint Detection Method in Titrimetry).
= 35.14 mg of C14H13N3O4S2.
20) and evaporate on a water-bath to dryness. Dissolve

the residue in 1 mL of warmed methanol and add 2
drops of strong ammonia water: a purple color develops.
(2) Dissolve 0.1 g of Melphalan in 10 mL of dilute
sodium hydroxide TS and heat in a water-bath for 10
minutes. After cooling, add dilute nitric acid to acidify
and filter: the filtrate responds to the Qualitative Tests
for chloride.
(3) Determine the absorption spectra of the solutions of Melphalan and Melphalan RS in methanol (1 in
Purity (1) Ionizable chlorideWeigh accurately
about 0.5 g of Melphalan, dissolve in 80 mL of diluted
nitric acid (1 in 40), stir for 2 minutes and titrate with
0.1 mol/L silver nitrate VS (potentiometric titration):
the consumed volume is not more than 1.0 mL to 0.50 g
of Melphalan.
(2) Heavy metalsProceed with 1.0 g of Melphalan according to Method 4 and perform the test. Prepare
the control solution with 2.0 mL of standard lead solution (not more than 20 ppm).
Melphalan according to Method 3 and perform the test
at a pressure not exceeding 0.67 kPa, 105 C, 2 hours).
Melphalan
H
ClH2CH2C
N
ClH2CH2C
CH2
CO2H
NH2
Cl3Hl8Cll2N2O2: 305.20
Melphalan contains not less than 93.0% and not more
than 101.0% of melphalan (Cl3Hl8Cl2N2O2), calculated
on the dried basis.
Description Melphalan is a white to pale yellowish
white, crystalline powder.
Mephalan is slightly soluble in water, in methanol or in
Mephalan dissolves in dilute hydrochloric acid or in dilute sodium hydroxide TS.
Mephalan is gradually colored by light.
D : About -32 (0.50
g, calculated on the dried basis, methanol, 100 mL, 100
mm).
Identification (1) Take 20 mg of Melphalan, add 50
mL of methanol, dissolve by warming, add 1 mL of a
solution of 4-(4-nitrobenzyl)pyridine in acetone (1 in
Assay Weigh accurately about 0.25 g of Melphalan,

add 20 mL of a solution of potassium hydroxide (1 in
5) and heat under a reflux condenser in a water-bath for
2 hours. After cooling, add 75 mL of water and 5 mL of
nitric acid, cool and titrate with 0.1 mol/L silver nitrate
VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Make any necessary correction by
using the results obtained in the Purity (1).
= 15.260 mg of Cl3Hl8Cll2N2O2
tight containers.
dl-Menthol
H
OH
H
H3C
H
CH3
CH
CH3
and enantiomer
C10H20O: 156.27
dl-Menthol contains not less than 98.0% and not more

than 101.0% of dl-menthol (C10H20O).
and -51.0 (2.5 g, ethanol, 25 mL, 100 mm).
Description dl-Menthol is colorless crystals, and has

characteristic and refreshing odor and burning taste,
followed by a cool taste.
dl-Menthol sublimes gradually at room temperature.
dl-Menthol is very soluble in ethanol or in ether and
very slightly soluble in water.
Identification Proceed as directed in the Identification under l-Menthol.

D : Between -2.0 and
+2.0 (2.5 g, ethanol, 25 mL, 100 mm).
Congealing Point Between 27 C and 28 C.
Purity Proceed as directed in the Purity under lMenthol
Assay Proceed as directed in the Assay under lMenthol
Each mL of 1 mol/L sodium hydroxide VS
= 156.27 mg of C10H20O
in a cold place.
l-Menthol
H
OH
H
H3C
H
CH3
CH
CH3
and enantiomer
C10H20O: 156.27
Purity (1) Non-volatile residueVolatilize 2.0 g of

l-Menthol on a water-bath and dry the residue at 105 C
for 2 hours: the residue is not more than 1.0 mg.
(2) ThymolAdd 0.20 g of l-Menthol to a cold
mixture of 2 mL of glacial acetic acid, 6 drops of sulfuric acid and 2 drops of nitric acid: no green to bluegreen color immediately develops.
(3) Nitromethane or nitroethaneTake 0.5 g of lMenthol placed in a flask, add 2 mL of sodium hydroxide solution (1 in 2) and 1 mL of strong hydrogen peroxide, connect a reflux condenser to the flask and boil
the mixture gently for 10 minutes. After cooling, add
water to make exactly 20 mL and filter. Take 1 mL of
the filtrate in a Nessler tube, add water to make 10 mL,
neutralize with dilute hydrochloric acid, add another 1
mL of dilute hydrochloric acid and cool. To the mixture,
add 1 mL of a solution of sulfanilic acid (1 in 100), allow to stand for 2 minutes and then add 1 mL of a solution of N-(1-naphthyl)-N'-diethyl-ehylenediamine oxalate (1 in 1000) and water to make 25 mL: no redpurple color immediately develops.
Assay Weigh accurately about 2.0 g of l-Menthol,
add exactly 20 mL of a mixture of dehydrated pyridine
and acetic anhydride (8 : 1), connect a reflux condenser
and heat on a water-bath for 2 hours. Wash the condenser, with 20 mL of water and titrate with 1 mol/L
sodium hydroxide VS (indicator: 5 drops of phenolphthalein TS). Perform a blank determination and make
any necessary correction
= 156.27 mg of C10H20O
in a cold place.
l-Menthol contains not less than 98.0% and not more

than 101.0% of l-menthol (C10H20O).
Mepenzolate Bromide
Description l-Menthol is colorless crystal, and has

characteristic and refreshing odor and burning taste,
followed by a cool taste.
l-Menthol is very soluble in ethanol or in ether and very
slightly soluble in water.
l-Menthol sublimes gradually at room temperature.
H3C
O
HO
Identification (1) Triturate l-Menthol with an equal

amount of camphor, chloral hydrate or thymol: the mixture liquefies.
(2) Shake 1 g of l-Menthol with 20 mL of sulfuric
acid: the mixture becomes turbid with a yellow-red
color. Allow to stand for 3 hours: a clear, oily layer
which possesses no aroma of menthol is separated.
[ ]20
D : Between -45.0
H
O
CH3
N
Br
and enantiomer
C21H26BrNO3: 420.34
Mepenzolate Bromide, when dried, contains not less
than 98.5% and not more than 101.0% of mepenzolate
KP 9 615
bromide (C21H26BrNO3).
Description Mepenzolate Bromide is a white to pale
yellow crystal or crystalline powder, is odorless and has
a bitter taste.
Mepenzolate Bromide is very soluble in formic acid,
freely soluble in methanol, soluble in hot water, slightly
soluble in water or in ethanol, very slightly soluble in
acetic anhydride and practically insoluble in ether.
Identification (1) Take 30 mg of Mepenzolate Bromide and add 10 drops of sulfuric acid: a red color develops.
(2) Dissolve 10 mg of Mepenzolate Bromide in 20
mL of water and 5 mL of dilute hydrochloric acid and
add 1 mL of Dragendorff's TS: an orange precipitate is
produced.
(3) Determine the absorption spectra of the solutions of Mepenzolate Bromide and Mepenzolate Bromide RS in 0.01 mol/L hydrochloric acid TS (1 in
2000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities at
(4) Dissolve 0.5 g of Mepenzolate Bromide in 50
mL of water and 3 mL of nitric acid by heating. This
solution respends to the Qualitative Tests for bromide.
Purity (1) Heavy metalsProceed with 1.0 g of Mepenzolate Bromide according to Method 2 and perform
Mepenzolate Bromide according to Method 3 and perform the test (not more than 2 ppm).
(3) Related substancesDissolve 0.40 g of Mepenzolate Bromide in exact 10 mL of methanol and use
this solution as the test solution. Pipet 1.0 mL of the
test solution, add methanol to make exactly 200 mL
and use this solution as the standard solution (1). Separately, dissolve 40 mg of benzophenone in methanol to
make exactly 100 mL, Pipet 2.0 mL of this solution,
add methanol to make exactly 10 mL and use this solution as the standard solution (2). Perform the test with
the test solution and the standard solutions (1) and (2)
10 L each of the test solution and the standard solutions (1) and (2) on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop
the plate with a mixture of n-butanol, methanol, water
and glacial acetic acid (3 : 3 : 2 : 1) to a distance of
about 10 cm, air-dry the plate and then dry the plate at
80 o C for 30 minutes. Examine under ultraviolet light
(main wavelength: 254 nm): the spots other than either
the principal spot or the spot corresponding to benzophenone from the test solution are not more intense
than the spot from standard solution (1) and the spot
corresponding to benzophenone from the test solution
is not more intense than the spot from standard solution
(2). Spray evenly Dragendorff's TS on the plate: the

are not more intense than the spot from standard solution (1).
hours).
Assay Weigh accurately about 0.35 g of Mepenzolate
Bromide, previously dried, dissolve in 2 mL of formic
acid, add 60 mL of acetic anhydride and titrate with 0.1
Endpoint Detection Method in Titrimetry), Perform a
= 42.03 mg of C21H26BrNO3
Mepitiostane
CH3O
O
H3C
H3C
C25H40O2S: 404.65
Mepitiostane contains not less than 96.0% and not
more than 102.0% of mepitiostane (C25H40O2S), calculated on the anhydrous basis.
Description Mepitiostane is a white to pale yellow
Mepitiostane is freely soluble in triethylamine, in chloroform, in ether or in cyclohexane, soluble in diethyleneglycoldimethylether or in petroleum ether, sparingly
soluble in acetone, slightly soluble in methanol or in
dehydrated ethanol and practically insoluble in water.
Mepitiostane is hydrolyzed in moist air.
Identification (1) Dissolve 1 mg of Mepitiostane in 1
mL of methanol and add 0.5 mL of palladium chloride
TS: an orange precipitate is formed. To this suspension,
add 1 mL of water and 2 mL of chloroform, shake well
and allow to stand: an orange color develops in the
chloroform layer.
(2) Dissolve 0.1 g of Mepitiostane in 2 mL of diethyleneglycoldimethylether, shake with 1 mL of 1
mol/L hydrochloric acid TS and filter. To the filtrate,
add 1.5 mL of 2,4-dinitrophenylhydrazine-diethylene

glycoldimethylether TS and 1.5 mL of diluted ethanol
(2 in 3): an orange-yellow precipitate is formed. Filter
the precipitate, recrystallize from dehydrated ethanol
and dry in a desiccator (in vacuum, P2O5) for 4 hours:
the crystals melt between 144 C and 149 C.
(3) Determine the infrared spectra of Mepitiostane
and Mepitiostane RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers
D : Between +20 and
+23 (0.1 g, chloroform, 10 mL, 100 mm).
0.10 g of Mepitiostane in 4 mL of petroleum ether: the
solution is clear and colorless to pale yellow.
(2) Heavy metalsProceed with 1.0 g of Mepitiostane according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
(3) Related substancesDissolve 20 mg of Mepitiostane in exactly 5 mL of a mixture of acetone and
triethylamine (1000 : 1) and use this solution as the test
solution. Separately, dissolve 10 mg of epitiostanol RS
in a mixture of acetone and triethylamine (1000 : 1) to
make exactly 10 mL. Pipet 1.0 mL and 3.0 mL of this
solution, add a mixture of acetone and triethylamine
(1000 : 1) to make exactly 25 mL and use these solutions as the standard solutions (1) and (2), respectively.
solutions (1) and (2) as directed under the Thin-layer
and the standard solutions (1) and (2) on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of hexane and acetone (3 : 1) to a distance of about 10 cm and
air-dry the plate. Spray evenly diluted sulfuric acid (1
in 5) on the plate, heat between 120 C and 130 C for
5 minutes and examine under ultraviolet light (main
spot from the test solution showing the same Rf value
as that from the standard solutions are not more intense
than the spot from the standard solution (2) and the remaining spots other than the principal spot are not more
intense than the spot from the standard solution (1).
about 45 mg of epitiostanol RS, dissolve in 2.0 mL of

the internal standard solution, add dehydrated ethanol
under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and
QS , of the peak area of epitiostanol to that of the internal standard for the test solution and the standard solution, respectively.
Amount (mg) of mepitiostane (C25H40O2S)
= amount (mg) of Mepitiostanol RS, calculated on the
Q
anhydrous basis T 5 1.3202
QS
Internal standard solutionA solution of noctylbenzene in dehydrated ethanol (1 in 300).
about 25 C.
Mobile phase: Mixture of methanol and water (20 :
3).
time of epitiostanol is about 6 minutes.
Selection of column: When the procedure is run
operating conditions, epitiostanol and the internal standard are eluted in this order with the resolution between
hermetic containers under nitrogen atmosphere.
Mepivacaine Hydrochloride
H3C
Water Not more than 0.7% (0.3 g, volumetric titration, back titration).
Residue on Ignition
Not more than 0.1% (0.5 g).
Assay Weigh accurately about 0.3 g of Mepitiostane

and dissolve in cyclohexane to make exactly 10 mL.
Pipet 2.0 mL of this solution, add 10 mL of dehydrated
ethanol, mix with 2.0 mL each of 0.01 mol/L hydrochloric acid TS and the internal standard solution, add dehydrated ethanol to make exactly 20 mL, allow to stand
at ordinary temperature for 30 minutes and use this solution as the test solution. Separately, weigh accurately
CH3
NH
HCl
H3C
C15H22N2OHCl: 282.81
Mepivacaine Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of mepivacaine hydrochloride (C15H22N2OHCl).
Description
Mepivacaine Hydrochloride is a white
KP 9 617
Mepivacaine Hydrochloride is freely soluble in water
or in methanol, soluble in glacial acetic acid, sparingly
soluble in dehydrated ethanol and practically insoluble
in ether.
A solution of Mepivacaine Hydrochloride (1 in 10)
of the solutions of Mepivacaine Hydrochloride and
Mepivacaine Hydrochloride RS (1 in 2500) as directed
same wavelengths.
(2) Determine the infrared spectra of Mepivacaine
Hydrochloride and Mepivacaine Hydrochloride RS as
similar intensities of absorption at the same wavenumbers.
(3) A solution of Mepivacaine Hydrochloride (1 in
50) responds to the Qualitative Tests for chloride.
pH Dissolve 0.2 g of Mepivacaine Hydrochloride in
and 5.0.
1.0 g of Mepivacaine Hydrochloride in 10 mL of water:
(2) SulfatePerform the test with 0.5 g of Mepivacaine Hydrochloride. Prepare the control solution with
than 0.038%).
(3) Heavy metalsProceed with 2.0 g of Mepivacaine Hydrochloride according to Method 1 and perform the test. Prepare the control solution with 2.0 mL
(4) Related substancesDissolve 0.10 g of Mepivacaine Hydrochloride in 5 mL of methanol and use
test solution and add methanol to make exactly 20 mL.
Pipet 4.0 mL of this solution, add methanol to make
exactly 50 mL and use this solution as the standard solution. Perform the test with the test solution and the
mixture of ether, methanol and strong ammonia water
(100 : 5 : 1) to a distance of about 10 cm and air-dry the
plate. Spray evenly bismuth nitrate-potassium iodide
TS on the plate: the spots other than the principal spot
hours).

Assay Weigh accurately about 0.4 g of Mepivacaine
glacial acetic acid and add 70 mL of acetic anhydride.
Titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry).
correction.
= 28.281 mg of C15H22N2OHCl
Mepivacaine Hydrochloride
Injection
Mepivacaine Hydrochloride Injection is an aqueous solution for injection. Mepivacaine Hydrochloride Injection contains not less than 95.0% and not more than
105.0% of the labeled amount of mepivacaine hydrochloride (C15H22N2OHCl: 282.81).
Method of Preparation Prepare as directed under Injections, with Mepivacaine Hydrochloride.
Description Mepivacaine Hydrochloride Injection is
a clear, colorless liquid.
Identification Take a volume of Mepivacaine Hydrochloride Injection, equivalent to 20 mg of Mepivacaine Hydrochloride according to the labeled amount,
add 1 mL of sodium hydroxide TS and extract with 20
mL of hexane. To 8 mL of the hexane extract, add 20
mL of 1 mol/L hydrochloric acid TS, shake vigorously
and determine the absorption spectrum of the water
layer as directed under the Ultraviolet-visible Spectrophotometry: it exhibits maxima between 261 nm and
265 nm and between 270 nm and 273 nm.
Insoluble Particulate Matter Test for Iinjection It

O
H2N
Assay Take an exactly measured volume of Mepivacaine Hydrochloride Injection, equivalent about 40 mg
of Mepivacaine Hydrochloride according to the labeled
amount, add 4.0 mL of the internal standard solution
and 0.001 mol/L hydrochloric acid TS to make exactly
20 mL and use this solution as the test solution. Separately, weigh accurately about 40 mg of Mepivacaine
Hydrochloride RS, previously dried at 105 C for 3
hours, dissolve in 0.001 mol/L hydrochloric acid TS,
add 4.0 mL of the internal standard solution and 0.001
mol/L hydrochloric acid TS to make exactly 20 mL and
test with 5 L each of the test solution and the standard
ratios, QT and QS , of the peak area of mepivacaine
hydrochloride to that of the internal standard for the
Amount (mg) of mepivacaine hydrochloride
(C15H22N2OHCl) = amount (mg) of Mepivacaine HyQ
drochloride RS T
QS
Internal standard solutionA solution of benzophenone in methanol (1 in 4000).
about 25 o C .
Mobile phase: Dissolve 2.88 g of sodium lauryl sulfate in 1000 mL of a mixture of 0.02 mol/L phosphate
buffer solution, pH 3.0 and acetonitrile (11:9).
time of mepivacaine is about 6 minutes.
System suitability
with 5 L of a standard solution under the above operating conditions, mepivacaine and the internal standard
are eluted in this order with the resolution between
tainers.
Meprobamate
CH3
O
CH2CCH2O
O
C
NH2
CH2CH2CH3
Methylphenidate Hydrochloride
C9H18N2O4: 218.25
Meprobamate contains not less than 97.0% and not

more than 101.0% of meprobamate (C9H18N2O4), calculated on the dried basis.
Description Meprobamate is a white powder and has
a characteristic odor and a bitter taste.
Meprobamate is slightly soluble in water, freely soluble
in acetone or in ethanol and sparingly soluble in ether.
Meprobamate and Meprobamate RS, previously dried,
as directed in the potassium bromide disk method under
the Infrared spectrophotometry: both spectra exhibit the
similar intensities of absorption at the same wavenumbers. If the maximum absorption wavenumbers are
different between Meprobamate and Meprobamate RS,
dissolve Meprobamate and Meprobamate RS in acetone
to make solution containing 8 mg per mL, mix 0.1 mL
of this solution with 1 mL of n-heptane and evaporate
the solvent below 30 C under nitrogen, respectively.
Dry the residues in vaccum at room temperature for 30
minutes and repeat the test.
(2) Perform the test as directed under the related
substances: spots from the test solution and the standard solution exhibit the same Rf value and color.
Melting Point Between 103 o C and 107 o C . The
difference between the beginning and the end temperature of melting is not more than 2 o C .
Purity (1) Related substancesWeigh accurately a
portion of Meprobamate, dissolve in ethanol to make a
solution containing 0.1 g per mL and use this solution
as the test solution. Add ethanol to the test solution and
use this solution as the identification solution to make a
solution containing 1.0 mg per mL. Separately, weigh
accurately a volume of Meprobamate RS, previously
dried at 60 C for 3 hours under vaccum and dissolve in
ethanol to make a solution containing 1.0 mg per mL.
Add ethanol, dilute quantitatively and use this solution
as the standard solution.
Standard
solutions
Dilution
A
B
C
D
E
No dilution
4 in 5
3 in 5
2 in 5
1 in 5
Concentration
(mg/mL)
1.0
0.8
0.6
0.4
0.2
Relative%
(%) to the
test solution
1.0
0.8
0.6
0.4
0.2
KP 9 619
solutions as directed under the Thin-layer Chromatography. Spot 2 L each of the test solution, the identification solution and the standard solutions on a plate of
plate with a mixture of hexane, acetone and pyridine
(7 : 3 : 1) to a distance of about 15 cm, air-dry the plate
for 15 minutes, heat at 100 C for 15 minutes and cool.
Spray evenly vanillin-sulfuric acid TS on the plate, heat
at 110 C for 15 to 20 minutes, cool and allow to stand
at room temperature until the spot of blue-purple color
is observed. It usually takes 30 to 60 minutes to develop color. The Rf value of the principal spot from the
standard solution and the spots other than the principal
spot from the test solution are not larger nor more intense than the spot from the standard solution A (not
more than 1.0%). Total intensity of all the spots other
than the principal spot from the test solution is not
more than 2.0%.
(2) Methyl carbamate: Weigh accurately about 1.0
g of finely powdered Meprobamate, transfer to a beaker,
add 5.0 mL of water and mix well. Filter the solution
through a funnel with glass wool and use the filtrate as
the test solution. Separately, weigh accurately a volume
of Meprobamate RS, previously dried in vacuum at
60 C for 3 hours, add water to make a solution containing 1.0 mg per mL and use this solution as the standard solution. Perform the test with 50 L each of the
operating conditions: the peak area of Meprobamate
from the test solution is not larger than that of Meprobamate from the standard solution (not more than
0.5%).
Column: A stainless steel column, 3.9 mm to 4.6
mm in inside diameter and 25 cm to 30 cm in length,
chromatography (3 m to 10 m in particle diameter).
System suitability
times with 20 L of standard solution under the above
operating conditions: the relative standard deviation of
the peak area of methyl carbamate is not more than
2.0%.
Loss on Drying Not more than 0.5% (1.0 g, 60 o C ,
in vacuum, 3 hours).
Assay Weigh accurately about 0.4 g of Meprobamate
in an Erlenmeyer flask, add 40 mL of hydrochloric acid
and a few boiling stones and reflux at the boiling temperature for 90 minutes. Boil the solution without the
refluxing apparatus to make 5 mL to 10 mL, cool, add

50 mL of water and 1 drop of methyl red TS and neutralize the solution with 10 mol/L of sodium hydroxide
TS carefully until the color of indicator changes. If necessary, add 1 mol/L of hydrochloric acid until the color of the solution changes to red and titrate with 0.1
mol/L of sodium hydroxide VS carefully, again. Add a
mixture of 15 mL of formaldehyde TS and 15 mL of
water previously neutralized with 0.1 mol/L of sodium
hydroxide VS to phenolphthalein TS. Again, add 0.2
mL of phenolphthalein TS and titrate with 0.1 mol/L of
sodium hydroxide until red color is observed. Perform
a blank determination and make any necessary correction.
Each mL of the total volmne 0.1 mol/L sodium
hydroxide TS consumed after the addition of
formaldehyde TS = 10.912 mg of C9H18N2O4
Meprobamate Tablets
Meprobamate Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of meprobamate (C9H18N2O4: 218.25).
Tablets, with Meprobamate.
Identification (1) Take a volume of powdered Meprobamate Tablets, equivalent to 0.8 g of Meprobamate
according to the labeled amount, add 5 mL of anhydrous ethanol, shake frequently and heat for 5 minutes
until it starts to boil. After cooling, filter, add 15 mL of
hexane and mix by shaking. Filter by suction and dry
the precipitate (crystal) at 60 C: Melting temperature
of the crystals is between 103 C and 107 C. The difference between the beginning and the end temperatures of melting is not more than 2 C.
(2) Proceed with the crystals as directed in the Identification (1) under Meprobamate.
Meprobamate Tablets at 100 revolutions per minute according to the Method 1 under Dissolution Test, using
900 mL of water as the dissolution solution. Pipet 30.0
mL of dissolved solution after 30 minutes and perform
the test with the filtrate as directed in the Assay.
Dissolution rate of Meprobamate Tablets in 30 minutes
is not less than 75%.
Meprobamate Tablets. Weigh accurately a portion of
the powder, equivalent to about 0.25 g of meprobamate

(C9H18N2O4), dissolve in 15 mL of acetonitrile by shaking, add water to make exactly 50 mL and filter. Discard the first 10 mL of the filtrate and use the subsequent filtrate as the test solution. Separately, weigh accurately about 50 mg of Meprobamate RS, dissolve in 3
mL of acetonitrile by shaking, add water to make exactly 10 mL and use this solution as the standard solution.
conditions and determine the peak areas, AT and AS ,
of the test solution and the standard solution, respectively.
Amount (mg) of meprobamate (C9H18N2O4)
A
= amount (mg) of Meprobamate RS T 5
AS
Column: A stainless steel column, 3.9 mm to 4.6
mm in inside diameter and 25 cm to 30 cm in length,
(7 : 3).
System suitability
System performance: Dissolve 25 mg of Meprobamate in 1 mL of acetonitrile, shake and add 1 mL of
phenacetin solution and water to make 5 mL. When the
procedure is run with 20 L each of the standard solution and phenacetin solution under the above operating
conditions, the response ratio of meprobamate
(C9H18N2O4) and phenacetin is not less than 2.0. The
peak area of phenacetin is 65.0 to 100.0% of that of
Meprobamate and the relative retention times of Meprobamate to phenacetin is about 0.7.
times under the above operating conditions, the relative
standard deviation of the peak areas of Meprobamate is
not more than 2.0%.
Phenacetin solutionDissolve 25 mg of phenacetin
in acetonitrile to make 200 mL. Pipet 20 mL of this solution and add 30 mL of acetonitrile and water to make
100 mL.
Mequitazine
H
N
and enantiomer
C20H22N2S: 322.47
Mequitazine, when dried, contains not less than 98.5%

and not more than 101.0% of mequitazine C20H22N2S).
Description Meauitazine is white crystal or crystalline powder.
Meauitazine is freely soluble in methanol or in glacial
acetic acid, soluble in ethanol, and practically insoluble
in water.
A solution of Meauitazine in methanol(1 in 50) shows
Meauitazine is gradually colored by light.
of solutions of Mequitazine and Mequitazine RS in
(2) Determine the infrared spectra of Mequitazine
and Mequitazine RS, previously dried, as directed in
Meauitazine according to Method 2, and perform the
(2) Related substancesPerform the test without
exposure to light, using light-resistant vessels. Dissolve
50 mg of Meauitazine in 5 mL of methanol, and use
test solution, add methanol to make exactly 50 mL, pipet 5.0 mL of this solution, add methanol to make exactly 50 mL, and use this solution as the standard solution. Perform the test with the test solution and the
Develop the plate with a mixture of ethylacetate, methanol and diethylamine (7 : 2 : 2) to a distance of
about 10 cm, and air-dry the plate. Examine the plate
number of the spots other than the principal spot from
the sample solution is not more than 3 and they are not
KP 9 621
P2O5, 60 C, 3 hours).
Assay Weigh accurately about 0.25 g of Meauitazine,
previously dried, dissolve in 50 mL of glacial acetic acid and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination, and make any
= 32.247 mg of C20H22N2S
tight containers.
Mercaptopurine Hydrate
S
N
HN
H2O
NH
N
Mercaptopurine
C5H4N4SH2O:170.19
Mercaptopurine Hydrate contains not less than 98.0%

and not more than 101.0% of mercaptopurine
(C5H4N4S: 152.18), calculated on the anhydrous basis.
Description Mercaptopurine Hydrate is a pale yellow
to yellow crystal or crystalline powder and is odorless.
Mercaptopurine Hydrate is practically insoluble in water, in acetone or in ether.
Mercaptopurine Hydrate dissolves in sodium hydroxide
TS or in ammonia TS.
Identification (1) Dissolve 0.6 g of Mercaptopurine
Hydrate in 6 mL of sodium hydroxide solution (3 in
100) and add slowly 0.5 mL of methyl iodide with vigorous stirring. Stir well for 10 minutes, cool in an icebath and adjust the pH to about 5 by dropping acetic
acid. Collect the separated crystals by filtration, recrystallize from water and dry at 120 C for 30 minutes: the
crystals melt between 218 C and 222 C (with decomposition).
(2) Determine the absorption spectra of the solutions of Mercaptopurine Hydrate and Mercaptopurine
Hydrate RS in 0.1 mol/L hydrochloric acid VS (1 in
0.2 g of Mercaptopurine Hydrate in 10 mL of ammonia
TS: the solution is clear and colorless.
(2) SulfateDissolve 50 mg of Mercaptopurine

Hydrate in 10 mL of dilute hydrochloric acid, add 5
drops of barium chloride TS and allow to stand for 5
minutes: no turbidity is produced.
(3) Heavy metalsProceed with 1.0 g of Mercaptopurine Hydrate according to Method 2 and perform
(4) HypoxanthineDissolve 50 mg of Mercaptopurine Hydrate in exact 10 mL of a solution of strong
ammonia water in methanol (1 in 10) and use this solution as the test solution. Separately, dissolve 5.0 mg of
hypoxanthine in exact 100 mL of a solution of strong
ammonia water in methanol (1 in 10) and use this solution as the standard solution. Perform the test with the
the Thin-layer Chromatography. Spot 10 L each of the
test solution and the standard solution on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of methanol, chloroform, n-butyl formate and strong ammonia (8 : 6 : 4 : 1) to a distance of about 10 cm and airdry the plate. Examine under ultraviolet light (main
wavelength: 254 nm): the spot from the test solution is
not larger than and not more intense than that from the
standard solution.
(5) PhosphorusTake 0.20 g of Mercaptopurine
Hydrate in a crucible, add 2 mL of diluted sulfuric acid
(3 in 7), then heat gently, slowly adding drop-wise several 0.5 mL volumes of nitric acid, until the liquid becomes colorless. Continue to heat until most of the liquid has evaporated, cool and dissolve the residue in 10
mL of water. Transfer the solution to a 25 mL volumetric flask, wash the crucible with two 4 mL volumes of
water, combine the washings with the solution in the
volumetric flask and use this solution as the test solution. Separately, dissolve 0.4396 g of monobasic potassium phosphate in water to make exactly 200 mL. To
2.0 mL of this solution, add water to make exactly 100
mL. Transfer 2.0 mL of this solution to a 25 mL volumetric flask, add 16 mL of water and use this solution
as the standard solution. To the test solution and the
standard solution, add 1 mL of diluted sulfuric acid (3
in 7), 0.5 mL of nitric acid, 0.75 mL of ammonium molybdate TS, 1 mL of 1-amino-2-naphthol-4-sulfonic acid TS and water to make 25 mL and allow to stand for 5
minutes. Perform the test with the test solution and the
standard solution as directed under the Ultravioletvisible Spectrophotometry, using water as the blank:
the absorbance of the subsequent solution of the test solution at 750 nm is not larger than that of the subsequent solution of the standard solution.
Water Between 10.0 and 12.0% (0.2 g, volumetric titration, back titration).
Assay Weigh accurately about 0.25 g of Mercaptopurine Hydrate, dissolve in 90 mL of dimethylammonium

hydroxide VS (potentiometric titration, Endpoint Detection Methods in Titrimetry). Perform a blank determination with a mixture of 90 mL of dimethylformamide and 15 mL of water and make any necessary correction.
hydroxide VS = 15.218 mg of C5H4N4S
Mesalazine
H2N
COOH
OH
5-Amino-2-hydroxybenzoic acid
C7H7NO3 : 153.14
Mesalazine contains not less than 98.5% and not more
than 101.0 % of mesalazine C7H7NO3, calculated on
the dried basis.
Description Mesalazine is a white or light grey or
light pink powder or crystal.
Mesalazine is very slightly soluble in water, and practically insoluble in ethanol.
Mesalazine dissolves in dilute sodium hydroxide solution and in dilute hydrochloric acid solution.
Identification (1) Dissolve 50 mg each of Mesalazine and Mesalazine RS in 10 mL of 1.03% hydrochloric acid to make 100 mL. Dilute 5 mL of these solutions with 1.03% hydrochloric acid to 200 mL. Determine the absorption spectra of both solutions as directed under the Ultraviolet-visible Spectrophotometry:
Mesalazine and Mesalazine RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
(3) Dissolve 50 mg each of Mesalazine and Mesalazine RS in 10 mL of a mixture of glacial acetic acid
and water (1:1), dilute with methanol to 20 mL, and use
these solutions the test solution and the standard solution, respectively. Perform the test with these solutions
on a plate of silica gel with fluorescent indicator for
thin-layer chromatography, develop with a mixture of
methyl isobutyl ketone, methanol, and glacial acetic acid (50 : 40 : 10) to a distance of about 10 cm, and dry
the plate in air. Examine in ultraviolet light at 365 nm.
The principal spot from the test solution corresponds to
that from the standard solution.

0.5 g of Mesalazine in 1 mol/L hydrochloric acid TS to
make 20 mL, maintain the solution at 40 C: the solution is clear. Maintaining the solution at 40 C, measure
the absorbance of the solution at 440 nm and 650 nm.
The absorbance is not greater than 0.15 at 440 nm and
0.10 at 650 nm.
(2) Reducing substancesDissolve 0.10 g of Mesalazine in dilute hydrochloric acid to make 25 mL, add
0.2 ml of starch solution TS and 0.01 mol/L iodine TS,
and allow to stand for 2 min: the solution is blue or violet-brown.
(3) Chlorides Dissolve 1.50 g of Mesalazine in
50 ml of anhydrous formic acid, add 100 mL of water
and 5 mL of 2 mol/L nitric acid, and titrate with 0.005
mol/L silver nitrate VS (potentiometric titration, Endpoint Detection Method in Titrimetry) (not more than
0.1%).
= 0.1773 mg of Cl
(4) SulfatesShake 1.0 g of Mesalazine with 20
mL of water for 1 min and filter. Rinse the filter paper
and residues on the filter paper. Combine the filtrate all
together, dilute with water to make 40 mL, and use this
solution as the test solution. Prepare the control solution with 0.42 mL of 0.005 mol/L sulfuric acid VS (not
more than 0.02%).
(5) Heavy metals Proceed with 1.0 g of Mesalazine according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
(6) Related substances I and IIDissolve 50.0 mg
of Mesalazine in mobile phase A to make 50.0 mL, and
use this solution as the test solution. Dissolve 5.0 mg of
2-aminophenol (related substance I) in mobile phase A
to make 100 mL, and use this solution as the standard
solution (1). Dissolve 5.0 mg of 4-aminophenol (related
substance II) in mobile phase A to make exactly 250
mL. Pipet 1.0 mL of this solution, combine with 1.0
mL of the standard solution (1), and dilute with mobile
phase A to make 100mL. Use this solution as the standard solution (2). Pipet 1 mL of the test solution, dilute
with mobile phase A to make 200 mL. Pipet 5 mL of
this solution, and mix with 5 mL of the standard solution (1). Use this solution as the standard solution (3).
Perform the test with 20 L each of the test solution,
the standard solution (2), and the standard solution (3)
as directed under the Liquid Chromatography according to the following conditions. Determine the peak
areas by the automatic integration method. The peak
area of the related substance II from the test solution is
not more than that from the standard solution (2) (not
more than 0.02%), and the peak area of the related substance I from the test solution is not more than 4 times
that from the standard solution (2) (not more than
0.02%).
KP 9 623
follows.
Mobile phase A Dissolve 2.2 g of perchloric
acid and 1.0 g of phosphoric acid in water to make
1000 mL.
Mobile phase B Dissolve 1.7 g of perchloric
acid and 1.0 g of phosphoric acid in acetonitrile to
make 1000 mL.
Time (min)
Mobile
Mobile
phase A (%) phase B (%)
Elution
0~8
100
isocratic
8 ~ 25
100 40
0 60
linear gradient
25 ~ 30
40 100
60 0
linear gradient
30 ~ 40
100
isocratic

System suitability
with 20 L of the standard solution (3) according to the
are about 0.5 for the related substance II, 0.9 for the related substance I and 1.0 for Mesalazine, respectively.
The resolution between the peaks of the related substance I and Mesalazine is not less than 3.0.
(7) Related substance IV Dissolve 40.0 mg of
Mesalazine in the mobile phase to make exactly 20 mL,
and use this solution as the test solution. Dissolve 27.8
mg of aniline hydrochloride in the mobile phase to
make 100 mL. Pipet 0.2 mL of this solution, dilute with
mobile phase to 20 mL, and use this solution as the
under the Liquid Chromatography according to the following conditions. Determine the peak areas by the automatic integration method. The peak area of the related substance IV from the test solution is not more
than that from the standard solution (0.001%).
about 40 C.
Mobile phase: A mixture of phosphate buffer at pH

8.0 and methanol (85:15).
System suitability
System performance: Perform the test with 50 L
of the standard solution according to the above operating conditions. The retention time of the related substance IV is about 15 minutes, and the signal-to-noise
ratio is not less than 10.
Phosphate buffer at pH 8.0Dissolve 1.41 g of potassium dihydrogen phosphate and 0.47 g of disodium
hydrogen phosphate dihydrate in water to make 1000
mL. Adjust the solution pH to 8.0 with 1 mol/L sodium
hydroxide solution.
(8) Related substances Use freshly prepared the
test solution, the standard solution, and mobile phases.
Dissolve 50.0 mg of Mesalazine in mobile phase A to
make 50.0 mL, and use this solution as the test solution.
Pipet 1.0 mL of the test solution, dilute with mobile
phase A to make exactly 100 mL, and use this solution
as the standard solution (1). Dissolve 5.0 mg of 3aminobenzoic acid (related substance V) in mobile
phase A to make exactly 100 mL. Pipet 1.0 mL of this
solution, dilute with mobile phase A to 25 mL, and use
this solution as the standard solution (2). Dissolve 5 mg
of the related substance V in mobile phase A to make
exactly 100 mL. Pipet 1 mL of the test solution, dilute
with mobile phase A to make 50 mL, and use this solution as the standard solution (3). Dissolve 10.0 mg of 3aminophenol (related substance III) in mobile phase A
to make exactly 100 mL. Dilute 1.0 mL to 50 mL with
mobile phase A, and use this solution as the standard
solution (4). Dissolve 5.0 mg of 2,5-dihydroxybenzoic
acid (related substance VI) in mobile phase A, and dilute to 100 mL with mobile phase A. Dilute 1.0 mL to
50 mL with mobile phase A, and use this solution as
the standard solution (5). Dissolve 15.0 mg of salicylic
acid (related substance VII) in mobile phase A, and dilute to 100 mL with mobile phase A. Dilute 1.0 mL to
50 mL with mobile phase A, and use this solution as
the standard solution (6). Use mobile phase A as the
blank solution. Perform the test with 10 L each of the
blank solution, the test solution, the standard solutions
(1), (3), (4), (5), and (6) as directed under the Liquid
Chromatography according to the following conditions.
Determine the peak areas by the automatic integration
method. The peak area of the related substance III from
the test solution is not more than that from the standard
solution (4) (0.2%); the peak area of the related substance V is not more than that from the standard solution (3) (0.1%); the peak area of the related substance
VI is not more than that from the standard solution (5)
(0.1%); the peak area of the related substance VII is not
more than that from the standard solution (6) (0.3%);
the peak area of any other related substances is not
more than 0.1 times the principal peak area from the
standard solution (1) (0.1%); and the total peak area of
all related substances is not more than the principal
peak area from the standard solution (1) (1.0%). Disre-

gard not only any peak areas that are not more than
0.05 times the principal peak area from the standard solution (1) but also any peaks from the blank solution.
follows.
Mobile phase A Dissolve 2.2 g of perchloric
acid and 1.0 g of phosphoric acid in water to make
1000 mL.
Mobile phase B Dissolve 1.7 g of perchloric
acid and 1.0 g of phosphoric acid in acetonitrile to
make 1000 mL.
Time (min)
Mobile
Mobile
phase A (%) phase B (%)
Elution
0~7
100
isocratic
7 ~ 25
100 40
0 60
linear gradient
25 ~ 30
40 100
60 0
linear gradient
30 ~ 40
100
isocratic

System suitability
with 10 L each of the standard solutions (2), (3), (4),
(5), and (6) according to the above operating conditions,
the relative retention times with reference to mesalazine are 0.8 for the related substance III, 1.2 for the related substance V, 3.1 for the related substance VI, and
3.9 for the related substance VII. The ratio of the height
above the baseline of the peak due to the related substance V to the height above the baseline of the lowest
point of the curve separating this peak from the peak
due to mesalazine is not less than 1.5.
constant mass).
Assay Dissolve 50 mg of Mesalazine, accurately
weighed, in 100 mL of boiling water. Cool rapidly to
room temperature, and titrate with 0.1 mol/L sodium
hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry).
= 15.31 mg of C7H7NO3
resistant containers.
Preserve in tight, light-
Mesterolone
CH3
OH
H
H3C
H
H
CH3
O
H
C20H32O2 : 304.47
Mesterolone contains not less than 98.0% and not more
than 102.0 % of mesterolone (C7H7NO3), calculated on
the dried basis.
Description Mesterolone is a white or yellowish
crystalline powder.
Mesterolone is sparingly soluble in acetone, in ethyl
acetate and in methanol, and practically insoluble in
water.
Identification Determine the infrared absorption
spectra of Mesterolone and Mesterolone RS as directed
in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
D : Between + 20 and
+ 24 (0.2 g after drying, methylene chloride, 10 mL,
100 mm).
Purity (1) Related substances IDissolve 0.1 g of
Mesterolone in a mixture of methanol and methylene
chloride (1:1) to make 10 mL, and use this solution as
the test solution. Pipet 1 mL of the test solution, dilute
to 200 mL with the mixture of methanol and methylene
chloride (1:1), and use this solution as the standard solution (1). Dissolve 5 mg of 1-methyl-5-androstan3,17-diol (related substance I) in the standard solution (1) to make 100 mL, and use this solution as the
standard solution (2). Perform the test with these solutions as directed under the Thin-layer Chromatography.
Spot 10 L each of the test solution, the standard solution (1), and the standard solution (2) on a plate of silica gel for thin-layer chromatography, develop with a
mixture of methanol, acetone, and toluene (2:15:85) to
a distance of about 15 cm, and dry the plate in air. Examine in ultraviolet light at 366 nm, or spray with a
20% toluenesulphonic acid in ethanol and heat the plate
for 10 min at 120 C. Any blue spots, excluding the
principal spot, from the test solution is not more intense
than the spot from the standard solution (1) (0.5%).
(2) Other related substancesDissolve 50.0 mg of
Mesterolone in a mixture of water and acetonitrile (1:4)
KP 9 625
to make 25 mL, and use this solution as the test solution. Separately, dissolve 50.0 mg of Mesterolone RS
in a mixture of water and acetonitrile (1:4) to make 25
mL, and use this solution as the standard solution (1).
Dissolve 10.0 mg of 17-Hydroxy-1-methyl-5androst-4-en-3-one (related substance II) in a mixture
of water and acetonitrile (1:4) to make 5 mL, and use
this solution as the standard solution (2). Combine 0.5
mL of the standard solution (1) and 0.5 mL of the standard solution (2), dilute with a mixture of water and
acetonitrile (1:4) to 100 mL, and use this solution as the
standard solution (3). Perform the test with 50 L each
of the test solution and the standard solution (3) as directed under the Liquid Chromatography according to
the following conditions. Determine the peak areas by
the automatic integration method. The peak area of the
related substance II from the test solution is not more
than that of the related substance II from the standard
solution (3) (0.5%); the peak area of any other related
substance is not more than half the peak area of Mesterolone from the standard solution (3) (0.25%); and the
sum of total peak areas is not more than 1.5 times the
peak area of Mesterolone from the standard solution (3)
(0.75%). Disregard any peak areas that are not more
than 0.1 times the peak area of Mesterolone from the
standard solution (3).
about 25 C.
Mobile phase: A mixture of acetonitrile, water, and
methanol (20:40:60).
System suitability
System performance: Combine 0.5 mL of the
standard solution (1) and 0.5 mL of the standard solution (2), and dilute with a mixture of water and acetonitrile (1:4) to 100 mL. When the procedure is run with
50 L of this solution, the resolution between the peaks
of mesterolone and the related substance II is not less
than 6.0.
constant mass).
Residue on Ignition Not more than 0.1% (1 g)
Assay Dissolve about 50 mg each of Mesterolone and
Mesterolone RS, accurately weighed, in a mixture of
water and acetonitrile (1:4) to make exactly 25 mL, and
use these solutions as the test solution and the standard
solution, respectively. Perform the test with 10 L each
in the Liquid Chromatography according to the above
operating conditions. Calculate the peak areas, AT

and AS , of mesterolone of these solutions.
Amount (mg) of mesterolone (C20H32O2)
A
= amount (mg) of Mesterolone RS T
AS
Mestranol
OH
CH3
C
CH
CH3O
C21H26O2: 310.43
Mestranol, when dried, contains not less than 97.0%
and not more than 102.0% of mestranol (C21H26O2).
Description Mestranol is a white to pale yellowish
white, crystalline powder and is odorless.
Mestranol is freely soluble in chloroform, soluble in
dioxane, sparingly soluble in dehydrated ethanol or
ether and practically insoluble in water.
Identification (1) Dissolve about 2 mg of Mestranol
in 1 mL of a mixture of sulfuric acid and dehydrated
ethanol (2 : 1): a red-purple color is observed with a
yellow-green fluorescence.
Mestranol and Mestranol RS in dehydrated ethanol (1
in 10000) as directed under the Ultraviolte-visible
(3) Determine the infrared spectra of Mestranol and
Mestranol RS, as directed in the potassium bromide
D : Between +2 and
+8 (0.2 g, after drying, dioxane, 10 mL, 100 mm).
Purity (1) Heavy metalsProceed with 1.0 g of Mestranol according to Method 2 and perform the test.
Mestranol according to Method 3 and perform the test

(3) Related substancesDissolve 0.1 g of Mestranol in 20 mL of chloroform and use this solution as the
chloroform to make exactly 200 mL and use this solution as the standard solution. Perform the test with the
test solution and the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate
with a mixture of chloroform and dehydrated ethanol
(29 : 1) to a distance of about 10 cm and air-dry the
plate. Spray evenly diluted sulfuric acid (1 in 5) on the
plate and heat at 105 C for 15 minutes: the spots other
than the principal spot from the test solution are not
3 hours).
Assay Weigh accurately about 10 mg of each of Mestranol and Mestranol RS, previously dried, dissolve in
dehydrated ethanol to make exactly 100 mL and use the
test solution and the standard solution as the test solution and the standard solution, respectively. Determine
the absorbances, AT and AS , of the test solution and
the standard solution, respectively, at 279 nm as directed under the Ultraviolet-visible spectrophotometry.
Amount (mg) of C21H26O2 = amount (mg) of
A
Mestranol RS T
AS
tight containers.
Metenolone Acetate
H3C
OCOCH3
H3C
H
H3C
O
H
C22H32O3: 344.49
Metenolone Acetate, when dried, contains not less than
97.0% and not more than 103.0% of metenolone acetate (C22H32O3).
Description Metenolone Acetate is a white to pale
yellowish white, crystalline powder and is odorless.
Metenolone Acetate is freely soluble in acetone, in dioxane or in chloroform, soluble in ethanol or in metha-
nol, sparingly soluble in ether or in sesame oil, slightly

soluble in hexane or in petroleum ether and practically
insoluble in water.
Identification (1) Dissolve 1 mg of Metenolone Acetate in 5 mL of a mixture of ethanol and sulfuric acid
(1 : 1) and heat for 30 minutes in a water-bath: a redbrown color develops.
(2) Take 10 mg of Metenolone Acetate, add 0.5 mL
of dilute sodium hydroxide-ethanol TS and heat for 1
minute on a water-bath. After cooling, add 0.5 mL of
diluted sulfuric acid (1 in 2) and boil gently for 1
minute: the odor of ethyl acetate is perceptible.
(3) Dissolve 50 mg of Metenolone Acetate in 3 mL
of methanol, add 0.3 mL of a solution of potassium
carbonate (1 in 6) and boil for 2 hours under a reflux
condenser. After cooling, add this solution gradually to
50 mL of cold water and stir for 15 minutes. Filter the
precipitate so obtained by suction through a glass filter
(G4), wash with 10 mL of water and dry at 105 C for 1
hour: it melts between 157 C and 161 C.
(4) Determine the infrared spectra of Metenolone
Acetate and Metenolone Acetate RS, previously dried,
the Infrared Spectrophotomtry: both spectra exhibit
D : Between +39 and
+42 (0.2 g, after drying, chloroform, 10 mL, 100 mm).
0.50 g of Metenolone Acetate in 10 mL of dioxane: the
(2) Heavy metalsProceed with 2.0 g of Metenolone Acetate according to Method 2 and perform the
(3) Related substancesDissolve 35mg of Metenolone Acetate in 20 mL of chloroform and use this solution as the test solution. Pipet 1.0 mL of the test solution, dilute with chloroform to exactly 250 mL and use
with the test solution and the standard solution as directed under the Thin-layer Chromatography. Spot 10
mixture of cyclohexane and ethyl acetate (1 : 1) to a
3 hours).
KP 9 627
Assay Weigh accurately about 10 mg of Metenolone
Acetate, previously dried and dissolve in methanol to
make exactly 100 mL. Pipet 5.0 mL of this solution and
dilute with methanol to exactly 50 mL. Determine the
absorbance, A, of this solution at the wavelength of
maximum absorption at about 242 nm as directed under
the Ultraviolet-visible Spectrophotometry.
Amount (mg) of metenolone acetate (C22H32O3)
A
= 391 10000
tight containers.
Metenolone Enanthate
of cyclohexane and ethyl acetate (1 : 1) to a distance of

about 15 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): any spot
other than the principal spot does not appear.
O
C
H3C
H3C
CH3
(CH2)5CH3
O
H
Loss on Drying Not more than 0.5% (0.5 g, in vacuum, P2O5, 4 hours).
O
H
C27H42O3: 414.62
Metenolone Enanthate, when dried, contains not less
than 97.0% and not more than 103.0% of metenolone
enanthate (C27H42O3).
Description Metenolone Enanthate is white crystals
or crystalline powder and is odorless.
Metenolone Enanthate is very soluble in ethanol, in
acetone, in dioxane or in chloroform, freely soluble in
methanol, in ethyl acetate, in ether, in cyclohexane, in
petroleum ether or in toluene, soluble in sesame oil and
Identification (1) Heat 1 mg of Metenolone Enanthate with 5 mL of a mixture of ethanol and sulfuric acid (1 : 1) in a water-bath for 30 minutes: a red-brown
color develops.
(2) Dissolve 50 mg of Metenolone Enanthate in 3
mL of methanol, add 0.3 mL of a solution of potassium
carbonate (1 in 6), boil under a reflux condenser for 2
hours, cool, add slowly this solution to 50 mL of cold
water and stir for 15 minutes. Filter the produced precipitate by suction through a glass filter (G4), wash with
water until the washings become neutral and dry at
105 C for 1 hour: it melts between 156 C and 162 C.
D : Between +39 and
+43 (0.2 g, after drying, chloroform, 10 mL, 100 mm).
0.5 g of Metenolone Enanthate in 10 mL of dioxane:
(2) Heavy metalsProceed with 2.0 g of Metenolone Enanthate according to Method 2 and perform the
(3) Related substancesDissolve 20 mg of Metenolone Enanthate in exactly 10 mL of chloroform and
use this solution as the test solution. Perform the test
with the test solution as directed under the Thin-layer
Chromatography. Spot 10 L of the test solution on a
plate of silica gel with a fluorescent indicator for thinlayer chromatography. Develop the plate with a mixture
Assay Weigh accurately about 0.1 g of Metenolone

Enanthate, previously dried and dissolve in methanol to
make exactly 100 mL. Pipet 10.0 mL of this solution
and dilute with methanol to make exactly 100 mL. Pipet 10.0 mL of this solution and dilute again with methanol to make exactly 100 mL. Determine the absorbance, A, of this solution at the wavelength of a maximum absorption at about 242 nm as directed under the
Ultraviolet-visible Spectrophotometry.
Amount (mg) of metenolone enanthate (C27H42O3)
A
= 325 100000
tight containers.
Preserve in light-resistant
Metenolone Enanthate Injection

Metenolone Enanthate Injection is an oily solution for
injection. Metenolone Enanthate Injection contains not
less than 90.0% and not more than 110.0% of the labeled amount of metenolone enanthate (C27H42O3:
414.62).
Method of Preparation Prepare as directed under Injections, with Metenolone Enanthate.
Description Metenolone Enanthate Injection is a
clear, pale yellow, oily liquid.
Identification (1) Measure a volume of Metenolone
Enanthate Injection, equivalent to 0.1 g of Metenolone
Enanthate according to the labeled amount, add 20 mL
of petroleum ether and extract with three 20 mL volumes of diluted acetic acid (5 in 7). Combine the extracts, wash with 20 mL of petroleum ether, add 300
mL of cold water while cooling with ice and stir sufficiently. Filter the produced precipitate by suction
through a glass filter (G4), wash with water until the
last washing becomes neutral and dry in a desiccator
(in vacuum, P2O5) for 6 hours. Proceed with this residue as directed in the Identification (1) under Metenolone Enanthate.
(2) Measure a volume of Metenolone Enanthate Injection, equivalent to 10 mg of Metenolone Enanthate
according to the labeled amount, dissolve in 10 mL of
chloroform and use this solution as the test solution.
KP 9 629
Separately dissolve 10 mg of Metenolone Enanthate RS
in 10 mL of chloroform and use this solution as the
with a fluorescent indicator for thin-layer chromatography. Develop the plate with toluene to a distance of
about 15 cm and air-dry the plate. Again develop this
plate with a mixture of cyclohexane and ethyl acetate
(1 : 1) to a distance of about 15 cm and air-dry the plate.
Examine under ultraviolet light (main wavelength: 254
nm): the principal spots from the test solution and the
standard solution show the same Rf value.
Sterility Test

Assay Take an exactly measured volume of Metenolone Enanthate Injection, equivalent to about 0.1 g of
metenolone enanthate (C27H42O3), add chloroform to
add chloroform to make exactly 50 mL and use this solution as the test solution. Weigh accurately about 0.1 g
of Metenolone Enanthate RS, previously dried in a desiccator (in vacuum, P2O5) for 4 hours and prepare the
standard solution in the same manner as directed for the
preparation of the test solution. Pipet 3.0 mL each of
the test solution and the standard solution and treat
each solution as follows: add 10 mL of isonicotinic acid
hydrazide TS, exactly measured, add methanol to make
exactly 20 mL and allow to stand for 60 minutes. Determine the absorbances of these solutions, AT and
AS , respectively, at 384 nm as directed under the Ultraviolet-visible Spectrophotometry, using a solution
obtained by proceeding with 3 mL of chloroform in the
same manner as the above procedure as the blank.
Amount (mg) of metenolone enanthate (C27H42O3)
A
= amount (mg) of Metenolone Enanthate RS T
AS
Metformin Hydrochloride
NH
NH
CH3
H2N
N
H
HCl
N
CH3
C4H11N5HCl: 165.63
Metformin Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of metformin hydrochloride (C4H11N5HCl).
Description Metformin Hydrochloride is a white
crystal.
Metformin Hydrochloride is freely soluble in water,
slightly soluble in ethanol and practically insoluble in
acetone or in dichloromethane.
Identification (1) Dissolve 20 mg each of Metformin
Hydrochloride and Metformin Hydrochloride RS in
water to make 5 mL and use these solutions as the test
solution and the standard solution, respectively. Perform the test with these solutions as directed under the
gel for thin-layer chromatography. Develop with a mixture of glacial acetic acid, n-butanol and water (10 :
40 : 50) to a distance of about 15 cm, and dry the plate
at 100 C to 105 C for 15 minutes. Spray with a mixture of sodium nitroprusside solution (1 in 10), potassium ferricyanide TS and sodium hydroxide solution (1
in 10) (1 : 1 : 1). (This solution is made when used): the
principal spot obtained from the test solution is the
same in Rf value and color as the principal spot obtained from the standard solution.
(2) Determine the infrared spectra of Metformin
Hydrochloride and Metformin Hydrochloride RS as directed in the potassium chloride disk method under the
(3) Dissolve Metformin Hydrochloride in water (1
in 200): the solution responds to the Qualitative Tests
for Chloride.
2.0 g of Metformin Hydrochloride in 20 mL of water:
(2) Heavy metalsProceed with 1.0 g of Metformin Hydrochloride according to Method 1, and perform
(3) Related substancesDissolve 0.50 g of Metformin Hydrochloride in a mobile phase to make exactly 100 mL, and use this solution as the test solution.

Separately, dissolve 20.0 mg of cyanoguanidine in water to make exactly 100 mL. Pipet 1.0 mL of this solution, add the mobile phase to make exactly 200 mL,
and use this solution as the standard solution (1). Pipet
1.0 mL of the test solution, and add the mobile phase to
make exactly 50 mL. And pipet 1.0 mL of this solution,
add the mobile phase to make exactly 20 mL, and use
this solution as the standard solution (2). Dissolve 10.0
mg of melamine in 90 mL of water, add 5 mL of the
test solution and add water to make exactly 100 mL.
Pipet 1.0 mL of this solution, add the mobile phase to
make exactly 50 mL, and use this solution as the standard solution (3). Perform the test with 20 L each of
the test solution, the standard solution (1) and the standard solution (2) as directed under the Liquid Chromatography according to the following conditions: in the
chromatogram obtained with the test solution, the area
of any peak corresponding to cyanoguanidine is not
greater than the area of the peak obtained from the
standard solution (1) (not more than 0.02%), and the
area of any peak other than the principal peak and any
peak corresponding to cyanoguanidine is not greater
than the area of the peak obtained from the standard solution (2) (not more than 0.1%).
benzenesulphonic acidized silica gel for liquid chromatography (5 m in particle diameter).
Mobile phase: Dissolve 17 g of ammonium dihydrogen phosphate in water to make 1000 mL. Adjust to
the pH to 3.0 with phosphoric acid.
System suitability
operating conditions, the resolution between peaks of
melamine and Metformin Hydrochloride being not less
than 10.0.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of Metformin Hydrochloride
obtained from 20 L of the standard solution (1) is at
least 50% of the full scale.
Time span of measurement: About twice as long as
the retention time of Metformin Hydrochloride.
Loss on Drying
105 C, 5 hours).
Not more than 0.5 percent (1 g,
Residue on Ignition
Assay Weigh accurately about 60 mg of Metformin

Hydrochloride, dissolve in 4 mL of anhydrous formic
Endpoint Detection Method in Titrimetry). In order to
avoid overheating in the reaction medium, mix thoroughly throughout the titration and stop the titration
immediately after the end-point has been reached. Perform a blank determination and make any necessary
correction.
= 8.281 mg of C4H11N5HCl
Methadone Hydrochloride
CH2CH3
CO
C
CH3
HCl
CH2CN
CH3
CH3
and enantiomer
C21H27NOHCl: 345.91
Methadone Hydrochloride contains not less than 98.5%
and not more than 100.5% of methadone hydrochloride
(C21H27NOHCl), calculated on the dried basis.
Description Methadone Hydrochloride is a colorless,
white crystalline powder and odorless.
Methadone Hydrochloride is freely soluble in ethanol
or in chloroform, soluble in water and practically insoluble in ether or in glycerin.
Methadone Hydrochloride and Methadone Hydrochloride RS, previously dried, as directed in the potassium
(2) A solution of Methadone Hydrochloride responds to the Qualitative Test for chloride.
pH The pH of a solution of Methadone Hydrochloride (1 in 10) is between 4.5 and 6.5.
Purity Related substancesWeigh 0.1 g of Methadone Hydrochloride, dissolve in 10 mL of ethanol and
10 mg of Methadone Hydrochloride RS, previously
dried at 105 o C for 1 hour and dissolve in 10 mL of
ethanol. To 0.1 mL, 0.5 mL, 1.0 mL and 2.0 mL volumes of the test solution, add ethanol to make 10 mL
and use this solutions as the standard solutions (1), (2),
(3) and (4), respectively. Perform the test with the test
solution and the standard solutions (1), (2), (3) and (4),
KP 9 631
20 L each of the test solution and standard solutions
(1), (2), (3) and (4), on the plate. Develop the plate with
a mixture of methanol and ammonium hydroxide (100 :
1.5) to a distance of 15 cm and air-dry the plate. Spray
the developing agent on the plate. Intensities of spots
other than the principal spot are not more than 1.0%,
relative to the principal spot.
pHA solution of Methamphetamine Hydrochloride (1 in 10) is between 5.0 and 6.0.
Developing agentDissolve 0.85 g of bismuth

subnitrate in 40 mL of water and 10 mL of glacial acetic acid and use this solution as solution A. Dissolve 8 g
of potassium iodide in 20 mL of water and use this solution as solution B. To 10 mL of the mixture of solution A and solution B, add 20 mL of glacial acetic acid
to make 100 mL.
Identification (1) Take 5 mL of a solution of Methamphetamine Hydrochloride (1 in 100) and add 0.5
mL of chloroplatinic acid TS: an orange-yellow, crystalline precipitate is produced.
(2) Take 5 mL of a solution of Methamphetamine
Hydrochloride (1 in 100) and add 0.5 mL of iodine TS:
a brown precipitate is produced.
(3) Take 5 mL of a solution of Methamphetamine
Hydrochloride (1 in 100) and add 0.5 mL of picric acid
TS: a yellow, crystalline precipitate is produced.
(4) A solution of Methamphetamine Hydrochloride
(1 in 20) responds to the Qualitative Tests for chloride.
Loss on Drying Not more than 0.3% (0.5 g, dried at

105 C for 1 hour).
Specific Optcal Rotation [ ]20

D : Between +16 and
+19 (0.2 g, after drying, water, 10 mL, 100 mm).
Assay Weigh accurately about 0.5 g of Methadone

Hydrochloride, dissolve in a mixture of 10 mL of glacial acetic acid and 10 mL of mercuric acetate and
warm slightly, if necessary. Cool the solution to room
temperature, add 10 mL of dioxane and titrate rapidly
with 0.1 mol/L perchloric acid VS (indicator: methylrosaniline chloride) as directed under the Endpoint Detection Method in Titrimetry. Perform a blank determination and make any necessary correction.
Each mL of 0.1 mol/L perchloric acid
= 34.591 mg of C21H27NOHCl
tight containers.

hours).
Methamphetamine
Hydrochloride
NHCH3
CH2
Purity (1) Acid or alkaliDissolve 2.0 g of Methamphetamine Hydrochloride in 40 mL of freshly

boiled and cooled water, add 2 drops of methyl red TS
and use this solution as the test solution. (i) To 20 mL
of the test solution, add 0.20 mL of 0.01 mol/L sulfuric
acid VS: a red color is observed. (ii) To 20 mL of the
test solution, add 0.20 mL of 0.02 mol/L sodium hydroxide VS: a yellow color is observed.
(2) SulfateDissolve 50 mg of Methamphetamine
Hydrochloride in 40 mL of water, add 1 mL of dilute
hydrochloric acid and 1 mL of barium chloride TS and
allow to stand for 10 minutes: the solution remains unchanged.
CH3
HCl
C10H15NHCl: 185.69
Methamphetamine Hydrochloride, when dried, contains
not less than 98.5% and not more than 101.0% of methamphetamine hydrochloride (C10H15NHCl).
Description Methamphetamine Hydrochloride is a
colorless crystal or white, crystalline powder and is
odorless.
Methamphetamine Hydrochloride is freely soluble in
water, in ethanol or in chloroform and practically insoluble in ether.

Assay Weigh accurately about 0.4 g of Methamphetamine Hydrochloride, previously dried and dissolve in
50 mL of a mixture of acetic anhydride and glacial
acetic acid (7 : 3). Titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and
tight containers.
DL-Methionine
H
CH3SCH2CH2
C
NH2
CO2H
and enantiomer
C5H11NO2S:149.21
DL-Methionine contains not less than 99.0% and not

than 101.0% of DL-methionine (C5H11NO2S), calculated on the dried basis.
Description DL-Methionine is a white crystal or crystalline powder.

DL-Methionine is sparingly soluble in water, slightly
DL-Methionine dissolves in dilute hydrochloric acid or
in dilute sodium hydroxide TS.
Identification (1) Dissolve about 0.1 g of DLMethionine and 0.1 g of glycine in 4.5 mL of 2 mol/L
sodium hydroxide TS, add 1 mL of 2.5% sodium nitroprusside solution and heat at 40 C for 10 minutes. After cooling, add 2 mL of a mixture of phosphoric acid
and hydrochloric acid (1 : 9): the color changes to dark
red.
(2) Determine the infrared spectra of DLMethionine and DL-Methionine RS as directed in the
(3) When proceed as directed in the Related substances under the Purity, the Rf value and color of the
principal spot from the test solution (2) are same as
those from the standard solution (1).
D : Between -0.05
and +0.05 (2.5 g, 1 mol/L hydrochloric acid TS, 50
mL, 100 mm).
pH Dissolve 1.0 g of DL-Methionine in 50 mL of water: the pH of this solution is between 5.4 and 6.1.
1.0 g of DL-Methionine in 50 mL of water: the solution
is clear and colorless.
(2) ChlorideDissolve 0.5 g of DL-Methionine in
20 mL of water and add 6 mL of dilute nitric acid and
control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS, 6 mL of dilute nitric acid and water to
make 40 mL. To the test solution and the control solution, add 10 mL each of silver nitrate TS (not more than
0.021%).
(3) SulfateProceed with 1.0 g of DL-Methionine
in 20 mL of water, heat at 60 C, then cool at 10 C,

add water to make 50 mL. Prepare the control solution
than 0.02%).
(4) Heavy metalsProceed with 1.0 g of DLMethionine according to Method 4 and perform the test.
(5) Related substancesDissolve 0.2 g of DLMethionine in water to make exactly 10 mL and use
this solution as the test solution (1). Pipet 1.0 mL of the
test solution and add water to make exactly 50 mL and
use this solution as the test solution (2). Separately dissolve 20 mg of DL-Methionine in water to make exactly
50 mL and use this solution as the standard solution (1).
Pipet 1.0 mL of this solution, add water to make exactly 10 mL and use this solution as the standard solution
(2). Perform the test with the test solutions and the
standard solutions as directed under the Thin-layer
Chromatography. Spot 5 L each of the test solutions
and the standard solutions on a plate of silica gel for
mixture of n-butanol, glacial acetic acid and water (60 :
plate. Spray evenly ninhydrin TS for spraying on the
plate and heat the plate at 100 C ~ 105 C for 15 minutes: the spots other than the principal spot from the
test solution (1) are not more intense than the spot from
the standard solution (2) (not more than 0.2%).
Loss on Drying Not more than 0.5% (1 g, 105 C).
Assay
Weigh accurately about 0.14 g of DLMethionine, dissolve in 3 mL of anhydrous formic acid,
add 30 mL of glacial acetic acid and titrate with 0.1
= 14.921 mg of C5H11NO2S
tight containers.
L-Methionine
H
CH3SCH2CH2
CO2H
NH2
C5H11NO2S: 149.21
L-Methionine,
and
not
when dried, contains not less than 98.5%

more than 101.0% of L-methionine
KP 9 633
(C5H11NO2S).
Identification (1) Add 25 mg of L-Methionine to 1

mL of sulfuric acid saturated with anhydrous cupric
sulfate: a yellow color is observed.
(2) Add 1 mL of ninhydrin TS to 5 mL of LMethionine solution (1 in 5000) and heat on a waterbath for 2 minutes: a blue-purple color is observed.
(3) Dissolve 0.3 g of L-Methionine in 10 mL of water and add 10 drops of dilute hydrochloric acid and 2
mL of sodium nitrate TS: a colorless gas is evolved
with effervescence.
perform the test (not more than 2 ppm)

(7) Related substancesDissolve 0.10 g of LMethionine in 10 mL of water and use this solution as
the test solution. Pipet 1.0 mL of the test solution and
add water to make exactly 50 mL. Pipet 5.0 mL of this
solution, add water to make exactly 20 mL and use this
of silica gel for thin-layer chromatography. After airdrying, develop the plate with a mixture of n-butanol,
water and glacial acetic acid (3 : 1 : 1) to a distance of
about 10 cm and air-dry the plate. Spray evenly a solution of ninhydrin in acetone (1 in 50) on the plate and
heat at 80 C for 5 minutes: the spots other than the
pH Dissolve 0.5 g of L-Methionine in 20 mL water:


hours).

D : Between +21.0
and +25.0 (0.5 g, after drying, 6 mol/L hydrochloric
acid TS, 25 mL, 100 mm).
Description L-Methionine is a white crystal or crystalline powder and has a characteristic odor.
L-Methionine is freely soluble in formic acid, soluble
in water, very slightly soluble in ethanol.
L-Methionine dissolves in dilute hydrochloric acid.

0.5 g of L-Methionine in 20 mL of water: the solution is
(2) ChlorideDissolve 0.5 g of in L-Methionine 20
mL of water and add 6 mL of dilute nitric acid and water to make 40 mL. Perform the test. Prepare the control
VS, 6 mL of dilute nitric acid and water to make 40 mL.
To the test solution and the control solution, add 10 mL
each of silver nitrate TS (not more than 0.021%).
(3) SulfatePerform the test with 0.5 g of LMethionine. Prepare the control solution with 0.35 mL
0.048%).
(4) AmmoniumPerform the test with 0.25 g of LMethionine. Prepare the control solution with 5.0 mL
of standard ammonium solution (not more than
0.028%).
(5) Heavy metalsDissolve 1.0 g of L-Methionine
in 40 mL of water and 2 mL of dilute acetic acid, dissolve by warming, cool and add water to make 50 mL.
Perform the test. Prepare the control solution as follows: to 2.0 mL of standard lead solution, add 2 mL of
than 20 ppm).
(6) ArsenicTransfer 1.0 g of L-Methionine to a
decomposition flask, add 5 mL of nitric acid and 2 mL
of sulfuric acid, put a small funnel on the mouth of the
flask and heat carefully until white fumes are evolved.
After cooling, add two 2 mL volumes of nitric acid,
heat, add 2 mL volumes of strong hydrogen peroxide
several times and heat again until white fumes are
evolved. After cooling, add water to make 5 mL and
Assay
Weigh accurately about 0.15 g of LMethionine, previously dried and dissolve in 3 mL of
formic acid, add 50 mL of glacial acetic acid and titrate
correction.
= 14.921 mg of C5H11NO2S
Methocarbamol
OH
OCH2CHCH2
OCH3
O
O
NH2
and enantiomer
C11H15NO5: 241.24
Methocarbamol contains not less than 98.5% and not

more than 101.5% of methocarbamol (C11H15NO5), calculated on the dried basis.
Description Methocarbamol is a white powder and is
odorless or has a characteristic odor.
Methocarbamol is soluble in ethanol, if heated, sparingly soluble in chloroform and practically insoluble in
benzene or in n-hexane.

of Methocarbamol and Methocarbamol RS in ethanol
solution (1 in 25000) as directed under the Ultravioletvisible Spectrophotometery: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Methocarbamol and Methocarbamol RS, previously dried, as directed in the potassium bromide disk method under the
Purity (1) Heavy metalsDissolve 1.0 g of Methocarbamol in 7 mL of methanol and 3 mL of 1 mol/L
acetic acid, add water to make 25 mL and perform the
test according to Method 1. Prepare the control solution
with 2.0 mL of standard lead solution (not more than 20
ppm).
(2) Related substancesDissolve 0.1 g of Methocarbamol in 13 mL of methanol, add pH 4.5 buffer solution to make 50 mL and use this solution as the test
solution. Use this solution within 24 hours. Dissolve
20.0 mg of Guanefesin RS in methanol to make exactly
50 mL. Separately, weigh 20 mg of Methocarbamol RS
in 1.0 mL of this solution and 2.0 mL of methanol and
add pH 4.5 buffer solution to make exactly 10 mL. Use
this solution as the standard solution. Use this solution
within 24 hour after preparation. Perform the test with
20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions. Measure
the peak area of Methocarbamol and the peak areas of
all peaks of which relative retention times to Methocarbamol are greater 0.5 (not more than 2.0%).
Amount (%) of related substances = 100
2.4 PE
G PT
G: Peak area of Guanefesin in the standard solution

(%),
PE : Peak areas of all impurities in the test solution.
PT : Peak areas of all impurities and Methocarbamol in the test solution.
Mobile phase: A mixture of pH 4.5 buffer solution
and methanol (75 : 25).
System suitability
operating conditions, the percentage of the peak area of
Guanefesin is 2.4 1.0% and Guanefesin and Metho-
carbamol are eluted in this order with the resolution between their peaks being not less than 2.0.
operating conditions, the relative standard deviation of
the peak area is not more than 4.0%.
pH 4.5 buffer solutionDissolve 6.8 g of monobasic potassium phosphate to 1000 mL of water and titrate
with 6 mol/L of phosphoric acid or 10 mol/L of potassium hydroxide to the pH of 4.5 0.05.
hours).
Loss on Ignition Not more than 0.1% (1 g).
Assay Weigh accurately about 0.1 g of Methocarbamol, transfer to a volumetric flask and add methanol to
make 100 mL. Pipet 4.0 mL of this solution, transfer to
a volumetric flask, add methanol to make 100 mL and
accurately about 0.1 g of Methocarbamol RS, dissolve
in methanol, proceed as directed with the test solution
and use this solution as the standard solution. Determine the absorbances, AT and AS as directed under
the Ultraviolet-visible spectrophotometry at the wavelength close to 274 nm of maximum absorption for the
Amount (mg) of methocarbamol (C11H15NO5)
A
= amount (mg) of Methocarbamol RS T
AS
Methocarbamol Injection
Methocarbamol Injection is an aqueous solution for injection. Methocarbamol Injection contains not less than
of methocarbamol (C11H15NO5: 241.24).
Method of Preparation Prepare as directed under Injections, with Methocarbamol.
Description Methocarbamol Injection is a clear, colorless liquid.
Identification Mix a volume of Methocarbamol Injection, equivalent to about 500 mg of Methocarbamol,
with 40 mL of water in a small separator. Extract with
10 mL of ethyl acetate and dry the ethyl acetate layer
over sodium sulfate anhydrous. Evaporate the ethyl
acetate in a 40 C water-bath with nitrogen gas and the
Methocarbamol so obtained responds to Identification
(1) under Methocarbamol.
KP 9 635
Purity AldehydesTransfer an accurately measured
volume of Methocarbamol Injection to a volumetric
flask, equivalent to 400 mg of Methocarbamol, add 2.0
mL of filtered solution of phenylhydrazine hydrochloride (1 in 100) in diluted ethanol (1 in 5) and allow to
stand for 10 minutes. Add 1 mL of potassium ferricyanide solution (1 in 100) and allow to stand for 5 minutes. Add 4 mL of hydrochloric acid, dilute with alcohol to make exactly 25 mL and use this solution as the
test solution. Separately pipet 4.0 mL of formaldehyde
solution (1 in 100000) and prepare under the same conditions as the test solution and use this solution as the
standard solution. Determine the absorption spectra of
under the Ultraviolet-visible spectrophotometry: the
absorbance of the test solution exhibit not more than
0.01% of the absorbance of the standard solution at the
wavelength of maximum absorption around 515 nm.
Bacterial Endotoxins Methocarbamol Injection contains less than 0.2 EU per mg of Methocarbamol.
Assay Accurately transfer a volume of Methocarbamol Injection, equivalent to 0.1 g of Methocarbamol, to
a flask. Add mobile phase to make exactly 100 mL and
use this solution as the test solution. Separately weigh
accurately about 0.1 g of Methocarbamol RS to a flask,
dissolve it in the mobile phase to make exactly 100 mL
standard solution as directed under the Liquid Chromatography. Measure the peak areas, AT and AS , for
the test solution and standard solution, respectively.
A
AS
about 30 C.
System suitability
the peak area of Methocarbamol is not more than 2.0%.
pH 4.5 buffer solutionDissolve 6.8 g of monobasic potassium phosphate in 1000 mL of water and adjust
the pH to 4.5 0.05 with 6 mol/L phosphoric acid TS
or 10 mol/L potassium hydroxide TS.
tainers.
Methocarbamol Tablets
Methocarbamol Tablets contain not less than 95.0%
methocarbamol (C11H15NO5: 241.24).
Tablets, with Methocarbamol.
Identification Mix a volume of finely powdered Tablet, equivalent to 1 g of Methocarbamol, with 25 mL of
water in a separatory funnel and extract with 25 mL of
chloroform. Filter the extract and evaporate to dryness:
the residue so obtained responds to Identification (1)
under Methocarbamol.
Dissolution Test Perform the test with 1 tablet of Methocarbamol Tablets at 50 revolutions per minute according to the Method 2 under the Dissolution Test, using 900 mL of the water as the dissolution solution. After 45 minutes from the start of the test, proceed with
the dissolved solution as directed in the Assay.
The dissolution rate of Methocarbamol Tablets in 45
ment.

Methocarbamol Tablets. Transfer an accurately
weighed portion of the powder, equivalent to about 100
mg of methocarbamol (C11H15NO5) to a flask. Add
about 50 mL of pH 4.5 buffer solution, 25 mL of methanol and 5.0 mL of the internal standard solution.
Shake vigorously for 10 minutes, dilute with pH 4.5
buffer solution to make exactly 100 mL and proceed as
directed in the Assay under Methocarbamol Injection.

A
AS
Amount (mg) of methotrexate (C20H22N8O5)

= amount (mg) of Methotrexate RS,
A
calculated on the anhydrous basis T
AS
Methotrexate
NH2
N
CH2
CH3
H
NH
CH2CH2CO2H
N
CO2H
H2N

Chromatography according the following operating
conditions and measure the peak areas, AT and AS ,
of Methotrexate for the test solution and the standard
solution, respectively.
C20H22N8O5: 454.44
Methotrexate is a mixture of 4-amino-10-methylfolic
acid and closely related compounds. Methotrexate contains not less than 94.0% and not more than 102.0% of
methotrexate (C20H22N8O5), calculated on the anhydrous basis.
Description Methotrexate is a yellow-brown, crystalline powder.
Methotrexate is slightly soluble in pyridine and practically insoluble in water, in acetonitrile, in ethanol or in
ether.
Methotrexate dissolves in dilute sodium hydroxide TS
or in dilute sodium carbonate TS.
Methotrexate is gradually colored by light.
of the solutions of 1 mg each of Methotrexate and Methotrexate RS in 100 mL of 0.1 mol/L hydrochloric acid
TS as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of
(2) Determine the infrared spectra of Methotrexate
and Methotrexate RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Water Take 5 mL of pyridine for water determination
and 20 mL of methanol for water determination in a
dried titration flask and titrate with Karl Fischer TS until the end point is achieved. Weigh accurately about
0.2 g of Methotrexate, immediately place in the titration flask and add a known excess volume of Karl
Fischer TS. Mix well for 30 minutes and perform the
test: the water content is not more than 12.0%.
Mobile phase: A mixture of 890 mL of dibasic sodium phosphate-citric acid buffer solution, pH 6.0 and
110 mL of acetonitrile.
time of Methotrexate is about 8 minutes.
System suitability
Methotrexate and folic acid in 100 mL of the mobile
phase. When the procedure is run with 10 L of this solution under the above operating conditions, folic acid
and Methotrexate are eluted in this order with the resolution between their peaks being not less than 8.0.
above operating conditions, the relative standard deviation of the peak areas of Methotrexate is not more than
2.5%.
tight containers.
Methoxsalen
OCH 3
O
C12H8O4: 216.19
Methoxsalen contains not less than 98.0% and not more

than 102.0% of methoxsalen (C12H8O4), calculated on
Assay Weigh accurately about 25 mg each of Methotrexate and Methotrexate RS, dissolve each in the mobile phase to make exactly 250 mL and use these as the
Description Methoxsalen is a white to pale yellow

crystal or crystalline powder, is odorless and tasteless.
Methoxsalen is freely soluble in chloroform, slightly
soluble in methanol, in ethanol or in ether and practi-
KP 9 637
cally insoluble in water.
Identification (1) Take 10 mg of Methoxsalen, add 5
mL of dilute nitric acid and heat: a yellow color is observed. Make this solution alkaline with a solution of
sodium hydroxide (2 in 5): the color changes to redbrown.
(2) Take 10 mg of Methoxsalen, add 5 mL of sulfuric acid and shake: a yellow color is observed.
(3) Determine the absorption spectra of the solutions of Methoxsalen and Methoxsalan RS in ethanol (1
= amount (mg) of Methoxsalen RS,

A
AS
Methyl Salicylate
O
C
OCH3
OH

Purity (1) Heavy metalsProceed with 1.0 g of Methoxsalen according to Method 4 and perform the test.
Methoxsalen according to Method 3 and perform the
(3) Related substancesDissolve 50 mg of Methoxsalen in 10 mL of chloroform and use this solution
as the test solution. Pipet 2.0 mL of the test solution
and add chloroform to make exactly 50 mL. Pipet 1.0
mL of this solution, add chloroform to make exactly 10
mL and use this solution as the standard solution. Perform the test with the test solution and the standard solution as directed under the Thin-layer Chromatography.
Spot 5 mL each of the test solution and the standard solution on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop the plate
with a mixture of chloroform, hexane and ethyl acetate
plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot
from the test solution are not more intense than spot
direct titration).
Assay Weigh accurately about 50 mg each of Methoxsalen and Methoxsalen RS and dissolve each in
ethanol to make exactly 100 mL. Pipet 2.0 mL each of
these solutions and dilute each with ethanol to make
exactly 25 mL. Pipet 10.0 mL each of these solutions
and dilute each again with ethanol to make exactly 50
mL and use these solutions as the test solution and the
standard solution, respectively. Determine the absorbances, AT and AS , of the test solution and the standard solution at 300 nm as directed under the Ultraviolet-visible Spectrophotometry, respectively.
Amount (mg) of methoxsalen (C12H8O4)
C8H8O3: 152.15
Methyl Salicylate contains not less than 98.0% and not
more than 101.0% of methyl salicylate (C8H8O3).
Description Methyl Salicylate is a colorless to pale
yellow liquid and has a strong and characteristic odor.
Methyl Salicylate is very slightly soluble in water.
Methyl Salicylate is miscible with ethanol or ether.
20
Specific gravity d 20
: Between 1.182 and 1.192.
Boiling pointBetween 219 C and 224 C.
Identification Shake 1 drop of Methyl Salicylate thoroughly with 5 mL of water for 1 minute and add 1
drop of ferric chloride TS: a purple color develops.
Purity (1) AcidShake 5.0 mL of Methyl Salicylate
thoroughly with 25 mL of freshly boiled and cooled
water and 1.0 mL of 0.1 mol/L sodium hydroxide VS
for 1 minute, add 2 drops of phenol red TS and titrate
with 0.1 mol/L hydrochloric acid VS until the red color
disappears: not more than 0.45 mL of 0.1 mol/L sodium
hydroxide VS is consumed.
(2) Heavy metalsShake 10.0 mL of Methyl Salicylate thoroughly with 10 mL of water, add 1 drop of
hydrochloric acid and saturate with hydrogen sulfide by
passing through the mixture: neither the oily layer nor
the aqueous layer shows a dark color.
Assay Weigh accurately about 2.0 g of Methyl Salicylate, add an exactly measured 50 mL of 0.5 mol/L
potassium hydroxide-ethanol VS and heat in a waterbath for 2 hours under a reflux condenser. Cool and titrate the excess potassium hydroxide with 0.5 mol/L
hydrochloric acid VS (indicator: 3 drops of phenolphthalein TS). Perform a blank determination and make
Each mL of 0.5 mol/L potassium hydroxide-ethanol VS
= 76.07 mg of C8H8O3

Methylbenactyzium Bromide

hours).
CH2CH3
O
HO
OCH2CH2
CH3
Br
CH2CH3
C21H28BrNO3: 422.36
Methylbenactyzium Bromide, when dried, contains not
less than 99.0% and not more than 101.0% of methylbenactyzium bromide (C21H28BrNO3).
Description Methylbenactyzium Bromide is a white
crystal or crystalline powder, is odorless and has an extremely bitter taste.
Methylbaenactyzium Bromide is freely soluble in water
or in glacial acetic acid, soluble in ethanol, slightly soluble in acetic anhydride and practically insoluble in
ether.
pHpH of a solution of Methylbenactyzium Bromide (1 in 50) is between 5.0 and 6.0.
Identification (1) Shake 0.5 mL of a solution of Methylbenactyzium Bromide (1 in 100) with 5 mL of
phosphate buffer solution, pH 7.0, 2 to 3 drops of bromothymol blue TS and 5 mL of chloroform: a yellow
color develops in the chloroform layer.
(2) Take about 1 g of Methylbenactyziurn Bromide,
add 5 mL of water and 10 mL of sodium hydroxide TS,
allow to stand for 5 minutes, add 5 mL of dilute hydrochloric acid, collect the precipitate, wash well with
water, recrystallize from a mixture of water and ethanol
(10 : 3) and dry at 105 C for 1 hour: the crystals melt
between 145 C and 150 C. Continue the heating up to
about 200 C: a red color develops.
(3) Add 2 mL of dilute nitric acid to 5 mL of a solution of Methylbenactyzium Bromide (1 in 10): the solution responds to the Qualitative Tests (1) for bromide.
1.0 g of Methylbenactyzium Bromide in 10 mL of water: the solution is clear and colorless.
(2) SulfatePerform the test with 0.5 g of Methylbenactyzium Bromide. Prepare the control solution
more than 0.038%).
(3) Heavy metalsProceed with 2.0 g of Methylbenactyzium Bromide according to Method 2 and perform the test. Prepare the control solution with 2.0 mL
Assay Weigh accurately about 0.5 g of Methylbenactyzium Bromide, previously dried and dissolve in 80
mL of a mixture of acetic anhydride and glacial acetic
acid (4 : 1). Titrate with 0.1 mol/L perchloric acid VS
(potentiometric titration, Endpoint Detection Method in
Titrimetry). Perform a blank determination and make
Each mL of 0.1 mol/ L perchloric acid VS
Methyldopa Hydrate
CH3
HO
CH2
CO2H
1 1/2 H2O
NH2
HO
Methyldopa
C10H13NO411/2H2O: 238.24
Methyldopa Hydrate contains not less than 98.0% and

not more than 101.0% of methyldopa (C10H13NO4:
211.22), calculated on the anhydrous basis.
Description Methyldopa Hydrate is a white to pale
grayish white, crystalline powder.
Methyldopa Hydrate is slightly soluble in water, in methanol or in glacial acetic acid, very slightly soluble in
Methyldopa Hydrate dissolves in dilute hydrochloric
acid.
Identification (1) Take 10 mg of Methyldopa Hydrate, add 3 drops of ninhydrin TS and heat on a waterbath for 3 minutes: A purple color is observed.
Methyldopa Hydrate and Methyldopa Hydrate RS in
0.1 mol/L hydrochloric acid TS (1 in 25000) as directed
same wavelengths.
(3) Determine the infrared spectra of Methyldopa
Hydrate and Methyldopa Hydrate RS as directed in the
D : Between -25 and 28 (1 g, calculated on the anhydrous basis, aluminum
chloride TS, 20 mL, 100 mm).
KP 9 639
Purity (1) AcidShake 1.0 g of Methyldopa Hydrate

with 100 mL of freshly boiled and cooled water and
add 0.20 mL of 0.1 mol/L sodium hydroxide VS and 2
drops of methyl red TS: a yellow color is observed.
(2) ChloridePerform the test with 0.5 g of Methyldopa Hydrate. Prepare the control solution with
0.40 mL of 0.01 mol/L hydrochloric acid VS (not more
than 0.028%).
(3) Heavy metalsProceed with 2.0 g of Methyldopa Hydrate according to Method 2 and perform the
Methyldopa Hydrate in 5 mL of dilute hydrochloric acid and perform the test (not more than 2 ppm).
(5) 3-O-MethylmethyldopaDissolve 0.10 g of
Methyldopa Hydrate in methanol to make exactly 10
dissolve 5 mg of 3-O-methylmethyldopa RS in methanol to make exactly 100 mL and use this solution as the
and the standard solution as directed under the Thinlayer Chromatography. Spot 20 L each of the test solution and the standard solution on a plate of cellulose
mixture of n-butanol, water and glacial acetic acid (13 :
5 : 3) to a distance of about 10 cm and air-dry the plate.
Spray evenly p-nitroaniline-sodium nitrite TS on the
plate and air-dry the plate. Then spray evenly a solution
of sodium carbonate (1 in 4) on the plate: the spot from
the test solution corresponding to that from the standard
solution is not more intense than the spot from the
standard solution.
Assay Weigh accurately about 0.3 g of Methyldopa
Hydrate, dissolve in 80 mL of glacial acetic acid and titrate with 0.1 mol/L perchloric acid VS until the color
of the solution changes from purple through blue to
blue-green (indicator: 2 to 3 drops of methylrosaniline
chloride TS). Perform a blank determination and make
= 21.121 mg of C10H13NO4
Methyldopa Tablets
Methyldopa Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of methyldopa (C10H13NO4: 211.21).
Tablets, with Methyldopa Hydrate.
Identification (1) Take a portion of powdered Methyldopa Tablets, equivalent to 0.1 g of Methyldopa according to the labeled amount, add 10 mL of water and
heat on a water-bath for 5 minutes with occasional
shaking. After cooling, centrifuge for 5 minutes at 2000
rotations per minute, apply 1 drop of the supernatant
solution to a filter paper and dry with warm air. Place 1
drop of ninhydrin TS over the spot and heat for 5 minutes at 100 o C : a purple color is observed.
(2) Take 0.5 mL of the supernatant liquid obtained
in the Identification (1), add 2 mL of 0.05 mol/L sulfuric acid TS, 2 mL of ferrous tartrate TS and 4 drops of
ammonia TS and shake well: a deep purple color is observed.
(3) Take 0.7 mL of the supernatant liquid obtained
in the Identification (1) and add 0.1 mol/L hydrochloric
acid TS to make 20 mL. To 10 mL of this solution, add
0.1 mol/L hydrochloric acid TS to make 100 mL and
determine the absorption spectrum of the solution as directed under the Ultraviolet-visible Spectrophotometry:
it exhibits a maximum between 277 nm and 283 nm.
Methyldopa Tablets at 50 revolutions per minute according to Method 2 under the Dissolution Test, using
900 mL of water as the dissolution solution. Take 30
mL or more of the dissolved solution after 60 minutes
from the start of the test and filter through a membrane
filter with pore size of not more than 0.8 m. Discard
the first 10 mL of the filtrate, pipet the subsequent V
mL, add water to make exactly V mL so that each mL
contains about 25 g of methyldopa (C10H13NO4:
211.22) according to the labeled amount and use this
solution as the test solution. Separately, weigh accurately about 56 mg of Methyldopa RS (separately determine its loss on drying at 125 o C for 2 hours) and
dissolve in water to make exactly 200 mL. Pipet 10.0
mL of this solution, add water to make exactly 100 mL
and use this solution as the standard solution. Determine the absorbances, AT and AS , of the test solution and the standard solution at 280 nm as directed under the Ultraviolet-visible Spectrophotometry, respectively.
The dissolution rate of Methyldopa Tablets in 60 minutes should be not less than 75%.
Dissolution rate (%) to labeled amount of
A
V' 1
methyldopa (C10H13NO4) = W S T 45
AS V C
W S : Amount (mg) of Methyldopa RS, calculated

on the dried basis
C: Labeled amount (mg) of methyldopa
(C10H13NO4: 211.22) in 1 tablet.

ment.

Methyldopa Tablets. Weigh accurately a portion of the
powder, equivalent to about 0.1 g of methyldopa
(C10H13NO4), add 50 mL of 0.05 mol/L sulfuric acid TS,
shake thoroughly for 15 minutes, add 0.05 mol/L sulfuric acid TS to make exactly 100 mL and filter through
a dry filter paper. Discard the first 20 mL of the filtrate
and use the subsequent filtrate as the test solution. Separately, weigh accurately about 0.11 g of Methyldopa
RS (separately determine its loss on drying at 125 C
for 2 hours), dissolve in 0.05 mol/L sulfuric acid TS to
make exactly 100 mL and use this solution as the standard solution. Pipet 5.0 mL each of the test solution and
the standard solution, add exactly 5 mL of ferrous tartrate TS and add ammonia-ammonium acetate buffer
solution, pH 8.5, to make exactly 100 mL. Perform the
test with the test solution and the standard solution as
directed under the Ultraviolet-visible Spectrophotometry, using a solution prepared with 5 mL of 0.05 mol/L
sulfuric acid TS in the same manner, as the blank. Determine the absorbances, AT and AS , of the subsequent solutions of the test solution and the standard solution at 520 nm, respectively.
Amount (mg) of methyldopa (C10H13NO4: 211.22)
= amount (mg) of Methyldopa RS,
A
calculated on the dried basis T
AS
dl-Methylephedrine
Hydrochloride
H
N(CH 3)2
OH
CH3
HCl
and enantiomer
C11H17NOHCl: 215.72
dl-Methylephedrine Hydrochloride, when dried, contains not less than 99.0% and not more than 101.0% of
dl-methylephedrine hydrochloride (C11H17NOHCl).
Description dl-Methylephedrine Hydrochloride is a
colorless crystal or a white, crystalline powder, is odor-
less and has a bitter taste.

dl-Methylephedrine Hydrochloride is freely soluble in
water, soluble in ethanol, slightly soluble in glacial
acetic acid and practically insoluble in acetic anhydride
or in ether.
A solution of dl-Methylephedrine Hydrochloride (1 in
of solutions of dl-Methylephedrine Hydrochloride and
dl-Methylephedrine Hydrochloride RS (1 in 2000) as
(2) Determine the infrared spectra of dlMethylephedrine
Hydrochloride
and
dlMethylephedrine Hydrochloride RS, previously dried,
as directed in the potassium chloride disk method under
(3) A solution of dl-Methylephedrine Hydrochloride
1.0 g of dl-Methylephedrine Hydrochloride in 10 mL of
water: the solution is clear and colorless.
(2) Heavy metalsProceed with 1.0 g of dlMethylephedrine Hydrochloride according to Method 4,
1.0 mL of Standard Lead Solution (not more than 10
ppm).
(3) Related substancesDissolve 50 mg of dlMethylephedrine Hydrochloride in 20 mL of water, and
use this solution as the test solution. Pipet 1 mL of the
test solution, add water to make exactly 100 mL, and
test with exactly 20 L each of the test solution and the
standard solution as directed under the Liquid Chromatography according to the following method, and determine each peak area by the automatic integration
method: the total area of the peaks other than the peak
of methylephedrine is not more than the peak area of
methylephedrine from the standard solution.
Column: A stainless steel column, 4.6 mm in inside
particle diameter).
about 40 C.
Mobile phase: Dissolve 13.6 g of potassium dihydrogen phosphate and 3 g of sodium 1-heptane sulfonate in 1000 mL of water, and adjust the pH to 2.5 with
KP 9 641
phosphoric acid. To 900 mL of this solution, add 200
mL of acetonitrile.
time of methylephedrine is about 10 minutes.
System suitability
of the standard solution, add water to make exactly 20
mL. Confirm that the peak area of methylephedrine obtained from 20 L of this solution is equivalent to 7 to
13% of that of methylephedrine obtained from 20 L of
System performance: Dissolve 50 mg of dlMethylephedrine Hydrochloride and 0.4 mg of methyl
parahydroxybenzoate in 50 mL of water. When the procedure is run with 20 L of this solution under the
above operating conditions, methylephedrine and methyl parahydroxybenzoate are eluted in this order with
the resolution between these peaks being not less than 3.
above operating conditions, the relative standard deviation of the peak area of methylephedrine is not more
than 2.0%.
as the retention time of methylephedrine beginning after the solvent peak.
hours).
Assay
Weigh accurately about 0.4 g of dlMethylephedrine Hydrochloride, previously dried, dissolve in 80 mL of a mixture of acetic anhydride and
glacial acetic acid (7 : 3) and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
10% dl-Methylephedrine Hydrochloride Powder

10% dl-Methylephedrine Hydrochloride Powder contains not less than 9.3% and not more than 10.7% of dlmethylephedrine
hydrochloride
(C11H17NOHCl:
215.72).
dl-Methylephedrine Hydrochloride
100 g
Starch, lactose or their mixture

To make 1000 g
Prepare as directed under Powders, with the above ingredients.
Identification Weigh accurately about 0.5 g of 10%
dl-Methylephedrine Hydrochloride Powder, add 100
mL of water, shake occasionally for 20 min, and, if necessary, filter. Determine the absorption spectrum of
this solution as directed under the Ultraviolet-visible
Spectrophotometry: it exhibits maxima between 250
nm and 253 nm, between 255 nm and 259 nm, and between 261 nm and 264 nm.
Particle Size Distribution Test It meets the requirement.
Uniformity of Dosage Units(divided) It meets the
requirement.
Assay Weigh accurately about 0.5 g of 10% dlMethylephedrine Hydrochloride Powder, add exactly 4
mL of the internal standard solution and 25 mL of water,
shake vigorously for 20 minutes to dissolve, add water
to make 50 mL, and filter through a membrane filter
with pore size of 0.45 m, if necessary. Discard the
first 10 mL of the filtrate, and use the subsequent filtrate as the test solution. Separately, weigh accurately
about 50 mg of 10% dl-Methylephedrine Hydrochloride RS, previously dried at 105 o C for 3 hours, add
exactly 4 mL of the internal standard solution and water
to make 50 mL, and use this solution as the standard
conditions, and determine the ratios of the peak area,
QT and QS , of methylephedrine to that of the internal
standard.
Amount (mg) of dl-methylephedrine
hydrochloride (C11H17NOHCl) = amount (mg)
Q
of dl-Methylephedrine Hydrochloride RS T
QS
Internal standardA solution of methyl parahydroxybenzoate in acetonitrile ( 1 in 10000)
particle diameter).
about 40 C.

Mobile phase: Dissolve 13.6 g of potassium dihydrogen phosphate and 3 g of sodium 1-heptane sulfonate in 1000 mL of water, and adjust the pH to 2.5 with
phosphoric acid. To 900 mL of this solution, add 200
mL of acetonitrile.
time of methylephedrine is about 10 minutes.
System suitability
operating conditions, methylephedrine and the internal
standard are eluted in this order with the resolution between these peaks being not less than 3.
above operating conditions, the relative standard deviation of the ratio of the peak area of methylephedrine to
Time span of measurement: About 2 times as
long as the retention time of methylephedrine beginning after the solvent peak.

Methylergometrine Maleate
O
H
H
CH2OH
C
N
H
CH2CH3
H
N
H
CO2H
C
CH3
C
H
spectrum with a solution of Methylergometrine Maleate

RS prepared in the same manner as the test solution:
(3) Take 5 mL of a solution of Methylergometrine
Maleate (1 in 500) and add 1 drop of potassium permanganate TS: the red color of the solution fades immediately.
D : Between +44 and
+50 (0.1 g, after drying, water, 20 mL, 100 mm).
Purity Related substancesPerform the test without
exposure to daylight, using light-resistant vessels.
Dissolve 8 mg of Methylergometrine Maleate in 2 mL
of a mixture of ethanol and strong ammonia water (9 :
1) and use this solution as the test solution. Pipet 1.0
mL of the test solution, add a mixture of ethanol and
strong ammonia water (9 : 1) to make exactly 100 mL
for thin-layer chromatography and immediately develop the plate with a mixture of chloroform, methanol
and water (75 : 25 : 3) to a distance of about 10 cm and
air-dry the plate. Examine under ultraviolet light (main
CO2H
HN
C20H25N3O2C4H4O4: 455.50
Methylergometrine Maleate, when dried, contains not
less than 95.0% and not more than 105.0% of methylergometrine maleate (C20H25N3O2-C4H4O4).
Description Methylergometrine Maleate is a white to
pale yellow, crystalline powder and is odorless.
Methylergometrine Maleate is slightly soluble in water,
in methanol or in ethanol and practically insoluble in
ether.
The color of Methylergometrine Maleate is gradually
changed to yellow by light.
Identification (1) A solution of Methylergometrine
Maleate (1 in 200) shows a blue fluorescence.
(2) The colored solution obtained in the Assay
shows a deep blue color. Determine the absorption
spectrum of the colored solution as directed under the
Ultraviolet-visible Spectrophotometry, and compare the
Assay Weigh accurately about 10 mg of Methylergometrine Maleate, previously dried, add water to
make exactly 250 mL and use this solution as the test
Methylergometrine Maleate RS, previously dried over
silica gel for 4 hours, add water to make exactly 250
mL and use this solution as the standard solution. Pipet
2.0 mL each of the test solution and the standard solution into brown glass-stoppered test tubes, add 4.0 mL
each of p-dimethylaminobenzaldehyde-ferric chloride
TS in ice-water and after heating for 10 minutes at
45 C, allow to stand for 20 minutes at room temperature. Perform the test with the test solution and the
standard solution as directed under the Ultravioletvisible Spectrophotometry, using a solution, prepared
with 2 mL of water in the same manner, as the blank.
Determine the absorbances, AT and AS , of the subsequent solutions of the test solution and the standard
solution at 545 nm, respectively.
Amount (mg) of methylergometrine maleate
(C20H25N3O2C4H4O4)
= amount (mg)
KP 9 643
of Methylergometrine Maleate RS
tight containers.
AT
AS
Methylergometrine Maleate
Tablets
Methylergometrine Maleate Tablets contain not less
amount of methylergometrine maleate (C20H25N3O2
C4H4O4: 455.50).
Tablets, with Methylergometrine Maleate.
Identification (1) The test solution obtained in the
Assay shows a blue fluorescence.
(2) The colored solution obtained in the Assay
shows a deep blue color. Determine the absorption
spectrum of the colored solution as directed under the
Ultraviolet-visible Spectrophotometry: it exhibits maxima between 543 nm and 547 nm and between 620 nm
and 630 nm.
Methylergometrine Maleate Tablets at 100 revolutions
per minute according to Method 2 under the Dissolution Test, using 900 mL of water. Take 20 mL or more
of the dissolved solution 30 minutes after starting the
test and filter by membrane filter with less than 0.8 m
diameter. Discard the first 10 mL of the filtrate and use
the subsequent solution as the test solution, or pipet V
mL of this filtrate, add water to make exactly V mL so
that each mL contains about 0.13 g of methylergometrine maleate (C20H25N3O2C4H4O4) according to the
labeled amount and use this solution as the test solution.
Separately, weigh accurately about 25 mg of Methylergometrine Maleate RS, previously dried in a desiccator
for 4 hours (in vacuum, P2O5) and dissolve in water to
add water to make exactly 100 mL, then pipet 1.0 mL
of this solution, add water to make exactly 100 mL and
use this solution as the standard solution. Determine the
fluorescence intensities, FT and FS, of the test solution
and the standard solution, respectively, at 338 nm as the
excitation wavelength and at 427 nm as the fluorescence wavelength as directed under the Fluorometry.
The dissolution rate of Methylergometrine Maleate
Tablets in 30 minutes is not less than 70%.
Dissolution rate (%) with respect to the labeled
amount of methylergometrine maleate
F
V' 1
(C20H25N3O2C4H4O4) = W S T 0.45
FS V C
WS : Amount (mg) of Methylergometrine Maleate
RS,
C: Labeled amount (mg) of methylergometrine maleate (C20H25N3O2C4H4O4) in 1 tablet.
Transfer 1 tablet of Methylergometrine Maleate
Tablets to a brown glass-stoppered centrifuge tube, add
10 mL of water, shake for 10 minutes vigorously and
disintegrate the tablet. Add 3 g of sodium chloride and
2 mL of strong ammonia water, add exactly 25 mL of
chloroform and after vigorous shaking for 10 minutes,
centrifuge for 5 minutes. Discard the water layer, take
the chloroform extracts, add chloroform to make exactly V mL of a solution containing about 5 g of methylergometrine maleate (C20H25N3O2C4H4O4) per mL and
accurately about 1.3 mg of Methylergometrine Maleate
RS, previously dried in a desiccator (silica gel) for 4
hours, dissolve in water and add water to make exactly
100 mL. Pipet 10.0 mL of this solution into a brown
glass-stoppered centrifuge tube and add 3 g of sodium
chloride and 2 mL of strong ammonia water. Add exactly 25 mL of chloroform and after vigorous shaking
for 10 minutes, centrifuge for 5 minutes. Discard the
water layer, take the chloroform extract and use this solution as the standard solution. Pipet 20.0 mL each of
the test solution and the standard solution into brown
glass-stoppered centrifuge tubes, add immediately exactly 10 mL of dilute p-dimethylaminobenzaldehydeferric chloride TS, respectively and shake for 5 minutes
vigorously. Centrifuge the test solution and the standard
solution for 5 minutes, take the water layers and allow
to stand for 1 hour. Perform the test with the test solution and the standard solution as directed under the Ultraviolet-visible Spectrophotometry, using dilute pdimethylaminobenzaldehyde-ferric chloride TS as the
blank. Determine the absorbances, AT and AS , of
the subsequent solutions of the test solution and the
standard solution at 545 nm, respectively.
(C20H25N3O2C4H4O4) = amount (mg) of
A
V
Methylergometrine Maleate RS T
AS 250
Methylergometrine Maleate Tablets. Weigh accurately
a portion of the powder, equivalent to about 0.3 mg of
methylergometrine maleate (C20H25N3O2C4H4O4),
transfer to a brown separatory funnel, add 15 mL of sodium bicarbonate solution (1 in 20) and extract with
four 20 mL volumes of chloroform. Filter each volume
of the chloroform extracts through a pledget of absorbent cotton, previously moistened with chloroform into
another dried, brown separatory funnel, combine all the

extracts and use this extract as the test solution. Separately, weigh accurately about 10 mg of Methylergometrine Maleate RS, previously dried in a desiccator (silica gel) for 4 hours, dissolve in water and add water to
make exactly 100 mL. Pipet 3.0 mL of this solution and
transfer to a brown separator, proceed in the same
manner as the preparation of the test solution and use
this extract as the standard solution. To each total volume of the test solution and the standard solution, add
25.0 mL each of dilute p-dimethylaminobenzaldehydeferric chloride TS and after vigorous shaking for 5 minutes allow to stand for 30 minutes. Draw off the water
layer, centrifuge and allow to stand for 1 hour. Perform
as directed under the Ultraviolet-visible Spectrophotometry, using dilute p-dimethylaminobenzaldehydeferric chloride TS as the blank. Determine the absorbances, AT and AS , of the subsequent solutions of
the test solution and the standard solution at 545 nm,
respectively.
(C20H25N3O2C4H4O4) = amount (mg) of
A
3
Methylergometrine Maleate RS T
A S 100
O
H
OCH3
H
N
HCl
C14H19NO2HCl: 269.77
Methylphenidate Hydrochloride, when dried, contains
not less than 98.0% and not more than 100.5% of methylphenidate hydrochloride (C14H19NO2 HCl).
Description Methylphenidate Hydrochloride is a
white fine crystal and is odorless.
Methylphenidate Hydrochloride is freely soluble in water or in methanol, soluble in ethanol and practically insoluble in chloroform or in acetone.
A solution of Methylphenidate Hydrochloride changes
the color of litmus paper to red.
Methylphenidate Hydrochloride and Methylphenidate
Hydrochloride RS, previously dried at 60 C for 4
hours in vacuum as directed in the paste method under
similar intensities of absorption at the same wave-
numbers.
(2) A solution of Methylphenidate Hydrochloride
responds to the Qualitative Tests for chloride.
Purity (1) Erythro[(R*,S*)] isomerDissolve Methylphenidate Hydrochloride and Methylphenidate Hydrochloride erythro isomer RS in methanol to contain
50 mg per mL and 0.5 mg per mL and use these solutions as the test solution and the standard solution, respectively. Perform the test with the test solution and
the standard solution as directed under the Thin-layer
mixture of chloroform, methanol and strong ammonia
water (190 : 10 : 1) to a distance of about 15 cm and
air-dry the plate. Spray evenly the plate with the developing agent and then with 0.5 mol/L of sulfuric acid:
the spot of the erythro isomer from the test solution is
same in Rf and is not larger and not more intense than
that from the standard solution (not more than 1.0%).
Developing agentDissolve 0.7 g of bismuth subnitrate in 40 mL of a mixture of glacial acetic acid and
water (1 : 4). Add 40 mL of potassium iodide solution
(2 in 5) and then add 120 mL of glacial acetic acid and
250 mL of water.
(2) -Phenyl-2-piperidineacetic acid hydrochlorideDissolve 0.4 g of Methylphenidate Hydrochloride, accurately weighed, in a solution of sodium hydroxide in methanol (1 in 2500) to make 10.0 mL and
use this solution as the test solution (use immediately
after preparation). Separately, dissolve a portion of phenyl-2-piperidineacetic acid hydrochloride RS in the
solution of sodium hydroxide in methanol (1 in 2500)
to obtain a solution having a known concentration of
about 240 g per mL and use this solution as a standard
mixture of chloroform, methanol and acetic acid (65 :
plate. Spray evenly the developing agent and then hydrogen peroxide solution: any spot from the test solution having the same Rf value as the principal spot from
the standard solution is not larger and is not more intense than that from the standard solution (not more
than 0.6%).
Developing agent Dissolve 0.85 g of bismuth
subnitrate in 40 mL of a mixture of glacial acetic acid
and water (1 : 4) (solution A). Dissolve 8.0 g of potassium iodide in 20 mL of water (solution B). Add 20 mL
of glacial acetic acid to 10 mL of the mixture of solution A and B and water to make 100 mL.
(3) Heavy metalsProceed with 1.0 g of Methyl-
KP 9 645
phenidate Hydrochloride according to Method 2 and
test solution and proceed as directed under the Assay.

The dissolution rate of Methylphenidate Hydrochloride
Tablets in 45 minutes is not less than 75%.

60 C, 4 hours).

ment.

Methylphenidate Hydrochloride Tablets. Weigh accurately a portion of the powder, equivalent to about 20
mg of Methylphenidate Hydrochloride, add about 70
mL of the mobile phase and shake by mechanical
means for 15 minutes. Cool to room temperature and
add the mobile phase to make exactly 100 mL. Filter
this solution and discard the first 10 mL of the filtrate.
Combine the subsequent 10.0 mL of the filtrate with
5.0 mL of the internal standard solution and use this solution as the test solution after shaking. Separately,
weigh accurately about 20 mg of Methylphenidate Hydrochloride RS and dissolve in the mobile phase to
make exactly 100 mL. To 5.0 mL of this solution, add
5.0 mL of the internal standard solution and use this solution as the standard solution. Perform the test with 50
directed under the Liquid Chromatography. Calculate
the ratios, QT and QS , of the peak areas of Methylphenidate Hydrochloride to that of the internal standard
Assay Weigh accurately about 0.225 g of Methylphenidate Hydrochloride and dissolve in 50 mL of glacial
acetic acid in an Erlenmeyer flask. Add 15 mL of mercuric acetate and 5 drops of -naphtholbenzeine and titrate with 0.1 mol/L perchloric acid VS to a green endpoint. Perform a blank determination and make any necessary correction.
Tablets
Methylphenidate Hydrochloride Tablets contain not
less than 93.0% and not more than 107.0% of the labeled amount of methylphenidate hydrochloride
(C14H19NO2HCl: 269.77).
Tablets, with Methylphenidate Hydrochloride.
Identification Place a portion of powdered Methylphenidate Hydrochloride Tablets, equivalent to about
50 mg of Methylphenidate Hydrochloride, in a 40-mL
centrifuge tube, add 10 mL of chloroform, shake and
centrifuge. Filter the clear extract through a mediumsized sintered-glass funnel into a beaker and repeat the
extraction with an additional 10 mL of chloroform.
Evaporate the combined chloroform extracts on a water-bath to dryness. Agitate the dried residue with 2 mL
of acetonitrile and filter the mixture through a small
sintered-glass funnel. Wash the crystal with an additional 2 mL of acetonitrile and dry with the aid of suction. Determine the infrared spectra of the residue and
Methylphenidate Hydrochloride RS as directed in the
paste method under the Infrared Spectrophometry: both
same wavenumbers.
Methylphenidate Hydrochloride Tablets at 100 resolutions per minute using 900 mL of water as the dissolution solution. Filter the dissolved solution after 45 minutes from the start of the test. Use the filtrate as the
Amount (mg) of methylphenidate hydrochloride

(C14H19NO2HCl) = amount (mg) of Methylphenidate
Q
Hydrochloride RS T
QS
Phenylephrine Hydrochloride and dissolve in mobile
phase to make 25 mL.
octadesylated silica gel for liquid chromatography (5
m to 10 m in particle diameter).
Mobile phase: Dissolve 1.64 g of anhydrous sodium acetate in 900 mL of water, adjust the pH with
acetic acid to 4.0 and add water to make 1000 mL. Add
300 mL of acetonitrile and 400 mL of methanol in 300
mL of this solution and mix.
System suitability
operating conditions, phenylephrine and methylphenidate are eluted in this order with the resolution between

above operating conditions, the relative standard deviation of the peak areas of methylphenidate is not more
than 2.0%.
Methylprednisolone
form the test with the test solution and the standard solution as directed under the Thin-layer Chromatography.
solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of dichloromethane, ether, methanol and water (385 : 75 : 40 : 6)
to a distance of about 12 cm and air-dry the plate. Then
heat at 105 C for 10 minutes, cool and spray evenly
alkaline blue tetrazolium TS on the plate: the spots other than the principal spot from the test solution are not
O
C
H3C
CH2OH
OH
HO
H
H3C
Not more than 0.20% (0.2 g).
Residue on Ignition
H
O
H

3 hours).
CH3
C22H30O5: 374.47
Methylprednisolone, when dried, contains not less than
96.0% and not more than 104.0% of methylprednisolone (C22H30O5).
Description Methylprednisolone is a white, crystalline powder and is odorless.
Methylprednisolone is sparingly soluble in methanol or
in dioxane, slightly soluble in ethanol or in chloroform
and practically insoluble in water or in ether.
decomposition).
Identification (1) Add 2 mL of sulfuric acid to 2 mg
of Methylprednisolone: a deep red color is observed
with no fluorescence. Then add 10 mL of water to this
solution: the color fades and a gray, flocculent precipitate is produced.
(2) Dissolve 10 mg of Methylprednisolone in 1 mL
of methanol, add 1 mL of Fehlings TS and heat: a red
(3) Determine the absorption spectra of the solutions of Methylprednisolone and Methylprednisolone
RS in methanol (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
D : Between +79 and
+86 (after drying, 0.1 g, dioxane, 10 mL, 100 mm).
Purity Related substancesDissolve 50 mg of Methylprednisolone in 5 mL of a mixture of chloroform
and methanol (9 : 1) and use this solution as the test solution. Pipet 1.0 mL of this solution, add a mixture of
chloroform and methanol (9 : 1) to make exactly 200
mL and use this solution as the standard solution. Per-
Assay Weigh accurately about 10 mg of Methylprednisolone, previously dried and dissolve in methanol to
methanol to make exactly 50 mL and determine the absorbance, A at the wavelength of maximum absorption
at about 243 nm, as directed under the Ultravioletvisible Spectrophotometry.
Amount (mg) of methylprednisolone (C22H30O5)
A
= 400 10000
Methylprednisolone Sodium
Succinate
O
ONa
O
CH3
HO
O
OH
CH3
CH3
C26H33NaO8 : 496.53
Methylprednisolone Sodium Succinate contains not
less than 97.0% and not more than 103.0% of methylprednisolone sodium succinate (C26H33NaO8), calculated on the dried basis.
Description Methylprednisolone Sodium Succinate
is a white, amorphous powder.
Methylprednisolone Sodium Succinate is very soluble
in water or in ethanol, very slightly soluble in acetone,
and practically insoluble in chloroform.
KP 9 647
Identification (1) Dissolve Methylprednisolone Sodium Succinate, previously dried, in methanol to make
a concentration of 20 g/mL. Perform the same procedure with Methylprednisolone Sodium Succinate RS.
Determine the absorption spectra of both solutions as
(2) Dissolve 0.1 g each of Methylprednisolone Sodium Succinate and Methylprednisolone Sodium Succinate RS in 10 mL of water. Add 1 mL of 3 mol/L hydrochloric acid, and extract immediately with 50 mL of
chloroform. Filter the chloroform extract through cotton, evaporate on a steam bath to dryness, and dry in
vacuum at 60 C for 3 hours. Determine the infrared
absorption spectra of both residues so obtained as directed in the paste method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
(3) Methylprednisolone Sodium Succinate responds
to the Qualitative Tests (1) for sodium.
absorbances, AT and AS , of the test solution and the

standard solution as directed under the Ultravioletvisible Spectrophotometry, and calculate the amount of
Methylprednisolone Sodium Succinate.
Amount (mg) of methylprednisolone sodium succinate
A
(C26H33NaO8) = 8.37 C T
AS
C is the concentration (g/mL) of Methylprednisolone Sodium Succinate RS in the standard solution.
Packaging and Storage Preserve in light-resistant
tight containers.
Methylrosanilinium Chloride

D : Between +96 and
+104 (0.1 g after drying, ethanol, 10 mL, 100 mm).
Purity Sodium Weigh accurately about 1.0 g of
Methylprednisolone Sodium Succinate, previously
dried, and dissolve in 75 mL of glacial acetic acid with
gentle heating. Add 20 mL of dioxane, and titrate with
0.1 N perchloric acid VS to a blue-green endpoint (indicator: 1 drop of methylrosaniline chloride TS). Perform a blank determination, and make any necessary
correction (4.49 4.77%).
= 2.299 mg Na
Loss on Drying Not more than 3.0% (1g, 105 C, 3
hours)
Assay Weigh accurately about 0.1 g of Methylprednisolone Sodium Succinate, and dissolve it in ethanol to
make 200 mL. Pipet 5 mL of this solution, dilute with
ethanol to make 200 mL, and use this solution as the
test solution. Separately, weigh accurately about 12.5
mg of Methylprednisolone Sodium Succinate RS, and
dissolve in ethanol to make exactly 100 mL. Pipet 5 mL
of this solution, dilute with ethanol to make 50 mL, and
use this solution as the standard solution. Use ethanol
as the blank solution. To each of the glass-stoppered
flasks containing 20 mL of the blank solution, the test
solution, and the standard solution, add 2.0 mL of a solution prepared by dissolving 50 mg of blue tetrazolium
in 10 mL of alcohol, and mix. Then, add to each flask
4.0 mL of a mixture of ethanol and tetramethylammonium hydroxide TS (9:1). Mix, allow to stand in the
dark for 90 minutes, and add 1.0 mL of glacial acetic
acid. Using the blank solution as control, determine the
N+(CH3)2Cl-
(H3C)2N
N(CH3)2
Crystal Violet
C25H30ClN3: 407.98
Methylrosanilinium Chloride is hexamethylpararosaniline chloride and is usually admixed with pentamethylpararosaniline chloride and tetramethylpararosaniline
chloride.
Methylrosanilinium Chloride contains not less than
96.0% and not more than 101.0% of Methylrosanilinium Chloride [as hexamethylpararosaniline chloride
(C25H30ClN3)].
Description Methylrosanilinium Chloride is a green
fragment having a metallic lust or a dark green powder,
is odorless or has a slight ordor.
Methylrosanilinium Chloride is soluble in ethanol, sparingly soluble in water and practically insoluble in ether.
Identification (1) Take 1 mL of sulfuric acid and add
1 mg of Methylrosanilinium Chloride: Methylrosanilinium Chloride dissolves and shows an orange to
red-brown color. To this solution, add water drop-wise:
the color of the solution changes from brown through
green to blue.
(2) Dissolve 20 mg of Methylrosanilinium Chloride
in 10 mL of water, add 5 drops of hydrochloric acid and
use this solution as the test solution. To 5 mL of the test
solution, add tannic acid TS drop-wise: an intense blue
(3) Take 5 mL of the test solution obtained in (2),
add 0.5 g of zinc powder and shake: the solution is decolorized. Place 1 drop of this solution on filter paper

and apply 1 drop of ammonia TS adjacent to it: a blue
color is observed at the zone of contact of both solutions.
Methyltestosterone
CH3
Purity
(1) Ethanol-insoluble substancesWeigh
accurately about 1 g of Methylrosanilinium Chloride,
previously dried at 105 C for 4 hours, heat with 50 mL
of ethanol under a reflux condenser for 15 minutes in a
water-bath and filter the mixture through a tared glass
filter (G4). Wash the residue on the filter with warm
ethanol until the last washing does not show a purple
color and dry at 105 C for 2 hours: the weight of the
residue is not more than 1.0%.
(2) Heavy metalsProceed with 1.0 g of Methylrosanilinium Chloride according to Method 2 and perform the test. Prepare the control solution with 3.0 mL
(3) ZincTake 0.10 g of Methylrosanilinium Chloride, add 0.1 mL of sulfuric acid and incinerate by ignition. After cooling, boil with 5 mL of dilute hydrochloric acid, 0.5 mL of dilute nitric acid and 4 mL of water,
add 5 mL of ammonia TS, boil again and filter. To the
filtrate, add 2 to 3 drops of sodium sulfide TS: no turbidity is produced.
of Methylrosanilinium Chloride, according to Method 3
hours).
Assay Transfer about 0.4 g of Methylrosanilinium
Chloride, accurately weighted, to a wide-mouthed Erlenmeyer flask, add 25 mL of water and 10 mL of hydrochloric acid, dissolve and add 50.0 mL of 0.1 mol/L
titanium trichloride VS while passing a stream of carbon dioxide through the flask. Boil gently for 15 minutes, swirling the liquid frequently. Cool while passing a stream of carbon dioxide through the flask, titrate
the excess titanium trichloride with 0.1 mol/L ferric
ammonium sulfate VS until a faint, red color is observed (indicator: 5 mL of ammonium thiocyanate TS).
correction.
Each mL of 0.1 mol/L titanium trichloride VS
= 20.399 mg of C25H30ClN3
CH3
CH3
OH
C20H30O2: 302.45
Methyltestosterone, when dried, contains not less than
98.0% and not more than 102.0% of methyltestosterone
(C20H30O2).
Description Methyltestosterone is a white to pale
yellow crystal or crystalline powder and is odorless.
Methyltestosterone is freely soluble in methanol or in
ethanol, soluble in acetone, sparingly soluble in ether
and practically insoluble in water.
of the solutions of Methyltestosterone and Methyltestosterone RS in ethanol (1 in 100000) as directed under
(2) Determine the infrared spectra of Methyltestostrone and Methyltestosterone RS, previously dried, as
directed n the potassium bromide disk method under
D : Between +79 and
+85 (0.1 g, after drying, ethanol, 10 mL, 100 mm).
Purity Related substancesDissolve 40 mg of Methyltestosterone in 2 mL of ethanol and use this solution as the test solution. Pipet 1.0 mL of this solution,
add ethanol to make exactly 100 mL and use this solution as the standard solution. Perform the test with the
test solution and the standard solution on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform and diethylamine (19 : 1) to a distance of about
15 cm and air-dry the plate. Examine under ultraviolet
light (main wavelength: 254 nm): the spots other than
the principal spot from the test solution are not more intense than the spot from the standard solution.
KP 9 649
Assay Weigh accurately about 20 mg each of Methyltestosterone and Methyltestosterone RS, previously
dried in a desiccator (in vacuum, phosphorous (V)
oxide) for 10 hours, dissolve each in methanol to make
exactly 200 mL. Pipet 5 mL each of these solutions,
add exactly 5 mL of the internal standard solution, add
method to make 50 mL, and use these solutions as the
test solution and the standard solution. Perform the test
according to the following conditions. Determine the
ratios, QT and QS , of the peak area of methyltestosterone to that of the internal standard.
Amount (mg)of Methyltestosterone (C20H30O2) =
Q
amount (mg) of Methyltestosterone RS T
QS
Internal standard solutionA solution of propyl
parahydroxybenzoate in methanol (1 in 10000)
Column: A stainless steel column 6 mm in inside
particle diameter).
about 35 C
(11:9)
time of methyltestosterone is about 10 minutes.
System suitability
operating conditions, the internal standard and methyltestosterone are eluted in this order with the resolution
between these peaks being not less than 9.
times with L of the standard solution under the above
the ratios of the peak area of methyltestosterone to that
tight containers.
Methyltestosterone Tablets
Methyltestosterone Tablets contain not less than 90.0%
and not more than 110.0% of the labeled amount of methyltestosterone (C20H30O2: 302.45).

Tablets, with Methyltestosterone.
Identification (1) Take a portion of powdered Methyltestosterone Tablets, equivalent to 10 mg of Methyltestosterone according to the labeled amount, add
50 mL of chloroform, shake for 30 minutes and filter.
Evaporate the filtrate to dryness, dissolve the residue in
10 mL of acetone and use this solution as the test solution. Separately, dissolve 10 mg of Methyltestosterone
RS in 10 mL of acetone and use this solution as the
mixture of chloroform and ethanol (9 : 1) to a distance
of about 12 cm and air-dry the plate. Spray evenly dilute sulfuric acid on the plate and heat at 110 C for 10
minutes: the spots from the test solution and the standard solution show the same Rf value.
Take 1 tablet of Methyltestosterone Tablets, add 5
mL of water to disintegrate, add 50 mL of methanol
and shake for 30 minutes. Add methanol to make exactly 100 mL and centrifuge. Measure exactly V mL of the
supernatant, add methanol to make exactly V mL of a
solution containing about 10 g of methyltestosterone
(C20H30O2) per mL and use this solution as the test solution. Separately, weigh accurately about 10 mg of
Methyltestosterone RS, previously dried in a desiccator
(in vacuum, P2O5) for 10 hours, dissolve in 5 mL of
water and 50 mL of methanol and then add methanol to
add methanol to make exactly 50 mL and use this solution as the standard solution. Determine the absorbances, AT and AS , of the test solution and the standard solution, respectively, at the wavelength of a maximum absorption at about 241 nm as directed under the
Amount (mg) of methyltestosterone (C20H30O2)
= amount (mg) of Methyltestosterone RS
AT V ' 1

A S V 10
Methyltestosterone Tablets. Weigh accurately a portion
of the powder, equivalent to about 25 mg of methyltestosterone (C20H30O2), add about 70 mL of methanol,
mix by shaking for about 30 minutes, add methanol to
make exactly 100 mL. Pipet 2 mL of this solution, add
exactly 5 mL of the internal standard solution and
methanol to make exactly 50 mL, filter through a

membrane filter (not exceeding 0.45 m in pore size),
weigh accurately about 20 mg of Methyltestosterone
RS, previously dried in a desiccator (in vacuum, P2O5)
for 10 hours and dissolve in methanol to make exactly
200 mL. Pipet 5 mL of this solution and 5 mL of the
internal standard solution, add methanol to make
exactly 50 mL, and use this solution as the standard
Liquid Chromatography according to the following operating conditions, and calculate the ratios, QT and
QS , of the peak area of methyltestosterone to that of
the internal standard for the test solution and the standard solution, respectively.
Metildigoxin
O
O
H
CH3
H
CH3
H
CH3
Amount (mg) of methyltestosterone (C20H30O2)

Q 5
= amount (mg) of Methyltestosterone RS T
QS 4
Internal standard solutionA solution of propyl
paraoxybenzoic acid in methanol (1 in 10000).
Column: A stainless steel column 6 mm in inside
particle diameter).
about 35 C.
(11:9).
time of Methyltestosterone is about 10 minutes.
System suitability
operating conditions, the internal standard and Methyltestosterone are eluted in this order with the resolution
between their peaks being not less than 9.
above operating conditions, the relative standard deviation of the ratio of the peak area of methyltestosterone
CH3
H
CH3O
O
H
H
CH3
H
OH
H
O
1/2 H3C
CH3
OH
O
H
H
OH
O
H
H
OH
OH
C42H66O141/2C3H6O: 824.01
Metildigoxin contains not less than 96.0% and not
more than 103.0% of metildigoxin (C42H66O14
1/2C3H6O), calculated on the anhydrous basis.
Description Metildigoxin is a white to pale yellowish
Metildigoxin is freely soluble in dimethylformamide, in
pyridine or in glacial acetic acid, soluble in chloroform,
sparingly soluble in methanol, slightly soluble in ethanol or in acetone, very slightly soluble in water and
Identification (1) Dissolve 2 mg of Metildigoxin in 2
mL of glacial acetic acid, shake well with 1 drop of ferric chloride TS and add gently 2 mL of sulfuric acid to
divide into two layers: a brown color is observed at the
interface and a deep blue color gradually develops in
the layer.
(2) Dissolve 2 mg of Metildigoxin in 2 mL of mdinitrobenzene TS, add 2 mL of a solution of tetramethylammonium hydroxide in ethanol (1 in 200) and
shake: a purple color gradually develops and changes to
blue-purple.
Metildigoxin and Metildigoxin RS in methanol (1 in
Metildigoxin and Metildigoxin RS as directed in the
spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers. If any difference appears, dissolve Metildigoxin and Metildigoxin RS in acetone, respectively, evaporate to dryness and
repeat the test on the residues.
KP 9 651
D : Between +22.0
and +25.5 (1 g, after drying, pyridine, 10 mL, 100
mm).
Purity (1) ArsenicPrepare the test solution with
0.5 g of Metildigoxin according to Method 3 and perform the test (not more than 4 ppm).
(2) Related substancesDissolve 10 mg of Metildigoxin in 10 mL of chloroform and use this solution as
the test solution. Pipet 1.0 mL of the test solution, add
chloroform to make exactly 50 mL and use this solution
test solution and the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate
with a mixture of methyl ethyl ketone and chloroform
(3 : 1) to a distance of about 15 cm and air-dry the plate.
Spray evently dilute sulfuric acid on the plate and heat
at 110 C for 10 minutes: the spots other than the principal spot from the test solution are not more intense
than the spot from the standard solution.
Acetone Weigh accurately about 0.1 g of Metildigoxin, dissolve in 2.0 mL of the internal standard solution,
add dimethylformamide to make exactly 10 mL and use
this solution as the test solution. Separately, weigh accurately about 0.4 g of acetone in a volumetric flask
containing about 10 mL of dimethylformamide and add
dimethylformamide to make 50 mL. Pipet 5.0 mL of
this solution, add 20.0 mL of the internal standard solution, then add dimethylformamide to make exactly 100
mL and use this solution as the standard solution. Perform the test with 1 L each of the test solution and the
standard solution as directed under the Gas Chromatography and calculate the ratios, QT and QS , of the
peak area of acetone to that of the internal standard for
the test solution and the standard solution, respectively:
the amount of acetone is between 2.0% and 5.0% in the
test solution and standard solution, repectively.
Amount (%) of acetone
amount (g) of acetone taken
QT
amount (g) of the sample taken
=
QS

time of acetone is about 2 minutes.
System suitability
with 1 L of the standard solution under the above operating conditions, acetone and the internal standard are
Assay Weigh accurately about 0.1 g each of Metildigoxin and Metildigoxin RS and dissolve each in methanol to make exactly 50 mL. Pipet 5.0 mL each of the
solutions, add methanol to each to make exactly 100
standard solution, respectively. Pipet 5.0 mL each of
the test solution and the standard solution, add 15 mL
of picric acid-ethanol TS and 2 mL of sodium hydroxide TS to each, shake well, add methanol to make exactly 25 mL and allow to stand at 20 0.5 C for 20
minutes. Perform the test with the subsequent solutions
obtained from the test solution and the standard solution as directed under the Ultraviolet-visible Spectrophotometry using a solution prepared by mixing 15 mL
of picric acid-ethanol TS and 2 mL of sodium hydroxide TS and adding methanol to make exactly 25 mL as
the blank. Determine the maximum absorbances, AT
and AS , of the subsequent solutions obtained from the
test solution and the standard solution, respectively, by
measuring every 5 minutes, at 495 nm.
Amount (mg) of metildigoxin (C42H66O141/2C3H6O)
= amount (mg) of Metildigoxin RS,
A
AS
Metoclopramide
Internal standard solutionA solution of tertbutanol in dimethylformamide (1 in 2000).

Column: A glass column, about 2 mm in inside diameter and 1 m to 2 m in length, packed with porous
ethylvinylbenzene-divinylbenzene copolymer for gas
Column temperature: A constant temperature between 170 C and 230 C.
Cl
O
H2N
NHCH2CH2N(CH2CH3)2
OCH3
C14H22ClN3O2: 299.80
Metoclopramide, when dried, contains not less than
99.0% and not more than 101.0% of metoclopramide
(C14H22ClN3O2).
Description Metoclopramide is a white crystal or a

Metoclopramide is freely soluble in glacial acetic acid,
soluble in methanol or in chloroform, sparingly soluble
in acetic anhydride, in ethanol or in acetone, very
Metoclopramide dissolves in dilute hydrochloric acid.
Assay Weigh accurately about 0.4 g of Metoclopramide, previously dried and dissolve in 50 mL of glacial
acetic acid, add 5 mL of acetic anhydride and warm for
5 minutes. After cool, titrate with 0.1 mol/L perchloric
acid VS (indicator: 2 drops of methylrosaniline chloride TS). Perform a blank determination and make any
Identification (1) Dissolve 10 mg of Metoclopramide in 1 mL of dilute hydrochloric acid and 4 mL of

water: the solution responds to the Qualitative Tests for
(2) Dissolve 10 mg of Metoclopramide in 5 mL of
dilute hydrochloric acid and 20 mL of water and to 5
mL of this solution, add 1 mL of Dragendorffs TS: a
reddish orange precipitate is produced.
(3) Dissolve 0.1 g each of Metoclopramide and Metoclopramide RS in 1 mL of 1 mol/L hydrochloric acid
TS and dilute with water to make 100 mL. Determine
the absorption spectra of the solutions, prepared by diluting 1 mL of both solutions with water to make 100
mL, as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of

= 29.980 mg of C14H22ClN3O2
Metoclopramide Hydrochloride
Hydrate
O
Cl
CH2CH3
HCl
NHCH2CH2N
H2O
CH2CH3
H2N
OCH3
Melting Pinot Between 146 C and 149 C.

1.0 g of Metoclopramide in 10 mL of 1 mol/L hydrochloric acid TS: the solution is clear and colorless.
(2) Heavy metalsProceed with 1.0 g of Metoclopramide as directed under Method 2 and perform the
(3) ArsenicDissolve 1.0 g of Metoclopramide in
5 mL of 1 mol/L hydrochloric acid TS and use this solution as the test solution. Perform the test (not more
than 2 ppm).
(4) Related substancesDissolve 0.10 g of Metoclopramide in 10 mL of methanol and use this solution
as the test solution. Dilute 1 mL of this solution, exactly measured, with methanol to make exactly 200 mL
mixture of n-butanol and strong ammonia water (19 : 1)
to a distance of about 10 cm. Dry the plate, first in air
and then at 80 C for 30 minutes. Examine under ultraviolet light (main wavelength: 254 nm): the spots other
hours).
Metoclopramide Hydrochloride
C14H22ClN3O2HClH2O: 354.27
Metoclopropamide Hydrochloride Hydrate contains not
less than 98.0% and not more than 101.0% of metoclopropamide hydrochloride (C14H22ClN3O2HCl: 336.26),
Description Metoclopropamide Hydrochloride Hydrate is a white crystalline powder and is orderless or
has a faint odor.
Metoclopropamide Hydrochloride Hydrate is very soluble in water, freely soluble in ethanol, sparingly soluble in chloroform and practically insoluble in ether.
Identification (1) Dissolve 50 mg of Metoclopropamide Hydrochloride Hydrate in 5 mL of water and add
5 mL of p-dimethylaminobenzaldehyde in 1 mol/L hydrochloric acid (1 in 100): a yellow-orange color is observed.
(2) The Rf value of the principal spot in the chromatogram of the identification solution corresponds to
that of the standard solution A, as directed under the
Purity test.
(3) Determine the infrared spectrum of Metoclopropamide Hydrochloride Hydrate and Metoclopropamide Hydrochloride Hydrate RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
of absorption at the same waveunmbers.
Purity Related substancesDissolve an accurately
weighed quantity of Metoclopropamide Hydrochloride
KP 9 653
Hydrate in methanol to obtain a solution containing 50
mg per mL and use this solution as the test solution. Dilute a volume of the test solution quantitatively with
methanol to obtain a solution containing 0.5 mg per mL
and use this solution as the identification solution. Dilute a volume of the test solution quantitatively with
methanol to obtain three standard solutions, designated
below by letters, having the following concentrations:
Standard
solutions
Dilution
Concentration
(g/mL)
A
B
C
(1 in 4)
(3 in 20)
(1 in 20)
250
150
50
Percentage
(%) for comparison with
test specimen
0.5
0.3
0.1
Perform the test with the test solution, the identification

solution and the standard solutions, A, B, and C as directed under the Thin-layer Chromatography. Spot 10
L each of the test solution, the identification solution
and the standard solutions on a plate of silica gel for
mixture of chloroform, methanol, toluene and strong
ammonia water (140 : 60 : 20 : 1) to a distance of about
15 cm and air-dry the plate. Examine the plate under
ultraviolet light (main wavelength: 254 nm): any spot
other than the principal spot from the test solution is
not larger and is not more intense than the principal
spot from the standard solution A (0.5%) and the sum
of the intensities all secondary spots from the test solution is not more than 1.0%.
Assay Weigh accurately about 0.3 g of Metoclopropamide Hydrochloride Hydrate, add 10 mL of mercuric
acetate and 2 mL of acetic anhydride and allow to stand
for 3 hours. Add 80 mL of glacial acetic acid and titrate
correction.
tight containers.
Metronidazole
CH2CH2OH
O2N
CH3
C6H9N3O3: 171.15
Metronidazole, when dried, contains not less than
99.0% and not more than 101.0% of metronidazole
(C6H9N3O3).
Description Metronidazole is a white to pale yellowish white crystal or crystalline powder, is odorless
and has a slightly bitter taste.
Metronidazole is freely soluble in glacial acetic acid,
sparingly soluble in ethanol or in acetone, slightly soluble in water and very slightly soluble in ether.
Metronidazole dissolves in dilute hydrochloric acid.
Metronidazole is affected by light.
of the solutions of Metronidazole and Metronidazole
RS in 0.1 mol/L hydrochloric acid TS (1 in 100000) as
(2) Determine the infrared spectra of Metronidazole
and Metronidazole RS as directed in the potassium
Purity (1) Heavy metalsProceed with 1.0 g of Metronidazole according to Method 2 and perform the test.
(2) 2-Methyl-5-nitroimidazoleDissolve 0.10 g of
Metronidazole in acetate to make exactly 10 mL and
use this solution as the test solution. Separately, dissolve 20 mg of 2-methyl-5-nitroimidazole RS in acetone to make exactly 20 mL, then pipet 5.0 mL of this
solution, add acetone to make exactly 100 mL and use
thin-layer chromatography. Immediately develop the
plate with a mixture of acetone, water and ethyl acetate
plate. Examine under ultraviolet light (main wavelength: 254 nm): the spot form the test solution corresponding to the spot from the standard solution is not

Assay Weigh accurately about 0.2 g of Metronidazole,
previously dried and dissolve in 30 mL of glacial acetic
acid. Titrate with 0.1 mol/L perchloric acid VS (indicator: 0.5 mL of -naphtholbenzeine TS) until the color
of the solution changes from orange-yellow to green.
correction.
= 17.115 mg of C6H9N3O3
tight containers.
Metronidazole Tablets
Metronidazole Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of metronidazole (C6H9N3O3: 171.15).
Tablets with Metronidazole.
Identification (1) Determine the absorption spectrum
of the test solution obtained in the Assay as directed
under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 275 and 279 nm.
(2) Powder Metronidazole Tablets, weigh a quantity
equivalent to 0.20 g of Metronidazole according to the
labeled amount, shake vigorously with 20 mL of acetone for 10 minutes, centrifuge, and use the supernatant
liquid as the test solution. Separately, dissolve 0.10 g of
Metronidazole RS in 10 mL of acetone, and use this solution as the standard solution. Perform the test with
these solutions as directed under the Thin-layer Chromatography. Spot 5 L of each of the test solution and
the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate immediately with a mixture of acetone, water and ethyl acetate (8:1:1) to a distance of 10 cm, and
wavelength: 254 nm): the Rf value of the principal
solution is the same.
Metronidazole Tablets at 100 revolutions per minute
according to Method 1 under the Dissolution Test, using 900 mL of 0.1 mol/L hydrochloric acid TS as the
dissolution solution. Take 30 mL or more of the dissolved solution after 60 minutes from the start of the
test and filter. Discard the first 10 mL of the filtrate, pipet exactly V mL of the subsequent filtrate, add water
to make exactly V mL so that each mL contains about

25 g of metronidazole (C6H9N3O3) according to the
labeled amount and use this solution as the test solution.
Separately, weigh accurately about 50 mg of Metronidazole RS and dissolve in 0.1 mol/L hydrochloric acid
TS to make exactly 200 mL, pipet 10.0 mL of this solution, add water to make exactly 100 mL and use this solution as the standard solution. Determine the absorbances, AT and AS , of the test solution and the standard solution at 278 nm as directed under the Ultraviolet-visible Spectrophotometry, respectively.
The dissolution rate of Metronidazole Tablets in 60 minutes is not less than 85%.
V' 1
amount of Metronidazole = WS 45
V C
WS: Amount (mg) of Metronidazole RS, calculated
on dried basis,
C: Labeled amount (mg) of Metronidazole in 1 tablet.
To 1 tablet of Metronidazole Tablets, add 25 mL of a
mixture of wate and methanol (1:1), shake vigorously
for 25 minutes, and add the mixture of water and methanol (1:1) to make exactly 50 mL. Pipet 5 mL of this
solution, and add a mixture of water and methanol (1:1)
to make exactly 100 mL. Filter the solution through a
membrane filter with pore size of 0.45 m, discard the
first 3 mL of the filtrate, and use the subsequent filtrate
as the test solution. Hereinafter, proceed as directed
under the Assay.
Amount (mg) of metronidazole (C6H9N3O3:)
A
= amount (mg) of Metronidazole RS T 10
AS
Metronidazole Tablets. Weigh accurately a portion of
the powder, equivalent to about 0.25 g of Metronidazole (C6H9N3O3), dissolve in methanol to make exactly
100 mL and filter. Discard the first 10 mL of the filtrate,
pipet 20.0 mL of the subsequent filtrate and add the
mobile phase to make exactly 100 mL. Use this solution as the test solution. Separately, weigh accurately
about 50 mg of Metronidazole RS and dissolve in methanol to make exactly 10 mL. Pipet 5.0 mL of this solution, add the mobile phase to make exactly 50 mL
standard solution as directed under the Liquid Chromatography. Determine peak areas, AT and AS , of Metronidazole for the test solution and standard solution,
respectively, by the automatic integration method.
KP 9 655
Amount (mg) of metronidazole (C6H9N3O3: 171.16)
A
= amount (mg) of Metronidazole RS T 5
AS
Mobile phase: A mixture of water and methanol
(80 : 20).
System suitability
operating conditions, the symmetry factor is not more
than 2.0.
above operating conditions, the relative standard deviation of the peak areas of Metronidazole is not more
than 2.0%.
Metyrapone
N
CH3 O
bit similar intensities of absorption at the same wavelengths.

0.5 g of Metyrapone in 5 mL of methanol: the solution
is clear and colorless to pale yellow.
(2) Heavy metalsProceed with 2.0 g of Metyrapone according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
Metyrapone, according to Method 3 and perform the
(4) Related substanceDissolve 0.25 g of Metyrapone in 5 mL of methanol and use this solution as the
test solution. Pipet 1.0 mL of the test solution and add
methanol to make exactly 50 mL. Pipet 5.0 mL of this
solution, add methanol to make exactly 50 mL and use
plate of silica gel with a fluorescent indicator for thinlayer chromatography. Develop the plate with a mixture
of chloroform and methanol (15 : 1) to a distance of
about 10 cm and air dry the plate for about 15 minutes.
test solution is not more intense than the spot from the
standard solution.
N
C
CH3
C14H14N2O: 226.27
Metyrapone, which dried, contains not less than 98.0%
and not more than 101.0% of metyrapone (C14H14N2O).
Description Metyrapone is a white to pale yellow,
crystalline powder and has a characteristic odor and a
bitter taste.
Metyrapone is very soluble in methanol, in ethanol, in
acetic anhydride, in chloroform, in ether, or in nitrobenzene and sparingly soluble in water.
Metyrapone dissolves in 0.5 mol/L sulfuric acid TS.
Identification (1) Mix 5 mg of Metyrapone with 0.01
g of 2,4-dinitrochlorobenzene, melt by gently heating
for 5 to 6 seconds, cool and add 4 mL of potassium hydroxide ethanol TS: a dark red color develops.
(2) Determine the absorption spectra of the solutions of Metyrapone and Metyrapone RS in 0.5 mol/L
sulfuric acid TS (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhi-
Assay Weigh accurately about 0.2 g of Metyrapone,

previously dried and dissolve in 10 mL of nitrobenzene
and 40 mL of acetic anhydride and titrate with 0.1
= 11.314 mg of C14H14N2O
tight containers.
Mexiletine Hydrochloride
CH3
CH3
OCH2CNH2
HCl
H
CH3
and enantiomer
C11H17NOHCl: 215.72
Mexiletine Hydrochloride, when dried, contains not

less than 98.0% and not more than 102.0% of mexiletine hydrochloride (C11H17NOHCl).
Description Mexiletine Hydrochloride is a white
powder.
Mexiletine Hydrochloride is freely soluble in water or
in ethanol, slightly soluble in acetonitrile, and practically insoluble in ether.
A solution of Mexiletine Hydrochloride (1 in 20) shows
of the solutions of Mexiletine Hydrochloride and Mexiletine Hydrochloride RS in 0.01 mol/L hydrochloric
acid TS (1 in 2000) as directed under the the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Mexiletine
Hydrochloride and Mexiletine Hydrochloride RS, previously dried, as directed in the potassium bromide disk
method under the Infrared Spectrophotometry, both
same wavenumbers. If any difference appears between
the spectra, recrystallize the sample from ethanol, filter,
dry the crystals, and repeat the test with the crystals.
(3) A solution of Mexiletine Hydrochloride (1 in
100) responds to the Qualitative Tests (2) for chloride.
Melting Point
Between 200 C and 204 C.
pH Dissolve 1.0 g of Mexiletine Hydrochloride in 10

mL of water. The pH of this solution is between 3.8 and
5.8.
1.0 g of Mexiletine Hydrochloride in 10 mL of water:
(2) Heavy MetalsProceed with 2.0 g of Mexiletine Hydrochloride according to Method 1, and perform
(3) Related substancesDissolve 20 mg of Mexiletine Hydrochloride in 20 mL of the mobile phase,
of the test solution, add the mobile phase to make exactly 250 mL, and use this solution as the standard solution. Perform the test with 20 L each of the test so-
lution and the standard solution as directed under the

Liquid Chromatography according to the following operating conditions. Determine each peak area of the test
solution and the standard solution by automatic integration method: each peak area of the peaks other than the
principal peak from the test solution is not larger than
the principal peak area from the standard solution.
phase, flow rate, and selection of column: Proceed as
directed in the operating conditions in the Assay under
Mexiletine Hydrochloride.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of mexiletine obtained from
20 L of the standard solution is between 5 mm and 10
mm.
as the retention time of mexiletine after peaks of the
solvent.
hours).
Assay Weigh accurately about 20 mg each of Mexiletine Hydrochloride and Mexiletine Hydrochloride RS,
previously dried, and dissolve each in the mobile phase
to make exactly 20 mL. Pipet 5.0 mL each of these solutions, add 5.0 mL of the internal standard solution,
then add the mobile phase to make exactly 100 mL, and
under the Liquid Chromatography according to the following operating conditions, and determine the ratios,
QT and QS , of the peak area of Mexiletine to that of
the internal standard, for the test solution and the standard solution, repectively.
Amount (mg) of mexiletine hydrochloride
(C11H17NOHCl) = amount (mg) of Mexiletine
Q
Hydrochloride RS T
QS
Internal standard solutionA solution of phenetylamine hydrochloride in the mobile phase (3 in 5000).
with octadecylsilanized silica gel for liquid chromatography (about 7 m in particle diameter).
about 30 C.
Mobile phase: Dissolve 2.5 g of sodium lauryl sul-
KP 9 657
fate and 3 g of monobasic sodium phosphate in 600 mL
of water, and add 420 mL of acetonitrile.
time of mexiletine is about 6 minutes.
operating conditions, the internal standard and mexiletine are eluted in this order with the resolution between

tight containers.
Miconazole Nitrate
Cl
H
Cl
O
Cl
Cl
CH2
HNO3
and enantiomer
Cl8H14Cl4N2OHNO3: 479.14
Miconazole Nitrate, when dried, contains not less than
98.5% and not more than 101.0% of miconazole nitrate
(Cl8H14Cl4N2OHNO3).
Description Miconazole Nitrate is a white crystalline
powder.
Miconazole Nitrate is freely soluble in dimethylformamide, sparingly soluble in methanol, slightly soluble in
ethanol, in acetone or in glacial acetic acid and very
slightly soluble in water or in ether.
Identification (1) Take 2 mL of a solution of Miconazole Nitrate in methanol (1 in 100) and add 2 mL of
Reinecke salt TS: a pale red precipitate is formed.
(2) Determine the absorption spectra of the solutions of Miconazole Nitrate and Miconazole Nitrate RS
in methanol (1 in 2500) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(3) Perform the test with a solution of Miconazole
Nitrate in methanol (1 in 100) as directed under the
Flame Coloration Test (2): a green color appears.
(4) A solution of Miconazole Nitrate in methanol (1
in 100) responds to the Qualitative Tests for nitrate.
1.0 g of Miconazole Nitrate in 100 mL of methanol: the
(2) ChlorideDissolve 0.10 g of Miconazole Nitrate in 6 mL of dilute nitric acid and dimethylformamide to make 50 mL. Perform the test. Prepare the con-
trol solution as follows: to 0.25 mL of 0.01 mol/L hydrochloric acid VS, add 6 mL of dilute nitric acid and
dimethylformamide to make 50 mL (not more than
0.09%).
(3) Heavy metalsProceed with 1.0 g of Miconazole Nitrate according to Method 2 and perform the test.
Miconazole Nitrate according to Method 3 and perform
(5) Related substancesDissolve 0.10 g of Miconazole Nitrate in 10 mL of methanol and use this solution as the test solution. Pipet 1.0 mL of the test solution, add methanol to make exactly 20 mL, pipet 1.0
mL of this solution, add methanol to make exactly 20
solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of n-hexane,
chloroform, methanol and strong ammonia water (60 :
plate. Expose the plate in iodine vapor for 20 minutes:
silica gel, 60 C, 3 hours).
Assay Weigh accurately about 0.35 g of Miconazole
Nitrate, previously dried, dissolve in 50 mL of glacial
acetic acid by warming, cool and titrate with 0.1 mol/L
= 47.91 mg of Cl8H14Cl4N2OHNO3
tight containers.
Midazolam
C18H13ClFN3 : 325.77
Midazolam contains not less than 98.5% and not more
than 101.5% of midazolam (C18H13ClFN3), calculated
on a dried basis.
Description Meloxicam is a whilte or yellowish,
crystalline powder.
Midazolam is freely soluble in acetone or in ethanol,
and soluble in methanol, and practically insoluble in
water.
spectra of Midazolam and Midazolam RS as directed in
(2)The principal spot from the test solution (2) and
the principal spot from the standard solution (2), as obtained in the test of the related substances in the Purity
show same Rf value.
(3) Mix 90 mg of Midazolam with 0.30 g of anhydrous sodium carbonate and ignite in a crucible until
an almost white residue is obtained (normally in less
than 5 minutes). Allow to cool, dissolve the residue in
5 mL of dilute nitric acid, and filter. Add 1.0 mL of the
filtrate to a freshly prepared mixture of 0.1 mL of alizarin S TS and 0.1 mL of zirconyl nitrate TS. Mix, allow
to stand for 5 minutes. This solution is yellow and the
blank solution prepared in the same manner is red.
(4) To 1 mL of the filtrate obtained in the Indentification test (2), add 1 mL of water. The solution responds to the Qualitative Tests (1) for chloride.
Purity (1) Clarity and color of solutionThe solution obtained by dissolving 0.1 g of Meloxicam in 0.1
mol/L hydrochloric acid TS is clear.
(2) Related substances Dissolve 0.2 g of Meloxicam in ethanol to make 5 mL, and use this solution as
the test solution (1). Dilute 1.0 mL of this solution with
ethanol to 50 mL, and use this solution as the test solution (2). To 1.0 mL of the test solution (1), add ethanol
to make 10 mL. Pipet 2.0 mL of this solution, dilute
with ethanol to 100 mL, and use this solution as the
standard solution (1). Dissolve 8 mg of Midazolam RS
in ethanol to make 10 mL, and use this solution as the
standard solution (2). Separately, dissolve 8 mg each of
Midazolam RS and chlorodiazepoxide in ethanol to
make 10 mL, and use this solution as the standard solution (3). Perform the test with these solutions as directed under the Thin-layer Chromatography. Spot 5 L
each of the test solution and the standard solutions on a
plate of silica gel with fluorescent indicator for thinlayer chromatography, develop with a mixture of ethyl
acetate, methanol, water, and glacial acetic acid
(80:20:15:2) to a distance of about 12 cm, and dry the
plate in air. Examine in ultraviolet light at 254 nm. Any
spot due to related substances from the test solution (1)
is not more intense than the spot from the standard solution (1) (not more than 0.2%). This test passes system
suitability when the chromatogram obtained with the
standard solution (3) shows 2 clearly separated spots.
hours).
Assay Dissolve 0.120 g of Midazolam in 30 mL of
glacial acetic acid, add 20 mL of acetic anhydride, and
= 16.29 mg of C18H13ClFN3
Minocycline Hydrochloride
OH
OH
OH
NH2
OH
H
N
H3C
N
CH3
H3C
HCl
CH3
C23H27N3O7HCl: 493.94
Minocycline Hydrochloride is the hydrochloride of a
derivative of tetracycline.
Minocycline Hydrochloride contains not less than 780
g (potency) per mg of minocycline (C23H27N3O:
Description
Minocycline Hydrochloride is yellow
KP 9 659
crystal or crystalline powder, is odorless, and has a bitter taste.
Minocycline Hydrochloride is freely soluble in methanol, sparingly soluble in water or ethanol, and practically insoluble in ether.
Identification (1) Dissolve about 20 mg of Minocycline Hydrochloride in 3 mL of water, and add silver nitrate TS: the solution turns to turbid.
(2) Determine the infrared spectra of Minocycline
Hydrochloride and Minocycline Hydrochloride RS, as
the Infrared spectrophotometry: both spectra exhibit
of Minocycline Hydrochloride in 10 mL of water is between 3.5 and 4.5.
1%
Absorbance E1cm (358 nm): 296 ~ 328 (8 mg,

0.01 mol/L hydrochloric acidmethanol TS, 500 mL).
Purity Heavy metalsProceed with 1.0 g of Minocycline Hydrochloride according to Method 2 and perform the test. Prepare the control solution with 5.0 mL
Sterility Test It meets the requirement, when Minocycline Hydrochloride is used in a sterile preparation.
the following operating conditions, and determine the

peak areas, AT and AS, of minocycline.
Amount [g (potency)] of minocycline (C23H27N3O)
A
= Amount [g (potency)] of minocycline RS T
AS
inside diameter and about 250 mm in length, packed
Mobile phase: Adjust the pH of a mixture of 0.1
mol/L ammonium oxalate solution, 0.01 mol/L ethylenediamine tetraacetate, tetrahydrofuran, and N,Ndimethylformamide (180:108:96:72) to 4.5 with acetic
acid
Flow rate: 1.0 mL/ minute.
Mitomycin C
O
NH2
H2N
CH3
H
Pyrogen Test It meets the requirement, when Minocycline Hydrochloride is used in a sterile preparation.
Weigh appropriate amount of Minocycline Hydrochloride, dissolve in water, make the solution so that each
mL contains 5.0 mg, and use the solution as the test solution. The amount of injection is 1.0 mL of the test solution per kg of body weight.
Histamine It meets the requirement, when Minocycline Hydrochloride is used in a sterile preparation.
Weigh appropriate amount of Minocycline Hydrochloride, dissolve in Isotonic Sodium Chloride Injection,
make the solution so that each mL contains 5.0 mg, and
use the solution as the test solution. Use 0.6 mL of the
solution for the test.
Residue on Ignition Not more than 2.0 % (1.0 g).
of Minocycline Hydrochloride and Minocycline Hydrochloride RS, dissolve in water and make exactly 50
mL, and use these solutions as the test solution and the
standard solution. Perform the test with exactly 10 L
each of the test solution and the standard solution as directed under the Liquid Chromatography according to
H3C
O
NH
H
C15H18N4O5: 334.33
Mitomycin C is a substance having antitumor activity
produced by the growth of Streptomyces caespitosus.
Mitomycin C contains not less than 850 g (potency)
per mg of mitomycin C (C15H18N4O5: 334.33), calculated on the dried basis.
Description Mitomycin C is blue-purple crystal or
crystalline powder.
Mitomycin C is slightly soluble in water or ethanol,
and practically insoluble in ether.
Identification (1) Weigh about 2 mg of Mitomycin C,
dissolve in water, and make to 200 mL. Determine the
absorption spectrum of the solution as directed under
Ultraviolet-visible Spectrophotometry: it exhibits maxima between 215 nm and 220 nm, and between 360 nm
and 365 nm.
(2) Weigh about 2 mg of Mitomycin C, and dissolve in 4 mL of water. Determine the absorption spectrum of the solution as directed under Ultravioletvisible Spectrophotometry: it exhibits maximum between 550 nm and 600 nm.

of Mitomycin C in 10 mL of water is between 5.5 and
7.5.
1%
Absorbance E1cm (362 nm): 650 ~ 750 (1.0 mg,

water, 100 mL).
mycin C peak is less than 1.3, and the relative retention

time of 3-ethoxy-4-hydroxybenzaldehyde to mitomycin
C is about 1.4.
tight containers.
Sterility Test It meets the requirement, when Mitomycin C is used in a sterile preparation.
Mometasone Furoate
Bacterial Endotoxins Less than 50 EU per mg of

mitomycin C, when Mitomycin C is used in a sterile
preparation.
O
O
Cl
Amount [g (potency)] of mitomycin C (C15H18N4O5)

A
= Amount [g (potency)] of mitomycin C RS T
AS
with phenylated silica gel for liquid chromatography
Mobile phase: Dissolve 1.54 g of ammonium acetate, add 5 mL of 0.83 mol/L acetic acid and add water
to make exactly 1000 mL. To 750 mL of this solution
add 250 mL of methanol and use this mixture as mobile
phase.
System suitability
System performance: Dissolve about 25 mg of
Mitomycin C RS and about 0.375 g of 3-ethoxy-4hydroxybenzaldehyde in 50 mL of N, N-dimethyl acetamide. When the procedure is run with 10 L of this
solution under the above operating conditions, mitomycin C and 3-ethoxy-4-hydroxybenzaldehyde are eluted
in this order with the resolution between these two
peaks being not less than 3. Symmetry factor of mito-
CH3
HO
CH3

Assay Weigh accurately about 20 mg (potency) of
Mitomycin C, dissolve in N, N-dimethylacetamide, and
make exactly to 50 mL. Pipet exactly 10 mL of this solution, add N, N-dimethylacetamide to make exactly 50
mL, and use this solution as the test solution. Separately, weigh accurately about 20 mg (potency) of Mitomycin C RS, dissolve in N, N-dimethylacetamide, and
make exactly to 50 mL. Pipet exactly 10 mL of this solution, add N, N-dimethylacetamide to make exactly 50
mL, and use this solution as the standard solution. Perform the test with 10 L each of the test solution and
mitomycin C.
Cl
O
O
O
CH3
C27H30Cl2O6 : 521.43
Mometasone Furoate contains not less than 97.0% and

not more than 102.0% of mometasone furoate
(C27H30Cl2O6), calculated on the dried basis.
Description Mometasone Furoate is a white powder.
Mometasone Furoate is freely soluble in acetone or in
dichloromethane, slightly soluble in ethanol, and practically insoluble in water.
Mometasone Furoate and Mometasone Furoate RS as
directed in the paste method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
(2) When the procedure in the Assay is performed,
the retention time of the major peak in the chromatogram obtained from the test solution corresponds to that
of the standard preparation.
D : Between +56 and
+62 (0.1 g, agter drying, dioxane, 20 mL, 100 mm).
Mometasone Furoate according to Method 2 and perform the test. Prepare the control solution with 3.0 mL
0.1 g of Mometasone Furoate, dissolve in dichloromethane to make exactly 10 mL, and use this solution as
the test solution. Separately, dissolve an accurately
weighed 0.1 g of Mometasone Furoate RS in dichloromethane to make exactly 10 mL. Dilute portions of this
solution with dichloromethane to obtain standard solutions (1), (2), (3), (4), and (5) containing 0.5, 0.2, 0.1,
0.02, and 0.01 mg per mL, respectively. Perform the
test with these solutions as directed under the Thinlayer Chromatography. Spot 40 L each of the test solution and the standard solutions (1), (2), (3), (4), and
(5) on a plate of silica gel for thin-layer chromatogra-
KP 9 661
phy. Develop the chromatogram in a chamber, previously equilibrated with a solvent system consisting of
a mixture of chloroform and ethyl acetate (3 : 1), to a
distance of about 15 cm. Remove the plate from the
developing chamber, and air-dry the plate. Examine the
plate under ultraviolet light (main wavelength: 254 nm).
Compare the intensities of any secondary spots observed in the chromatogram of the test solution with
those of the principal spots in the chromatogram of the
standard solutions: no secondary spot from the chromatogram of the test solution is more intense than the
principal spot obtained from the standard solution (3)
(not more than 0.1%), and the sum of the intensities of
the secondary spots from the test solution is not more
than 2.0%.
hours).

are about 1.6 for beclomethasone dipropionate and 1.0
for mometasone furoate, the resolution between these
peaks is not less than 4.0, and the symmetry factor for
the mometasone furoate peak is not more than 1.8.
the above conditions, the relative standard deviation of
the peak area of mometasone furoate is not more than
2.0%.
Morphine Hydrochloride
Hydrate
Residue on Ignition Not more than 0.1% (1g).

Assay Weigh accurately about 50 mg each of Mometasone Furoate and Mometasone Furoate RS, and dissolve in methanol to make exactly 50 mL. Pipet 5.0 mL
each of these solutions, and dilute with a mixture of
methanol, water, and acetic acid (65:35:0.2) to make
exactly 50 mL. Pipet 10 mL of these solutions and 10.0
mL of the internal standard solution into a 50-mL volumetric flask, and dilute with a mixture of methanol,
water, and acetic acid (65:35:0.2) to make exactly 50
mL. Use these solutions as the test solution and the
standard solution, respectively. Perform the test with
exactly 20 L each of the test solution and the standard
according to the following conditions, and calculate the
ratios, QT and QS , of the peak area of mometasone
furoate to that of the internal standard, respectively.
Amount (mg) of mometasone furoate (C27H30Cl2O6) =
Q
amount (mg) of Mometasone Furoate RS T
QS
Internal standardWeigh 40 mg of beclomethasone dipropionate, and dissolve in a mixture of methanol, water, and acetic acid (65:35:0.2) to make 100 mL.
particle diameter).
(65:35).
System suitability
System performance: When the test is performed
CH3
N
HCl
3 H2O
O
HO
H OH
C17H19NO3HCl3H2O: 375.84
Morphine Hydrochloride Hydrate contains not less than
98.0% and not more than 102.0% of morphine hydrochloride (C17H19-NO3HCl: 321.80), calculated on
Description Morphine Hydrochloride Hydrate is a
white crystal or crystalline powder.
Morphine Hydrochloride Hydrate is freely soluble in
formic acid, soluble in water, sparingly soluble in methanol, slightly soluble in ethanol and practically insoluble in ether.
Morphine Hydrochloride Hydrate is colored by light.
of the aqueous solutions of Morphine Hydrochloride
Hydrate and Morphine Hydrchloride Hydrate RS (1 in
of absorption at the same wavelengths. Separately, determine the absorption spectra of the solutions of Morphine Hydrochloride Hydrate and Morphine Hydrochloride Hydrate RS in dilute sodium hydroxide TS (1 in
(2) Determine the infrared spectra of Morphine Hydrochloride Hydrate and Morphine Hydrochloride Hydrate RS as directed in the potassium bromide disk me-

thod under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same
wavenumbers.
(3) A solution of Morphine Hydrochloride Hydrate
(1 in 50) responds to the Qualitative Tests (2) for Chloride.
[ ]20
D :

Between -111 and
-116 (0.5 g calculated on the anhydrous basis, water,
25 mL, 100 mm).
0.10 g of Morphine Hydrochloride Hydrate in 10 mL of
(2) SulfateDissolve 0.20 g of Morphine Hydrochloride Hydrate in 5 mL of water and add 2 to 3
drops of barium chloride TS: no turbidity is produced.
(3) Meconic acidDissolve 0.20 g of Morphine
Hydrochloride Hydrate in 5 mL of water and add 5 mL
of dilute hydrochloric acid and 2 drops of ferric chloride TS: no red color is observed.
(4) Related substancesDissolve 0.1 g of Morphine Hydrochloride Hydrate in 10 mL of diluted ethanol (1 in 2) and use this solution as the test solution.
Pipet 1.0 mL of the test solution, add diluted ethanol (1
in 2) to make exactly 200 mL and use this solution as
test solution and the standard solution on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of dehydrated ethanol, toluene, acetone and strong ammonia
water (14 : 14 : 7 : 1) to a distance of about 15 cm and
Injection
Morphine Hydrochloride Injection is an aqueous solution for injection. Morphine Hydrochloride Injection
contains not less than 93.0% and not more than 107.0%
of the labeled amount of morphine hydrochloride hydrate (C17H19-NO3HCl3H2O: 375.85).
Method of Preparation Prepare as directed under Injections, with Morphine Hydrochloride Hydrate.
Description Morphine Hydrochloride Injection is a
clear, colorless liquid.
Morphine Hydrochloride Injection is affected by light.
Identification Take a volume of Morphine Hydrochloride Injection, equivalent to 40 mg of Morphine Hydrochloride Hydrate according to the labeled amount,
add water to make 20mL and use this solution as the
test solution. Add water to 5 mL of the test solution to
make 100 mL and determine the absorption spectrum
as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 283 nm and 287
nm. Add diluted sodium hydroxide TS to 5 mL of the
test solution to make 100 mL and determine the absorption spectrum: it exhibits a maxiumum between 296 nm
and 300 mn.
Determination of Volume of Injection in Container It

Assay Weigh accurately about 0.5 g of Morphine
Hydrochloride Hydrate, dissolve in 3.0 mL of formic
acid, add 80 mL of a mixture of acetone and glacial
acetic acid (1 : 1) and 3.0 mL of bismuth nitrate TS,
mix and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make a
tight containers.
Assay Take accurately a volume of Morphine Hydrochloride Injection, equivalent to about 80 mg of

morphine hydrochloride hydrate (C17H19NO3HCl
3H2O) according to the labeled amount and add water
to make exactly 20 mL. Pipet 5 mL of this solution, add
10 mL of the internal standard solution and add water
to make exactly 50 mL. Use this solution as the test solution. Separately, weigh accurately about 25 mg of
Morphine Hydrochloride RS (previously measure the
water content), dissolve in 10 mL of the internal standard solution, add water to make 50 mL, and use this
20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions and calculate the ratios, QT and QS , of the peak area of
KP 9 663
morphine to that of the internal standard for the test solution and the standard solution, respectively.
Amount (mg) of morphine hydrochloride hydrate
(C17H19NO3HCl3H2O)
= amount (mg) of Morphine Hydrochloride Hydrate RS,
Q
calculated on the anhydrous basis T 4 1.1679
QS
Internal standard solutionA solution of etilefrine
hydrochloride (1 in 500).
particle diameter).
about 40 C
Mobile phase: Dissolve 1.0 g of sodium lauryl sulfate in 500 mL of diluted phosphoric acid (1 in 1000),
and adjust the pH to 3.0 with sodium hydroxide TS. To
240 mL of this solution, add 70 mL of tetrahydrofuran,
and mix.
Flow rate: Adjust the flow rate so that retention time of
morphine is about 10 minutes.
System suitability
operating conditions, morphine and the internal standard are eluted in this order with the resolution between
their peaks being not less than 3.
above operating conditions, the relative standard deviation of ratios of the peak area of morphine to that of the
internal standard is not more than 1.0%.
Morphine Sulfate Hydrate

CH3
N
H2SO4
5H2O
O
HO
H OH
Morphine Sulfate
(C17H19NO3)2H2SO45H2O: 758.83
Morphine Sulfate Hydrate contains not less than 98.0%

and not more than 102.0% of morphine sulfate
[(C17H19NO3)2H2SO4: 668.75], calculated on the anhydrous basis.
Description Morphine Sulfate Hydrate is a lustrous
crystal like hair or silk, columnar crystal or white crystalline powder, is orderless and loses its water of hydration gradually on stand in the air.
Morphine Sulfate Hydrate is very soluble in hot water,
soluble in water, sparingly soluble in ethanol or in
warm ethanol and practically insoluble in chloroform
or in ether.
Morphine Sulfate is colored by light.
Identification (1) Take 1 mg of Morphine Sulfate
Hydrate in a porcelain crucible or small dish, add 0.5
mL of sulfuric acid containing 1 drop of formaldehyde
TS per mL: an intense purple color is observed at once
and quickly changes to deep blue-violet (distinction
from codeine, which gives at once an intense violetblue color and from hydromorphone, which gives at
first a yellow to brown color, changing to purplish pink
and then to purplish red).
(2) Dissolve 5 mg of Morphine Sulfate Hydrate in 5
mL of sulfuric acid, add 1 drop of ferric chloride TS,
mix and heat in boiling water for 2 minutes: a blue color is observed and when 1 drop of nitric acid is added,
it changes to dark red-brown (codeine and ethylmorphine give the same color reactions, but hydromorphone and papaverine do not produce this color
change).
(3) Determine the infrared spectra of Morphine Sulfate Hydrate and Morphine Sulfate Hydrate RS, previously dried at 145 C for 1 hour, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
(4) An aqueous solution of Morphine Sulfate Hydrate (1 in 50) responds to the Qualitative Tests for sulfate.
D : Between -107 and
-109.5 (0.1 g, calculated on the dried basis, water, 10
mL, 100 mm).
Purity (1) AcidDissolve 0.5 g of Morphine Sulfate
Hydrate in 15 mL of water, add 1 drop of methyl red
TS and titrate with 0.02 mol/L sodium hydroxide until
a yellow color is observed: not more than 0.50 mL is
required.
(2) ChlorideTake 10 mL of a aqueous solution (1
in 100) of Morphine Sulfate Hydrate, add 1 mL of 2
mol/L nitric acid and 1 mL of silver nitrate TS: no precipitate or turbidity is produced immediately.
(3) Ammonium saltsHeat 0.2 g of Morphine Sulfate Hydrate with 5 mL of 1 mol/L sodium hydroxide
TS in a water-bath for 1 minute: no odor of ammonia is
perceptible.

(4) Related substancesDissolve 1.0 g of Morphine Sulfate Hydrate in 10 mL of 1 mol/L sodium hydroxide in a separatory funnel and shake the solution
with three successive portions of 15 mL, 10 mL and 10
mL of chloroform, passing the chloroform solutions
through a small filter previously moistened with chloroform. Shake the combined chloroform solutions with
5 mL of water, separate the chloroform layer and evaporate on a water-bath to dryness. To the residue, add
10.0 mL of 0.01 mol/L sulfuric acid VS and heat gently
until dissolved. Cool, add 2 drops of methyl red TS and
titrate the excess acid with 0.02 mol/L sodium hydroxide VS: not less than 7.5 mL is required (1.5%).

above operating conditions, the relative standard deviation of the peak areas of morphine is not more than
2.0%.
Mupirocin
CH3
H
HO

H3C
H
O
CH3
Assay Weigh accurately about 24 mg of Morphine

Sulfate Hydrate, add the mobile phase to make exactly
100 mL and use this solution as the test solution. Separately, weigh accurately a portion of Morphine Sulfate
Hydrate RS, previously measured the content of water,
dissolve in mobile phase to obtain a solution having a
known concentration of about 0.24 mg per mL and use
this solution as the standard solution. Prepare the standard solution when used. Perform the test with 25 L
the following conditions and determine the peak areas,
AT and AS , of morphine for the test solution and the
Amount (mg) of morphine sulfate
A
[(C17H19NO3)2H2SO4] = 100 C T
AS
C: Concentrtion (mg/mL) of Morphine Sulfate in
inside diameter and about 30 cm in length, having octadecylsilanized silica gel for liquid chromatography (3
Mobile phase: Dissolve 0.73 g of sodium 1heptanesulfonate in 720 mL of water, add 280 mL of
methanol and 10 mL of glacial acetic acid, mix and filter.
System suitability
above operating conditions, the symmetry factor is not
more than 2.0.
OH
O
H
H
H
HO
OH
C26H44O9: 500.62
Mupirocin is a substance having antibacterial activity
produced by the growth of Peudomonas fluorescens.
Mupirocin contains not less than 920 g (potency) per
mg of mupirocin (C26H44O9 : 500.62), calculated on the
anhydrous basis.
Description Mupirocin is white powder.
Mupirocin is freely soluble in methanol, in ethanol, in
acetone or in chloroform, slightly soluble in ether, and
Mupirocin and Mupirocin RS as directed in the paste
method under Infrared Spectrophotometry, both spectra
exhibit similar intensities of absorption at the same wavenumvers.
Purity Total related substancesWeigh accurately
about 0.1 g (potency) of Mupirocin, dissolve in the
mixture of 0.1 mol/L ammonium acetate buffer solution,
pH 4.0 and methanol (1:1), make to exactly 10 mL and
use this solution as the test solution A. Pipet exactly 5
mL of the test solution A, add the mixture of 0.1 mol/L
ammonium acetate buffer solution, pH 4.0 and methanol (1:1) to make exactly 200 mL and use this solution
as the test solution B. Perform the test with 20 L of
the test solution B as directed under the Liquid Chromatography according to the following operating conditions and obtain the peak areas of related substances
except solvent, A1 and A2 (not more than 8.0 %).
Total amount [%] of related substances
A2
=
100
A1 + A2
A1: Peak area of mupirocin / Amount of mupirocin
(mg) in one mL of the test solution B
A2: (Total peak areas of related substances Total
peak of solvent) / Amount of mupirocin (mg) in one
mL of the test solution
KP 9 665
with octadecylsilanized silica gel for liquid chromatography (6 m in particle diameter)
Mobile phase: The mixture of 0.1 mol/L ammonium acetate buffer solution, pH 5.7 and tetrahydrofuran (75:25).
Flow rate: 2.0 mL / minute
Water Not more than 1.0 % (1.0 g, volumetric titration, direct titration).
of Mupirocin and Mupirocin Lithium RS, dissolve in
0.1 mol/L sodium phosphate buffer solution, pH 6.3
and make to exactly 250 mL and use these solution as
the test solution and the standard solution. Perform the
test with 20 L of the test solution and the standard solution as directed under the Liquid Chromatography
according to the following operating conditions, and
determine the peak areas, AT and AS of mupirocin.
Amount [g (potency)] of mupirocin (C26H44O9)
= Amount [g (potency)] of Mupirocin Lithium RS
A
T
AS
Mobile phase: The mixture of 0.1 mol/L sodium phosphate buffer solution, pH 6.3 and acetonitrile (75:25).
tight containers
Mupirocin Calcium Hydrate

HO
H3C
H
CH3
H
CH3
O
O
O-
Ca2+ 2H2O
H
H
H
HO
Mupirocin Calcium Hydrate contains not less than 865

g (potency) per mg of mupirocin (C26H44O9: 500.62),
Description Mupirocin Calcium Hydrate is a yellowish white powder.
Mupirocin Calcium Hydrate is freely soluble in methanol, sparingly soluble in water or ethanol, and practically insoluble in ether.
of Mupirocin Calcium Hydrate as directed in the paste
method under Infrared Spectrophotometry, it exhibits
absorption at the wavenumbers about 1708 cm 1 ,
1648 cm 1 , 1558 cm 1 , 1231 cm 1 , 1151 cm 1
and 894 cm 1 .
(2) Mupirocin Calcium Hydrate responds to the
Qualitative Test (1) for calcium salt.
0.1 g (potency) of Mupirocin Calcium Hydrate, dissolve in the mixture of 0.1 mol/L ammonium acetate
buffer solution, pH 4.0 and methanol (1:1), make to exactly 10 mL and use this solution as the test solution.
Perform the test with 10 L of the test solution as directed under the Liquid Chromatography according to
the following operating conditions (not more than
6.0 %)
Amount [%] of related substances
A
= T 100
AS
AT: Total peak areas from the test solution
AS: Total peak areas other than of mupirocin from
the test solution
Flow rate: 1.0 mL/minute
Time span of measurement: Adjust the flow rate so
that the retention time of mupirocin is about 12 minutes
and measure for 30 minutes.
OH
2
C52H86O18Ca2H2O: 1075.34
Mupirocin Calcium Hydrate is the calcium salt of a

growth of Peudomonas fluorescens.

Mupirocin Calcium Hydrate and Mupirocin Lithium
RS, dissolve in 5 mL of methanol, add 0.1 mol/L am-

monium acetate buffer solution, pH 5.7 and make to
exactly 200 mL and use these solution as the test solution and the standard solution. Perform the test with 10
L of the test solution and the standard solution as directed under the Liquid Chromatography according to
peak areas, AT and AS , of mupirocin.
Amount [g (potency)] of mupirocin (C26H44O9)
= Amount [g (potency)] of Mupirocin Lithium RS
A
T
AS
with octylsilanized silica gel for liquid chromatography
Nabumetone
O
CH3
H3CO
C15H16O2: 228.29
Nabumetone contains not less than 98.0% and not more
than 101.0% of nabumetone (C15H16O2), calculated on
Description
Nabumetone is a white, crystalline
powder.
Nabumetone is freely soluble in acetone, sparingly soluble in ethanol or in methanol and practically insoluble
in water.
Nabumetone and Nabumetone RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
Purity (1) Heavy metalsProceed with 2.0 g of Glutamine according to Method 2, and perform the test.

0.1 g of Nabumetone, add acetonitrile to make exactly
100 mL and use this solution as the test solution. Perform the test with 10 L of the test solution as directed
under the Liquid Chromatography according to the following operating conditions and determine the area of
the peaks from the test solution: the content of the related substance having the relative retention time of 2.7
is not more than 0.3%, the content of any other related
substance is not more than 0.1% and total content of
the related substances is not more than 0.6%.
Amount (%) of each related substance
= 100 F Ai /( AN + F Ai )
F: Relative response factor (0.12 for the related
substance having the relative retention time of 0.73,
0.10 for the related substance having the relative retention time of 2.7, 0.25 for the related substance having
the relative retention time of 0.93, 0.42 for the related
substance having the relative retention time of 1.2, 0.94
for the related substance having the relative retention
time of 0.85, 1.02 for the related substance having the
relative retention time of 1.9, 0.91 for the related substance having the relative retention time of 2.6).
Ai : Peak area of each related substance.
AN : Peak area of nabumetone.
Detector, column, mobile phase and flow rate: proceed as directed in the operating conditions under Assay.
System suitability
System performance: Weigh a portion of Nabumetone RS and nabumetone related substance I RS,
dissolve in acetonitrile, dilute suitably with acetonitrile
to render the concentration of the solution of about 1
mg/mL and 1 g/mL, respectively, and use this solution as the test solution for system suitability. When the
procedure is run with 10 L of the test solution for system suitability, the relative retention time for nabumetone peak and the related substance I peak is 1.0 and
0.9, respectively, with the resolution between the two
times with 10 L of the test solution for system suitability under the above operating conditions, the relative
standard deviation of the areas of nabumetone peak is
not more than 2.0%.
direct titration).
Assay Weigh accurately about 0.1 g of Nabumetone,
add acetonitrile to make exactly 100 mL and use this
solution as the test solution. Separately, weigh accu-
KP 9 667
rately about 0.1 g of Nabumetone RS, add acetonitrile
the test solution and the standard solution as directed in
operating conditions and determine the area of nabumetone peak in the test solution, AT , and in the standard
solution, AS .
Amount (mg) of nabumetone (C15H16O2)
A
= amount (mg) of Nabumetone RS T
AS
Mobile phase A: A mixture of water and glacial
acetic acid (999:1).
Mobile phase B: A mixture of acetonitrile and tetrahydrofuran (7:3)
Time
(min)
0
0-12
12-28
Mobile
phase A
(vol%)
60
60
6020
Mobile
phase B
(vol%)
40
40
4080
28-29
2060
8040
29-30
60
40
Elution condition
Equilibration
Isocratic
Linear gradient
Linear gradient
Isocratic

System suitability
deviation of the areas of nabumetone peak is not more
than 2.0%.
tight containers.
Nalidixic Acid
CH2CH3
H3C
CO2H
O
C12H12N2O3: 232.24
Nalidixic Acid, when dried, contains not less than
98.5% and not more than 101.0% of nalidixic acid
(C12H12N2O3).
Description Nalidixic Acid is a white to pale yellow
Nalidixic Acid is sparingly soluble in dimethylformamide, very slightly soluble in dehydrated ethanol and
Nalidixic Acid dissolves in sodium hydroxide TS.
of solutions of Nalidixic Acid and Nalidixic Acid RS in
0.01 mol/L sodium hydroxide TS (1 in 200000) as directed under the Ultraviolet-visible Spectrophotometry:
Nalidixic Acid and Nalidixic Acid RS, previously
wavenumbers.
Purity (1) ChlorideTake 2.0 g of Nalidixic Acid,
add 50 mL of water, warm at 70 C for 5 minutes, cool
quickly and filter. To 25 mL of the filtrate, add 6 mL of
dilute nitric acid and water to make 50 mL and perform
the test with this solution as the test solution. Prepare
the control solution with 0.35 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.012%).
(2) Heavy metalsProceed with 1.0 g of Nalidixic
(3) Related substancesDissolve 20 mg of Nalidixic Acid in 20 mL of 0.01 mol/L sodium hydroxide
TS. Pipet 5 mL exactly of this solution, add water to
solution. Pipet exactly 2 mL of the test solution, add
water to make exactly 1000 mL, and use this solution
as the standard solution. Perform the test with exactly
10 L each of the test solution and the standard solution according to the following conditions as directed
under the Liquid Chromatography, and determine each
peak area by the automatic integration method. The
area of the peak other than nalidixic acid with the test
solution is not larger than the peak area of nalidixic acid with the standard solution, and the total area of the

peaks other than the peak of nalidixic acid with the test
solution is not larger than 2.5 times the peak area of nalidixic acid with the standard solution .
particle diameter).
about 40 C.
Mobile phase: Dissolve 6.24 g of sodium dihydrogen phosphate dihydrate in 950 mL of water, adjust the
pH to 2.8 with phosphoric acid, and add water to make
1000 mL. To 300 mL of this solution add 200 mL of
methanol.
time of nalidixic acid is about 19 minutes.
System suitability
Test for required detectability: Pipet 5 mL of
the standard solution, and add water to make exactly 10
mL. Confirm that the peak area of nalidixic acid obtained with 10 L of this solution is equivalent to 40 to
60% of that with 10 L of the standard solution.
System performance: Dissolve 25 mg of methyl
parahydroxybenzoate in 100 mL of a mixture of water
and methanol (1:1). To 1 mL of this solution add water
to make 10 mL. To 5 mL of this solution add 5 mL of
the standard solution. When the procedure is run with
10 L of this solution under the above operating conditions, methyl parahydroxybenzoate and nalidixic acid
6 times with 10 L of the standard solution under the
above operating conditions, the relative standard deviation of the peak area of nalidixic acid is not more than
2.0%.
hours).
Assay Weigh accurately about 0.3 g of Nalidixic Acid, previously dried, dissolve in 50 mL of N,Ndimethylformamide, and titrate with 0.1 mol/L tetramethyl ammonium hydroxide VS (potentiometric titration,
Endpoint Detection Method in Titrimetry). Separately,
to 50 mL of N,N-dimethylformamide add 13 mL of a
mixture of water and methanol (89:11), perform a
blank determination with the solution, and make any
Each mL of 0.1 mL/L tetramethyl ammonium hydroxide VS = 23.22 mg of C12H12N2O3
Naloxone Hydrochloride
CH2
HCl
HO
HO
C19H21NO4HCl: 363.84
Naloxone Hydrochloride contains not less than 98.5%
and not more than 101.0% of naloxone hydrochloride
(C19H21NO4HCl), calculated on the dried basis.
Description Naloxone hydrochloride is a white to
yellowish white crystals or crystalline powder.
Naloxone Hydrochloride is freely soluble in water, soluble in methanol, slightly soluble in anhydrous ethanol
and in glacial acetic acid, and very slightly soluble in
acetic anhydride.
Naloxone Hydrochloride is hygroscopic.
Naloxone Hydrochloride is gradually colored by light.
of solutions of Naloxone Hydrochloride and Naloxone
Hydrochloride RS (1 in 10000) as directed under the
Ultraviolet-visible Spectrophotometry, respectively:
the same wavelength.
(2) Determine the infrared spectra of Naloxone Hydrochloride and Naloxone Hydrochloride RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same
wavenumbers.
(3) A solution of Naloxone Hydrochloride (1 in 50)
responds to the Qualitative Test (2) for chloride.
pH Dissolve 0.10 g of Naloxone Hydrochloride in 10
mL of freshly boiled and cooled water: the pH of the
solution is between 4.5 and 5.5.
D : -170 to -181
(0.25 g, water, 10 mL, 100 mm).
Purity Related substancesPerform the test as rapidly as possible without exposure to light, using lightresistant container. Dissolve 80 mg of Naloxone Hydrochloride in 10 mL of methanol, and use this solution
KP 9 669
add methanol to make exactly 200 mL, and use this solution as the standard solution. Perform the test with
of silica gel for thin-layer chromatography. Develop
with a mixture of ammonia saturated n-butanol and methanol (20 : 1) to a distance of about 12 cm, and air-dry
the plate. Spray evenly iron(III) chloride-potassium
hexacyanoferrate(III) TS on the plate: the number of
the spot other than the principal spot from the test solution is not more than one and it is not more intense than
Ammonia-saturated n-butanolTake 100 mL of nbutanol, add 60 mL of ammonia solution (1 in 100),
shake up and then use a layer of n-butanol.
5 hours, Use a desiccator (P2O5), for cooling).

decomposition).
Identification (1) Take 10 mL of a solution of Naphazoline Hydrochloride (1 in 100), add 5 mL of bromine TS and boil: a deep purple color develops.
(2) Take 30 mL of a solution of Naphazoline Hydrochloride (1 in 100), add 2 mL of sodium hydroxide
TS and extract with two 25 mL volumes of ether. Evaporate the combined ether extracts to dryness with the
aid of a current of air. Dry the residue at 80 C for 1
hour: the residue melts between 117 C and 120 C.
(3) Dissolve 20 mg of the residue obtained in (2) in
2 to 3 drops of dilute hydrochloric acid and 5 mL of
water and add 2 mL of Reinecke salt TS: a red-purple,
crystalline precipitate is formed.
(4) A solution of Naphazoline Hydrochloride (1 in
pH Dissolve 0.10 g of Naphazoline Hydrochloride in

10 mL of freshly boiled and cooled water: the pH of the
solution is between 5.0 and 7.0.
Assay Weigh accurately about 0.3 g of Naloxone Hydrochloride, and dissolve in 80 mL of glacial acetic acid by warming. After cooling, add 80 mL of acetic anhydride, and titrate with 0.1 mol/L perchloric acid VS
Titrimetry). Perform a blank determination, and make

1.0 g of Naphazoline Hydrochloride in 10 mL of water:
(2) Heavy metalsProceed with 1.0 g of Naphazoline Hydrochloride according to Method 2 and perform


hours).

tight containers.
Naphazoline Hydrochloride
H
N
Assay Weigh accurately about 0.4 g of Naphazoline

Hydrochloride, previously dried, dissolve in 50 mL of a
mixture of acetic anhydride and glacial acetic acid (7 :
3) and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any
= 24.674 mg of C14H14N2HCl
CH2
HCl
C14H14N2HCl: 246.74
Naphazoline Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of naphazoline hydrochloride (C14H14N2HCl).
Description Naphazoline Hydrochloride is a white,
crystalline powder, is odorless and has a bitter taste.
Naphazoline Hydrochloride is freely soluble in water,
soluble in ethanol or in glacial acetic acid, very slightly
soluble in acetic anhydride and practically insoluble in
ether.

tight containers.
Naphazoline Nitrate
H
N
CH2
HNO3
N

C14H14N2HNO3: 273.29
Naphazoline Nitrate, when dried, contains not less than
98.5% and not more than 101.0% of naphazoline nitrate
(C14H14N2HNO3).
Description Naphazoline Nitrate is a white, crystalline powder, is odorless and has a bitter taste.
Naphazoline Nitrate is freely soluble in glacial acetic
acid, soluble in ethanol sparingly soluble in water,
slightly soluble in acetic anhydride and practically insoluble in ether.
Naproxen
CH3
H
C
CH3O

pH Dissolve 0.1 g of Naphazoline Nitrate in 10 mL
of freshly boiled and cooled water: the pH of the solution is between 5.0 and 7.0.
Identification (1) Take 10 mL of a solution of Naphazolin Nitrate (1 in 100), add 5 mL of bromine TS
and boil: a deep purple color develops.
(2) Take 20 mL of a solution of Naphazoline Nitrate
(1 in 100), add 5 mL of sodium hydroxide TS and extract with two 25 mL volumes of ether. Combine the
ether extracts, evaporate to dryness with the aid of a
current of air and dry the residue at 80 o C for 1 hour:
the residue so obtained melts between 117 o C and
120 o C .
(3) A solution of Naphazoline Nitrate (1 in 20) respond to the Qualitative Tests for nitrate.
0.5 g of Naphazoline Nitrate in 50 mL of water: the solution is clear and colorless.
(2) Heavy metalsProceed with 1.0 g of Naphazolin Nitrate according to Method 2 and perform the test.
hours)
Assay Weigh accurately about 0.4 g of Naphazoline
Nitrate, previously dried, dissolve in 10 mL of glacial
acetic acid and 40 mL of acetic anhydride and titrate
with 0.1 mol/L perchloric acid VS (indicator: 3 drops of
methylrosaniline chloride TS). Perform a blank determination and make any necessary correction.
= 27.329 mg of C14H14N2HNO3
tight containers.
CO2H
C14H14O3: 230.26
Naproxen, when dried, contains not less than 98.5%
and not more than 101.0% of naproxen (C14H14O3).
Description Naproxen is a white crystal or crystalline
Naproxen is freely soluble in acetone, soluble in methanol, in dehydrated ethanol or in chloroform, sparingly soluble in ether and practically insoluble in water.
Naproxen dissolves in sodium hydroxide TS.
Identification (1) Dissolve 10 mg of Naproxen in 5
mL of methanol, add 5 mL of water, then add 2 mL of
potassium iodide TS and 5 mL of a solution of potassium iodate (1 in 100) and shake: a yellow to yellowbrown color is observed. To this solution, add 5 mL of
chloroform and shake: a pale red-purple color is observed in the chloroform layer.
(2) Take 1 mL of a solution of Naproxen in dehydrated ethanol (1 in 300), add 4 mL of hydroxylamine
perchlorate-dehydrated ethanol TS and 1 mL of N,Ndicyclohexylcarbodiimide-dehydrated ethanol TS,
shake well and allow to stand in lukewarm water for 20
minutes. After cooling, add 1 mL of ferric perchloratedehydrated ethanol TS and shake: a red-purple color is
observed.
Naproxen and Naproxen RS in dehydrated methanol (1
(4) Determine the infrared spectra of Naproxen and
Naproxen RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
25
Specific Optical Rotation [ ]D : Between +63.0

and +68.5 (0.1 g, after drying, chloroform, 10 mL, 100
mm).
Purity (1) Clarity and color of solutionPrepare
with 2.0 g of Naproxen in 20 mL of acetone: the solu-
KP 9 671
tion is clear. Perform the test with this solution as directed under the Ultraviolet-visible Spectrophotometry:
the absorbance at 400 nm is not more than 0.070.
(2) Heavy metalsProceed with 2.0 g of naproxen
Naproxen according to Method 3 and perform the test
exposure to daylight, using light-resistant vessels. Dissolve 0.10 g of Naproxen in 10 mL of a mixture of
chloroform and dehydrated ethanol (1 : 1) and use this
solution as the test solution. Pipet 2.0 mL of the test solution and add a mixture of chloroform and ethanol (1 :
1) to make exactly 100 mL. Pipet 5.0 mL of this solution, add a mixture of chloroform and ethanol (1 : 1) to
with a fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of hexane, dichloromethane, tetrahydrofuran and glacial acetic acid
(50 : 30 : 17 : 3) to a distance of about 12 cm and airdry the plate. Examine under ultraviolet light (main
spot and the spot of the starting point from the test solution are not more intense than the spot from the standard solution.
Tablets, with Naproxen.

hours).

Naproxen Tablets. Weigh accurately a portion of the
powder, equivalent to about 0.25 g of Naproxen(C14H14O3) according to the labeled amount. Proceed
as directed in the Assay under Naproxen Sodium Tablets. Seperately, weigh accurately a suitable amount of
Naproxen RS. Instead of Naproxen Sodium RS, dissolve and add a mixture of acetonitrile and water (90 :
10) to obtain a solution having 2.5 mg of Naproxen in
each mL.

Assay Weigh accurately about 0.5 g of Naproxen,
previously dried, add 100 mL of diluted methanol (4 in
5), dissolve by gentle warming, if necessary and titrate
with 0.1 mol/L sodium hydroxide VS (indicator: 3
drops of phenolphthalein TS). Perform a blank determination and make any necessary correction.
= 23.026 mg of C14H14O3
Identification Prepare a mixture of the test solution

and the standard solution (1 : 1) under the Assay and
perform the test as directed under the Assay. The chromatogram so obtained exhibits two main peaks, corresponding to naproxen and the internal standard.
Dissolution Test Perform the test with 1 tablet of Naproxen Tablets at 50 revolutions per minutes according
to Method 2 under the Dissolution Test, using 900 mL
of 0.1 mol/L of phosphate buffer (pH 7.4). Take dissolved solution after 45 minutes from the start of the
test and filter. Dilute this solution with the phosphate
buffer, if necessary and use this solution as the test solution. Separately, weigh accurately a portion of Naproxen RS, make the same concentration with the test
solution and use this solution as the standard solution.
Determine the absorbances, AT and AS, of the test solution and the standard solution, respectively, at 332 nm
as directed under the Ultraviolet-visible Spectrophotometry.
The dissolution rate of Naproxen Tablets in 45 minutes
0.1 mol/L phosphate buffer (pH 7.4)Prepared by
dissolving 2.62 g of sodium phosphate, monobasic and
11.50 g of anhydrous dibasic sodium phosphate in water to make 1000 mL
ment.
Amount (mg) of naproxen (C14H14O3) = 10 C
QT
QS
C: Concentration of Naproxen RS in the standard

solution (g/mL).
Naproxen Tablets
Naproxen Sodium
Naproxen Tablets contain not less than 90.0% and not
more than 110.0% of the labeled amount of naproxen
(C14H14O3: 230.26).
Prepare as directed under

CH3
H
C
CO2Na
CH3O
C14H13NaO3: 252.24
Naproxen Sodium, when dried, contains not less than
98.0% and not more than 102.0% of naproxen sodium
(C14H13NaO3).
Description Naproxen Sodium is a white to pale yellowish, white crystalline powder.
Naproxen Sodium is soluble in water or in methanol,
sparingly soluble in ethanol, very slightly soluble in
acetone and practically insoluble in chloroform or in toluene.
of solutions of Naproxen Sodium and Naproxen Sodium RS in methanol (1 in 40000) as directed under the
Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Naproxen Sodium and Naproxen Sodium RS, previously dried, as
the Infrared Spectrophotometry: both spectra exhibits
D : Between -15.3
and -17.0 (0.5 g, after drying, 0.1 mol/L sodium hydroxide TS, 10 mL, 100 mm).
Purity (1) Heavy metalsDissolve 1.0 g of Naproxen Sodium in 20 mL of water in a separatory funnel,
add 5 mL of 1 mol/L hydrochloric acid TS and extract
with successive 20 mL, 20 mL and 10 mL volumes of
dichloromethane. Discard the dichloromethane extracts,
proceed with the aqueous layer and perform the test according to Method 1. Prepare the control solution with
2.0 mL of standard lead solution (not more than 20
ppm).
(2) Related substancesDissolve about 0.1 g of
Naproxen Sodium, accurately weighed, in 5 mL of
ethanol and use this solution as the test solution. Separately, dissolve a suitable quantity of Naproxen Sodium
RS in methanol to obtain a standard solution having a
known concentration of about 20 mg per mL. Pipet 1.0
mL, 3.0 mL and 5.0 mL of this solution and add methanol to make exactly 100 mL, respectively. Pipet 1.0 mL
each of these solutions, add methanol to make exactly
10 mL and use these solutions as the standard solutions
(1), (2) and (3). Perform the test with the test solution
and the standard solutions (1), (2) and (3) as directed
of the test solution and the standard solutions (1), (2)
and (3) on a plate of silica gel for thin-layer chromatography. Then, develop the plate with a mixture containing toluene, tetrahydrofuran and glacial acetic acid
plate. Examine under ultraviolet light (main wavelength: 254 nm): the Rf values of the principal spot
obtained from the test solution and the standard solution are the same and the spots other than the principal
spot obtained from the standard solution (3). The spots
other than the principal spot are not more than 2.0% of
total spots, as compared to those obtained from the
standard solutions (1), (2) and (3), respectively (0.1%,
0.3% and 0.5%, respectively).
(3) Free naproxenDissolve about 5.0 g of Naproxen Sodium in 25 mL of water in a separatory funnel and extract the solution with three 15 mL volumes
of chloroform. Evaporate the combined extracts on a
steam-bath to dryness. Dissolve the residue in 10 mL of
a mixture of methanol and water (3 : 1), previously
neutralized with 0.1 mol/L sodium hydroxide VS to the
phenolphthalein end-point. Add phenolphthalein TS
and titrate with 0.1 mol/L sodium hydroxide VS: not
more than 2.2 mL is consumed (not more than 1.0%).
105 C, 3 hours).
Assay Dissolve about 0.2 g of previously dried Naproxen Sodium, accurately weighed, in 50 mL of glacial acetic acid previously neutralized with 0.1 mol/L
perchloric acid VS using 2 drops of p-naphtholbenzeine,
if necessary and titrate with 0.1 mol/L perchloric acid
VS.
= 25.224 mg of C14H13NaO3
Naproxen Sodium Tablets

Naproxen Sodium Tablets contain not less than 90.0%
and not more than 110.0% of the labeled amount of naproxen sodium (C14H13NaO3: 252.25).
Tablets, with Naproxen Sodium.
Identification (1) Transfer a portion of finely powdered Naproxen Sodium Tablets, equivalent to about
0.25 g of Naproxen Sodium, to a centrifuge tube and
add 12 mL of water and 1 mL of hydrochloric acid: a
white precipitate is produced. Centrifuge the mixture:
the clear, supernatant solution responds to the Qualitative Tests for sodium salt.
(2) Prepare a mixture of the test solution and the
standard solution (1 : 1) under the Assay and perform
KP 9 673
the test as directed under the Assay. The chromatogram
so obtained exhibits two main peaks, corresponding to
Naproxen and the internal standard.
Dissolution Test Perform the test with 1 tablet of Naproxen Sodium Tablets at 50 revolutions per minutes
according to Method 2 under the Dissolution Test, using 900 mL of 0.1 mol/L of phosphate buffer (pH 7.4)
as the dissolution solution. Take dissolved solution after 45 minutes from the start of the test, filter, if necessary and dilute with the dissolution solution to obtain a
solution having a concentration of about 50 g/mL of
naproxen sodium (C14H13NaO3) and use this solution as
the test solution. Separately, weigh a portion of Naproxen Sodium RS, dissolve in the dissolution solution
to make a solution containing 50 g/mL and use this
solution as the standard solution. Determine the absorbances, AT and AS, of the test solution and the standard
solution, respectively, at 332 nm as directed under the
The dissolution rate of Naproxen Sodium Tablets in 45
0.1 mol/L phosphate buffer (pH 7.4)Prepared by
dissolving 2.62 g of monobasic sodium phosphate and
11.50 g of anhydrous dibasic sodium phosphate in water to make 1000 mL.
ment.

Naproxen Sodium Tablets and transfer an accurately
weighed portion of the powder, equivalent to about 275
mg of naproxen sodium (C14H13NaO3), to a volumetric
flask. Add 10 mL of water and shake until it is completely dispersed. Dilute with acetonitrile to make exactly 100 mL and mix. Allow any insoluble matter to
settle, then transfer 1.0 mL of the clear supernatant solution to a volumetric flask, add 2.0 mL of the internal
standard solution, dilute with the mobile phase to make
exactly 100 mL, mix and use this solution as the test
solution. Separately, dissolve an accurately weighed
quantity of Naproxen Sodium RS in the mobile phase
to obtain a solution having a known concentration of
about 2.75 mg per mL. Transfer 1.0 mL of the resulting
solution and 2.0 mL of the internal standard solution to
a volumetric flask, dilute with the mobile phase to
make 100 mL, mix and use this solution as the standard
Liquid Chromatography according to the following operating conditions and calculate the ratios, QT and
QS , of the peak area of Naproxen Sodium to that of the
internal standard, for the test solution and the standard
Amount (mg) of naproxen sodium (C14H13NaO3)
QT
QS
= 10 C
C: Concentration of Naproxen Sodium RS in the

standard solution (g/mL).
Internal standard solutionAcetonitrile solution of
butyrophenone (1 in 2000).
Mobile phase: A mixture of acetonitrile, water and
glacial acetic acid (50 : 49 : 1).
System suitability
operating conditions, Naproxen Sodium and internal
above operating conditions, the relative standard deviation of the ratios of the peak area of Naproxen Sodium
Neomycin Sulfate
HO
O
HO
R1
NH2
O
R2
OH
OH
H2N
OH
NH2
NH2
OH
3H2SO4
OH
Neomycin B: R1 = H
Neomycin C: R1 = CH2NH2
NH2
R2 = CH2NH2
R2 = H
Neomycin Sulfate is the sulfate of a mixture of aminoglycoside substances having antibacterial activity produced by the growth of Streptomyces fradiae Waksman.
Neomycin Sulfate contains not less than 600 g (potency) of neomycin (C23H46N6O13: 614.65) per mg, calculated on the dried basis
Description Neomycin Sulfate is a white to light yellowish white powder, and is odorless.

Neomycin Sulfate is very soluble in water, and practically insoluble in ethanol or in ether.
Identification (1) Dissolve 5 mg of Neomycin Sulfate in 1 mL of sulfuric acid, and mix with shaking: the
solution is colorless. To this solution add 6 ~ 8 mL of
water, the color does not change.
(2) To 5 mL of aqueous solution of Neomycin Sulfate (1 in 1000), add 1 mL of ninhydrin TS and 0.5 mL
of pyridine, and boil for 10 minutes: blue-purple color
develops.
(3) A solution (1 in 20) responds to the tests for sulfate.
tively. Perform the test with these solutions according

to the Cylinder-plate method (I 8) as directed under

tight containers.
Neostigmine Bromide
CH3
pH The pH of a solution obtained by dissolving 0.33

g of Neomycin Sulfate in 10 mL of water is between
5.0 and 7.5.
Sterility Test It meets the requirement, when Neomycin Sulfate is used in a sterile preparation.
Assay The Cylinder-plate method (1) Agar media
for seed and base layerPeptone
6.0 g Sodium chloride 2.5 g
Yeast extract
3.0 g Glucose
1.0 g
Meat extract
1.5 g Agar
15.0 20.0 g
Water
1000 mL
Mix all the ingredients, and sterilize. Adjust the pH of
the solution so that it will be 7.8 to 8.0 after sterilization.
(2) Test organism and the suspension of test organism- Staphylococcus aureus ATCC 6538 P. The suspension of test organism has 80 % of transmission at 650
nm.
(3) Weigh accurately an amount of Neomycin Sulfate, equivalent to about 20 mg (potency), dissolve in
0.1 mol/L phosphate buffer solution, pH 8.0 to make
the solution so that each mL contains 1 mg (potency),
and use the solution as the test stock solution. Take exactly a suitable amount of the test stock solution, add
solutions so that each mL contains 80.0 g (potency)
and 20.0 g (potency), and use these solutions as the
high concentration test solution and low concentration
test solution, respectively. Separately, weigh accurately
an amount of Neomycin Sulfate RS previously dried,
equivalent to about 20 mg (potency), dissolve in 0.1
mol/L phosphate buffer solution, pH 8.0 to make the
solution so that each mL contains 1 mg (potency), and
use the solution as the standard stock solution. Keep the
standard stock solution at not exceeding 5 C and use
within 30 days. Take exactly a suitable amount of the
standard stock solution, add 0.1 mol/L phosphate buffer
solution, pH 8.0 to make solutions so that each mL contains 80.0 g (potency) and 20.0 g (potency), and use
these solutions as the high concentration standard solution and low concentration standard solution, respec-
H3C
CH3
Br
O
C
O
N(CH3)2
C12H19BrN2O2 : 303.20
Neostigmine Bromide contains not less than 98.0% and
not more than 102.0% of neostigmine bromide
(C12H19BrN2O2), calculated on the anhydrous basis.
Description Neostigmine Bromide is a white, crystalline powder, is odorless and has a bitter taste.
Neostigmine Bromide is very soluble in water, soluble
in ethanol and practically in soluble in ether.
A solution of Neostigmine Bromide is neutral.
Neostigmine Bromide and Neostigmine Bromide RS as
(2) A solution of Neostigmine Bromide (1 in 50) responds to the Qualitative Tests for bromide.
Melting Point Between 171 C and 176 C (with decomposition).
Purity Sulfate Dissolve 0.25 g of Neostigmine
Bromide in 10 mL of water, add 1 mL of 3 mol/L hydrochloric acid TS and 1 mL of barium chloride TS: no
turbidity is produced immediately.
hours).
Assay Weigh accurately about 0.75 g of Neostigmine
Bromide, dissolve in 70 mL of glacial acetic acid and
20 mL of mercuric sulfate TS and titrate with 0.1 mol/L
hyperchloric acid VS to blue (indicator: methylrosaniline chloride TS 4 drops). Perform a blank determina-
KP 9 675
tion and make any necessary correction.
Each mL of 0.1 mol/L hyperchloric acid VS
= 30.320 mg of C12H19BrN2O2

Neostigmine Methylsulfate
CH3
H3C
CH3
CH3SO4
O
O
N(CH3)2
C13H22N2O6S: 334.39
Neostigmine Methylsulfate, when dried, contains not
less than 98.0% and not more than 102.0% of neostigmine methylsulfate (C13H22N2O6S).
Description Neostigmine Methylsulfate is a white,
crystalline powder.
Neostigmine Methylsulfate is very soluble in water and
freely soluble in ethanol.
of solutions of Neostigmine Methylsulfate and Neostigmine Methylsulfate RS (1 in 2000) as directed under
Neostigmine Methylsulfate and Neostigmine Methylsulfate RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
pH Dissolve 1.0 g of Neostigmine Methylsulfate in
10 mL of freshly boiled and cooled water. The pH of
this solution is between 3.0 and 5.0.
1.0 g of Neostigmine Methylsulfate in 10 mL of water:
(2) SulfateDissolve 0.20 g of Neostigmine Methylsulfate in 10 mL of water, add 1 mL of dilute hydrochloric acid and 1 mL of barium chloride TS: no
turbidity is observed immediately.
(3) DimethylaminophenolDissolve 0.10 g of
Neostigmine Methylsulfate in 5 mL of water, add 1 mL
of sodium hydroxide TS and while cooling with ice,
add 1 mL of diazobenzenesulfonic acid TS: no color is
observed.
hours).
Assay Weigh accurately about 25 mg each of Neostigmine Methysullfate and Neostigmine Methylsulfate
RS, previously dried, dissolve each in the mobile phase
to make exactly 50 mL and use these solutions as the
and the standard solution as directed under the Liqiud
conditions and determine the peak areas, AT and AS ,
neostigmine methylsulfate in the test and the standard
solutions, respectively.
Amount (mg) of neostigmine methylsulfate
(C13H22N2O6S: 334.39) = amount (mg) of
A
Neostigmine Methylsulfate RS T
AS
about 25 C.
Mobile phase: Dissolve 3.12 g of sodium dihydrogen phosphate dihydrate in 1000 mL of water, adjust
the pH to 3.0 with phosphoric acid, and add 0.871 g of
sodium 1-pentanesulfonate to dissolve. To 890 mL of
this solution, add 110 mL of acetonitile.
time of Neostigmine Methylsulfate is about 9 minutes.
System suitability
System performance: Dissolve 25 mg of Neostigmine Methylsulfate and 4 mg of dimethylaminophenol in 50 mL of the mobile phase. When the procedure
is run with 10 L of this solution under the above operating conditions, dimethylaminophenol and Neostigmine Methylsulfate are eluted in this order with a resolution between their peaks being not less than 6.0.
above operating conditions, the relative standard deviation of the peak areas of Neostigmine Methylsulfate is
not more than 1.0%.
Neostigmine Methylsulfate
Injection
Neostigmine Methylsulfate Injection is an aqueous solution for injection. Neostigmine Methylsulfate Injec-
KP 9 677
tion contains not less than 93.0% and not more than
107.0% of the labeled amount of neostigmine methylsulfate (C13H22N2O6S: 334.39).
Method of Preparation Prepare as directed under Injections, with Neostigmine Methylsulfate.
Netilmicin Sulfate
OH
O
CH3
NH
H2N
CH3
OH
Description Neostigmine Methylsulfate Injection is a

clear, colorless liquid. Neostigmine Methylsulfate Injection is gradually affected by light.
pHBetween 5.0 and 6.5
O
5H2SO4
O
NH2
OH
NH
NH2
CH3
2
Identification Transfer a volume of Neostigmine

Methylsulfate Injection, equivalent to 5 mg of Neostigmine Methylsulfate according to the labeled amount,
if necessary, add water to make 10 mL. Determine the
absorption specra of this solution as directed under the
Ultraviolet-visible Spectrophotometry: it exhibits a
maxima between 257 nm and 261 nm.
Bacterial Endotoxins Less than 5 EU per 1 mg of
Neostigmine Methylsulfate.
Assay Use Neostigmine Methylsulfate Injection as
mg of Neostigmine Methylsulfate RS, previously dried
at 105 o C for 3 hours and dissolve in the mobile phase
to make exactly 50 mL. And use this solution as the
standard solution. Proceed as directed in the Assay under Neostigmine Methylsulfate.
Amount (mg) of neostigmine methylsulfate
(C13H22N2O6S) = amount (mg) of Neostigmne
A
Methylsulfate RS T
AS
(C21H41N5O7)25H2SO4: 1441.55
Netilmicin Sulfate is the sulfate of a derivative of sisomicin.
Netilmicin Sulfate contains not less than 595 g (potency) of netilmicin (C21H41N5O7: 475.58) per mg, calculated on the dried basis
Description Netilmicin Sulfate is a white to light yellowish white powder.
of Netilmicin Sulfate and Netilmicin Sulfate RS as directed in the paste method under Infrared Spectrophotometry, both spectra exhibit similar intensities of absorption at the same wavenumvers.
(2) Dissolve an amount each of Netilmicin Sulfate
and Netilmicin Sulfate RS in water to make solutions
so that each mL contains 1 mg, and use these solutions
as the test solution and the standard solution. Perform
the test with these solutions as directed under Thinlayer Chromatography. Spot 10 L each of the test solution and the standard solution on a plate of silica gel
mixture of methanol, ammonia solution (28) and chloroform (60:30:25), and air-dry the plate. Spray evenly
1 % ninhydrin-pyridine TS on the plate: The principle
spots from the test solution and the standard solution
exhibit the same Rf value.
(3) A solution of Netilmicin Sulfate responds to the
Qualitative Tests for sulfate.
Specific Optical Rotation [ ] 20
D : +88 ~ +96 (30
mg calculated on the dried basis, water, 10 mL, 100
mm)
of Netilmicin Sulfate in 10 mL of water is between 3.5
and 5.5.
Sterility Test It meets the requirement, when Netilmicin Sulfate is used in a sterile preparation.
netilmicin, when Netilmicin Sulfate is used in a sterile
preparation.

Assay The Standard curve method (1) Media Use
1 under Microbial
the culture medium in I 2 1) (3)
Assay for Antibiotics. The pH of the media is adjusted
to 7.8 8.0.
(2) Test organism- Staphylococcus epidermidis
ATCC 12228
(3) Weigh accurately an amount of Netilmicin Sulfate, dissolve in 0.1 mol/L phosphate buffer solution,
pH 8.0 to make the solution containing 1 mg (potency)
netilmicin per mL and use the solution as the test stock
solution.. Take exactly a suitable amount of the test
stock solution, add 0.1 mol/L phosphate buffer solution,
pH 8.0 to make solution so that each mL contains 0.100
g (potency), and use the solution as the test solution.
Separately, weigh accurately an amount of Netilmicin
Sulfate RS, dissolve in 0.1 mol/L phosphate buffer solution, pH 8.0 to make the solution containing 1 mg
(potency) netilmicin per mL and use the solution as the
standard stock solution. Keep the standard solution at
not exceeding 5 C and use within 7 days. Take exactly
a suitable amount of the standard stock solution, add
solutions so that each mL contains 0.064, 0.080, 0.100,
0.125 and 0.156 g (potency), and use these solutions
as the standard solutions. Perform the test with these
solutions according to the Standard curve method (II 4)
tight containers (not exceeding 5 C).
Nicardipine Hydrochloride
H3C
H
N
CH3
O
O
CH3O
CH3
OCH2CH2NCH2
HCl
NO2
and enantiomer
C26H29N3OHCl: 515.99
Nicardipine hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of nicardipine hydrochloride (C26H29N3OHCl).
Description Nicardipine Hydrochloride is a pale
greenish yellow, crystalline powder.
Nicardipine Hydrochloride is freely soluble in methanol or in glacial acetic acid, and sparingly soluble in
dehydrated ethanol, and slightly soluble in water, in

acetonitrile or in acetic anhydride.
A solution of Nicardipine Hydrochloride in methanol (1
in 20) shows no optical rotation.
Nicardipine Hydrochloride is gradually affected by
light.
of solutions of Nicardipine Hydrochloride and Nicardipine Hydrochloride RS in dehydrated ethanol (1 in
(2) Determine the infrared spectra of Nicardipine
Hydrochloride and Nicardipine Hydrochlorid RS, previously dried, as directed in the potassium bromide disk
method under the Infrared Spectrophotometry: both exhibit similar intensity of absorption at the same wavenumbers.
(3) Dissolve 20 mg of Nicardipine Hydrochloride in
10 mL of water and 3 mL of nitric acid: the solution responds to the Qualitative Tests for chloride.
Purity (1) Heavy metalsProceed with 1.0 g of Nicardipine Hydrochloride according to Method 4 and
exposure to daylight, using light-resistant vessels. Dissolve 0.10 g of Nicardipine Hydrochloride in 50 mL of
the mobile phase and use this solution as the test solution. Pipet 1.0 mL of the test solution, add the mobile
phase to make exactly 50 mL, then take 1.0 mL of this
solution, add the mobile phase to make exactly 10 mL
standard solution as directed under the Liquid Chromatography according to the following operating conditions. Determine each peak area of both solutions by
the automatic integration method: the area of each peak
other than the peak of nicardipine from the test solution
is not larger than the peak area of nicardipine from the
standard solution and the total area of each peak other
than the peak of nicardipine from the test solution is not
more than twice the peak area of nicardipine from the
standard solution.
about 30 C.
Mobile phase: A mixture of a solution of perchloric
acid (43 in 50000) and acetonitrile (3 : 2).
KP 9 679
time of nicardipine is about 6 minutes.
System suitability
System performance: Dissolve 2 mg each of Nicardipine Hydrochloride and Nifedipine RS in 50 mL
of the mobile phase. When the procedure is run with 10
L of this solution according to the above operating
conditions, nicardipine and nifedipine are eluted in this
order with the resolution between their peaks being not
less than 3.0.
System repeatability: When test is repeated 6
deviation of the peak area of nicardipine is not more
than 3.0%.
Detection sensitivity: Take 2.0 mL of the standard solution add the mobile phase to make exactly 20
mL. Adjust the peak area of nicardipine obtained from
20 L of this solution is equivalent to 8% to 12% of the
peak area of nicardipine.
Time span of measurement: About four times as
long as the retention time of Nicardipine after the solvent peak.
hours).
Assay Perform the test without exposure to day-light,
using light-resistant vessels. Weigh accurately about
0.9 g of Nicardipine Hydrochloride, previously dried,
dissolve in 100 mL of a mixture of acetic anhydride
Nicomol
N
N
O
C
CH2
CH2 O
CH2
CH2 O
O
N
OH
C
O
N
C34H32N4O9: 640.64
Nicomol, when dried, contains not less than 98.0% and
not more than 101.0% of nicomol (C34H32N4O9).

Description Nicomol is a white, crystalline powder
and is odorless and tasteless.
Nicomol is soluble in chloroform and practically insoluble in water, in ethanol or in ether.
Nicomol dissolves in dilute hydrochloric acid or in dilute nitric acid.
Identification (1) Mix 10 mg of Nicomol with 20 mg
of 2,4-dinitrochlorobenzene, add 2 mL of dilute ethanol,
heat in a water-bath for 5 minutes, cool and add 4 mL
of potassium hydroxide-ethanol TS: a dark red color is
observed.
(2) Dissolve 0.1 g of Nicomol in 5 mL of dilute hydrochloric acid and add 5 drops of Reinecke salt TS: a
pale red precipitate is produced.
Nicomol and Nicomol RS in 1 mol/L of hydrochloric
acid TS (1 in 100000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(4) Determine the infrared spectra of Nicomol and
Nicomol RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both exhibit similar intensity of absorption
at the same wavenumbers.
1.0 g of Nicomol in 10 mL of 1 mol/L hydrochloric acid TS: the solution is clear and colorless.
(2) AcidTake 1.0 g of Nicomol, add 50 mL of
freshly boiled and cooled water, shake for 5 minutes,
filter and to 25 mL of the filtrate, add 0.60 mL of 0.01
mol/L sodium hydroxide VS and 2 drops of phenolphthalein TS: a red color is observed.
(3) ChlorideDissolve 0.6 g of Nicomol in 15 mL
of dilute nitric acid and add water to make 50 mL. Perform the test. Prepare the control solution as follows: to
0.40 mL of 0.01 mol/L hydrochloric acid VS, add 15
mL of dilute nitric acid and water to make 50 mL (not
more than 0.024%).
(4) Heavy metalsProceed with 1.0 g of Nicomol
Nicomol according to Method 3 and perform the test
(6) Related substancesDissolve 0.20 g of Nicomol in 20 mL of chloroform and use this solution as the
chloroform to make exactly 20 mL. Pipet 2.0 mL of
this solution, add chloroform to make exactly 20 mL
10 L each of the test solution and the standard solu-

tion on a plate of silica gel with a fluorescent indicator
mixture of dichloromethane, ethanol, acetonitrile and
ethyl acetate (5 : 3 : 1 : 1) to a distance of about 10 cm
hours).
Assay Weigh accurately about 1.5 g of Nicomol, previously dried, add 40.0 mL of 0.5 mol/L sodium hydroxide VS and boil gently at low temperature under a
reflux condenser connected to a carbon dioxide absorption tube (soda lime) for 10 minutes. After cooling, titrate immediately the excess sodium hydroxide with
0.25 mol/L sulfuric acid VS (indicator: 3 drops of phenolphthalein TS). Perform a blank determination and
= 80.08 mg of C34H32N4O9
Nicomol Tablets
Nicomol Tablets contain not less than 95.0% and not
more than 105.0% of the labeled amount of nicomol
(C34H32N4O9: 640.64).
Tablets, with Nicomol.
Identification Take a portion of powdered Nicomol

Tablets, equivalent to 0.5 g of Nicomol according to the
labeled amount, add 20 mL of chloroform, shake and
filter. Evaporate the filtrate on a water-bath to dryness.
Proceed with the residue as directed in the Identification (1) and (2) under Nicomol.
Dissolution Test Perform the test with 1 tablet of Nicomol Tablets at 75 revolutions per minute according to
Method 2 under the Dissolution Test, using 900 mL of
the first fluid under the Disintegration Test as the dissolution solution. Take 20 mL or more of the dissolved
solution after 60 minutes from the start of the test and
filter through a membrane filter with pore size of not
more than 0.8 m. Discard the first 10 mL of the filtrate, pipet 2.0 mL of the subsequent filtrate, add the
first fluid under the Disintegration Test to make exactly
25 mL and use this solution as the test solution. Separately, weigh accurately about 0.1 g of Nicomol RS,
previously dried at 105 C for 4 hours, dissolve in the
first fluid under the Disintegration Test to make exactly

100 mL, then pipet 2.0 mL of this solution, add the first
fluid under the Disintegration Test to make exactly 100
mL and use this solution as the standard solution. Determine the absorbances, AT and AS , of the test solution and the standard solution, respectively, at 262 nm
The dissolution rate of Nicomol Tablets in 60 minutes
Dissolution rate (%) with respect to the labeled amount
of Nicomol (C34H32N4O9)
A
1
= WS T 225
AS C
WS : Amount (mg) of Nicomol RS,
C: Labeled amount (mg) of nicomol (C34H32N4O9)
in 1 tablet.

ment.

Nicomol Tablets. Weigh accurately a portion of the
powder, equivalent to about 1 g of nicomol
(C34H32N4O9), add 100 mL of 1 mol/L hydrochloric acid TS, shake well, add water to make exactly 500 mL
and filter. Discard the first 50 mL of the filtrate, pipet
2.0 mL of the subsequent filtrate, add 50 mL of 1 mol/L
hydrochloric acid TS and water to make exactly 250
weigh accurately about 80 mg of Nicomol RS, previously dried at 105 C for 4 hours, dissolve in 50 mL
of 1 mol/L hydrochloric acid TS and add water to make
exactly 100 mL. Pipet 2.0 mL of this solution, add 20
mL of 1 mol/L hydrochloric acid TS and water to make
exactly 100 mL and use this solution as the standard solution. Determine the absorbances, AT and AS , of
the test solution and the standard solution, respectively,
at 262 nm as directed under the Ultraviolet-visible
Spectrophotometry.
Amount (mg) of nicomol (C34H32N4O9)
A
25
= amount (mg) of Nicomol RS T
AS 2
Nicotinamide
N
NH2
C
O
KP 9 681
C6H6N2O: 122.13
Nicotinamide, when dried, contains not less than 98.5
and not more than 102.0% of nicotinamide (C6H6N2O).
Description Nicotinamide is a white crystal or crystalline powder, is odorless and has a bitter taste.
Nicotinamide is freely soluble in water or in ethanol
and slightly soluble in ether.
Identification (1) Mix 5 mg of Nicotinamide with 10
mg of 2,4-dinitrochlorobenzene, heat gently for 5 to 6
seconds and fuse the mixture. Cool and add 4 mL of
potassium hydroxide-ethanol TS: a red color is observed.
(2) Take 20 mg of Nicotinamide, add 5 mL of sodium hydroxide TS and boil carefully: the gas evolved
turns moistened red litmus paper blue.
(3) Determine the absorption spectra of solutions
containing 20 mg of Nicotinamide and Nicotinamide
RS in 1000 mL of water as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
pH Dissolve 1.0 g of Nicotinamide in 20 mL of water: the pH of this solution is between 6.0 and 7.5.
1.0 g of Nicotinamide in 20 mL of water: the solution is
(2) ChlorideTake 0.5 g of Nicotinamide and perform the test. Prepare the control solution with 0.30 mL
0.021%).
(3) SulfateTake 1.0 g of Nicotinamide and perform the test. Prepare the control solution with 0.40 mL
0.019%).
(4) Heavy metalsProceed with 1.0 g of Nicotinamide according to Method 1 and perform the test.
(5) Readily carbonizable substancesTake 0.20 g
of Nicotinamide and perform the test. The solution has
no more color than Color Matching Fluid A.
Assay Weigh accurately about 25 mg each of Nicotinamide and Nicotinamide RS, previously dried, dissolve separately in 3 mL of water, and add the mobile
phase to make them exactly 100 mL each. Pipet 8 mL
each of these solutions, and add the mobile phase to
make exactly 50 mL each. Pipet 5 mL each of these so-
lutions, add exactly 5 mL each of the internal standard

solution, and use these solutions as the test solution and
the standard solution, respectively. Perform the test
calculate the ratios, QT and Q S , of the peak area of
nicotinamide to that of the internal standard for the test
Amount (mg) of nicotinamide (C6H6N2O)
Q
= amount (mg) of Nicotinamide RS T
QS
Internal standard solutionA solution of nicotinic
acid (1 in 1250).
( wavelength: 254 nm).
(particle diameter of 5 m).
about 25 C.
Mobile phase: Dissolve 1.0 g of sodium 1-heptane
sulfonate in water to make 1000 mL. To 700 mL of this
solution, add 300 mL of methanol.
Flow rate: Adjust the flow rate to make the retention time of nicotinamide being about 7 minutes.
System suitability
operating conditions, nicotinic acid and nicotinamide
above operating conditions, the relative standard deviation of the ratio of the peak area of nicotinamide to that
Nicotinamide Injection
Nicotinamide Injection is an aqueous solution for injection.
Nicotinamide Injection contains not less than 95.0%
and not more than 110.0% of the labeled amount of nicotinamide (C6H6N2O: 122.13).
Method of Preparation Prepare as directed under Injections, with Nicotinamide.

Description Nicotinamide Injection is a clear, colorless liquid.
Identification Dilute a portion of Nicotinamide Injection, equivalent to about 200 mg of nicotiamide
(C6H6N2O), with water to about 10 mL. Add 1 mL of
2.5 mol/L sodium hydroxide TS and evaporate on a
steam-bath to dryness. To the residue, add 5 mL of water and evaporate to about 1 mL. During the initial evaporation, the odor of ammonia is perceptible. Neutralize to litmus paper with 3 mol/L hydrochloric acid TS,
add 1 mL of 3 mol/L hydrochloric acid TS in excess
and place the solution in a refrigerator for 2 hours.
Then, filter, wash the precipitated nicotinamide with
small portion of ice cold-water until free from chloride,
and dry at 105 C for 1 hour. Separately, Nicotiamide
RS is similarly processed as indicated above. Measure
the infrared spectra of the test and the standard specimen as directed in the potassium bromide disk method
under the Infrared Spectrophotometry: both spectra exhibits similar intensities of absorption at the same wavenumbers.
pH
Between 5.0 and 7.0

Nicotinamide Injection.
Assay Measure exactly a volume of Nicotinamide Injection, equivalent to about 50 mg of nicotinamide
(C6H6N2O) and add water to make exactly 500 mL. Pipet 10.0 mL of this solution, add water to make exactly
100 mL and use this solution as the test solution. Weigh
accurately about 50 mg of Nicotinamide RS, previously
dried in vacuum in a desiccator (silica gel) for 4 hours
and prepare the standard solution in the same manner
as the test solution. Measure 2.0 mL each of the test solution and the standard solution, add 10 mL each of
boric acid-potassium chloride-sodium hydroxide buffer
solution, pH 9.2 and 3 mL each of cyanogen bromide
TS and allow to stand at 40 C for 60 minutes. Cool
immediately with ice and add boric acid-potassium
chloride-sodium hydroxide buffer solution, pH 9.2, to
make exactly 25 mL. Perform the test with the subsequent solutions as directed under the Ultraviolet-visible
Spectrophotometry, using a solution prepared with 2
mL of water in the same manner as the blank. Determine the absorbances, AT and AS , of the subsequent
solutions of the test solution and the standard solution,
respectively, at 398 nm.

Amount (mg) of nicotinamide (C6H6N2O)
A
= amount (mg) of Nicotinamide RS T
AS
tainers.
Nicotinic Acid
N
CO2H
C6H5NO2: 123.11
Nicotinic Acid, when dried, contains not less than
99.5% and not more than 101.0% of nicotinic acid
(C6H5NO2).
Description Nicotinic Acid is a white crystal or crystalline powder, is odorless and has a slightly acid taste.
Nicotinic Acid is sparingly soluble in water, slightly soluble in ethanol and very slightly soluble in ether.
Nicotinic Acid dissolves in sodium hydroxide TS or
sodium carbonate TS.
Identification (1) Triturate 5 mg of Nicotinic Acid
with 10 mg of 2,4-dinitrochlorobenzene and fuse the
mixture by gentle heating for 5 to 6 seconds. Cool and
add 4 mL of potassium hydroxide-ethanol TS: a dark
containing 20 mg of Nicotinic Acid and Nicotinic Acid
RS in 1000 mL of water as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
pH Dissolve 0.20 g of Nicotinic Acid in 20 mL of
water: the pH of this solution is between 3.0 and 4.0.
0.20 g of Nicotinic Acid in 20 mL of water: the solution
(2) ChloridePerform the test with 0.5 g of Nicotinic Acid. Prepare the control solution with 0.30 mL of
0.021%).
(3) SulfateDissolve 1.0 g of Nicotinic Acid in 3
mL of dilute hydrochloric acid and water to make 50
0.40 mL of 0.005 mol/L sulfuric acid VS and 3 mL of
dilute hydrochloric acid and dilute with water to make
50 mL (not more than 0.019%).
KP 9 683
(4) Nitro compoundsDissolve 1.0 g of Nicotinic
Acid in 8 mL of sodium hydroxide TS and add water to
make 20 mL: the solution has no more color than Color
Matching Fluid A.
(5) Heavy metalsProceed with 1.0 g of Nicotinic
bances of this solution , A1 and A2, at each wavelength

of maximum and minimum absorption, respectively:
the ratio A2/ A1 is between 0.35 and 0.39.

hour).


Assay Weigh accurately about 0.3 g of Nicotinic Acid,

with 0.1 mol/L sodium hydroxide VS (indicator: 5
drops of phenolphthalein TS).
= 12.311 mg of C6H5NO2
Nicotinic Acid Injection

Nicotinic Acid Injection is an aqueous solution for injection. Nicotinic Acid Injection contains not less than
of nicotinic acid (C6H5NO2: 123.11).
Method of Preparation Prepare as directed under Injections, with Nicotinic Acid. Nicotinic Acid Injection
may contain sodium carbonate or sodium hydroxide as
a solubilizer.

Assay Measure exactly a volume of Nicotinic Acid

Injection, equivalent to about 0.1 g of nicotinic acid
(C6H5NO2) and add the mobile phase to make exactly
100 mL. Pipet 10.0 mL of this solution, add 10.0 mL of
the internal standard solution, then add the mobile
phase to make exactly 100 mL and use this solution as
the test solution. Separately, weigh accurately about 0.1
g of Nicotinic acid RS, previously dried at 105 o C for
1 hour and dissolve in the mobile phase to make exactly 100 mL, pipet 10.0 mL of this solution, add 10.0 mL
of the internal standard solution, then add the mobile
the standard solution. Perform the test with 10L each
under the Liquid Chromatography according to the following operating conditions and calculate the ratios,
QT and Q S , of the peak area of Nicotinic Acid to
that of the internal standard, for the test solution and
Amount (mg) of nicotinic acid (C6H5NO2)
Q
= amount (mg) of Nicotinic acid RS T
QS
Description Nicotinic Acid Injection is a clear, colorless liquid.

Internal standard solutionA solution of Caffeine

in the mobile phase (1 in 1000).
Identification (1) Take a volume of Nicotinic Acid

Injection, equivalent to 0.1 g of Nicotinic Acid, according to the labeled amount, add 0.3 mL of dilute hydrochloric acid and evaporate on a water-bath to 2 mL.
After cooling, collect the precipitated crystals, wash
with small volumes of ice-cold water until the last
washing shows no turbidity on the addition of silver nitrate TS and dry at 105 C for 1 hour: the crystals melt
between 234 C and 238 C. With the crystals, proceed
as directed in the Identification (1) under Nicotinic Acid.
(2) Dissolve 20 mg of the dried crystals obtained in
(1) in water to make 1000 mL, and determine the absorption spectrum as directed under the Ultravioletvisible Spectrophotometry: it exhibits a maximum between 261 nm and 263 nm, and a minimum between
235 nm and 239 nm. Separately, determine the absor-
about 35 C.
Mobile phase: Dissolve 1.1 g of sodium 1octanesulfonate in a mixture of 0.05 mol/L sodium dihydrogen phosphate TS, pH 3.0 and methanol (4 : 1) to
make 1000 mL.
time of Caffeine is about 9 minutes.
System suitability

operating conditions, Nicotinic Acid and the internal
above operating conditions, the relative standard deviation of the ratios of the peak area of nicotinic acid to
tainers.
Nifedipine
H3C
H3CO
H
N
CH3
OCH3
NO2
C17H18N2O6: 346.34
Nifedipine, when dried, contains not less than 98.0%
and not more than 102.0% of nifedipine (C17H18N2O6).
Description Nifedipine is a yellow, crystalline powder and is odorless and tasteless.
Nifedipine is freely soluble in acetone or in dichlormethane, sparingly soluble in methanol, in ethanol or in
glacial acetic acid, slightly soluble in ether and practically insoluble in water.
Nifedipine is affected by light.
Identification (1) Dissolve 50 mg of Nifedipine in 5
mL of ethanol and add 5 mL of hydrochloric acid and 2
g of zinc powder. Allow to stand for 5 minutes and filter. Perform the test with the filtrate as directed under
the Qualitative Tests for primary aromatic amines: a
red-purple color is observed.
Nifedipine and Nifedipine RS in methanol (1 in
(3) Determine the infrared spectra of Nifedipine
and Nifedipine RS, previously dried, as directed in the
Spectrophotometry: both exhibit similar intensity of
0.5 g of Nifedipine in 5 mL of acetone: the solution is
clear and yellow.
(2) ChlorideTake 2.5 g of Nifedipine, add 12 mL

of dilute acetic acid and 13 mL of water and heat to
boil. After cooling, filter and discard the first 10 mL of
the filtrate. To 5 mL of the subsequent filtrate, add 6
mL of dilute nitric acid and water to make 50 mL and
0.021%).
(3) SulfateTake 4 mL of the filtrate obtained in
(2) and add 1 mL of dilute hydrochloric acid and water
to make 50 mL. Perform the test. Prepare the control
solution with 0.45 mL of 0.005 mol/L sulfuric acid VS
(not more than 0.054%).
(4) Heavy metalsProceed with 2.0 g of Nifedipine according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
Nifedipine according to Method 3 and perform the test
(6) Basic substancesPerform the test without exposure to light using light-resistant vessels. Dissolve
5.0 g of Nifedipine in 80 mL of a mixture of acetone
and acetic acid (5 : 3) and titrate with 0.02 mol/L perchloric acid VS (potentiometric titration). Perform a
blank determination and make any necessary correction: not more than 1.9 mL of 0.02 mol/L perchloric acid VS is consumed.
(7) Related substancesPerform the test quickly
without exposure to light using light-resistant vessels.
Weigh accurately 25 mg of Nifedipine, dissolve in 25
mL of methanol, add the mobile phase to make exactly
250 mL and use this solution as the test solution. Separately, weigh precisely a suitable amount of Nifedipine
RS and dissolve in methanol to render the concentration of 1 mg in 1 mL. Pipet accurately a portion of this
solution, add mobile phase to render the concentration
of 0.3 mg in 1 mL and use this solution as the standard
solution for nifedipine. In addition, weigh a suitable
portion of nifedipine nitrophenylpyridine analog RS,
dissolve in methanol to render the concentration of the
solution to be 1 mg in 1 mL. Pipet accurately a portion
of this solution, add mobile phase to render the concentration of 0.6 mg in 1 mL and use this solution as the
standard solution (1). Weigh a suitable portion of nifedipine nitrosophenylpyridine analog RS, dissolve in
methanol to render the concentration of the solution to
be 1 mg in 1 mL. Pipet accurately a portion of this solution, add mobile phase to render the concentration of
0.6 g in 1 mL and use this solution as the standard solution (2). Transfer accurately 5 mL each the standard
solution (1) and the standard solution (2) to a container,
add 5 mL to the container and use the solution as the
standard solution for nifedipine related substances. Perform the test with 25 L each of the test solution and
the standard solutions as directed under the Liquid
Measure the peak areas of the nifedipine anlalogs in the
test ( AT ) and the standard ( AS ) solution to determine
KP 9 685
the amount of the nifedipine analogs: the amounts for
nifedipine nitrophenylpyridine analog and nifedipine
nitrosophenylpyridine analog are not more than 0.2%.
Use the operating conditions indicated under the
Assay of Nifedipine Capsule.
2 hours).
Assay Perform the test protecting from the exposure
to daylight, using light-resistant vessels. Weigh accurately about 0.12 g of Nifedipine and dissolve in methanol to make exactly 200 mL. Measure 5.0 mL of this
solution and add methanol to make exactly 100 mL.
Determine the absorbance of this solution, A, at the
wavelength of a maximum absorption at about 350 nm,
Amount (mg) of nifedipine (C17H18N2O6)
A
=
40000
142.3
tight containers.
Nifedipine Capsules
Nifedipine Capsules contains not less than 90.0% and
not more than 110.0% of labeled amount of nifedipine
(C17H18N2O6: 346.34).
Capsules, with Nifedipine.
Identification (1) Transfer the contents of 3 Nifedipine Capsules to a centrifuge tube, add 20 mL of 0.1
mol/L sodium hydroxide TS and 25 mL of dichloromethane. Insert a stopper, invert several times, and carefully release the pressure in the tube. Insert the stopper
again, and shake gently for 1 hour. Centrifuge the tube
for 10 minutes at 2000 to 2500 revolution per minute,
use the clarified lower layer as the test solution. Separately, transfer a portion of Nifedipine RS, dissolve in
dichloromethane to contain 1.2 mg per mL, and use this
solution as the standard solution. Mix equal volumes of
the standard solution and the test solution, use this solution as the mixture. Perform the test with these solutions as directed under the Thin-layer Chromatography.
Spot 500 L each of the test solution, the standard solution and the mixture on a plate with a 0.5 mm layer of
plate with a mixture of ethyl acetate and cyclohexane

(1 : 1), to a distance of about 15 cm and air-dry the
plate. Immediately examine the plate under UV light
(main wavelength 254 nm): each solution exhibits a
dark blue major band at a same Rf value of about 0.3.
Spray the plate with the visualizing solution: each solution exhibits a compact light orange band on a yellow
background.
(2) The retention time of the principal peak in the
chromatogram of the test solution corresponds to that in
the chromatogram of the standard solution, as obtained
in the Assay.
Visualizing solutionDissolve 3 g of bismuth subnitrate and 30 g of potassium iodide with 10 mL of 3
mol/L hydrochloric acid and add water to make 100 mL.
Prior to use, transfer exactly 10 mL of solution, add 10
mL of 3 mol/L hydrochloric acid and water to make
100 mL.
Nifedipine Capsules at 50 revolutions per minute according to Method 2 under the Dissolution Test, using
900 mL of Dissolution medium, solution 1 water. Take
the dissolved solution 20 minutes after starting the test,
filter, and use the filtrate as the test solution for the Assay. If necessary, suitably dilute with dissolution solution. Separately, weigh accurately a portion of Nifedipine RS, add the dissolution solution to make the same
concentration with the test solution, and use this solution as the standard solution. Determine the ultraviolet
absorbance at the wave length of a maximum absorbance at about 340 nm of the test solution and the standard solution as directed under the Ultraviolet-visible
Spectrophotometry using the dissolution solution as the
blank.
The dissolution rate of Nifedipine Capsules in 20 minutes is not less than 80%.
ment.
Related Substances Perform this procedure quickly

Prepare the test solution as same as that of Assay. Separately, weigh accurately suitable amount of Nifedipine
RS in methanol to make contain 1 mg per mL. Pipet
exactly suitable amount of this solution, add the mobile
phase to make contain 0.3 mg per mL and use this solution as the standard solution for nifedipine. Weigh accurately nifedipine nitrophenylpyridine analog RS, dissolve in methanol to make the concentration of 1 mg
per mL. Pipet exactly suitable amount of this solution,
add the mobile phase to render the concentration of 6
g per mL and use this solution as the standard solution
(1). Weigh accurately nifedipine nitrosophenylpyridine
analog RS, dissolve in methanol to make the concentration of 1 mg per mL. Pipet exactly suitable amount of
this solution, add the mobile phase to render the concentration of 1.5 g per mL and use this solution as the

standard solution (2). Pipet 5.0 mL each of the standard
solution (1) and (2), add 5.0 mL of the mobile phase.
Use this solution as the standard solution for nifedipine
related substances. Perform the test with 25 L each of
the test solution and the standard solutions as directed
under the Liquid Chromatography according to the following operating conditions. Determine each peak area,
AT and AS , of nifedipine related substances from
each solution, calculate the amounts of nifedipine related compounds. It is not valid unless 4-(2nitropheny)-2,6-dimethylpyrine-3,5-dicarboxylic acid,
corresponding to nifedipine nitrophenylpyridine, is not
more than 2.0 % and dimethyl 4-(2-nitrosophenyl)-2,6dimethylpyridine-3,5-dicarboxylic acid, corresponding
to nifedipine nitrosophenylpyridine, is not more than
0.5%.
Detector, Column, Column temperature, Mobile
phase, Flow rate: Proceed as directed in the operating
conditions under the Assay
System suitability
with 25 L of the mixture of the standard solution for
nifedipine and the standard solutions (1), (2) (1 : 1 : 1)
under the above operating conditions, nifedipine nitrophenylpyridine, nifedipine nitrosophenylpyridine and
nifedipine are eluted in this order. The resolution between the peak of nifedipine nitrophenylpyridine and
nifedipine nitrosophenylpyridine is not less than 1.5,
that between the peak of nitrosophenylpyridine and nifedipine is not less than 1.0.
times with 25 L of mixture according to above conditions, the relative standard deviation calculated on the
peak area of each related compound is not more than
10%.
VC AT
AS
5
C : concentration of Nifedipine in the standard solution (mg/mL)

diameter and about 25 cm in length, packed with octadecylsilyl silica gel for liquid chromatography (5 m in
particle diameter). The assistant column contains octadecylsilyl silica gels.
Mobile phase: A mixture of water, acetonitril, and
methanol (50 : 25 : 25).
System suitability
more than 1.5.
times with 25 L of the standard solution according the
above operating conditions, the relative standard deviation calculated on the peak area of Nifedipine is not
more than 1.0%.
tight containers at a temperature between 15C and
25C.
Nifuroxazide
OH
Assay Perform this procedure quickly without exposure to light using light-resistant vessels. Transfer the
contents of 5 capsules with the aid of a small amount of
methanol to a volumetric flask, quantitatively dilute
with mobile phase to obtain a total volume, V mL, of
solution having a concentration of about 0.1 mg of Nifedipine per mL. Separately, take accurately suitable
amount of Nifedipine RS, dissolve in methanol to make
contain 0.1 mg per mL. Pipet exactly suitable amount
of this solution, add the mobile phase to make contain
0.1 mg per mL. Use this solution as the standard solution. Perform the test with 25 L each of the test solution and the standard solution as directed under the
Liquid Chromatography according to the following operating conditions. Determine each peak area, AT and
AS , of Nifedipine for the test solution and the standard
solution.
Amount (mg) of nifedipine (C17H18N2O6) in 1 capsule
NO2
H
N
O
N
C12H9N3O5: 275.22
Nifuroxazide, when dried, contains not less than 98.5%
and not more than 101.5% of nifuroxazide (C12H9N3O5).
Description Nifuroxazide is a bright yellow crystalline powder.
Nifuroxazide is slightly soluble in dichloromethane or
Identification Determine the infrared spectra of Nifuroxazide and Nifuroxazide RS, both previously dried,
KP 9 687
Absorbance
E 11%
cm
(367 nm): Between 940 and 1000.
Under the protection of light, weigh accurately 10.0 mg

of Nifuroxazide, add 10 mL of ethylene glycol monomethyl ether and methanol to make exactly 100 mL.
Pipet 5.0 mL of the solution and add methanol to make
100 mL.
Purity (1) Heavy metalsProceed with 1.0 g of Nifuroxazide according to Method 2, and perform the test.
(2) Related substance IDissolve 1 g of Nifuroxazide in 10 mL of dimethylsulfoxide and use this solution as the test solution (1). To 5.5 mL of the test solution (1), add 50.0 mL of water while stirring, allow the
solution to stand for 15 minutes, filter and use the filtrate as the test solution (2). To 0.5 mL of the test solution (1), dissolve 50 mg of nifuroxazide related substance I (4-hydroxybenzohydroxazide) and add dimethylsulfoxide to make 1000 mL. To 5 mL of this solution, add 50.0 mL of water while stirring, allow the solution to stand for 15 minutes, filter and use the filtrate
as the standard solution. To 10 mL each of the test solution (2) and the standard solution, add 0.5 mL each of
phosphomolybdotungstic acid TS and 10.0 mL each of
2 mol/L sodium carbonate TS and allow the mixture to
stand for 1 hour. Determine the absorbances of the test
solution (2) and the standard solution at 750 nm as directed under the Ultraviolet-visible Spectrophotometry:
the absorbance obtained from the test solution (2) is not
greater than that from the standard solution (not more
than 0.05%).
(3) Other related substancesWeigh accurately
0.1 g of Nifuroxazide, dissolve in dimethylsulfoxide,
add the mobile phase to make exactly 100 mL and use
this solution as the test solution. Weigh accurately 10
mg of nifuroxazide related substance II (methyl parahydroxybenzoate), dissolve in 2 mL of dimethylformamide and add the mobile phase to make 20 mL. Pipet 1 mL of this solution, add the mobile phase to make
exactly 100 mL and use this solution as the standard solution (1). Weigh accurately 5 mg of Nifuroxazide and
10 mg of nifuroxazide related substance II, dissolve in
2 mL of dimethylformamide and add the mobile phase
to make 20 mL. Pipet 1 mL of this solution, add the
mobile phase to make exactly 100 mL and use this solution as the standard solution (2). Protect the test solution, the standard solution (1) and (2) from light after
the preparation and perform the test with 20 L each of
these solutions as directed under the Liquid Chromatography: the number of peak having 0.6 times the area
of the principal peak obtained from the standard solution (1) is not more than 1 from the test solution (0.3%),
the area of such peak from the test solution is greater
than 0.2 times the area of the principal peak obtained
from the standard solution (1) (0.1%) and total area of
the peaks of the related substances from the test solution is not greater than the area of the principal peak
from the standard solution (1) (0.5%). Disregard any

peak having the area not more than 0.1 times the area
of the principal peak obtained from the standard solution (1) (0.05%).
spherical octadecylsilanized silica gel for liquid chromatography (5 m in particle diameter).
(35:65).
System suitability
operating conditions, the resolution between the nifuroxazide and the related substance II is not less than 4.
With the reference retention time of nifuroxazide of 6.5
minute, the retention time of the related substance I, II,
III and IV is about 0.4, 1.2, 2.8 and 5.2 minutes, respectively.
hours).
Assay Weigh accurately about 0.2 g of Nifuroxazide,
previously dried, dissolve in 30 mL of dimethylformamide, heat, if necessary, to dissolve, add 20 mL of water and titrate with 0.1 mol/L sodium hydroxide VS
(potentiometric titration endpoint detection method in
titrimetry). Perform a blank determination and make
= 27.52 mg of C12H9N3O5
well-closed containers
Nimodipine
and enantiomer

C21H26N2O7: 418.44
Nimodipine contains not less than 98.5 % and not more
than 101.5 % of nimodipine (C21H26N2O7), calculated
on the dried basis.
Description Nimodipine is a light yellow or yellow
crystalline powder.
Nimodipine is freely soluble in ethyl acetate, sparingly
soluble in ethanol and practically insoluble in water.
Nimodipine is affected by light.
Nimodipine shows crystalline polymorphism.
Nimodipine and Nimodipine RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
is same as that from the standard solution.
D : Between -10 and
+10 (1g, acetone, 20 mL, 100 mm).
40 mg of Nimodipine, dissolve in 2.5 mL of tetrahydrofuran, add the mobile phase to make exactly 25 mL and
accurately about 40 mg of Nimodipine RS, dissolve in
2.5 mL of tetrahydrofuran, add the mobile phase to
the mobile phase to make 100 mL, pipet 2.0 mL of this
and use this solution as the standard solution (1). Weigh
accurately about 20 mg of nimodipine related substance
I [2-methoxyethyl 1-methylethyl 2,6-dimethyl-4-(3nitrophenyl)pyridine-3,5-dicarboxylate], dissolve in 2.5
mL of tetrahydrofuran, add the mobile phase to make
exactly 25 mL, pipet 5.0 mL of this solution, add the
mobile phase to make exactly 100 mL and use this solution as the standard solution (2). Pipet 2.5 mL of the
standard solution (1), add the mobile phase to make exactly 100 mL and use this solution as the standard solution (3). Pipet 1.0 mL each of the standard solution (2)
and the test solution, transfer to a 25 mL volumatic
flask, add the mobile phase to make exactly 25 mL and
use this solution as the standard solution (4). Perform
the test with 20 L each of the test solution, the standard solution (1) and the standard solution (4) as directed under the Liquid Chromatography according the
following operating conditions and determine the area
of the peak of each related substance in the test solution,
A i , and the area of the peak of the related substance I
in the standard solution (4), A S : the related substance
I is not more than 0.1%, each related substance other
than the related substance I is not more than 0.2%, and
the total related substances is not more than 0.5%.
Content (%) of each related substance

A
= 100 C i
AS
C: Concentration (mg/mL) of nimodipine related
substance I in the standard solution (4).
with octadecylsilanized silica gel for liquid chromatography (3-10 m in particle diameter).
about 40 C.
Mobile phase: A mixture of water, methanol and tetrahydrofuran (3:1:1).
System suitability
operating conditions, the relative retention time for the
peak of the related substance I and of nimodipine is 0.9
and 1.0, respectively, with the resolution between these
two peaks being not less than 1.5.
times with 20 L each of the standard solution (4) under the above operating conditions, the relative standard deviation of the peak area of nimodipine is not
more than 2.0%.
4 hours).
Assay Weigh accurately about 0.180 g of Nimodipine,
add to a mixture of 25 mL of t-butyl alcohol and 25 mL
perchloric acid TS and heat gently to dissolve. Cool
and titrate with 0.1 mol/L cerium sulfate VS (indicator:
0.1 mL of ferroin TS). Perform a blank determination
Each mL of 0.1 mol/L cerium sulfate VS
= 20.92 mg of C21H26N2O7
tight containers and store between 15 C and 30 C.
Nitrazepam
KP 9 689
O
H
N
O 2N
C15H11N3O3: 281.27
Nitrazepam, when dried, contains not less than 99.0%
and not more than 101.0% of nitrazepam (C15H11N3O3).
Description Nitrazepam is a white to yellow crystal
Nitrazepam is freely soluble in glacial acetic acid, soluble in acetone or in chloroform, slightly soluble in
methanol, in ethanol or in dehydrated ethanol, very
Identification (1) Take 3 mL of a solution of Nitrazepam in methanol (1 in 500) and add 0.1 mL of sodium hydroxide TS: a yellow color is observed.
(2) Take 20 mg of Nitrazepam, add 15 mL of dilute
hydrochloric acid, boil for 5 minutes, cool and filter:
the filtrate responds to the Qualitative Tests for primary
aromatic amines.
(3) Neutralize 0.5 mL of the filtrate obtained in (2)
with sodium hydroxide TS, add 2 mL of ninhydrin TS
and heat on a water-bath: a purple color is observed.
of Nitrazepam and Nitrazepam RS in dehydrated ethanol (1 in 100000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
0.10 g of Nitrazepam in 20 mL of acetone: the solution
is clear and pale yellow in color.
(2) Heavy metalsProceed with 1.0 g of Nitrazepam according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
Nitrazepam according to Method 3 and perform the test
(4) Related substancesDissolve 0.25 g of Nitrazepam in 10 mL of a mixture of methanol and chloroform (1 : 1) and use this solution as the test solution.
Pipet 1.0 mL of the test solution, add a mixture of methanol and chloroform (1 : 1) to make exactly 20 mL.
Pipet 2.0 mL of this solution, add a mixture of methanol and chloroform (1 : 1) to make exactly 50 mL and
directed under the Thin-layer Chromatography. Spot 10

mixture of nitromethane and ethyl acetate (17 : 3) to a
Loss on Drying Not more than 0.5% (1 g, 105 o C , 4
hours).
Assay Weigh accurately about 0.4 g of Nitrazepam,
previously dried and dissolve in 40 mL of glacial acetic
acid. Titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any
= 28.127 mg of C15H11N3O3
tight containers.
Nitrendipine
and enantiomer
C18H20N2O6: 360.36
Nitrendipine, when dried, contains not less than 98.5%
and not more than 101.0% of nitrendipine
(C18H20N2O6).
Description Nitrendipine is a yellow crystalline
powder.
Nitrendipine is soluble in acetonitrile, sparingly soluble
in methanol or in dehydrated ethanol and practically insoluble in water.
Nitrendipine is gradually colored to brownish yellow
by light.
A solution of Nitrendipine in acetonitrile (1 in 50)
of solutions of Nitrendipine and Nitrendipine RS in

methanol (1 in 80000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared spectra of Nitrendipine
and Nitrendipine RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Purity (1) Heavy metalsProceed with 2.0 g of Nitrendipine according to Method 4, and perform the test.
(2) Related substancesPerform the test quickly
Dissolve 40.0 mg of Nitrendipine in 5 mL of acetonitrile, add the mobile phase to make exactly 25 mL and
use this solution as the test solution. Pipet 1.0 mL of
the test solution, add the mobile phase to make exactly
conditions and determine the area of the peak other
than the principal peak in the test solution, Ai, and the
area of the nitrendipine peak in the standard solution,
AS, by the automatic integration method: the related
substance having the retention time relative to nitrendipine of about 0.8 is not more than 1.0%, the related
substance having the retention time relative to nitrendipine of about 1.3 is not more than 0.25%, the individual
amount of any other related substances is not more than
0.2%, and the total amount of related substances other
than nitrendipine is not more than 2.0%.
Content (%) of each related substance =
Ai
AS
Column: A stainless steel column about 6 mm in
about 25 C.
Mobile phase: A mixture of water, tetrahydrofuran
and acetonitrile (14:6:5).
Flow rate: Adjust the flow rate so that the retention time of nitrendipine is about 12 minutes.
System suitability
Test for required detectability: Pipet accurately 2
mL of the standard solution and add the mobile phase
to make exactly 10 mL. Confirm that the peak area of
nitredipine from 10 L of this solution is equivalent to
between 14% and 26% of that from the standard solu-
tion.
System performance: Dissolve 10 mg of Nitrendipine and 3 mg propyl parahydroxybenzoate in 5 mL
of acetonitrile and add the mobile phase to make 100
mL. When the procedure is run with 5 L of this solution under the above operating conditions, propyl parahydroxybenzoate and nitrendipine are eluted in this order with the resolution between their peaks being not
less than 6.
deviation of the peak area of nitrendipine is not more
than 2.0%.
long as the retention time of nitrendipine beginning after the solvent peak.
2 hours).
Assay Weigh accurately about 0.3 g of Nitrendipine,
previously dried, add 60 mL of sulfuric acid in dehydrated ethanol (3 in 100), add 50 mL of water and titrate with 0.1 mol/L ceric ammonium sulfate VS (indicator: 3 drops of o-phenanthroline TS) until the brownish-red color of the solution disappears. Perform a
Each mL of ceric ammonium sulfate VS
= 18.02 mg of C18H20N2O6
tight containers.
Nitroglycerin Tablets
Nitroglycerin Tablets contain not less than 80.0% and
not more than 120.0% of the labeled amount of nitroglycerin (C3H5N3O9: 227.09).
the Tablets, with nitroglycerin.
Identification (1) Weigh a portion of powdered Nitroglycerin Tablets, equivalent to 6 mg of nitroglycerin
(C3H5N3O9) according to the labeled amount, shake
thoroughly with 12 mL of ether, filter and use the filtrate as the test solution. Evaporate 5 mL of the test solution, dissolve the residue in 1 to 2 drops of sulfuric
acid and add 1 drop of diphenylamine TS: a deep blue
color is observed.
(2) Evaporate 5 mL of the test solution obtained in
(1), add 5 drops of sodium hydroxide TS, heat over a
low flame and concentrate to about 0.1 mL. Cool and
heat the residue with 20 mg of potassium bisulfate: the
KP 9 691
odor of acrolein is perceptible.
Purity Free nitrate ionTransfer an accurately
measured portion of powdered Nitroglycerin Tablets,
equivalent to 20 mg of nitroglycerin (C3H5N3O9) according to the labeled amount, to a separatory funnel,
add 40 mL of isopropylether and 40 mL of water, shake
for 10 minutes, collect the aqueous layer, filter and use
the filtrate as the test solution. Separately, transfer 10
mL of standard nitric acid solution to a separatory funnel, add 30 mL of water and 40 mL of the isopropyl
ether layer of the first extraction of the test solution,
shake for 10 minutes, continue the procedure in the
same manner as the test solution and use this solution
as the standard solution. Transfer 20 mL each of the test
solution and the standard solution to Nessler tubes,
shake well with 30 mL of water and 60 mg of GriessRomijins nitric acid reagent, allow to stand for 30 minutes and observe the tubes horizontally: the test solution has no more color than the standard solution.
Disintegration Test It meets the requirement, provided that the time limit of the test is 2 minutes and the
use of the auxiliary disks is omitted.
Uniformity of Dosage Units It meets the requirement when the content uniformity test is performed according to the following procedure. Transfer 1 tablet of
Nitroglycerin Tablets to a glass-stoppered centrifuge
tube and add exactly V mL of glacial acetic acid to
make a solution containing about 30 g of nitroglycerin
(C3H5N3O9) per mL. Shake vigorously for 1 hour and
after disintegrating the tablet, centrifuge and use the
supernatant liquid as the test solution. When the tablet
does not disintegrate during this procedure, transfer 1
tablet of Nitroglycerin Tablets to a glass-stoppered centrifuge tube, wet the tablet with 0.05 mL of glacial acetic acid and grind with a glass rod. While rinsing the
glass rod, add glacial acetic acid to make exactly V mL
of a solution containing about 30 g of nitroglycerin
(C3H5N3O9) per mL. Shake for 1 hour, centrifuge and
use the supernatant liquid as the test solution. Separately, weigh accurately about 90 mg of potassium nitrate,
previously dried at 105 C for 4 hours, dissolve in 5 mL
of water and add glacial acetic acid to make exactly
100 mL. Pipet 5.0 mL of the solution, add glacial acetic
acid to make exactly 100 mL and use this solution as
the standard solution. Measure exactly 2 mL each of
the test solution and the standard solution, add 2.0 mL
each of salicylic acid TS, shake, allow to stand for 15
minutes and add 10 mL each of water, cooling with ice.
Render the solution alkaline with about 12 mL of a solution of sodium hydroxide (2 in 5) while cooling in ice
and add water to make exactly 50 mL. Perform the test
with the test solution and the standard solution as directed under the Ultraviolet-visible Spectrophotometry,
using a solution prepared with 2 mL of glacial acetic
acid in the same manner, as the blank. Determine the
absorbances, AT and AS , of the subsequent solutions
of the test solution and the standard solution at 410 nm,
respectively.
Amount (mg) of nitroglycerin (C3H5N3O9)
= amount (mg) of Potassium nitrate RS 0.7487
AT
V
2000
AS
Assay Weigh accurately and disintegrate, by soft

pressing, not less than 20 Nitroglycerin Tablets. Weigh
accurately a portion of the powder, equivalent to about
3.5 mg of Nitroglycerin (C3H5N3O9), add exactly 50
mL of glacial acetic acid, shake for 1 hour, filter and
use this filtrate as the test solution. Separately, weigh
accurately about 90 mg of potassium nitrate, previously
dried at 105 C for 4 hours, dissolve in 5 mL of water
and add glacial acetic acid to make exactly 100 mL. Pipet 10.0 mL of the solution, add glacial acetic acid to
make exactly 100 mL and use this solution as the standard solution. To 2.0 mL each of the test solution and
the standard solution, add 2 mL of salicylic acid TS,
shake, allow to stand for 15 minutes and add 10 mL of
water, cooling with ice. Render the solution alkaline
with about 12 mL of a solution of sodium hydroxide (2
in 5) while cooling in ice and add water to make exactly 50 mL. Perform the test with these solutions as directed under the Ultraviolet-visible Spectrophotometry,
using a solution, prepared with 2 mL of glacial acetic
acid in the same manner, as the blank. Determine the
absorbances, AT and AS , of the subsequent solutions
of the test solution and the standard solution at 410 nm,
respectively.
Amount (mg) of nitroglycerin (C3H5N3O9)
= amount (mg) of potassium nitrate
A
1
0.7487 T 20
A
S

tight containers at not more than 20 C.
Nitrous Oxide
N2O: 44.01
Nitrous Oxide contains not less than 97.0 vol% and not
more than 101.0 vol% of nitrous oxide (N2O).
Description Nitrous Oxide is a colorless gas at room
temperature and at atmospheric pressure and is odorless.
Nitrous Oxide is soluble in ether or in fatty oils.
1 mL of Nitrous Oxide dissolves in 1.5 mL of water or
0.4 mL of ethanol at 20 C and at 101.3 kPa.
1000 mL of Nitrous Oxide at 0 C and at 101.3 kPa
weighs about 1.96 g.
Identification (1) A glowing splinter of wood held in

Nitrous Oxide: it bursts into flame immediately.
(2) Transfer 1 mL each of Nitrous Oxide and nitrous oxide directly from metal cylinders with a pressurereducing valve to gas measuring tubes or syringes for
gas chromatography, using a polyvinyl chloride induction tube. Perform the test with these gases as directed
under the Gas Chromatography according to the operating conditions under the Assay: the retention time of
the main peak from Nitrous Oxide corresponds with
that of nitrous oxide.
Purity Maintain the containers of Nitrous Oxide between 18 C and 22 C for more than 6 hours before
the test and correct the volume at 20 C and at 101.3
kPa.
(1) Acid or alkaliTake 400 mL of freshly boiled
and cooled water, add 0.3 mL of methyl red TS and 0.3
mL of bromthymol blue TS and boil for 5 minutes.
Transfer 50 mL of this solution to each of three Nessler
tubes marked A, B and C. Add 0.10 mL of 0.01 mol/L
hydrochloric acid VS to tube A, 0.20 mL of 0.01 mol/L
hydrochloric acid VS to tube B, stopper each of the
tubes and cool. Pass 1000 mL of Nitrous Oxide through
the solution in tube A for 15 minutes, employing delivery tube with an orifice approximately 1 mm in diameter and extending to within 2 mm of the bottom of
the Nessler tube: the color of the solution in tube A is
not deeper orange-red than that of the solution in tube
B and not deeper yellow-green than that of the solution
in tube C.
(2) Carbon dioxidePass 1000 mL of Nitrous
Oxide through 50 mL of barium hydroxide TS in a
Nessler tube, in the same manner as directed in (1): any
turbidity produced does not exceed that produced in the
Control solutionTake 50 mL of barium hydroxide
TS in a Nessler tube, add 1 mL of a solution of 0.1 g of
sodium bicarbonate in 100 mL of freshly boiled and
cooled water.
(3) Oxidizing substancesTransfer 15 mL of potassium iodide-starch TS to each of two Nessler tubes
marked A and B, add 1 drop of glacial acetic acid to
each of the tubes, shake and use these solutions as solution A and solution B, respectively. Pass 2 L of Nitrous
Oxide through solution A for 30 minutes in the same
manner as directed in (1): the color of solution A is the
same as that of the stoppered, untreated solution B.
(4) Potassium permanganate and reducing substancePour 50 mL of water into each of two Nessler
tubes marked A and B, add 0.10 mL of 0.02 mol/L potassium permanganate VS to each of the tubes and use
these solutions as solutions A and B, respectively. Pass
1000 mL of Nitrous Oxide through solution A in the
manner as directed in (1): the color of solution A is the
same as that of solution B.
(5) ChloridePour 50 mL of water into each of
two Nessler tubes marked A and B, add 0.5 mL of silver nitrate TS to each of the tubes, shake and use these
solutions as solutions A and B, respectively. Pass 1000

mL of Nitrous Oxide through solution A in the same
manner as directed in (1): the turbidity of solution A is
the same as that of solution B.
(6) Carbon monoxideIntroduce 5.0 mL of Nitrous Oxide into a gas-cylinder or a syringe for gas
chromatography from a metal cylinder holding gas under pressure and fitted with a pressure-reducing valve,
through a directly connected polyvinyl tube. Perform
the test according to the Gas Chromatography under the
following conditions: no peak is observed at the same
retention time as that of carbon monoxide.
Detector: A thermal conductivity detector.
Column: A column, about 3 mm in inside diameter
and about 3 m in length, packed with 300 m to 500
m zeolite for gas chromatography (0.5 nm in pore
size).
Column temperature: A constant temperature of about
50 C.
Carrier gas: Hydrogen.
time of carbon monoxide is about 20 minutes.
System suitability
System performance: Take 0.1 mL each of carbon monoxide and air in a gas mixer, add carrier gas to
make 100 mL and mix well. When the procedure is run
with 5.0 mL of the mixed gas under the above operating conditions, oxygen, nitrogen and carbon monoxide
are eluted in this order with well resolved peaks.
Detection sensitivity: Adjust the sensitivity so
that the peak height of carbon monoxide obtained from
5.0 mL of the mixed gas used in the system performance is about 10 cm.
Assay Take Nitrous Oxide as directed in the Purity.
Introduce 1.0 mL of Nitrous Oxide into a gasmeasuring tube or syringe for gas chromatography
from a metal cylinder under pressure through a pressure-reducing valve and a directly connected polyvinyl
tube. Perform the test with this gas as directed under
the Gas Chromatography according to the following
operating conditions and determine the peak area, AT ,
of nitrogen. Separately, introduce 3.0 mL of nitrogen
into a gas mixer, add carrier gas to make exactly 100
mL, mix thoroughly and use this gas as the standard
mixed gas. Proceed with 1.0 mL of this mixture in the
same manner and determine the peak area, AS , of nitrogen.
Amount (vol%) of nitrous oxide (N2O) = 100 3
AT
AS
Detector: A thermal conductivity detector.
and about 3 m in length, packed with silica gel for gas
KP 9 693
about 50 C.
Carrier gas: Hydrogen.
time of nitrogen is about 2 minutes.
System suitability
System performance: Take 3.0 mL of nitrogen in
a gas mixer, add nitrous oxide to make 100 mL and mix
well. When the procedure is run with 1.0 mL of the
mixed gas under the above operating conditions, nitrogen and nitrous oxide are eluted in this order with well
resolved peaks.
times with the standard mixed gas under the above operating conditions, the relative standard deviation of the
peak area of nitrogen is not more than 2.0%.
Packaging and Storage Preserve in metal cylinders
hermetic containers. Store at not exceeding 40 C.
Nizatidine
NH
CH3
O2N
H3C
N
HN
S
CH3
C12H21N6O2S2: 331.46
Nizatidine contains not less than 98.0% and not more
than 101.0% of nizatidine (C12H21N6O2S2), calculated
on the anhydrous basis.
Description Nizatidine is a white or buff, crystalline
powder.
Nizatidine is freely soluble in glacial acetic acid, soluble in methanol, sparingly soluble in water, slightly
soluble in acetic anhydride, in dehydrated ethanol or in
isopropanol and practically insoluble in ether.
Nizatidine and Nizatidine RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
Purity (1) Heavy metalsProceed with 0.1 g of Nizatidine according to Method 2, and perform the test.
50 mg of Nizatidine, add a mixture of ammonium acetate buffer and methanol (76:24) to make exactly 10

weigh accurately about 50 mg of Nizatidine RS, add a
mixture of ammonium acetate buffer and methanol
(76:24) to make exactly 100 mL, pipet 5.0 mL of this
solution, add a mixture of ammonium acetate buffer
and methanol (76:24) to make exactly 50 mL and use
this solution as the standard solution (1). Pipet two portions of the standard solution (1), dilute each with a
mixture of ammonium acetate buffer and methanol
(76:24) to render the concentrations of 25 g per mL
and 15 g per mL, respectively, and use these solutions
as the standard solution (2) and the standard solution
(3), respectively. Perform the test with 50 L each of
the test solution, the standard solutions (1), (2) and (3)
as directed in the peak area percentage method under
operating condition: total area of the peaks other than
the principal peak obtained from the test solution is not
more than 3 times the area of the principal peak obtained from the standard solution (2) (1.5%) and the
area of each peaks other than the principal peak from
the test solution is not more than the area of the principal peak from the standard solution (3) (0.3%).
Mobile phase A: Ammonium acetate buffer
Mobile phase B: Methanol
Adjust the composition of the mobile phase so that
the retention time of nizatidine is about 12 minutes.
Time
(min)
0-3
3-20
Mobile
phase A
(vol%)
76
7650
Mobile
phase B
(vol%)
24
2450
20-45
45-50
50
5076
50
5024
50-70
76
24
Elution
condition
Isocratic
Linear
gradient
Isocratic
Linear
gradient
Isocratic

System suitability
operating conditions, the symmetry factor for the nizatidine peak is not more than 2.0.
long as the retention time of nizatidine peak.
Ammonium acetate bufferWeigh 5.9 g of ammo-

nium acetate, dissolve in 760 mL of water to render the
concentration of the solution to be 0.1 mol/L, add 1 mL
of dimethylamine and adjust the pH to 7.5 with acetic
acid.
Loss on Drying
hour).
Not more than 1.0% (2 g, 100 C, 1

Assay Weigh accurately about 15 mg of Nizatidine,
this solution as the test solution. Separately, weigh accurately about 15 mg of Nizatidine RS, add the mobile
under the Liquid Chromatography according to the following operating conditions and determine the area of
nizatidine peak in the test solution, AT , and in the
standard solution, AS .
Amount (mg) of nizatidine (C12H21N6O2S2)
A
= amount (mg) of Nizatidine RS T
AS
Mobile phase: A mixture of ammonium acetate buffer
and methanol (76:24).
System suitability
operating conditions, the number of theoretical plates is
not less than 1500 with the symmetry factor being not
more than 2.0.
deviation of the peak area of nizatidine is not more than
1.5%.
tight containers.
Norepinephrine
H
HO
OH
C8H11NO3: 169.18
Norepinephrine, when dried, contains not less than

98.0% and not more than 101.0% of dl-norepinephrine
(C8H11NO3).
Description Norepinephrine is a white to pale brown
or slightly reddish brown, crystalline powder.
Norepinephrine is freely soluble in glacial acetic acid,
very slightly soluble in water and practically insoluble
in ethanol or in ether.
Norepinephrine dissolves in dilute hydrochloric acid
and in dilute acetic acid.
Norepinephrine gradually changes to brown in color by
air and by light.
of solutions of Norepinephrine and Norepinephrine RS
in 0.1 mol/L hydrochloric acid TS (3 in 100000) as directed under the Ultraviolet-visible Spectrophotometry:
the same wavelengths .
Noradrenaline and Noradrenaline RS, previously dried,
0.10 g of Norepinephrine in 10 mL of 0.1 mol/L hydrochloric acid TS and add water to make 100 mL: the
(2) ArterenoneDissolve 50 mg of Norepinephrine in 0.01 mol/L hydrochloric acid TS to make exactly 100 mL. Determine the absorbance of the solution at
310 nm, as directed under the Ultraviolet-visible Spectrophotometry: it is not more than 0.1.
(3) EpinephrineDissolve 10.0 mg of Norepinephrine in 2.0 mL of diluted glacial acetic acid (1 in 2).
Pipet 1.0 mL of this solution, add water to make exactly 10 mL, then mix with 0.3 mL of a solution of sodium
nitrite (1 in 100) and allow to stand for 1 minute: the
solution has no more color than the following control
solution.
Control solutionDissolve 2.0 mg of epinephrine
bitartrate RS and 90 mg of norepinephrine bitartrate RS
in water to make exactly 10 mL. Measure 1.0 mL of
this solution, add 1.0 mL of diluted glacial acetic acid
(1 in 2) and water to make exactly 10 mL, then mix
with 0.3 mL of a solution of sodium nitrite (1 in 100)
and allow to stand for 1 minute.
CCH2NH2
HO
Noradrenaline
Norepirenamine
and enatiomer
KP 9 695
Assay Weigh accurately about 0.3 g of Norepinephrine, previously dried, dissolved in 50 mL of glacial
acetic acid, for nonaqueous titration by warming, if necessary and titrate with 0.1 mol/L perchloric acid VS
until the color of the solution changes from blue-purple
through blue to blue-green (indicator: 2 drops of methylrosaniline chloride TS). Perform a blank determination and make any necessary correction.
(2) EpinephrineMeasure a volume of Norepinephrine Injection, equivalent to 5 mg of Norepinephrine according to the labeled amount, add 1 mL of diluted glacial acetic acid (1 in 2) and water to make exactly 10 mL and proceed as directed in the Purity (3)
under Norepinephrine.

= 16.918 mg of C8H11NO3

tight containers under nitrogen atmosphere and in a
cold place.

Norepinephrine Injection
Assay Transfer an exactly measured volume of Norepinephrine Injection, equivalent to about 5 mg of dlnorepinephrine (C8H11NO3), add water to make exactly
25 mL and use this solution as the test solution. Separately, weigh accurately about 10 mg of Norepinephrine
Bitartrate RS, previously dried in a desiccator (in vacuum, silica gel) for 24 hours, dissolve in water to
make exactly 25 mL and use this solution as the standard solution. Pipet 5.0 mL each of the test solution and
the standard solution, add 0.2 mL each of starch TS,
then add iodine TS drop-wise with swirling until a persistent blue color is observed. Add 2 mL of iodine TS
and shake. Adjust the pH of the solution to 6.5 with
0.05 mol/L disodium hydrogenphosphate TS, add 10
mL of phosphate buffer solution, pH 6.5 and shake.
Immediately after allowing to stand for 3 minutes, add
sodium thiosulfate TS drop-wise until a red-purple color is observed and then add water to make exactly 50
mL. Determine the absorbances, AT and AS , of the
subsequent solutions of the test solution and the standard solution, respectively, at 515 nm within 5 minutes
Noradrenaline hydrochloride injection

Norepinephrine hydrochloride injection
Norepirenamine hydrochloride injection
Norepinephrine Injection is an aqueous solution for injection.
Norepinephrine Injection contains not less than 90.0%
and not more than 110.0% of the labeled amount of dlnorepinephrine (C8H11NO3: 169.18).
Method of Preparation Dissolve Norepinephrine in
0.01 mol/L hydrochloric acid and prepare as directed
under Injections.
Description Norepinephrine Injection is a clear, colorless liquid.
The color is gradually changed to a pale red color by
light and by air.
Identification Transfer a volume of Noradrenaline
Injection, equivalent to 1 mg of Noradrenaline according to the labeled amount, to each of two test tubes A
and B, and add 1 mL of water to each tube. Add 10 mL
of potassium hydrogen phthalate buffer solution, pH
3.5, to A, and 10 mL of phosphate buffer solution, pH
6.5, to B. To each of these solutions add 1.0 mL of
iodine TS, allow to stand for 5 minutes, and add 2.0
mL of sodium thiosulfate TS : no color or a pale red
color develops in test tube A, and a deep red-purple
color develops in test tube B.
Purity (1) ArterenoneMeasure a volume of Norepinephrine Injection, equivalent to 10 mg of Norepinephrine according to the labeled amount, add water to
make exactly 20 mL and determine the absorbance of
Spectrophotometry at 310 nm: the absorbance is not
more than 0.10.

Amount (mg) of dl-norepinephrine (C8H11NO3)

= amount (mg) of Norepinephrine Bitartrate RS
A
T 0.5016
AS
hermetic containers. Colored containers may be used.
Norethisterone

H3C
CH
OH
Norethisterone Tablets
Norethindrone Tablets
C20H26O2: 298.42
Norethisterone Tablets contains not less than 90.0%

and not more than 110.0% of the labeled amount of norethisterone (C20H26O2: 298.42).
Norethisterone, when dried, contains not less than

97.0% and not more than 103.0% of norethisterone
(C20H26O2).

the Tablets, with Norethisterone.
Description Norethisterone is a white to pale yellowish white, crystalline powder and is odorless.
Norethisterone is soluble in chloroform, sparingly soluble in ethanol or in tetrahydrofuran, slightly soluble
in ether and very slightly soluble in water.
Norethisterone is affected by light.
Identification (1) Take 2 mg of Norethisterone and
add 2 mL of sulfuric acid: the solution shows a redbrown color and a yellow-green fluorescence. Add 10
mL of water to this solution cautiously: a yellow color
is observed and a yellow-brown precipitate is produced.
(2) Take 25 mg of Norethisterone and add 3.5 mL
of a solution of 50 mg of hydroxylamine hydrochloride
and 50 mg of anhydrous sodium acetate in 25 mL of
methanol. Heat under a reflux condenser in a waterbath for 5 hours, cool and add 15 mL of water. Collect
the precipitate formed, wash with 1 mL to 2 mL of water, recrystallize from methanol and dry in a desiccator
(in vacuum, silica gel) for 5 hours: the crystals melt between 112 C and 118 C.
Melting Point

20
Specific Optical Rotation [ ]D : Between -23 and

-27 (after drying, 0.25 g, chloroform, 25 mL, 200 mm).
Loss on Drying Not more than 0.5% (0.5 g, in vacuum, silica gel, 4 hours).
Assay Weigh accurately about 0.2 g of Norethisterone, previously dried, dissolve in 40 mL of tetrahydrofuran and add 10 mL of a solution of silver nitrate (1 in
20) and titrate with 0.1 mol/L sodium hydroxide VS
= 29.843 mg of C20H26O2
tight containers.
Identification Weigh a portion of powdered Norethisterone Tablets, equivalent to 50 mg of Norethisterone according to the labeled amount, add 15 mL of
hexane, shake occasionally for 15 minutes, centrifuge
the mixture and discard the hexane layer. Extract the
residues with 10 mL of hexane twice, centrifuge and
discard the hexane layer. To the residue, add 25 mL of
chloroform, shake for 1 to 2 minutes and filter. Evaporate the filtrate until it is concentrated to 3 mL, add a
suitable amount of hexane to make crystals and evaporate to dryness. Determine the infrared spectra of this
residue and Norethisterone RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
Disintegration Test It meets the requirement, provided that the time limit of the test is 15 minutes and
the use of the auxiliary disks is omitted.
ment.
Assay Weigh accurately not less than 20 Norethisterone Tablets and powder. Weigh accurately a portion of
the powder, equivalent to about 0.7 mg of norethisterone (C20H26O2), add dehydrated methanol, to make exactly 50 mL, shake occasionally and stand for 10 minutes. Filter the mixture, transfer 10.0 mL of the filtrate
to a glass-stoppered flask, add 2.0 mL of isonicotinic
hydrazine TS and stand for 30 minutes. Use this solution as the test solution. Separately, transfer 10.0 mL of
the remaining filtrate to a suitable container, add 2.0
mL of methanol and use this solution as a control solution of the test solution. Pipet 10.0 mL of methanol to a
glass-stoppered flask, add 2.0 mL of isonicotinic hydrazine reagent, shake after capping and stand for 30
minutes. Use this solution as a control solution of the
reagent solution. Separately, weigh accurately a portion
of Norethisterone RS and dissolve in methanol to make
a solution containing 14 g per mL. Pipet 10.0 mL of
this solution to a glass-stoppered flask, add 2.0 mL of
isonicotinic hydrazine TS, shake after capping and
stand for 30 minutes. Use this solution as the standard
solution. Determine the absorbances, AT , AB and
AS , of the test solution, the control solution of the test
KP 9 697
solution and the standard solution, respectively, at 380
nm as directed under the Ultraviolet-visible Spectrophotometry using methanol as a blank of the control solution of the test solution and using the control solution
of the test solution as a blank of the reagent solution
and the standard solution.
Amount (mg) of norethisterone (C20H26O2)
A AB
= 0.05 C T
AS
C: Concentration of norethisterone (C20H26O2) in
the standard solution (g/mL).
Norethisterone Acetate
H3C
OCOCH3
C
CH
Norethindrone Acetate
Norethisterone Acetate
C22H28O3: 340.46
Norethisterone Acetate contains not less than 97.0%

and not more than 103.0% of norethisterone acetate
(C22H28O3), calculated on the dried basis.
Description Norethisterone Acetate is a white to
milky white crystalline powder and is odorless.
Norethisterone Acetate is soluble in ether or in ethanol
Identification Determine the infrared spectra of Norethisterone Acetate and Norethisterone Acetate RS,
both previously dried, as directed under the potassium
D : Between -32 and 38 (calculated on the dried basis, 0.5 g, dioxane, 25
mL, 100 mm)
Purity (1) Clarity and color of solutionWhen 0.5
g of Norethisterone Acetate is dissolved in 25 mL of
dioxane, the solution is clear.
(2) Related substances1) Dissolve 0.1 g of Norethisterone Acetate in chloroform to make exactly 10
dissolve 0.1 of Norethisterone Acetate RS in chloroform to make exactly 10 mL and dilute this solution by
the addition of chloroform to render the standard solutions (1), (2), (3) and (4) having the concentration of
150, 50, 30 and 10 g in 1 mL, respectively. Perform
the test with the standard and the test solution as directed under the Thin Layer Chromatography. Then,
develop the plate with a mixture containing toluene and
ethylacetate (1 : 1) to a distance of about 15 cm and airdry the plate. Spray evenly with a mixture of methanol
and sulfuric acid and heat the plate at 100 o C for 5 minutes. The spots other than the principal spot from the
test solution are not more intense than the spot obtained
from the standard solution (2). And the total intensity
of the spots other than the principal spot from the test
solution is not more intense than that from the standard
solution (1).
2) Dissolve 62.5 mg of Norethisterone Acetate in the
mobile phase to make exactly 25 mL and use this solution as the test solution. Pipet 1.0 mL of test solution,
this as the standard solution. Perform the test with 20
directed under the Liquid Chromatography. Determine
each peak area of these solutions: the area of each peak
of the test solution, except the pricipal peak, is not
more than 1/2 of the peak area of the principal peak of
the standard solution (0.5 %). And the total area of
peaks of the test solution is not more than the area of
the principal peak of the standard solution (1.0%). Exclude the peak which has not more than 0.025 times of
the area of the principal peak of the standard solution in
the calculation of the total area.
octadecylsilanized silica gel (3-10 m) for liquid chromatography.
Mobile phase: Acetonitrile : water (6:4)
System suitability
System performance: Dissolve 8 mg each of desoxycorticosterone acetate RS and Norethisterone Acetate RS in the mobile phase to make exactly 100 mL.
When the test is performed with 20 L of the solution
as directed under the above operating conditions, desoxycorticosterone acetate and Norethisterone Acetate
Time span of measurement: About twice as long
as the retention time of Norethisterone Acetate.
(3) Ethinyl-groupWeigh accurately about 0.2 g
of Norethisterone Acetate and dissolve in 40 mL of tetrahydrofuran. Add 10 mL of silver nitrate solution (1
in 10) and tritrate with 0.1 mol/L sodium hydroxide VS

The content of ethinyl group is between 7.13 % and
7.17 %
Each mL of 0.1 mol/L sodium hydroroxide VS
= 2.503 mg of CCH
hours).
Assay Weigh accurately about 0.1 g each of Norethisterone Acetate and Norethisterone Acetate RS and dissolve in ethanol to make exactly 200 mL each. Pipet
5.0 mL each of the solution and add ethanol to make
exactly 250 mL each. Use the solution as the test solution and the standard solution, respectively. Measure
the absorbances of the test solution ( AT ) and the standard solution ( AS ) at the wavelength of 240 nm as directed under the Ultraviolet-visible Spectrophotometry.
Amount (mg) of norethisterone acetate (C22H28O3)
A
= Amount (mg) of Norethisterone Acetate RS T
AS
Norfloxacin
C2H5
HN
N
COOH
O
C16H18FN3O3: 319.33
Norfloxacin, when dried, contains not less than 99.0%
and not more than 101.0% of norfloxacin
(C16H18FN3O3).
Description Norfloxacin is a white to pale yellow
crystalline powder.
Norfloxacin is freely soluble in glacial acetic acid,
slightly soluble in anhydrous ethanol and in acetone,
very slightly soluble in methanol, and practically insoluble in water.
Norfloxacin dissolves in dilute hydrochloric acid and in
sodium hydroxide.
Norfloxacin is hygroscopic.
Norfloxacin is gradually colored by light.
Identification (1) Dissolve 10 mg of Norfloxacin and
Norfloxacin RS in a solution of sodium hydroxide (1 in
250) to make 10 mL. To 5 mL each of these solutions
add a solution of sodium hydroxide (1 in 250) to make
100 mL. Determine the absorption spectra of solutions
(2) Dissolve a suitable amount of Norfloxacin and
Norfloxacin RS in a suitable amount of acetone, evaporate the acetone under reduced pressure, and dry the residue. Determine the infrared spectra of the residues as
Purity (1) SulfatesDissolve 1.0 g of Norfloxacin
in 7 mL of 0.5 mol/L sodium hydroxide TS and 23 mL
of water, and add 1 drop of phenolphthalein TS. Add
gradually diluted hydrochloric acid (1 in 3) to this solution until the red color disappears, then add 0.5 mL of
dilute hydrochloric acid, and cool in ice for 30 minutes.
Filter through a glass filter (G4), and wash the residue
with 10 mL of water. Combine the filtrate and the
washing, and add 1 mL of dilute hydrochloric acid and
water to make exactly 50 mL and perform the test. Prepare the control solution as follows. To 0.50 mL of
0.005 mol/L sulfuric acid VS add 7 mL of 0.5 mol/L
sodium hydroxide TS and 1 drop of phenolphthalein TS,
add diluted hydrochloric acid (1 in 3) until the red color
disappears, then add 1.5 mL of dilute hydrochloric acid,
1 or 2 drops of bromophenol blue TS and water to
make exactly 50 mL (not more than 0.024%).
(2) Heavy metalsProceed with 2.0 g of Norfloxacin according to Method 2, and perform the test. Prepare the control solution with 3.0 mL of standard lead
Norfloxacin according to Method 3, and perform the
exposure to light, using light-resistant vessels. Dissolve
0.10 g of Norfloxacin in 50 mL of mixture of methanol
and acetone (1 : 1), and use this solution as the test solution. Pipet 1.0 mL of the test solution, and add a mixture of methanol and acetone (1 : 1) to make exactly
100 mL. Pipet 2.0 mL of this solution, add a mixture of
methanol and acetone (1 : 1) to make exactly 10 mL,
for thin-layer chromatography (5 m to 7 m in particle diameter). Develop the plate with a mixture of methanol, chloroform, toluene, Diethylamine and water
(20 : 20 : 10 : 7 : 4) to a distance of about 9 cm, and airdry the plate. Examine under ultraviolet light (main
wavelength: 254 nm and 366 nm): the number of the
spot other than the principal spot from the test solution
is not more than 2 and these spots are not more intense
KP 9 699
hours).
Assay Weigh accurately about 0.5 g of Norfloxacin,
previously dried, dissolve in 50 mL of glacial acetic acid, and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination, and make any
= 31.933 mg of C16H18FN3O3


hours).
Norgestrel
H3C
H2C
CH
OH
ppm).
(2) Related substancesDissolve 30 mg of Norgestrel in 5 mL of chloroform and use this solution as the
chloroform to make exactly 100 mL and use this solution as the standard solution. Perform the test with the
test solution and the standard solution on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of dichloromethane and ethyl acetate (2 : 1) to a distance of
about 10 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots
other than the principal spot from the test solution is
not more intense than the spot from the standard solution.
C21H28O2: 312.45

Assay Weigh accurately about 0.2 g of Norgestrel,
previously dried, dissolve in 40 mL of tetrahydrofuran,
add 10 mL of a solution of silver nitrate (1 in 20) and
titrate with 0.1 mol/L sodium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any
Norgestrel, when dried, contains not less than 98.0%

and not more than 101.0% of norgestrel (C21H28O2).

= 31.245 mg of C21H28O2
Description Norgestrel is a white crystal or crystalline powder.

Norgestrel is soluble in tetrahydrofuran or in chloroform, sparingly soluble in ethanol, slightly soluble in
Identification (1) Dissolve 1 mg of Norgestrel in 2

mL of ethanol and add 1 mL of sulfuric acid: a redpurple color is observed. With this solution, examine
solution shows a red-orange fluorescence.
(2) Determine the infrared spectra of Norgestrel and
Norgestrel RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
Purity (1) Heavy metalsTake 1.0 g of Norgestrel,
heat gently to carbonize, cool, add 10 mL of a solution
of magnesium nitrate in ethanol (1 in 10) and ignite the
ethanol to burn. After cooling, add 1 mL of sulfuric acid, proceed with this solution according to Method 4
Nortriptyline Hydrochloride
HCl
CHCH2CH2NHCH3
C19H21NHCl: 299.84
Nortriptyline Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of nortriptyline hydrochloride (C19H21NHCl).
Description Nortriptyline Hydrochloride is a white to
yellowish white, crystalline powder, is odorless, or has
a pale, characteristic odor.
Nortriptyline Hydrochloride is freely soluble in glacial
acetic acid or in chloroform, soluble in ethanol, sparingly soluble in water and practically insoluble in ether.
pHThe pH of a solution of Nortriptyline Hydrochloride (1 in 100) is about 5.5.

Melting pointBetween 215 C and 220 C.
Identification (1) Take 5 mL of a solution of Nortriptyline Hydrochloride (1 in 100) and add 1 mL of bromine TS: the color of the test solution disappears.
(2) Take 5 mL of a solution of Nortriptyline Hydrochloride (1 in 100) and add 1 to 2 drops of a solution of quinhydrone in methanol (1 in 40): a red color
gradually develops.
Nortriptyline Hydrochloride and Nortriptyline Hydrochloride RS (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
Nortriptyline Hydrochloride and Nortriptyline Hydrochloride RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
(5) A solution of Nortriptyline Hydrochloride (1 in
0.10 g of Nortriptyline Hydrochloride in 10 mL of water: the solution is clear and colorless to very pale yellow.
(2) Heavy metalsProceed with 1.0 g of Nortriptyline Hydrochloride according to Method 2 and perform
Nortriptyline Hydrochloride according to Method 3 and
(4) Related substancesDissolve 0.50 g of Nortriptyline Hydrochloride in 20 mL of chloroform and
use this solution as the test solution. Pipet 2.0 mL of the
test solution and add chloroform to make exactly 100
mL. Pipet 5.0 mL of this solution, add chloroform to
with a fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of cyclohexane,
methanol and diethylamine (8 : 1 : 1) to a distance of
other than the principal spot from the test solution are
hours).
Assay Weigh accurately about 0.5 g of Nortriptyline

glacial acetic acid, add 50 mL of acetic anhydride and
correction.
Noscapine
O
N
CH3
H
CH3O
O
OCH3
O
OCH3
Narcotine
C22H23NO7: 413.42
Noscapine, when dried, contains not less than 98.5%

and not more than 101.0% of noscapine (C22H23NO7).
Description Noscapine is a white crystal or crystalline powder and is odorless and tasteless.
Noscapine is very soluble in glacial acetic acid, slightly
soluble in ethanol or in ether and practically insoluble
in water.
of solutions of Noscapine and Noscapine RS (1 in
(2) Determine the infrared spectra of Noscapine and
Noscarpine RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
D : Between +42 and
+48 (after drying, 0.5 g, 0.1 mol/L hydrochloric acid
TS, 25 mL, 100 nm).
Purity (1) ChlorideDissolve 0.7 g of Noscapine in
20 mL of acetone, add 6 mL of dilute nitric acid and
water to make 50 mL and perform the test with this solution. Prepare the control solution as follows: to 0.4
mL of 0.01 mol/L hydrochloric acid VS, add 20 mL of
acetone, 6 mL of dilute nitric acid and water to make
KP 9 701
50 mL (not more than 0.02%).
(2) Heavy metalsProceed with 2.0 g of Noscapine according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
(3) MorphineDissolve 10 mg of Noscapine in 1
mL of water and 5 mL of -nitroso--naphthol TS
with shaking, add 2 mL of a solution of potassium nitrate (1 in 10) and warm at 40 C for 2 minutes. Then
add 2 mL of sodium subnitrate TS and warm at 40 C
for 5 minutes. After cooling, shake the solution with 10
mL of chloroform, centrifuge and collect the aqueous
layer: the solution so obtained has no more color than a
pale red.
(4) Related substancesDissolve 0.7 g of Noscapine in 50 mL of acetone and use this solution as the
acetone to make exactly 50 mL. Pipet 5.0 mL of this
on a plate of silica gel for thin-layer chromatography.
Develop the plate with a mixture of acetone, toluene,
dehydrated ethanol and strong ammonia water (60 :
plate. Spray evenly dilute bismuth subnitrate-potassium
iodide TS for spray on the plate: the spots other than
hours).
Assay Weigh accurately about 0.8 g of Noscapine,
previously dried, dissolve in 30 mL of glacial acetic acid and titrate with 0.1 mol/L perchloric acid VS (indicator: 3 drops of methylrosaniline chloride TS). Perform
= 41.34 mg of C22H23NO7
Noscapine Hydrochloride
Hydrate
O
N
CH3
H
HCl
x H2O
CH3O
O
OCH3
O
Narcotine Hydrochloride
OCH3
C22H23NO7HClxH2O
Noscapine Hydrochloride Hydrate, when dried, contains not less than 98.0% and not more than 101.0% of
noscapine hydrochloride (C22H23NO7HCl: 449.88).
Description Noscapine Hydrochloride Hydrate is a
colorless or white crystal or crystalline powder, is odorless and has a bitter taste.
Noscapine Hydrochloride Hydrate is freely soluble in
water, in glacial acetic acid or in acetic anhydride, soluble in ethanol and practically insoluble in ether.
Identification (1) Take 1 mg of Noscapine Hydrochloride Hydrate and add 1 drop of formalin-sulfuric acid
TS: a purple color, changing to yellow-brown, is produced.
(2) Take 1 mg of Noscapine Hydrochloride Hydrate
and add 1 drop of a solution of ammonium vanadate in
sulfuric acid (1 in 200): an orange color is produced.
(3) Dissolve 20 mg of Noscapine Hydrochloride
Hydrate in 1 mL of water and add 3 drops of sodium
acetate TS: a white, flocculent precipitate is produced.
(4) Dissolve 1 mg of Noscapine Hydrochloride Hydrate in 1 mL of diluted sulfuric acid (1 in 35), shake
with 5 drops of a solution of chromotropic acid (1 in
50) and add 2 mL of sulfuric acid drop-wise: a purple
color is produced.
(5) Dissolve 0.1 g of Noscapine Hydrochloride Hydrate in 10 mL of water, make the solution alkaline
with ammonia TS and shake with 10 mL of chloroform.
Separate the chloroform layer, wash with 5 mL of water
and filter. Distil most of the filtrate in a water-bath, add
1 mL of dehydrated ethanol and evaporate to dryness.
Dry the residue at 105 C for 4 hours: the residue so
obtained melts between 174 C and 177 C.
(6) Make a solution of Noscapine Hydrochloride
Hydrate (1 in 50) alkaline with ammonia TS and filter
the precipitate. Acidify the filtrate with dilute nitric acid: the solution responds to the Qualitative Tests (2) for
chloride.
Purity MorphineDissolve 10 mg of Noscapine
Hydrochloride Hydrate in 1 mL of water, add 5mL of
-nitroso--naphthol TS and 2 mL of a solution of potassium nitrate (1 in 10) and warm at 40 C for 2 minutes. Add 1 mL of a solution of sodium nitrite (1 in
5000) and warm at 40 C for 5 minutes. After cooling,
shake the mixture with 10 mL of chloroform, centrifuge
and separate the aqueous layer: the solution so obtained

is not more colored than a pale red color.
4 hours).
lengths.
(2) Dissolve 10 mg of Nystatin in 5 mL of water
with shaking well. To this solution add two drops of the
solution of phosphomolybdic acid tungstic acid TS
and stand for 1 hour: a green color develops.

Assay Weigh accurately about 0.5 g of Noscapine
Hydrochloride Hydrate, previously dried, dissolve in 50
acid (7 : 3) and titrate with 0.1 mol/L perchloric acid
Nystatin
OH
H3C
R
OH
OH
O
CH3
OH
OH
OH
OH
O
COOH
H3C
O
O
CH3
OH
OH NH2
A1
R:
A3
R: O
OH
OH
CH3
O
OH
Nystatin A1 C47H75NO17: 926.10

Nystatin is a mixture of polyene macrolide substances
having antifungal activity produced by the growth of
Streptomyces noursei.
Nystatin contains not less than 4400 units (potency) per
mg of nystatin A1 (C47H75NO17), calculated on the dried
basis.
Description Nystatin is a white to light yellow-brown
powder.
Nystatin is very soluble in formamide, sparingly soluble in ethanol, slightly soluble in water, and practically insoluble in ether.
Identification (1) To 10 mg of each Nystatin and
Nystatin RS, add 0.25 mL of 1 mol/L sodium hydroxide TS and 50 mL of diluted methanol (4 in 5), heat at
not exceeding 50 C to dissolve, then add diluted methanol (4 in 5) to make 500 mL. Determine the absorption spectra of these solutions as directed under Ultraviolet-visible Spectrophotometry, both spectra exhibit
pH The pH of a suspension obtained by suspending

0.3 g of Nystatin in 10 mL of water is between 6.5 and
8.0.
for seed and base layer- Use the culture medium in I 2
1) (4)
(2) Test organism- Saccharomyces cerevisiae ATCC
9763
(3) Weigh accurately 10 mg (potency) of Nystatin,
dissolve in dimethylformamide to make a solution of
3000 units (potency) per mL, and use the solution as
the test stock solution. Take exactly a suitable amount
of the test stock solution, add 1 % phosphate buffer solution, pH 6.0 to make solutions so that each mL contains 300 units and 150 units (potency), and use these
solutions as the high concentration test solution and
low concentration test solution, respectively. Separately,
weigh accurately 10 mg (potency) of Nystatin RS, dissolve in dimethylformamide to make a solution of 3000
units (potency) per mL, and use this solution as the
standard solution. Keep the standard solution at not exceeding 5 C and use within 3 days. Take exactly a
suitable amount of the standard stock solution, add 1 %
phosphate buffer solution, pH 6.0 to make solutions so
that each mL contains 300 units and 150 units (potency), and use these solutions as the high concentration
standard solution and low concentration standard solution, respectively. Perform the test with these solutions
according to the Cylinder-plate method (I 8) as directed
under Microbial Assay for Antibiotics.
tight containers.
Ofloxacin
CH3
H3C
N
O
N
CO2H
F
O
and enantiomer
C18H20FN3O : 361.37
Ofloxacin, when dried, contains not less than 99.0%
KP 9 703
and mot more than 101.0% of ofloxacin (C18H20FN3O ).
Description Ofloxacin occurs as pale yellowish
white to light yellowish white, crystals or crystalline
powder.
Ofloxacin is freely soluble in glacial acetic acid,
slightly soluble in water, and very slightly soluble in
acetonitrile and in dehydrated ethanol.
A solution of Ofloxacin in sodium hydroxide TS (1 in
20) does not show optical rotation.
Ofloxacin is changed in color by light.
of the solutions of Ofloxacin and Ofloxacin RS in 0.1
mol/L hydrochloric acid TS (1 in 150000) as directed
same wavelengths.
(2) Determine the infrared spectra of Ofloxacin and
Ofloxacin RS as directed in the potassium bromide disk
same wavenumbers.
Purity (1) Heavy metalsProceed with 2.0 g of Ofloxacin according to Method 4, and perform the test.
Prepare the control solution with 2.0 mL of Standard
Lead Solution (not more than 10 ppm).
(2) Related substancesPerform this procedure
without exposure to light. Dissolve 10 mg of Ofloxacin
in 50 mL of a mixture of water and acetonitrile (6:1),
and use this solution as the test solution. Pipet 1 mL of
the test solution, and add a mixture of water and acetonitrile (6:1) to make exactly 20 mL. Pipet 1 mL of this
solution, add a mixture of water and acetonitrile (6:1)
to make exactly 10 mL, and use this solution as the
each of the sample solution and the standard solution as
the following conditions, and determine each peak area
by the automatic integration method: the area of the
peak other than ofloxacin from the test solution is not
more than 0.4 times the peak are of ofloxacin from the
standard solution, and the total area of the peaks other
than ofloxacin from the test solution is not more than
the peak area from the standard solution.
particle diameter).
about 45 C.
Mobile phase: Dissolve 7.0 g of sodium perchlorate
monohydrate and 4.0 g of ammonium acetate in 1300
mL of water, adjust the pH to 2.2 with phosphoric acid,
and add 240 mL of acetonitrile.

time of ofloxacin is about 20 minutes.
Time span of measurement: About 1.8 times as long
as the retention time of ofloxacin beginning after the
solvent peak.
System suitability
Test for required detectability: Measure 1 mL of
the standard solution, and add a mixture of water and
acetonitrile (6:1) to make exactly 20 mL. Confirm that
the peak area of ofloxacin obtained from 10 L of this
solution is equivalent to 4 to 6% of that from 10 L of
System performance: To 0.5 mL of the test solution, add 1 mL of a solution of ofloxacin demethyl substance in a mixture of water and acetonitrile (6:1) (1 in
20000) and a mixture of water and acetonitrile (6:1) to
make 100 mL. When the procedure is run with 10 L
ofloxacin demethyl substance and ofloxacin are eluted
in this order with the resolution between these peaks
being not less than 2.5.
above operating conditions, the relative standard deviation of the peak area of ofloxacin is not more than 2.0%.
Loss on Drying Not less than 0.2% (1 g, 105 C, 4
hours)
Assay Weigh accurately about 0.3 g of Ofloxacin,
previously dried, dissolve in 100 mL of glacial acetic
acid, and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any
= 36.14 mg of C18H20FN3O4
tight containers.
Omeprazole
OCH3
H
N
CH3
CH3
S
CH3O
C17H19N3O3S: 345.42
Omeprazole contains not less than not less than 98.0%
and not more than 102.0% of omeprazole
(C17H19N3O3S), calculated on the dried basis.

Description Omeprazole is a white to pale red-purple
powder.
Omeprazole is soluble in dichloromethane, in methanol
or in ethanol and practically insoluble in water.
Omeprazole and Omeprazole RS, previously dried, as
(2) Perform the test with Omeprazole according to
the Related substances (i) under the Purity: the spots
obtained from the test solution and the standard solution have the same Rf value.
Purity (1) Clarity of solutionDissolve 0.2 g of
Omeprazole in 10 mL of methanol: the solution is clear.
Perform the test with this solution as directed under the
Ultraviolet-visible Spectrophotometry, using dichloromethane as the blank: the absorbance at 440 nm is not
more than 0.10.
(2) Heavy metalsProceed with 1.0 g of Omeperazole according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
(3) Related substances(i) Weigh 1.0 g of Omeprazole and dissolve in a mixture of dichloromethane
and methanol (1 : 1) to make exactly 20 mL. Pipet 1.0
mL of this solution, add a mixture of dichloromethane
and methanol (1 : 1) to make exactly 200 mL and use
this solution as the test solution. Separately, weigh accurately 15 mg of Omeprazole RS, dissolve in a mixture of dichloromethane and methanol (1 : 1) to make
exactly 100 mL and use this solution as the standard solution (1). Pipet 10.0 mL of this solution, add a mixture
of dichloromethane and methanol (1 : 1) to make exactly 30 mL and use this solution as the standard solution
(2). Perform the test with the test solution and the standard solutions (1) and (2) as directed under the Thinlayer Chromatography. Spot 10 L each of the test solution and the standard solutions (1) and (2) on a plate
of silica gel with a fluorescent indicator for thin-layer
chromatography. Develop the plate with a mixture of
dichloromethane, saturated with ammonia, dichloromethane and isopropanol (2 : 2 : 1) to a distance of about
15 cm and air-dry the plate. Examine under ultraviolet
the principal spot from the test solution are not more intense than the spot from the standard solution (1)
(0.3%) and total intensity of the spots other than the
principal spot of the test solution is not more than 1.0%
when compared to the principal spots from the standard
solutions (1) and (2).
(ii) Weigh accurately 16 mg of Omeprazole, dissolve
in the mobile phase to make exactly 100 mL and use
this solution as the test solution (make this solution at
the time of use). Determine the amount of the related
substances with 40 L each of the test solution and the

mobile phase as directed under the Liquid Chromatography according to the following operating conditions.
The area of each peak which is not obsereved in the
mobile phase other than the principal peak compared to
the total area is not more than 0.3% and the total area
of the peaks which are not obsereved in the mobile
phase is not more than 1.0%.
Detector, column, mobile phase and flow rate: Proceed as directed under the Assay.
Time span of measurement: Not less than twice of
the retention time of Omeprazole.
60 C, 4 hours).
Assay Weigh accurately about 0.1 g of Omeprazole
and Omeprazole RS and dissolve in 50 mL each of a
mixture of 0.01 mol/L of sodium borate and acetonitrile
(3 : 1) to make exactly 50 mL. Pipet 5.0 mL each of
these solutions, add 0.01 mol/L sodium borate and acetonitrile (3 : 1) to make exactly 50 mL and use these solutions as the test solution and the standard solution, respectively. Perform the test with 20 L each of the test
Liquid Chromatography according to the following operating conditions and calculate the ratio, AT and AS ,
of the peak area of Omeprazole for the test solution and
the standard sollution, respectively.
Amount (mg) of omeprazole (C17 H19 N3O3S)
= amount (mg) of Omeprazole RS
AT
AS
Mobile phase: A mixture of the phosphate buffer
and acetonitrile (3 : 1).
System repeatability: Take 10 mL of the standard
solution, add 0.01 mol/L sodium borate and acetonitrile
mixture (3 : 1) to make 20 mL. When the test is repeated 6 times with 20 L of this solution according to
deviation of the peak areas of Omeprazol is not more
than 1.0%.
Phosphate bufferDissolve 0.725 g of sodium
monobasic phosphate and 4.472 g of sodium dibasic
phosphate in 300 mL of water and add water to make
KP 9 705
1000 mL. Take 250 mL of this solution and add water
to make 1000 mL.
at cold place.
Ondansetron Hydrochloride
Hydrate
O
H3C
HCl
2H2O
H3C
C18H19N3OHCl2H2O : 365.85
Ondansetron Hydrochloride Hydrate contains not less
than 98.0% and not more than 102.0% of ondansetron
hydrochloride (C18H19N3OHCl : 329.82), calculated
Description Ondansetron Hydrochloride Hydrate is a
white powder. Ondansetron Hydrochloride Hydrate is
soluble in water or methanol, sparingly soluble in ethanol, slightly soluble in 2-propanol or in dichloromethane, and very slightly soluble in chloroform or in
ethyl acetate.
Ondansetron Hydrochloride Hydrate and Ondansetron
Hydrochloride Hydrate RS, previously dried, as directed in the paste method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar
intensities of absorption at the same wavenumbers.
(2) Dissolve 20 mg of Ondansetron Hydrochloride
Hydrate in 2 mL of water, mix with 1 mL of 2 mol/L
nitric acid, and filter. The filtrate responds to the Qualitative Tests (2) for chlorides.
Purity (1) Related substance IWeigh accurately
about 50 mg of Ondansetron Hydrochloride Hydrate,
add mobile phase to make exactly 100 mL and use this
solution as the test solution. Separately, weigh accurately about 4.0 mg of Ondansetron Related Substance
I (1,2,3,9-Tetrahydro-9-methyl-3-methylene-4H-carba
zol-4-one) RS, dissolve in mobile phase to make 100
mL, pipet 1.0 mL of this solution, add mobile phase to
make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 L each
of the test and the standard solution as directed under
conditions, determine each peak area, AT and AS respectively, and calculate the percentage of related substance
I in the portion of ondansetron hydrochloride by the
formula (not more than 0.1%).
Amount (%) of ondansetron related substance I
C A
10 T
W AS
C : the concentration of Ondansetron Related Substance I RS in the standard solution (g/mL)

W : weight of Ondansetron Hydrochloride Hydrate
(mg)
nitrile silica gel for Liquid Chromatography (between 3
to 10 m in particle diameter).
Mobile phase: A mixture of phosphate buffer solution and acetonitrile (80 : 20).
System suitability
System performance: Dissolve 6 mg of Ondansetron Related Substance I RS and 10 mg of Ondansetron
Related Substance II (1,2,3,9-Tetrahydro-9-methyl-4Hcarbazol-4-one) RS in mobile phase to make 100 mL.
Pipet 1.0 mL of this solution and add mobile phase to
make 100 mL. When the procedure is run with 20 L of
the this solution under the above operating condition,
the relative retention times of ondansetron related substance I and ondansetron related substance II are about
0.8 and 1, respectively. with resolution, R, between
their peaks being not less than 1.5. When the procedure
is run with 20 L of the standard solution under the
above operating condition, the number of theoretical
plate is not less than 400.
System repeatability: When the test is repeated 5 times
with 20 L of the standard solution under the above operating conditions, the relative standard deviation of the
peak area of ondansetron is not more than 2.0%.
phosphate buffer solutionTo 0.02 mol/L monobasic potassium phosphate buffer add 1 mol/L sodium hydroxide TS to adjust pH of 5.4.
(2) the other related substancesA) Weigh accurately 125 mg of Ondansetron Hydrochloride Hydrate,
add methanol to make exactly 10 mL and use this solution as the test solution. Separately, weigh accurately
25 mg of Ondansetron Hydrochloride Hydrate RS, add
methanol to make exactly 100 mL. Quantitatively dilute this solution with methanol to obtain those standard solutions, designated below by letter, having the
following compositions:
Standard
solution
1
2
3
Dilution
1 in 5
1 in 10
1 in 20
Concentration (g/mL)
50
25
12.5
Percentage
(%, for comparison with
sample)
0.4
0.2
0.1
Separately, dissolve 1.0 mg of Ondansetron Related

Substance III {3-[(Dimethylamino)methyl]-1,2,3,9tetrahydro-9-methyl-4H-carbazol-4-one} RS in metha-
KP 9 707
nol to make exactly 10 mL and use this solution as the
resolution solution. Also dissolve 1.0 mg of Ondansetron Related Substance IV{6,6'-Methylene-bis[(1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1Himidazol-1-yl)-methyl]-4H-carbazol-4-one} RS in methanol to make exactly 10 mL and use this solution as
the identification solution. Perform the test with these
solutions as directed under Thin-layer Chromatography.
Spot 20 L each of the test solution and standard solutions and 10 L of the identification solution on a plate
of silica gel with fluorescent indicator for thin-layer
chromatography. For system suitability test spot 20 L
of the test solution and 10 L of the identification solution on the same place of the plate. Develop the plate
with a mixture of chloroform, ethyl acetate, methanol
and strong ammonia water (90 : 50 : 40 : 1) to a distance of about 15 cm and air-dry the plate. Examine
under ultraviolet light (main wavelength: 254 nm) and
compare the spots other than the principal spot from the
test solution with the principal spot from the standard
solution: complete resolution of the three components
of the resolution solution spot is found, and any spot
other than the principal spot from the chromatogram of
the test solution, having the same Rf value as that of the
principal spot from the identification solution, is not
larger or more intense than the principal spot from the
standard solution (0.4%); no other secondary spot from
the test solution is larger or more intense than the principal spot from the standard solution (2) (0.2 %). The
total intensity of all spots other than the principal spot
from the test solution is not more than 1.0%.
B) Proceed as directed under Assay for the test solution
and the standard solutions, and operating conditions.
Perform the test with exactly 10 L of the test solution
as directed under Liquid Chromatography, and calculate the percentage of each peak area taken by the formula: the amount of each related substance is not more
than 0.2% and the total amount of all the related substances is not more than 0.5%.
Amount (%) of each related substance = 100
Ai
AS
Ai : the peak area for each related substance in the
RS (previously determine the content of water), dissolve in mobile phase to make exactly 100 mL and use
with exactly 10 L each of the test solution and the
standard solution as directed under Liquid Chromatography according to the following conditions, and determine each peak area of ondansetron, AT and AS ,
respectively.
Amount (mg) of Ondansetron Hydrochloride =
A
500 C T
AS
C : the concentration of Ondansetron hydrochloride
RS in the standard solution (mg/mL)
nitrile silica gel for Liquid Chromatography (between 3
and 10 m in particle diameter).
Mobile phase: The mixture of pH 5.4 phosphate
buffer solution and acetonitrile (50 : 50).
Flow rate: 1.5 minute/minute.
System suitability
System performance: Dissolve 9 mg of Ondansetron Hydrochloride RS and 5 mg of Ondansetron Related Substance III RS in mobile phase to make exactly
100 mL. When the procedure is run with 10 L of this
solution under the above operating condition, the relative retention times of ondansetron and ondansetron related substance III are 1.0 and 1.1, respectively; with
the resolution, R, between their peaks is not less than
1.5. When the procedure is run with 10 L of the standard solution, the symmetry factor of the peak of ondansetron is not more than 2.0.
above operating conditions, the relative standard deviation of the peak area of ondansetron is not more than
1.5%.
test solution
AS : the total area of all peaks of each related substances
Phosphate buffer solutionTo 0.02 mol/L potassium dihydrogen phosphate buffer solution add 1 mol/L
sodium hydroxide TS to adjust pH 5.4.
Water Not less than 9.0 % and not more than 10.5 %

tight containers.

Assay Weigh accurately about 45 mg of Ondansetron
Hydrochloride Hydrate, dissolve in mobile phase to
mobile phase to make exactly 50 mL and use this solution as the test solution. Separately, weigh accurately
about 9.0 mg of Ondansetron Hydrochloride Hydrate
Orciprenaline Sulfate

HO
H
H2SO4
CCH2NHCH
OH
HO

105 C, 4 hours).
CH3
CH3

2
and enantiomer
(C11H17NO3)2H2SO4: 520.59
Orciprenaline Sulfate contains not less than 98.5% and
not more than 101.0% of orciprenaline sulfate
[(C11H17NO3)2H2SO4], calculated on the dried basis.
Description Orciprenaline Sulfate is a white crystal
or crystalline powder.
Orciprenaline Sulfate is freely soluble in water, slightly
soluble in glacial acetic acid, and practically insoluble
in ether.
A solution of Orciprenaline Sulfate (1 in 20) has no
optical rotation.
of solutions of Orciprenaline Sulfate and Orciprenaline
Sulfate RS, respectively, in 0.01 mol/L hydrochloric acid TS (1 in 10000) as directed under Ultraviolet-visible
Spectrophotometry : both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Orciprenaline
Sulfate and Orciprenaline Sulfate RS, previously dried,
the Infrared Spectrophotometry, respectively: both
same wavenumbers.
(3) A solution of Orciprenaline Sulfate (1 in 100)
responds to the Qualitative Tests for sulfate.
pH Dissolve 1.0 g of Orciprenaline Sulfate in 10 mL
1.0 g of Orciprenaline Sulfate in 10 mL of water: the
solution is clear and has no more color than the following control solution.
Control solutionTake 3 mL of Color Matching
Fluid T and add 1 mL of diluted hydrochloric acid (1 in
40).
(2) Heavy metalsProceed with 2.0 g of Orciprenaline Sulfate according to Method 2 and perform the
(3) Orciprenalone sulfateDissolve 0.200 g of
Orciprenaline Sulfate in 0.01 mol/L hydrochloric acid
TS to make exactly 20 mL. Perform the test with this
solution as directed under the Ultraviolet-visible Spectrophotometry: the absorbance at 328 nm is not more
than 0.075.
Assay Weigh accurately about 0.7 g of Orciprenaline

Sulfate, dissolve in 100 mL of glacial acetic acid by
warming in a water-bath and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
= 52.06 mg of (C11H17NO3)2H2SO4
tight containers.
Orphenadrine Hydrochloride
CH3
HCl
N
CH3
CH3
And enantiomer
C18H23NOHCl : 305.84
Orphenadrine Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of orphenadrine hydrochloride (C18H23NOHCl).
Description Orphenadrine Hydrochloride is a white
crystalline powder.
Orphenadrine Hydrochloride is freely soluble in water
or ethanol.
Orphenadrine Hydrochloride and Orphenadrine Hydrochloride RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) A solution of Orphenadrine Hydrochloride in water
(1 in 50) responds to the Qualitative Test (2) for chlorides.
Melting Point
about 160 C.
Purity (1) Clarity and color of solutionWeigh accurately 0.7 g of Orphenadrine Hydrochloride, and dissolved methanol to make exactly 10 mL: it is clear. Determine the absorbance of this solution as directed un-
KP 9 709
der Ultraviolet-visible Spectrophotometry at the wavelength of 436 nm: it is not more than 0.050.
(2) Heavy metalsProceed with 2.0 g of Orphenadrine Hydrochloride according to Method 2 and perform the test. Prepare the control solution with 2.0 mL
(3) Related substanceDissolve 0.300 g of Orphenadrine Hydrochloride in water to make 50 mL, add
2 mL of strong ammonia water and extract 3 times with
each of 10 mL of toluene. Combine the extracts, add
anhydrous sodium sulfate, shake, filter and evaporate
the filtrate at a temperature not exceeding 50 C using a
rotary evaporator. Dissolve the residue in toluene to
make exactly 20 mL and use this solution as the test solution. Separately, dissolve 20 mg of Orphenadrine
Hydrochloride RS and 20 mg of Orphenadrine Related
Substance I {(RS)-N,N-Dimethyl-2-[(3-methylphenyl)
phenylmethoxy]ethanamine} RS in 20 mL of water,
add 1 mL of strong ammonia water and extract 3 times
with each of 5 mL of toluene. Combine upper layers,
add anhydrous sodium sulfate, shake, filter and evaporate the filtrate at a temperature not exceeding 50 C
using a rotary evaporator. Dissolve the residue in toluene to make 20 mL and use this solution as the standard solution. Perform the test with exactly 2 L of the
test solution as directed under Gas Chromatography according to the following conditions, and determine and
calculate the percentage of each peak area : any related
substance is not more than 0.3%; total of related substances is not more than 1.0%. Disregard the peak of
related substance not more than 0.02%.
Amount (%) of related substance = 100
related substance I and orphenadrine in not less than

1.5.
long as the retention time of orphenadrine beginning after the solvent peak.
Sterility Test It meets the requirement. When the test
is applied to the case of using Orphenadrine Hydrochloride in preparation of sterile dosage form without the
steriligation process.
hours).
Assay Weigh accurately 0.25 g of Orphenadrine Hydrochloride, previously dried, dissolve in 50 mL of
acetic anhydride, and titrate with 0.1 mol/L perchloric
acid VS (potentiometric titration, Endpoint Detection
Method in Titrimetry). Perform a blank determination
well-closed containers or light-resistant, hermetic containers.
Oxaliplatin
Ai
AS
Ai : the peak area for each related substance obtained from the test solution
AS : the total peak area of all related substances obtained from the test solution
Column: A fused-silica column about 0.32 mm in
inside diameter and about 60 m in length, coated the
inner surface with poly(dimethyl)(diphenyl)siloxane for
Gas Chromatography 1 m in thickness.
Split ratio: about 1 : 25
Injector temperature: A constant temperature of
about 290 C.
about 240 C.
Detector temperature: A constant temperature of
about 290 C.
Carrier gas: Helium
System suitability
with 2 L of the standard solution under the above operating conditions, the resolution between the peaks of
H2
N
Pt
N
H2
C8H14N2O4Pt : 397.29
Oxaliplatin contains not less than 98.0% and not more
than 102.0% of oxaliplatin (C8H14N2O4Pt), calculated
on the dried basis.
Description Oxaliplatin is a white crystalline powder.
Oxaliplatin is slightly soluble in water, very slightly soluble in methanol, and practically insoluble in ethanol.
Identification Determine the infrared spectra of Oxaliplatin and Oxaliplatin RS, previously dried, as directed in the potassium bromide disk method under the
Infrared Spectrophotometry, respectively: both spectra
D : Between +74.5
and +74.8 (after drying, 0.250 g, water, 50 mL, 100

mm).
0.10 g of Oxaliplatin in water to make 50 mL: it is colorless and clear.
(2) Acidity and alkalinity Dissolve 0.10 g of
Oxaliplatin in water to make 50 mL, add 0.5 mL of
phenolphthalein TS, the resulting solution is colorless.
Not more than 0.6 mL of 0.01 mol/L sodium hydroxide
VS is required to change the color of the indicator to
pink.
(3) Related substancei) Related substance I :
Weigh accurately about 0.10 g of Oxaliplatin, dissolve
in water to make 50 mL and use this solution as the test
solution. Separately, weigh accurately 14.0 mg of oxaliplatin related substance I (oxalic acid), dissolve in water to make 250 mL, pipet 5.0 mL of this solution, add
the standard solution. When the procedure is run with
20 L each of the test and standard solution as directed
under Liquid Chromatography according to the above
operating condition, the peak area of the related substance I obtained from the test solution is not larger
than 2 times the area of the principal peak in the chromatogram from the test solution (0.1%).
base-deactivated octadecylsilanized silica gel for Liquid Chromatography (5 m in particle diameter).
about 40 C.
Mobile phase: the mixture of pH 6.0 phosphate buffer solution and acetonitrile (8 : 2).
Flow rate: 2 mL/minute
System suitability
System performance: Dissolve 12.5 mg of sodium nitrate in water to make 250 mL, pipet 2.0 mL of
this solution, add 25.0 mL of the standard solution and
water to make 250 mL. When the procedure is run with
20 L of this solution under the above operating condition, resolution between the peaks of nitrate and related
substance I is not less than 9. When the procedure is
run with 20 L of the standard solution under the above
operating condition, signal-to-noise ratio for the peak
of related substance I is not less than 10.
Time span of measurement: About 2 times as long as
the retention time of related substance I beginning after
the solvent peak.
pH 6.0 phosphate buffer solutionDissolve 1.36 g
of potassium dihydrogen phosphate in 10 mL of 32%
solution of tetrabutylammonium hydroxide, add water
to make 1000 ml, and adjust this solution to pH 6.0
with phosphoric acid.
ii) Related substance II : Weigh accurately about 0.10
g of Oxaliplatin, add water to make 50 mL and use this

solution as the test solution. Separately, weigh accurately about 12.5 mg of Oxaliplatin Related Substance
II RS [(SP-4-2-)-Diaqua[(1R,2R)-cyclohexane-1,2diamine-N,N']platinum(diaquodiaminocyclohexane
platinum)], dissolve in 63 mL of methanol and water to
make exactly 250 mL. To 3.0 mL of this solution add
water to make 200 mL and use this solution as the
each of the test solution and the standard solution as directed under Liquid Chromatography according to the
following conditions, the peak area of oxaliplatin related substance II from the test solution is not more
than 3.3 times the area of the principal peak in the
chromatogram from the standard solution (not more
than 0.1%).
about 40 C.
Mobile phase: A mixture of pH 3.0 phosphate buffer solution and acetonitrile (8 : 2).
System suitability
System performance: Weigh 12.5 mg of oxaliplatin related substance II RS, dissolve in 63 mL of methanol, add water to make 250 mL, adjust to pH 6.0
with a 0.02% sodium hydroxide solution. Heat for 4
hour at 70 C and allow to cool (generation of related
substance V). When the procedure is run with 20 L of
the standard solution under the above operating condition, signal-to-noise ratio for the peaks of related substance II and related substance V is not less than of 10.
long as the retention time of related substance II beginning after the solvent peak.
pH 3.0 phosphate buffer solutionTo 1.36 g of potassium dihydrogen phosphate and 1 g of sodium heptanesulfonate add 1000 mL of water to dissolve and adjust to pH 3.0 with phosphoric acid.
iii) Related substance III and other related substances : Weigh accurately 0.10 g of Oxaliplatin, dissolve in water to make exactly 50 mL and use this solution as the test solution. Separately, dissolve 10 mg of
Oxaliplatin Related Substance III {(OC-6-33)[(1R,2R)-Cyclohexane-1,2-diamineN,N'][ethanedioato(2-)-O1,O2]dihydroxyplatinum}
RS and 10 mg of Oxaliplatin RS in water to make exactly 100 mL and use this solution as the standard solution (1). Dilute 1.0 mL of the standard solution (1) to
exactly 100 mL with water and use this solution as the
standard solution (2). Dissolve 5 mg of dichlorodiami-
KP 9 711
nocyclohexaneplatinum RS in methanol to make exactly 50 mL, pipet 10 mL of this solution, add 10 mL of
the standard solution (1) and water to make exactly 100
mL and use this solution as the standard solution (3).
Weigh 0.10 g of Oxaliplatin, add 1 mL of te standard
solution (1) and water to make exactly 50 mL and use
this solution as the standard solution (4). Perform the
test with exactly 10 L each of the test and standard solutions (2), (3), and (4) as directed under Liquid Chromatography according to the following conditions : the
peak area of the related substance III of the test solution
is not more than half the peak area of related substance
III in the chromatogram from the standard solution (4)
(0.1%); the peak area of any other related substance is
not more than twice the area of the peak of oxaliplatin
in the chromatogram from the standard solution (2)
(0.1%); disregard the peak area of oxaliplatin in the
chromatogram from the standard solution (2) and the
peak of within 2 minute of retention time.
about 40 C.
Mobile phase: a mixture of pH 3.0 phosphoric acid
and acetonitrile (99 : 1)
pH 3.0 phosphoric acid : To 1000 mL of water add 0.6
mL of phosphoric acid and adjust to pH 3.0 with either
sodium hydroxide TS or phosphoric acid.
System suitability
System performance: Dissolve 5 mg of dicyclodiaminocyclohexaneplatinum RS in methanol to make
exactly 50 mL. Pipet 10 mL of this solution, add 10 mL
of standard solution (1) and water to make exactly
solution under the above operating condition, oxaliplatin related substance III, dichlorodiaminocyclohexaneplatinum, oxaliplatin are eluted in this order with the
resolutions between the peaks of dichlorodiaminocyclohexaneplatinum and oxaliplatin being not less than 2
in the chromatogram from the standard solution (3).
When the procedure is run with 10 L of the standard
solution under the above operating condition, signal-tonoise ratio is not less than 50 for the peak of related
substance III and not less than 10 for the peak of oxaliplatin in the chromatogram from the standard solution
(2).
long as the retention time of oxaliplatin beginning after
the solvent peak.
iv) Total related substances : the sum of related substances I, II, III, and other related substances is not
greater than 0.30%.
(4) Related substance IVWeigh accurately 30

mg of Oxaliplatin, dissolve in methanol to make 50 mL
and use this solution as the test solution. Dissolve 5 mg
of Oxaliplatin Related Substance IV {(SP-4-2)[(1S,2S)-Cyclohexane-1,2-diamineN,N'][ethanediato(2-)-O1,O2]platinum} RS in methanol to make exactly 100 mL and use this solution as
the standard solution (1). Pipet 15.0 mL of the standard
solution (1), add methanol to make exactly 50 mL and
use this solution as the standard solution (2). Dissolve
0.150 g of Oxaliplatin RS in methanol to make exactly
200 mL and use this solution as the standard solution
(3). Dilute 5.0 mL of the standard solution (3) to exactly 100 mL with methanol and use this solution as the
standard solution (4). To 40 mL of the standard solution
(3) add 1.0 mL of the standard solution (1) and methanol to make exactly 50 mL and use this solution as the
standard solution (5). To 4.0 mL of the standard solution (1) add 5.0 mL of the standard solution (4) and methanol to make exactly 50 mL and use this solution as
the standard solution (6). Perform the test with exactly
20 L each of the test solution and standard solutions
(5) and (6) as directed under Liquid Chromatography
according to the following conditions, the peak height
of related substance IV from the test solution is not
more than twice that of related substance IV with the
standard solution (6) (0.1%).
silica gel OC for chiral separations for Liquid Chromatography.
about 40 C.
Mobile phase: A mixture of ethanol and methanol
(3 : 7)
System suitability
operating condition, oxaliplatin and related substance
IV are eluted in this order with the resolutions between
their peaks of oxaliplatin and related substance IV being not less than 1.5. When the procedure is run with
20 L of the standard solution (5) under the above operating condition, signal-to-noise ratio is not less than
10 for the peak of related substance IV.
long as the retention time of Oxaliplatin beginning after
the solvent peak.
(5) SilverWeigh accurately 0.1000 g of Oxaliplatin, dissolve in water to make exactly 50 mL. Pipet exactly 20 L of this solution, add 0.5 mol/L nitric acid
TS to make exactly 40 L and use this solution as the
test solution. Separately, weigh accurately about 1.575
g of silver nitrate, dissolve in 0.5 mol/L nitric acid TS

to make exactly 1000 mL. Dilute adequate amount of
this solution with 0.5 mol/L nitric acid TS to make a
solution containing 10 ppb silver per each mL and use
this solution as the standard solution (1). To 20 L of
the test solution add 8 L of the standard solution (1)
and 0.5 mol/L nitric acid to make 40 L and use this
solution as the standard solution (2). To 20 L of the
test solution add 16 L of the standard solution (1) and
0.5 mol/L nitric acid to make 40 L and use this solution as the standard solution (3). Perform the test with
the test solution and standard solutions (2) and (3) as
directed in the standard addition method under the
Atomic Absorption Spectrophotometry according to the
following conditions and calculate the silver content of
the test solution.(not more than 5 ppm.)
Gas: Combustible gas- Acetylene or hydrogen.
Supporting gas-Air.
Lamp: A silver hollow cathode lamp.
Bacterial Endotoxins Less than 1.0 EU/mg (if intended for use in the manufacture of parenteral dosage
forms without a further appropriate procedure for the
removal of bacterial endotoxins).
2 hours).
Assay Weigh accurately about 50 mg each of Oxaliplatin and oxaliplatin RS, dissolve in water to make 500
mL and use the solutions as the test solution and the
solution as directed in Related substance III and other
related substances of Purity according to the above operating condition and calculate the peak area of oxaliplatin, AT and AS , respectively.
Amount (mg) of oxaliplatin (C8H14N2O4Pt)
A
= 500 C T
AS
C : concentration of oxaliplatin RS in the standard
solution (mg/mL)
Operation conditions
System suitability
System performance: Weigh 5 mg of dichlorodiaminocyclohexaneplatinum RS, add a solution, prepared by dissolving 50 mg of Oxaliplatin RS in water
to make 500 mL, to make 50 mL. When the procedure
is run with 20 L of this solution under the above operating condition, the resolution between the peaks of
dichlorodiaminocyclohexaneplatinum and oxaliplatin is
not less than 2.0.
above operating conditions, the relative standard deviation of the peak area of oxaliplatin is not more than
2.0%.
Packaging and Storage Preserve in hermetic containers if intended for use in the manufacture of parenteral dosage forms without a further appropriate procedure for the removal of bacterial endotoxins.
Oxapium Iodide
CH2
CH3
N
and enantiomer
C22H34INO2: 471.42
Oxapium Iodide, when dried, contains not less than
98.5% and not more than 101.0% of oxapium iodide
(C22H34INO2).
Description Oxapium Iodide is a white, crystalline
powder.
Oxapium Iodide is soluble in acetonitrile, methanol or
in ethanol, slightly soluble in water, acetic anhydride or
in glacial acetic acid, and practically insoluble in ether.
A solution of Oxapium Iodide in methanol (1 in 100)
has no optical rotations.
Oxapium Iodide and Oxapium Iodide RS, previously
dried, as directed in the paste method under the Infrared
Spectrophotometry, respectively; both spectra exhibit
(2) Dissolve 0.1 g of Oxapium Iodide in 10 mL of
methanol and add 2 mL of dilute nitric acid and 2 mL
of silver nitrate TS: a greenish yellow precipitate is
produced.
Oxapium Iodide according to Method 2 and perform
(2) Related substancesDissolve 50 mg of Oxapium Iodide in 100 mL of a mixture of water and acetonitrile (1 : 1) and use this solution as the test solution.
Pipet exactly 1 mL of the test solution, add a mixture of
water and acetonitrile (1 : 1) to make exactly 50 mL
standard solution as directed under the Liquid Chromatography according to the following operating condi-
KP 9 713
tions. Determine each peak area of each solution by the
automatic integration method: the total area of all peaks
other than the principal peak of the test solution is not
greater than the area of the principal peak from the
standard solution.
Column temperature: A constant temperature between 20 C and 30 C.
Mobile phase: To 57 mL of glacial acetic acid and
139 mL of triethylamine, add water to make 1000 mL.
To 50 mL of this solution, add 500 mL of acetonitrile,
10 mL of dilute acetic acid and 440 mL of water.
time of Oxapium is about 4 minutes.
System suitability
System performance: Dissolve 50 mg of Oxapium Iodide and 3 mg of benzophenone in 100 mL of
the mobile phase. When the procedure is run with 20
conditions, Oxapium and benzophenone are eluted in
this order with the resolution between their peaks being
not less than 5.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of Oxapium obtained from
50 L of the standard solution composes 5% to 15% of
the full scale.
long as the retention time of Oxapium after the peak of
iodide ion.
hours).
Assay Weigh accurately about 0.7 g of Oxapium
Iodide, previously dried, dissolve in 50 mL of a mixture
of acetic anhydride and glacial acetic acid (9 : 1) and titrate with 0.1 mol/L perchloric acid VS (potentiometric
titration, Endpoint Detection Method in Titrimetry).
correction.
= 47.14 mg of C22H34INO2
tight containers.
Oxaprozin
CO2H
C18H15NO3: 292.32
Oxaprozin, when dried, contains not less than 98.5%
and not more than 101.0% of C18H15NO3.
Description Oxaprozin is a white to yellowish white
crystalline powder.
Oxaprozin is sparingly soluble in methanol or in ethanol, slightly soluble in ether, and practically insoluble
in water.
Oxaprozin is gradually affected colored by light.
Identification Determine the infrared spectra of
Oxaprozin and Oxaprozin RS, previously dried, as directed in the potassium bromide disk method under
%
Absorbance E11cm
(after drying, 10 mg, methanol, 1000 mL).

Oxaprozin according to Method 4, and perform the test.
Oxaprozin according to Method 3, and perform the test
(3) Related substancesDissolve 0.1 g of Oxaprozin in 10 mL of methanol, and use this solution as the
test solution. Pipet exactly 1 mL of the test solution, add
methanol to make exactly 100 mL, and use this solution
as the standard solution (1). Pipet 5 mL, 3 mL, and 1
mL of the standard solution, add methanol to each to
standard solutions (2), (3) and (4), respectively. Perform
the test with these solutions as directed under Thin
Layer Chromatography. Spot 10 L each of the test solution and standard solutions (1), (2), (3) and (4) on a
plate of silica gel with fluorescent indicator for thinlayer chromatography. Develop the plate with a mixture
of ethyl acetate and glacial acetic acid (99:1) to a distance of about 15 cm, and air-dry the plate. Examine
total intensity of all spots other than the principal spot
from the test solution is not more than 1.0% calculated
on the basis of intensities of the spots from the standard
solutions (1), (2), (3) and (4).

Loss on Drying Not more than 0.3% (1 g, 105 C 2
hours)
Assay Weigh accurately about 0.5 g of Oxaprozin,
previously dried, dissolve in 50 mL of ethanol, and titrate with 0.1 mol/L sodium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination, and make any
= 29.33 mg of C18H15NO3
tight containers.
and extract with 30 mL of dichloromethane. Dehydrate

with 3 g of anhydrous sodium sulfate, filter and evaporate the dichloromethane of the filtrate. Dissolve the residue in 20 mL of methanol by heating in a water-bath
and cool immediately in an ice-bath. Collect the crystals and dry in vacuum at 60 C for 1 hour: the crystals
melt between 96 C and 100 C.
Oxazolam and Oxazolam RS, respectively, in ethanol
(1 in 100000) as directed under Ultraviolet-visible
(5) Proceed with Oxazolam as directed under the
Flame Coloration Test (2) and perform the test: a green
color is observed.
%
Absorbance E11cm
(after drying, 1 mg, ethanol, 100 mL).
Oxazolam
O
H
N
Cl
O
CH3
C18H17ClN2O2: 328.79
Oxazolam, when dried, contains not less than 99.0%
and not more than 101.0% of oxazolam
(C18H17ClN2O2).
Description Oxazolam is a white crystal or crystalline powder, is odorless and tasteless.
Oxazolam is freely soluble in glacial acetic acid, soluble in dioxane or dichloromethane, slightly soluble in
ethanol or ether, and practically insoluble in water.
Oxazolam dissolves in dilute hydrochloric acid.
Oxazolam is gradually colored by light.
Identification (1) Dissolve 10 mg of Oxazolam in 10
mL of ethanol by heating and add 1 drop of hydrochloric acid: a pale yellow color is observed and the solution
shows a yellow-green fluorescence under ultraviolet
light (main wavelength: 365 nm). Add 1 mL of sodium
hydroxide TS to this solution: the color and fluorescence of this solution disappear immediately.
(2) Dissolve 10 mg of Oxazolam in 5 mL of dilute
hydrochloric acid by heating in a water-bath for 10 minutes. After cooling, 1 mL of this solution responds to
the Qualitative Tests for primary aromatic amines.
(3) Place 2 g of Oxazolam in a flask, add 50 mL of
ethanol and 25 mL of 6 mol/L hydrochloric acid TS and
boil under a reflux condenser for 5 hours. After cooling,
neutralize with a solution of sodium hydroxide (1 in 4)
Purity (1) ChlorideTake 1.0 g of Oxazolam, add

50 mL of water, allow to stand for 1 hour with occasional shaking and filter. To 25 mL of this filtrate, add 6
0.014%).
(2) Heavy metalsProceed with 1.0 g of Oxazolam
(3) ArsenicPlace 1.0 g of Oxazolam in a Kjedahl
flask, add 5 mL of sulfuric acid and 5 mL of nitric acid
and heat gently. Repeat the addition of 2 mL to 3 mL of
nitric acid at times and continue to heat until a colorless
to pale yellow solution is obtained. After cooling, add
15 mL of saturated ammonium oxalate solution, heat
the solution until dense white fumes are evolved and
evaporate to a volume of 2 mL to 3 mL. After cooling,
dilute with water to make 10 mL and perform the test
ppm).
(4) Related substancesDissolve 50 mg of Oxazolam in 10 mL of dichloromethane and use this solution
as the test solution. Pipet exactly 1 mL of this solution,
add dichloromethane to make exactly 200 mL and use
thin-layer chromatography. Immediately air-dry, develop the plate with a mixture of toluene and acetone (8 :
Examine under ultraviolet light (wavelength: 254 nm):
any spot other than the principal spot from the test solution are not more intense than the spot from the standard solution.
Loss on Drying Not more than 0.5 % (1 g, 105 C, 3
KP 9 715
hours).
Assay Weigh accurately about 0.65 g of Oxazolam,
previously dried and dissolve in 100 mL of a mixture of
glacial acetic acid and dioxane (1 : 1). Titrate with 0.1
mol/L perchloric acid VS until the color of the solution
changes from purple through blue to blue-green (indicator: 2 drops of methylrosaniline chloride TS). Perform a blank determination and make any necessary
correction.
= 32.879 mg of C18H17ClN2O2
tight containers.
Oxethazaine
CH3 CH3
CH2
NCOCH2
CH3
NCH2CH2OH
CH3
CH2
NCOCH2
CH3 CH3
C28H41N3O3: 467.64
Oxethazaine, when dried, contains not less than 98.5%
and not more than 101.0% of oxethazaine
(C28H41N3O3).
Description Oxethazaine is a white to pale yellowish
white, crystalline power.
Oxethazaine is very soluble in glacial acetic acid, freely
soluble in methanol or ethanol, sparingly soluble in
of the solutions of Oxethazaine and Oxethazaine RS,
respectively, in ethanol (1 in 2500) as directed under
Ultraviolet-visible Spectrophotometry : both spectra
(2) Determine the infrared spectra of Oxethazaine
and Oxethazaine RS, respectively, as directed in the potassium bromide disk method under the Infrared Spectrophotometry; both spectra exhibit similar intensities
Purity (1) ChlorideDissolve 1.0 g of Oxethazaine
in 20 mL of ethanol, add 6 mL of dilute nitric acid and
control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS, 20 mL of ethanol, 6 mL of dilute nitric
(2) Heavy metalsProceed with 2.0 g of Oxethazaine according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
(3) Related substancesDissolve 0.40 g of Oxethazaine in 10 mL of ethanol and use this solution as
the test solution. Pipet exactly 1 mL of the test solution,
add ethanol to make exactly 100 mL and use this solution as the standard solution. Perform the test with the
test solution and the standard solution on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of isopropylether, tetrahydrofuran, methanol and strong ammonia water (24 : 10 : 5 : 1) to a distance of about 10
cm and air-dry the plate. Examine under ultraviolet
(4) 2-AminoethanolTake 1.0 g of Oxethazaine,
add methanol to make exactly 10 mL, then add 0.1 mL
of a solution of 2,4-dinitrofluorobenzene in methanol (1
in 25), shake well and heat at 60 C for 20 minutes: the
solution has no more color than the following control
solution.
Control solutionTake 0.10 g of 2-aminoethanol,
add methanol to make exactly 200 mL, pipet 1.0 mL of
this solution and add methanol to make exactly 10 mL.
Proceed as directed above.
60 C, 3 hours).
Assay Weigh accurately about 0.9 g of Oxethazaine,
= 46.76 mg of C28H41N3O3
Oxprenolol Hydrochloride

OH
CH3
OCH2CCH2NHCH
H
OCH2CH
HCl
CH3
CH2
C15H23NO3HCl: 301.81
Oxprenolol Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of oxprenolol hydrochloride (C15H23NO3HCl).
Description Oxprenolol Hydrochloride is a white,
crystalline powder.
Oxprenolol Hydrochloride is very soluble in water,
freely soluble in ethanol or in glacial acetic acid,
slightly soluble in acetic anhydride, and practically insoluble in ether.
Identification (1) Take 2 mL of a solution of Oxprenolol Hydrochloride (1 in 100) and add 1 drop of cupric
sulfate TS and 2 mL of sodium hydroxide TS: a bluepurple color is observed. To this solution, add 1 mL of
ether, shake well and allow to stand: a red-purple color
is observed in the ether layer and a blue-purple color is
observed in the water layer.
(2) Take 3 mL of a solution of Oxprenolol Hydrochloride (1 in 150) and add 3 drops of Reinecke salt
(3) Determine the infrared spectra of Oxprenolol
Hydrochloride and Oxprenolol Hydrochloride RS, previously dried, as directed in the potassium bromide disk
method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(4) A solution of Oxprenolol Hydrochloride (1 in
pH Dissolve 1.0 g of Oxprenolol Hydrochloride in 10
6.0.
1.0 g of Oxprenolol Hydrochloride in 10 mL of water:
(2) Heavy metalsProceed with 2.0 g of Oxprenolol Hydrochloride according to Method 4 and perform
Oxprenolol Hydrochloride according to Method 3 and
(4) Related substancesDissolve 0.25 g of Oxprenolol Hydrochloride in 10 mL of water and use this solution as the test solution. Pipet exactly 4 mL of the test
solution and add water to make exactly 100 mL. Pipet
exactly 5 mL of this solution, add water to make exactly 100 mL and use this solution as the standard solution.
solution as directed under the Thin-layer Chromatography. Spot 10 L each of the test solution and the standard solution on a plate of silica gel with a fluorescent
indicator for thin-layer chromatography. Develop the
plate in a developing chamber saturated with ammonia
vapor with a mixture of chloroform and methanol (9 :
nm): any spot other than the principal spot from the test
standard solution.
hours).
Assay Weigh accurately about 0.6 g of Oxprenolol
Oxybuprocaine Hydrochloride
C2H5
H2N
COOCH2CH2N
HCl
C2H5
CH3CH2CH2CH2O
Benoxinate Hydrochloride
C17H28N2O3HCl: 344.88
Oxybuprocaine Hydrochloride, when dried, contains
not less than 99.0% and not more than 101.0% of oxybuprocaine hydrochloride (C17H28N2O3HCl).
Description Oxybuprocaine Hydrochloride is a white
crystal or crystalline powder, is odorless, has a saline
taste, and exhibits an anesthetic action when placed on
the tongue.
Oxybuprocaine Hydrochloride is very soluble in water,
freely soluble in ethanol or in chloroform, and practically insoluble in ether.
Oxybuprocaine Hydrochloride is colored by light.
pHThe pH of a solution of Oxybuprocaine Hydrochloride (1 in 10) is between 5.0 and 6.0.
Identification (1) Dissolve 10 mg of Oxybuprocaine
Hydrochloride in 1 mL of dilute hydrochloric acid and
KP 9 717
4 mL of water. This solution responds to the Qualitative
Tests for primary aromatic amines.
(2) Dissolve 0.1 g of Oxybuprocaine Hydrochloride
in 8 mL of water and add 3 mL of ammonium thiocyanate TS: an oily substance is produced. Rub the inner
surface of the container with a glass rod: white crystals
are formed. Collect the crystals so obtained, recrystallize from water and dry in a desiccator (in vacuum,
P2O5) for 5 hours: the crystals melt between 103 C and
106 C.
Oxybuprocaine Hydrochloride and Oxybuprocaine Hydrochloride RS, respectively, in water (1 in 100000) as
directed under Ultraviolet-visible Spectrophotometry :
(4) A solution of Oxybuprocaine Hydrochloride (1
= 34.488 mg of C17H28N2O3HCl
Oxycodone Hydrochloride
Hydrate
CH3

hours).
Assay Weigh accurately about 0.6 g of Oxybuprocaine Hydrochloride, previously dried, dissolve in 50
acid (7 : 3) and titrate with 0.1 mol/L perchloric acid
HCl
HO

1.0 g of Oxybuprocaine Hydrochloride in 10 mL of water: the solution is clear and colorless.
(2) Heavy metalsProceed with 1.0 g of Oxybuprocaine Hydrochloride according to Method 1 and
(3) Related substancesDissolve 0.25 g of Oxybuprocaine Hydrochloride in 10 mL of chloroform and
use this solution as the test solution. Pipet exactly 1 mL
of the test solution and add chloroform to make exactly
20 mL. Pipet exactly 1 mL of this solution, add chloroform to make exactly 50 mL and use this solution as the
mixture of chloroform, ethanol and formic acid (7 : 2 :
Spray evenly p-dimethylaminobenzaldehyde TS for
spraying on the plate: any spot other than the principal
spot from the test solution is not more intense than the
3 H2O
O
CH3O
C18H21NO4HCl3H2O: 405.87
Oxycodone Hydrochloride Hydrate contains not less
than 98.0% and not more than 101.0% of oxycodone
hydrochloride (C18H21NO4HCl: 351.83), calculated on
Description Oxycodone Hydrochloride Hydrate is a
Oxycodone Hydrochloride Hydrate is freely soluble in
water, methanol or glacial acetic acid, sparingly soluble
in ethanol, slightly soluble in acetic anhydride, and
The pH of a solution dissolved 1.0 g of Oxycodone
Hydrochloride Hydrate in 10 mL of water is between
3.8 and 5.8.
Oxycodone Hydrochloride Hydrate is colored by light.
of solutions of Oxycodone Hydrochloride Hydrate and
Oxycodone Hydrochloride Hydrate RS, respectively, in
water (1 in 10000) as directed under Ultraviolet-visible
(2) Determine the infrared spectra of Oxycodone
Hydrochloride and Oxycodone Hydrochloride Hydrate
RS, respectively, as directed in the potassium bromide
disk method under the Infrared Spectrophotometry;
(3) A solution of Oxycodone Hydrochloride Hydrate (1 in 50) responds to the Qualitative Tests (2) for
chloride.
-149 (calculated on the dried basis, 0.5 g, water, 25

mL, 100 mm).
0.5 g of Oxycodone Hydrochloride Hydrate in 10 mL
of water: the solution is clear and colorless.
(2) MorphineDissolve 10 mg of Oxycodone Hydrochloride Hydrate in 1 mL of water, add 5 mL of nitroso--naphthol TS and 2 mL of a solution of potassium nitrate (1 in 10) and warm 40 C for 2 minutes. To
this solution, add 1 mL of a solution of sodium nitrite
(1 in 5000) and warm at 40 C for 5 minutes. After
cooling, add 10 mL of chloroform, shake, centrifuge
and separate the water layer: the color of the solution is
not more intense than a pale red.
(3) CodeineDissolve 10 mg of Oxycodone Hydrochloride Hydrate in 5 mL of sulfuric acid, add 1
drop of ferric chloride TS and warm: no blue color is
observed. Add 1 drop of nitric acid: no red color is observed.
(4) ThebaineDissolve 0.1 g of Oxycodone Hydrochloride Hydrate in 2 mL of diluted hydrochloric
acid (1 in 10) and heat the solution in a water-bath for
25 minutes. After cooling, add 0.5 mL of 4aminoantipyrine hydrochloride TS and 0.5 mL of a solution of potassium ferricyanide (1 in 100) and shake.
Then shake the solution with 2 mL of ammonia TS and
3 mL of chloroform: no red color is observed in the
chloroform layer.
Water Between 12% and 15% (0.2 g, volumetric titration, direct titration).
Assay Weigh accurately about 0.5 g of Oxycodone
Hydrochloride Hydrate, dissolve in 50 mL of a mixture
of acetic anhydride and glacial acetic acid (7 : 3) and titrate with 0.1 mol/L perchloric acid VS (potentiometric
correction.
= 35.183mg of C18H21NO4HCl
tight containers.
Oxygen
O2: 32.00
Oxygen contains not less than 99.5 vol % and not more
than 101.0 vol % of Oxygen (O2).
Description Oxygen is a colorless gas and is odorless.
One mL of Oxygen dissolves in 32 mL of water and in

7 mL of ethanol at 20 C and at a pressure of 101.3 kPa.
1000 mL of Oxygen at 0 C and at 101.3 kPa weighs
about 1.429 g.
Identification (1) Put a glowing splinter of wood into
Oxygen: it bursts into flame immediately.
(2) Transfer 1 mL each of Oxygen and oxygen directly from metal cylinders with a pressure-reducing
valve to gas-measuring tubes or syringes for gas chromatography, using a polyvinyl chloride induction tube.
Perform the test with these gases as directed under the
Gas Chromatography according to the conditions of
Purity (2): the retention time of principal peak from
Oxygen coincides with that of oxygen.
Purity Keep the containers of Oxygen between 18 C
and 22 C for not less than 6 hours before carrying out
the following tests and calculate the volume to be used
with reference to the gas at 20 C and at 101.3 kPa.
(1) Acid or alkali, carbon dioxide, oxidizing substances and chloridePerform the test under the conditions of purity (1), (2), (3) and (5) of Nitrous Oxide.
(2) NitrogenIntroduce 1.0 mL of Oxygen into a
gas-measuring tube or syringe for gas chromatography
from a metal hermetic container under pressure through
a pressure-reducing valve and a directly connected polyvinyl tube. Perform the test as directed under the Gas
Chromatography according to the following conditions
and determine the peak area, AT, of nitrogen. Introduce
0.50 mL of nitrogen into the gas mixer, draw carrier gas
into the mixer to make exactly 100 mL and allow to
mix thoroughly. Perform the test in the same manner
with 1.0 mL of this mixture as directed above and determine the peak area, AS of nitrogen: AT is not larger
than AS.
Detector: A thermalconductivity detector.
and about 3 m in length, packed with 250 m to 355
m zeolite (0.5 mm pore size)for gas chromatography.
about 50 C.
Carrier gas: Hydrogen or Helium.
time of nitrogen is about 5 minutes.
Selection of column: Introduce 0.5 mL of nitrogen
into a gas mixer, add Oxygen to make 100 mL and mix
well. When the procedure is run with 1.0 mL of the
mixture under the above operating conditions, use a
column giving elution of oxygen and nitrogen in this
order with well-resolved peaks.
Assay (1) ApparatusThe apparatus is shown diagrammatically in the accompanying figure. A is a 100mL gas buret having a two-way stopcock, a, b - c, d - e
and e - f are graduated in 0.1 mL and c-d is graduated
in 2 mL. A is properly connected with a leveling tube,
B by a thick rubber tube. Fill ammonium chloride-
KP 9 719
ammonia TS up to the middle of A and B. Place in the
absorption ball, g of the gas pipette, C, a coil of copper
wire, not more than 2 mm in diameter, which extends
to the uppermost portion of the bulb, add 125 mL of
ammonium chloride-ammonia TS and stopper with a
rubber stopper, I. Connect C with A using the thick
rubber tube.
(2) ProcedureOpen a, set B downward and draw
the liquid in g to the stopcock opening a. Then close a.
Open a to the intake tube h and fill A and h with ammonium chloride-ammonia TS by lifting B. Close a,
connect h with a container of Oxygen, open a, set B
downward and measure accurately 100 mL of Oxygen.
Open a toward C and transfer the Oxygen to g by lifting B. Close a and rock C gently for 5 minutes. Open a,
draw the residual gas back into A by setting B downward and measure the volume of the residual gas. Repeat the procedure until the volume of residual gas is
constant and designate this as V (mL). With fresh ammonium chloride-ammonia TS in C, repeat the procedure at least four times and measure the volume of residual gas. Calculate V and the volume of Oxygen used
as the sample with reference to the gas at 20 C and at
101.3 kPa.
Volume (mL) of Oxygen (O2) = calculated volume of
the sample (mL) - calculated volume of V (mL)
C16H24N2OHCl: 296.84
Oxymetazoline Hydrochloride contains not less than
98.5% and not more than 101.5% of oxymetazoline hydrochloride (C16H24N2OHCl), calculated on the dried
basis.
Description Oxymetazoline Hydrochloride is a white,
fine crystalline powder
Oxymetazoline Hydrochloride is soluble in water or in
ethanol and practically insoluble in benzene, in chloroform or in ether.
Oxymetazoline Hydrochloride is hygroscopic.
of solutions of Oxymetazoline Hydrochloride and
Oxymethazoline Hydrochloride RS in ethanol (1 in
of absorption at the same wavelengths, and the difference of each absorbance of Oxymetazoline Hydrochloride and Oxymetazoline Hydrochloride RS at the wavelength of a maximum absorbance at about 279 nm is
not more than 3.0%.
(2) Determine the infrared spectra of Oxymetazoline
Hydrochloride and Oxymetazoline Hydrochloride RS,
previously dried, as directed in the paste method under
similar intensities of absorption at same wavenumbers
(3) Take a solution of about 50 mg in 3 mL of water
and add 1 mL of ammonium hydroxide TS, filter and
acidify the filtrate with nitric acid: the filtrate responds
to the Qualitative Tests for chloride.
pH The pH of the solution containing 1.0 g of Oxymetazoline Hydrochloride in 20 mL of water is between 4.0 and 6.5.
Purity Heavy metalsProceed with 1.0 g of Oxymetazoline Hydrochloride according to the Method 2 and
b-c = calibrated in 0.1 mL

c-d = calibrated in 2 mL
d-e = calibrated in 0.1 mL
e-f = calibrated in 0.1 mL
the graduations are marked with red line.
b-f = calibrated in 100 mL
Loss on Drying Not more than 1.0% (1 g 105 C for

3 hours).
Packaging and Storage Preserve in not exceeding 40

C, metal cylinders.
Oxymetazoline Hydrochloride
OH
(CH3)3C
CH3
HCl
N
CH2
CH3
HN

Assay Transfer about 25 mg of Oxymetazoline Hydrochloride, accurately weighed, to a volumetric flask,
dissolve in mobile phase, dilute with mobile phase to
make 50 mL and mix. Use this solution as the test solution. Prepare a solution in mobile phase of Oxymetazoline Hydrochloride RS, previously dried at 105 o C
for 3 hours, having a known concentration of about 0.5
mg per mL and use this solution as the standard solution. Perform the test with 20 L each of the test solution and the standard solution, as directed under the

Liquid Chromatography. Measure the peak areas, AT
and AS , of Oxymetazoline Hydrochloride for the test
Amount (mg) of oxymetazoline hydrochloride
A
(C16H 24 N 2O HCl) = 50 C T
AS
C: Concentration of Oxymetazoline Hydrochloride

in the standard solution (mg/mL).
multiple pore (strong acid cationic ion exchange resin)
silica gel for liquid chromatography.
Mobile phase: A mixture of water, methanol, 1
mol/L sodium acetic acid and glacial acetic acid (46 :
40 : 10 : 4).
System suitability
with 20 L of the standard solution, the symmetry factor is not more than 2.0.
above operating conditions, the relative standard deviation of the peak areas of Oxymetazoline is not more
than 2.0%.
rate and discard the chloroform layer. Transfer 8 mL of

the acidic aqueous layer to a test tube, neutralize by the
drop-wise addition of 1 mol/L sodium hydroxide, add 1
drop of 1 mol/L sodium hydroxide in excess and mix.
Add a few drops of sodium nitropruside and 2 drops of
sodium hydroxide solution (15 in 100), mix and allow
to stand for 10 minutes. Add 0.1 mol/L hydrochloric acid drop-wise until the pH is between 8 and 9 and allow
to stand for 10 minutes: a violet color is observed.
Assay Use Oxymetazoline Hydrochloride Nasal Solution as the test solution. Separately, weigh accurately
a portion of Oxymetazoline Hydrochloride RS, previously dried at 105 C for 3 hours, dissolve in the mobile phase having a known concentration, approximately equal to the labeled concentration of the Oxymetazoline Hydrochloride Nasal Solution. Use this solution as
the standard solution. Perform the test with the test solution and the standard solution, as directed in the Assay under Oxymetazoline Hydrochloride.
Amount (mg/mL) of oxymetazoline hydrochloride
A
(C16H24N2OHCl) = C T
AS
C: Concentration of Oxymetazoline Hydrochloride
in the standard solution (mg/mL)
Oxymetholone
H3C
Oxymetazoline Hydrochloride
Nasal Solution
H3C

Liquids, with Oxymetazoline Hydrochloride.
Description Oxymetazoline Hydrochloride Nasal Solution is a clear and colorless liquid.
Identification Place a volume of Oxymetazoline Hydrochloride Nasal Solution, equivalent to about 2.5 mg
of Oxymetazoline Hydrochloride, in a separatory funnel and add water to make about 10 mL. Add 2 mL of
sodium carbonate solution (1 in 10), extract with 10 mL
of chloroform and transfer the chloroform solution with
10 mL of 0.1 mol/L hydrochloric acid, allow to sepa-
CH3
HOCH
H
Oxymetazoline Hydrochloride Nasal Solution contains

labeled amount of oxymetazoline hydrochloride
(C16H24 N2OHCl: 296.84).
OH
O
H
C21H32O3: 332.48
Oxymetholone, when dried, contains not less than
97.0% and not more than 103.0% of oxymetholone
(C21H32O3).
Description Oxymetholone is a white to pale yellowish white, crystalline powder and is odorless.
Oxymetholone is freely soluble in chloroform, soluble
in dioxane, sparingly soluble in methanol, ethanol or
acetone, slightly soluble in ether, and practically insoluble in water.
Oxymetholone is gradually colored and decomposed by
light.
Identification (1) Dissolve 2 mg of Oxymetholone in
KP 9 721
1 mL of ethanol and add 1 drop of ferric chloride TS: a
(2) Dissolve 10 mg each of Oxymetholone and
Oxymetholone RS in methanol to make 50 mL. To 5
mL each of the solutions, add 5 mL of sodium hydroxide-methanol TS and methanol to make 50 mL. Determine the absorption spectra of these solutions as directed under Ultraviolet-visible Spectrophotometry, respectively : both spectra exhibit similar intensities of
(3) Determine the infrared spectra of Oxymetholone
and Oxymetholone RS, respectively, as directed in the
Amount (mg) of Oxymetholone (C21H32O3)

A
= 541 50000
tight containers.
Oxytetracycline Hydrochloride
OH
OH
OH
NH2
[ ]20
D :

Between +34 and
0.5 g of Oxymetholone in 25 mL of dioxane: the solution is clear and shows colorless to a pale yellow color.
(2) Related substancesDissolve 50 mg of Oxymetholone in 5 mL of chloroform and use this solution
as the test solution. Pipet exactly 1 mL of the test solution, add chloroform to make exactly 200 mL and use
on a plate of silica gel for thin-layer chromatography
and air-dry the spot. Develop immediately the plate
with a mixture of toluene and dehydrated ethanol (49 :
Spray evenly vanillin-sulfuric acid TS on the plate and
heat at 100 C for 3 minutes to 5 minutes: any spot other than the principal spot and starting point obtained
Assay Weigh accurately about 40 mg of Oxymetholone, previously dried, and dissolve in methanol to
make exactly 50 mL. Pipet exactly 5 mL of this solution and add methanol to make exactly 50 mL. To exactly measured 5 mL of this solution, add 5 mL of sodium hydroxide-methanol TS and methanol to make
exactly 50 mL. Determine the Ultraviolet-visible Spectrophotometry absorbance, A, of this solution at the
wavelength of a maximum absorption at about 315 nm,
using a solution, prepared by adding methanol to 5 mL
of sodium hydroxide-methanol TS to make 50 mL, as
the blank.
OH
H
H3C
OH
H
OH
N
H 3C
HCl
CH3
C22H24N2O9HCl: 496.90
Oxytetracycline Hydrochloride contains not less than
835 g (potency) per mg of oxytetracycline
(C22H24N2O9: 460.44), calculated on the dried basis.
Description Oxytetracycline Hydrochloride is yellow
crystal or crystalline powder, is odorless, and has a bitter taste.
Oxytetracycline Hydrochloride is freely soluble in water, soluble in ethanol, and practically insoluble in ether.
Identification (1) Weigh 10 mg of Oxytetracycline
Hydrochloride, and dissolve in 20 mL of water. To 1
mL of this solution add 1 mL of sodium carbonate solution ( 1 in 100) and 1 mL of diazobenzenesulfonic acid
TS: the orange-red color develops.
(2) Weigh 20 mg of Oxytetracycline Hydrochloride,
and dissolve in 3 mL of water, add one drop of silver
nitrate TS: the solution turns to be turbid.
0.1 g of Oxytetracycline Hydrochloride in 10 mL of
water is between 2.0 and 3.0.
Absorbance Ratio Weigh accurately about 50 mg
each of Oxytetracycline Hydrochloride and Oxytetracycline RS, dissolve each in 0.1 mol/L hydrochloric acid TS to make exactly 250 mL. Pipet 10 mL each of
these solutions, add 0.1 mol/L hydrochloric acid TS to
Determine the absorbances at 353 nm, AT and AS, of the
Ultraviolet-visible Spectrophotometry (92.5 4.3 %).
Absorbance ratio [%] =
AT
AS

Amount [ g (potency)] of Oxytetracycline RS
100
Amount [mg] of Oxytetracycline Hydrochloride 100 - m
Oxytocin
m: water content (%) of Oxytetracycline Hydrochloride

Sterility Test It meets the requirement, when Oxytetracycline Hydrochloride is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Oxytetracycline Hydrochloride is used in a sterile preparation,. Weigh an appropriate amount of Oxytetracycline
Hydrochloride, dissolve in water to make the solution
so that each mL contains 5.0 mg, and use the solution
as the test solution. The amount of injection is 1.0 mL
of the test solution per kg of body weight of rabbit.
Histamine It meets the requirement, when Oxytetracycline Hydrochloride is used in a sterile preparation.
Weigh an appropriate amount of Oxytetracycline Hydrochloride, dissolve in water to make the solution so
that each mL contains 5.0 mg, and use the solution as
the test solution. Use 0.6 mL of this solution for the test.
Loss on Drying Not more than 2.0 % (0.3 g, 100 C,
2 hours).
Oxytetracycline Hydrochloride, dissolve in 25 mL of
0.1 mol/L hydrochloric acid TS, add water to make exactly 250 mL, and use this solution as the test solution.
Separately, weigh accurately about 50 mg (potency) of
Oxytetracycline RS, dissolve in 25 mL of 0.1 mol/L
hydrochloric acid TS, add water to make exactly 250
mL, and use this solution as the standard solution. Keep
the standard solution at not exceeding 5 C and use
within 7 days. Pipet exactly 10 mL each of these solutions into individual test tubes, add exactly 10 mL of
ferric chloride TS, mix with shaking, and allow to stand
for 15 minutes. Separately, make the blank solution that
contains 10 mL of 0.1 mol/L hydrochloric acid TS and
10.0 mL of ferric chloride TS. Determine the absorbances at 490 nm, AT and AS, of the test solution and the
standard solution, compared to the blank solution, as
directed under Ultraviolet-visible Spectrophotometry.
Prepare ferric chloride TS as follows. Weigh 5.0 g of
ferric chloride and place in a 100 mL beaker, add about
10 mL of 1 mol/L hydrochloric acid TS and dissolve
with stirring, and add water to make exactly 50 mL.
Take exactly 10 mL of this solution, add 20 mL of 1
mol/L hydrochloric acid TS, and add water to make exactly 2000 mL. The pH of this solution is between 2.0
and 2.1.
Amount
[g
(C22H24N2O9)
(potency)]
of
oxytetracycline
= Amount [g (potency)] of Oxytetracycline RS
AT
AS
Cys
Tyr
Ile
Gln
Asn
Cys
Pro
Leu
Gly
NH2
C43H66N12O12S2: 1007.19
Oxytocin is a synthetic peptide having the property of
causing the contraction of uterine smooth muscle.
Oxytocin contains not less than 540 oxytocin Units and
not more than 600 oxytocin Units per mg, calculated on
the anhydrous and acetic acid-free basis.
Description Oxytocin is a white powder.
Oxytocin is very soluble in water, and freely soluble in
dehydrated ethanol.
Oxytocin dissolves in hydrochloric acid TS.
The pH of the solution prepared by dissolving 0.10 g of
Oxytocin in 10 mL of freshly boiled and cooled water
Oxytocin is hygroscopic.
solutions of Oxytocin and Oxytocin RS, respectively,
in water (1 in 2000) as directed under Ultravioletvisible Spectrophotometry: both spectra exhibit similar
Constituent Amino Acids Weigh about 1 mg of
Oxytocin, transfer into a test tube for hydrolysis, add 6
mol/L hydrochloric acid TS to dissolve, replace the air
in the tube with Nitrogen, seal the tube under reduced
pressure and heat at 110 to 115 C for 16 hours. After
cooling, open the tube, evaporate the hydrolyzate to
dryness under reduced pressure, add 2 mL of 0.02
mol/L hydrochloric acid TS to dissolve the residue, and
accurately about 24 mg of L-aspartic acid, about 24 mg
of L-threonine, about 21 mg of L-serine, about 29 mg
of L-glutamic acid, about 23 mg of L-proline, about 15
mg of glycine, about 18 mg of L-alanine, about 23 mg
of L-valine, about 48 mg of L-cystine, about 30 mg of
methionine, about 26 mg of L-isoleucine, about 26 mg
of L-leucine, about 36 mg of L-tyrosine, about 33 mg
of phenylalanine, about 36 mg of L-lysine hydrochloride, about 42 mg of L-histidine hydrochloride monohydrate and about 42 mg of L-arginine hydrochloride,
dissolve them in 10 mL of 1 mol/L hydrochloric acid
TS, and add water to make exactly 100 mL. Pipet 5 mL
of this solution, add water to make exactly 20 mL, and
standard solution as directed under Liquid Chromatography according to the following conditions, and calculate the respective molar ratios with respect to leu-
KP 9 723
cine: 0.95 ~ 1.05 for aspartic acid, 0.95 ~ 1.05 for glutamic acid, 0.95 ~ 1.05 for proline, 0.95 ~ 1.05 for glycine, 0.80 ~ 1.10 for isoleucine, 0.80 ~ 1.05 for tyrosine
and 0.80 ~ 1.05 for cystine, and not more than 0.01
each for others.
Detector: A visible spectrophotometer (wavelength:
440 nm and 570 nm).
strongly acidic ion-exchange resin for liquid chromatography (sodium type) composed with a sulfonated polystyrene copolymer (3 m in particle diameter).
about 57 C.
Chemical reaction bath temperature: A constant
temperature of about 130 C.
Color developing time: About 1 minute.
Mobile phase: Control the gradient by mixing the mobile phase A, B and C as directed in the following table.
of sample (min)
Mobile
phase A
(vol%)
Mobile
phase B
(vol%)
Mobile
phase C
(vol%)
0~9
100
9 ~ 25
100
25 ~ 61
1000
1000
61 ~ 80
100
Prepare mobile phases A, B and C according to the following table.

Mobile
phase
Citric acid
monohydrate
19.80 g
22.00 g
6.10 g
6.19 g
7.74 g
26.67 g
5.66 g
7.07 g
54.35 g
260.0 mL
20.0 mL
5.0 mL
5.0 mL
5.0 mL
4.0 mL
4.0 mL
4.0 mL
Caprylic acid
0.1 mL
0.1 mL
0.1 mL
Water
a sufficient
amount
a sufficient
amount
a sufficient
amount
Total amount
2000 mL
1000 mL
1000 mL
pH
3.3
3.2
4.9
Trisodium citrate
dihydrate
Sodium chloride
Dehydrated Ethanol
Benzyl alcohol
Thioglycol
Lauromacrogol
Solution
(1 in 4)
Flow rate of mobile phase: About 0.26 mL/minute.

Flow rate of reaction reagent: About 0.3 mL/minute.
System suitability

with 20 L of the standard solution under the above operating conditions, aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, cystine,
methionine, isoleucine, leucine, tyrosine, phenylalanine,
lysine, histidine and arginine are eluted in this order
with the resolutions between the peaks of threonine and
serine, glycine and alanine, and isoleucine and leucine
being not less than 1.5, 1.4 and 1.2, respectively.
above operating conditions, the relative standard deviations of the peak area of aspartic acid, proline, valine
and arginine are not more than 2.0%, respectively.
Reaction reagentMix 407 g of lithium acetate dihydrate, 245 mL of glacial acetic acid and 801 mL of 1methoxy-2-propanol, add water to make 2 L, stir for
more than 10 minutes while passing Nitrogen, and use
this solution as Solution A. Separately, to 1957 mL of
1-methoxy-2-propanol add 77 g of ninhydrin and 0.134
g of sodium borohydride, stir for more than 30 minutes
while passing nitrogen, and use this solution as Solution B. Mix Solution A and Solution B before use.
Purity (1) Acetic acidWeigh accurately about 15
mg of Oxytocin, dissolve in the internal standard solution to make exactly 10 mL, and use this solution as the
test solution. Separately, weigh accurately about 1 g of
glacial acetic acid, add the internal standard solution to
make exactly 100 mL. Pipet exactly 2 mL of this solution, add the internal standard solution to make exactly
and the standard solution as directed under Liquid
and calculate the ratios, QT and QS , of the peak area
of acetic acid to that of the internal standard: the
amount of acetic acid is not less than 6.0% and not
more than 10.0%.
Amount (%) of acetic acid (C2H4O2)
Q
W
1
= T S
QS WT 10
WS : Amount of glacial acetic acid (mg)
WT : Amount of Oxytocin (mg)
Internal standard solutionA solution of propionic

acid in the mobile phase (1 in 10000).
(wavelength : 210 nm).

about 40 C .
Mobile phase: To 0.7 mL of phosphoric acid add
900 mL of water, adjust the pH to 3.0 with 8 mol/L sodium hydroxide TS, and add water to make 1000 mL.
To 950 mL of this solution add 50 mL of methanol and
mix.
time of acetic acid is about 3 minutes.
System suitability
with 10 L of the standard solution under the above operating conditions, acetic acid and propionic acid are
above operating conditions, the relative standard deviation of the ratio of the peak area of acetic acid to that of
the internal standard is not more than 2.0%.
(2) Related substancesDissolve 25 mg of Oxytocin in 100 mL of the mobile phase A, and use this solution as the test solution. Perform the test with 50 L of
the test solution as directed under Liquid Chromatography according to the following conditions, determine
each peak area by the automatic integration method,
and calculate the amount of them by the area percentage method: the amount of each peak other than Oxytocin is not more than 1.5%, and the total of them is not
more than 5.0%.
phase, flowing of mobile phase, and flow rate: proceed
as directed in the operating conditions in the Assay.
System suitability
Test for required detectability: Pipet exactly 1
mL of the test solution, add the mobile phase A to make
exactly 100 mL, and use this solution as the solution
for system suitability test. Pipet exactly 1 mL of the solution for system suitability test, and add the mobile
phase A to make exactly 10 mL. Confirm that the peak
area of oxytocin obtained from 50 L of this solution is
equivalent to 5 to 15% of that from 50 L of the solution for system suitability test.
System performance: Pipet an adequate amount
of oxytocin and vasopressin, dissolve in the mobile
phase A, so that each mL contains about 0.1 mg each of
them. When the procedure is run with 50 L of this solution under the above operating conditions, vasopressin and oxytocin are eluted in this order with the resolution between these peaks being not less than 14, and the
symmetry factor of the peak of oxytocin is not more
than 1.5.
times with 50 L of the solution for system suitability
test under the above operating conditions, the relative
standard deviation of the peak area of oxytocin is not
more than 2.0%.

long as the retention time of oxytocin.
Water Not more than 5.0% (50 mg, coulometric titration).
Assay Weigh accurately an amount of Oxytocin,
equivalent to about 13000 Units, dissolve in the mobile
as the test solution. Separately, dissolve 1 vial of the
Oxytocin RS in the mobile phase A to make a known
concentration solution containing each mL contains
about 130 Units, and use this solution as the standard
solution. Perform the test with exactly 25 L each of
under Liquid Chromatography according to the following conditions, and determine the peak areas, AT and
AS of oxytocin, respectively.
Units per mg of Oxytocin, calculated on the anhydrous
A W
and acetic acid-free basis = T S 100
AS WT
WS : Units per mL of the standard solution
WT : Amount of Oxytocin, calculated on the anhydrous and acetic acid-free basis (mg)
(wavelength 220 nm).
about 25 C .
Mobile phase : Program as follows with mobile
phase A and mobile phase B in gradient or in isocratic.
Mobile phase A: Dissolve 15.6 g of sodium dihydrogen phosphate hydrate in 1000 mL of water.
Mobile B: A mixture of water and acetonitrile (1:1).
Time after
injection of
sample (min)
0 ~ 30
Mobile phase
A (vol%)
Mobile phase
B (vol%)
70 40
36 60
30 ~ 30.1
40 70
60 30
30.1 ~ 45
70
30

System suitability
System performance: Weigh accurately a portion
of Oxytocin and vasopressin, add mobile phase A to
obtain a solution having a known concentration of
about 0.1 mg per mL. When the procedure is run with
25 L of this solution under the above operating conditions, vasopressin and oxytocin are eluted in this order
with the resolution between these peaks being not less
KP 9 725
than 14, and the symmetry factor of the peak of oxytocin is not more than 1.5.
above operating conditions, the relative standard deviation of the peak area of oxytocin is not more than 1.0%.
Store at 2 C to 8 C.
Oxytocin Injection
Oxytocin Injection is an aqueous solution for injection.
Oxytocin Injection contains not less than 90.0% and
not more than 110.0% of the labeled Oxytocin units.
Method of Preparation Prepare as directed under Injections, with oxytocin obtained from the posterior lobe
of the pituitary or synthetic oxytocin.
Description Oxytocin Injection is a colorless, clear
liquid.
Bacterial Endotoxins
unit.
Less than 10 EU/Oxytocin
Sterility Test It meets the requirement of the Membrane filtration method under the Sterility Test.
Foreign Insoluble Matter Test It meets requirement .
Assay Measure exactly a portion of Oxytocin Injection according to the labeled Units, dilute with the diluent so that each mL contains about 1 Unit, and use this
solution as the test solution. Separately, dissolve 1 bottle of Oxytocin RS in the mobile phase A to make exactly 20 mL. Pipet a suitable volume concentration solution so that each mL contain about 1 Unit, and use
with exactly 100 L each of the test solution and the
standard solution as directed under Liquid Chromatography according to the following conditions, and determine the peak areas, AT and AS , of oxytocin.
Units per mL of Oxytocin Injection = WS

particle diameter).
Flowing of the mobile phase: Control the gradient
by mixing the mobile phase A and B as directed in the
following table.
Mobile phase A: Dissolve 15.6 g of sodium dihydrogen
phosphate dihydrate in 1000 mL of water.
Mobile phase B: A mixture of water and acetonitrile
(1:1).
of sample (min)
Mobile phase
A (vol %)
Mobile phase
B (vol %)
0 30
30 30.1
30.1 - 45
70 40
40 70
70
30 60
60 30
30
Flow rate of mobile phase: .0 mL / minute.

System suitability
System performance: Measure exactly a portion
each of oxytocin and vasopressin, dilute with mobile
phase A so that each mL contains about 20 g each.
under the above operating conditions, vasopressin and
oxytocin are eluted in this order with the resolutions
between these peaks being not less than 14, and the
symmetry factor of the peak of oxytocin is not more
than 1.5.
above operating conditions, the relative standard deviation of the peak area of oxytocin is not more than 2.0%.
Packaging and Storage Preserve in hermetic containers at a cold place and avoid freezing.
Paclitaxel
O
AT b
AS a
H3C
O
WS : Units per mL of the standard solution

a: Volume of sample (mL)
b: Total volume of the test solution prepared by diluting with the diluents (mL)
Diluent: Dissolve 5 g of chlorobutanol, 1.1 g of sodium

acetate trihydrate, 5 g of glacial acetic acid and 6 mL of
dehydrated ethanol in water to make 1000 mL.
O
O
CH3 OH
H3C
O
CH3
CH3
N
H
O
OH
HO
H
O O
H
O
CH3
C47H51NO14 : 853.91
Paclitaxel contains not less than 97.0% and not more
KP 9 727
1.10
1.40
1.85
than 102.0% of paclitaxel (C47H51NO14), calculated on

the anyhydrous and solvent-free basis.
Description Paclitaxel is a white powder.
Paclitaxel is soluble in ethanol and practically insoluble
in water.
spectra of Paclitaxel and Paclitaxel RS, as directed in
the potassium bromide disk method under lnfrared
Spectrophotornetry : both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) The retention times of the principal peaks from
the test solution and the standard solution in Assay are
same.
20
Specific Optical Rotation [] D : Between -49.0

and -55.0 (0.2 g, calculated on the anhydrous basis,
methanol, 20 mL, 100 mm).
Purity (1) Heavy metalsProceed with 1.0 g of Paclitaxel according to Method 1 and perform the test.
(2) Related substances(i) When labeled as isolated from natural products, weigh about 10 g of Paclitaxel, add a mixture of methanol and glacial acetic acid
(200 : 1), dissolve by sonication, if necessary, to make
exactly 10 mL and use this as the test solution. Perform
the test with 15 L of the test solution as directed under
conditions. Measure the amount (%) of each related
substance: the amount (%) of each related substance is
not more than that of Table 1, other related sybstances
are not more than 0.1% and total amount of the related
substances is not more than 2.0%.
FAi
Amount (%) of each related substance = 100 A
u
F : Relative response factor for each related substance peak (see Table 1)
Ai : Peak area of each related substance
Au : Peak area of paclitaxel
Table 1
Relative
retention
time
0.24
0.53
0.57
0.78
Relative
response
factor (F)
1.29
1.00
1.00
1.26
0.78
1.26
0.86
1.00
1.10
1.00
Name
Baccatin III
10-Deacetylpaclitaxel
7-Xylosylpaclitaxel
Cephalomannine (paclitaxel related substance I)
2,3Dihydrocephalomannine
10-Deacetyl-7epipaclitaxel (paclitaxel related substance II)
Benzyl analog3
Limit
(%)
0.2
0.5
0.2
a11
a21
0.5
b12
1.00
1.00
1.00
3,4-Dehydropaclitaxel C
7-Epicephanlomannine
7-Epipaclitaxel
b22
0.3
0.5
Resolution may be imcomplete for these peaks, depending upon the

relative amounts present; the sum of a1 and a2 is not more than 0.5%.
2
Resolution may be imcomplete for these peaks depending upon the
relative amounts present; the sum of b1 and b2 is not more than 0.5%.
3 The following chemical name is assigned to the related substance,
benzyl analog: Baccatin III 13-ester with (2R,3S)-2-hydroxy-3phenyl-3-(3-phenylacetylamino)propanoic acid).
pentafluorophenylpropyl silica gel for liquid chromatography (5 m in particle diameter).
about 30 C.
Mobile phase: Control the gradient by mixing acetonitrile and water as directed in the following table.
(minutes)
0 to 35
Acetonitrile
(vol%)
35
Water
(vol%)
65
35 to 60
35 80
65 20
60 to 70
80 35
20 65
65 to 70
35
65
Elution
condition
Isocratic
Linear
gradient
Linear
gradient
Isocratic

System suitability
System performance: Weigh 10 mg each of paclitaxel related substance I RS {cephalomannine} and
paclitaxel related substance II RS {10-Deacetyl-7epipaclitaxel}, and dissolve in methanol to make 100
mL. Pipet 5 mL of this solution, and add methanol to
make 50 mL. Pipet 5.0 mL of this solution, and add a
mixture of methanol and glacial acetic acid (200 : 1) to
this solution under the above operating conditions, the
relative retention time of the paclitaxel related substance I peak and the paclitaxel related substance II
peak to the paclitaxel peak is about 0.78 and 0.86, respectively, and the resolution between these peaks is
not less than 1.0.
System repeatability: Weigh about 10 mg of Paclitaxel RS, and dissolve in a mixture of methanol and
glacial acetic acid (200 : 1), with sonication, if necessary, to make 100 mL. When the test is repeated 5 times
conditions, the relative standard deviation of the peak
area of paclitaxel is not more than 2.0%.
(ii) When labeled as produced by a semisynthetic
process, weigh about 10 mg of Paclitaxel, dissolve in a
mixture of methanol and glacial acetic acid (200 : 1),
with sonication, if necessary, to make exactly 10 mL
test with 15 L each of the mixture of methanol and
glacial acetic acid (200 : 1) and the test solution as di-

rected under the Liquid Chromatography according to
the following conditions. Measure the amount (%) of
each related substance excluding the peaks obtained
from the mixture of methanol and glacial acetic acid
(200 : 1): the amount (%) of each related substance is
not more than that of Table 2, other related sybstances
are not more than 0.1% and total amount of the related
substances is not more than 2.0%.
FAi
Amount (%) of each related substance = 100 A
S
F : Relative response factor for each related substance peak (see Table 2)
Ai : Peak area of each related substance
AS : Sum of the areas of all the peaks obtained from
the test solution
Table 2
Relative
retention
time
0.11
0.20
0.42
0.47
0.80
Relative
response
factor (F)
1.24
1.29
1.39
1.00
1.00
0.921
1.00
0.921
0.941
1.00
1.00
1.37
1.45
1.00
1.00
1.54
1.80
2.14
1.00
1.75
1.00
Name
10-Deacetylbaccatin III
Baccatin III
Photodegradant2
10-Deacetylpaclitaxel
2-Debemzoylpaclitaxel-2pentenoate
Oxetane ring opened,
acetyl and benzoyl2
10-Acetoacetylpaclitaxel
10-Deacetyl-7epipaclitaxel (paclitaxel related substance II)
7-Epipaclitaxel
10,13Bissidechainpaclitaxel2
7-Acetylpaclitaxel
13-Tes-baccatin III
7-Tes-paclitaxel
Limit
(%)
0.1
0.2
0.1
0.5
0.7
x1
x2
x3
0.4
0.5
0.6
0.1
0.3
1
Resolution may be imcomplete for these peaks, depending upon the
relative amounts present; the sum of x1, x2 and x3 is not more than
0.4%.
2
The following chemical names are assigned to the related substances Photodegradant, Oxetane ring opened, acetyl and benzoyl,
and 10,13-Bussidechainpaclitaxel:
Photodegradant: (1R,2R,4S,5S,7,10S,11R,12S,13S,15S,16S)-2,10diacetyloxy-5,13-dihydroxy-4,16,17,17-tetramethyl-8-oxa-3-oxo-12phenylcarbonyloxypentacyclo[11.3.1.01.11.04.11.07.10]heptadec-15-yl
(2R,3S)-2-hydroxy-3-phenyl-3-(phenylcarbonylamino)propanoate
Oxetane ring opened, acetyl and benzoyl migrated:
(1S,2S,3R,4S,5S,7S,8S,10R,13S)-5,10-diacetyloxy-1,2,4,7-tetrahy
droxy-8,12,15,15-tetramethyl-9-oxo-4-(phenylcarbonyloxymethyl)
tricycle[9.3.1.03.8]pentadec-11-en-13-yl (2R,3S)-2-hydroxy-3-phenyl3-(phenylcarbonylamino)pronoate
10,13-Bussidechainpaclitaxel: Baccatin III 13-ester with (2R,3S)2-hydroxy-3-phenyl-3-(phenylcarbonylamino)propanoic acid, 10ester with (2S,3S)-2-hydroxy-3-phenyl-3-(phenylcarbonylamino)
propanoic acid

about 35 C.
Mobile phase: Control the gradient by mixing the
mobile phase A and B as directed in the following table.
Mobile phase A: A mixture of water and acetonitrile (3 : 2)
Mobile phase B: Acetonitrile
(minutes)
0 to 20
Acetonitrile
(vol%)
100
Water
(vol%)
0
20 to 60
100 10
0 90
60 to 62
10 100
90 0
62 to 70
100
Elution
condition
Isocratic
Linear
gradient
Linear
gradient
Isocratic
Flow rate: about 1.2 mL/minute.

System suitability
System performance: Weigh 96 mg of Paclitaxel
RS, dissolve in a mixture of methanol and glacial acetic
acid (200 : 1) by shaking to make 10 mL and use this
solution as the standard solution (1). Separately, weigh
8 mg of paclitaxel related substance II RS {10Deacetyl-7-epipaclitaxel}, dissolve in a mixture of methanol and glacial acetic acid (200 : 1) by shaking to
make 100 mL and use this solution as the standard solution (2). Pipet 5 mL each of the standard solution (1)
and the standard solution (2), add a mixture of methanol and glacial acetic acid (200 : 1) to make exactly 50
mL and use this solution as the system suitability solution. When the procedure is run with 15 L of this solution under the above operating conditions, the relative
retention time of the paclitaxel related substance II
peak and the paclitaxel peak is about 0.94 and 1.0, respectively, and the resolution between these peaks is
not less than 1.2.
times with 15 L of the system suitability solution under the above operating conditions, the relative standard deviation of the peak area of paclitaxel is not more
than 2.0%.
Baterial Endotoxins Less than 15 EU/mg of Paclitaxel.
Water Not more than 4.0% (0.1 g, coulometric titration)
Assay Weigh acculately about 10 mg each of Paclitaxel and Paclitaxel RS, dissolve in a mixture of methanol and glacial acetic acid (200 : 1), with sonication,
if necessary, to make exactly 10 mL and use these solutions as the test solution and the standard solution, respectively. Perform the test with 10 L each of the test
KP 9 729
conditions, measure the peak areas of paclitaxel obtained from each solutions, AT and AS.
Amount (mg) of paclitaxel (C47H51NO14)
A
= amount (mg) of Paclitaxel RS T
AS
pentafluorophenylpropyl silica gel for liquid chromatography (5 m in particle diameter).
(11 : 9)
System suitability
operating conditions, the symmetry factor of the paclitaxel peak is between 0.7 and 1.3.
above operating conditions, the relative standard deviation of the peak area of paclitaxel is not more than
1.5%.
tight containers and store at the temperature between
20 C and 25 C.
Pamabrom
O
H 3C
H
N
H 3C
NH 2
Br
OH
H 3C
ammonia TS, dissolve by gently shaking, add methanol

to make 100 mL and use this solution as the standard
standard solutions, as directed under Thin Layer Chromatography. Spot 10 L each of the test solution and
the standard solution on silica gel plate with fluorescent
plate with a mixture of xylene, methanol and glacial
acetic acid (11 : 2 : 1) to a distance of about 15 cm, and
wavelength: 254 nm): the Rf value of the principal spot
from the test solution corresponds to that obtained from
Purity (1) Heavy metalsProceed with 1.0 g of Pamabrom according to Method 2 and perform the test.
(2) TheophyllineWeigh accurately about 0.2 g of
Pamabrom, add 50 mL of a mixture of water and methanol (70 : 30), dissolve by sonication for 5 minutes,
cool, add a mixture of water and methanol (70 : 30) to
theophylline RS, dissolve in a mixture of water and methanol (70 : 30) by shaking, add 3 drops of strong ammonia water and a mixture of water and methanol (70 :
30) to make exactly 100 mL. Pipet 1.0 mL of this solution, add a mixture of water and methanol (70 : 30) to
test solution and the standard solution according to the
operating conditions of 8-Bromotheophylline under the
Assay as directed under the Liquid Chromatography,
and measure the peak areas of theophylline obtained
from each solutions, AT and AS.
Amount (%) of theophylline
C A
= 20 T
W AS
CH 3
C11H18BrN5O3 : 348.20
Pamabrom contains not less than 72.2% and not more
than 76.6% of 8-bromotheophylline (C7H7BrN4O2 ) and
not less than 24.6% and not more than 26.6% of 2amino-2-methyl-1-propanol (C4H11NO), calculated on
Description Pamabrom is a white powder.
Pamabrom is sparingly soluble in water.
Identification Weigh 25 mg of Pamabrom, dissolve
in 25 mL of water, by shaking to make exactly 100 mL
weigh 20 mg of 8-bromotheophylline RS, add 25 mL of
water, 50 mL of methanol and a small amount of dilute
C : the concentration (g/mL) of theophylline RS in

the standard solution
W : the amount (mg) of Pamabrom
Water Not more than 3.0% (1.0 g, volumetric titration, direct titration)
Assay (1) 8-BromotheophyllineWeigh accurately
about 0.2 g of Pamabrom, add 50 mL of a mixture of
water and methanol (70 : 30) amd 2 drops of strong
ammonia water, dissolve by sonication for 5 minutes,
cool, add a mixture of water and methanol (70 : 30) to
10.0 mL of the internal standard solution and the mobile phase to make exactly 100 mL, filter, and use the
filtrate as the test solution. Separately, weigh accurately
about 75 mg of 8-Bromotheophylline RS, dissolve in a
mixture of water and methanol (70 : 30) by shaking,

add 2 drops of strong ammonia water and a mixture of
water and methanol (70 : 30) to make exactly 100 mL.
To 5.0 mL of this solution, add 10.0 mL of the internal
standard and the mobile phase to make exactly 100 mL,
filter, use the filtrate as the standard solution. Perform
standard solution as directed under the Liquid Chromatography according to the following conditions, and
calculate the ratios of areas of 8-bromotheophylline
peak, QT and QS, to the area of the internal standard
peak, obtained from the test solution and the standard
Amount (mg) of 8-bromotheophylline (C7H7BrN4O2)
= 400 C
QT
QS
C : the concentration (mg/mL) of 8-Bromotheophy

lline RS in the standard solution
Internal standard solutionWeigh 12.5 mg of
caffeine and dissolve in a mixture of water and methanol (70 : 30) to make exactly 100 mL.
(3 to 10 m in particle diameter).
Mobile phase: A mixture of water, methanol and
glacial acetic acid (69 : 30 : 1)
System suitability
operating conditions, the relative retention times of
caffeine and 8-bromotheophylline are about 0.6 and 1.0,
respectively and the resolution between peaks of caffeine and 8-bromotheophylline is not less than 2.0.
above operating conditions, the relative standard deviation of the peak area of 8-bromotheophylline is not
more than 2.0%.
(2) 2-Amino-2-methyl-1-propanolWeigh accurately about 1 g of Pamabrom, dissolve in 10 mL of
water by warming gently on a steam bath until the solution is clear. Cool and and titrate with 0.5 mol/L hydrochloric acid VS (indicator: methyl orange TS). Perform a blank determination in the same manner, and
= 44.57 mg of C4H11NO
Pancreatin
Pancreatin is a substance containing enzymes which
have a starch digestive power, fat digestive power and
protein digestive power, obtained from the pancreas of
the editable animal, mainly the hog. Pancreatin contains, in each gram, not less than 2800 units of amylase
activity, not less than 28000 units of protease activity
and not less than 960 units of lipase activity. Pacreatin
is usually diluted by appropriate excipients.
Description Pancreatin is a white to pale yellow
powder and has a characteristic odor.
Purity (1) DeteriorationPancreatin has no unpleasant and deteriorated odor and taste.
(2) FatTake 1 g of Pancreatin, add 20 mL of ether, mix with shaking occasionally, extract for 30 minutes, filter, wash the filtrate with 10 mL of ether, combine the filtrate and the washing, evaporate the ether
and dry the residue at 105 C for 2 hours: the amount is
not more than 20 mg.
P2O5, 24 hours).
Assay (1) Starch digestive power(i) Test solution:
Weigh accurately about 0.1 g of Pancreatin and add a
suitable amount of water, cooled with ice, to make exactly 100 mL by shaking well. Pipet exactly 10 mL of
this solution and add water, cooled with ice, to make
exactly 100 mL. (ii) Substrate solution: Use potato
starch VS for test of starch digestive power. But, add 10
mL of phosphorus buffer solution for Pancreatin instead of 10 mL of 1 mol/L acetic acid-sodium acetate
buffer solution, pH 5.0. (iii) Operating method: Proceed
according to the Measuring method of starch saccharification power in the Test for starch digestive power (i)
in Test for digestion (1).
(2) Protein digestive power(i) Test solution:
Weigh accurately about 0.1 g of Pancreatin and add a
suitable amount of water, cooled with ice, by shaking
well and add water, cooled with ice, to make exactly
200 mL. (ii) Substrate solution: Use substrate solution
(2) for Test of protein digestive power (i) in the Test for
digestion (2). Adjust pH to 8.5. (iii) Operating method:
Proceed according to Test for protein digestive power
in the Test for digestion (2). But, trichloroacetic acid B
TS is used as a precipitating agent.
(3) Fat digestive power(i) Test solution: Weigh
accurately about 0.1 g of Pancreatin and add a suitable
amount of water, cooled with ice, by shaking well and
then add water, cooled with ice, to make exactly 100
mL. (ii) Emulsion: Weigh 18 g of polyvinyl alcohol I
and 2 g of polyvinyl alcohol II and prepare according to
the Test for fat digestive power in the Test for digestion
KP 9 731
(3). (iii) Substrate solution: Use the specified solution
in Test for fat digestive power in the Test for digestion
(3). (iv) Operating method: Proceed according to Test
for fat digestive power in the Test for digestion (3).
But, phosphorus buffer solution, pH 8.0, is used as a
buffer solution.
Store at a temperature not exceeding 30 C.
Pantethine
HO
CH2
CH3 OH
O
NHCH2CH2
NHCH2CH2S
CH3 H
HO
CH2
CH3 OH
O
NHCH2CH2
NHCH2CH2S
CH3 H
C22H42N4O8S2: 554.72
Pantethine is an aqueous solution containing 80.0% of
pantethine.
Pantethine contains not less than 98.0% and not more
than 101.0% of pantethine (C22H42N4O8S2), calculated
Description Pantethine is a clear, colorless to pale
yellow viscous liquid.
Pantethine is miscible with water, with methanol or
with ethanol.
Pantethine is affected by light.
Identification (1) Take 0.7 g of Pantethine, add 5 mL
of sodium hydroxide TS, shake and add 1 to 2 drops of
cupric sulfate TS: a blue-purple color is observed.
(2) Take 0.7 g of Pantethine, add 3 mL of water,
shake, add 0.1 g of zinc powder and 2 mL of glacial
acetic acid and boil for 2 to 3 minutes. After cooling,
add 1 to 2 drops of sodium nitroprusside TS: a redpurple color is observed.
(3) Take 1.0 g of Pantethine and add 500 mL of water and shake. To 5 mL of this solution, add 3 mL of 1
mol/L hydrochloric acid TS and heat in a water-bath for
30 minutes. After cooling, add 7 mL of a solution of
hydroxylamine hydrochloride in sodium hydroxide TS
(3 in 140) and allow to stand for 5 minutes. Add 3
drops of 2,4-dinitrophenol TS and add 1 mol/L hydrochloric acid TS drop-wise until the solution has no
color and then add 1 mL of ferric chloride TS: a redpurple color is observed.
D : Between +15.0
and +18.0 (1 g, calculated on the anhydrous basis, water, 25 mL, 100 mm).
Purity (1) Heavy metalsProceed with 2.0 g of Pan-
tethine according to Method 1 and perform the test.

Pantethine according to Method 3 and perform the test
(3) Related substancesDissolve 0.6 g of Pantethine in 10 mL of water and use this solution as the test
solution. Pipet 2.0 mL of the test solution, add water to
and the standard solution as directed under the Thinlayer Chromatography. Spot 2 L each of the test solution and the standard solution on a plate of silica gel for
thin-layer chromatography. Develop the plate with methyl ethyl ketone saturated with water to a distance of
about 10 cm and air-dry the plate. Allow the plate to
stand for about 10 minutes in iodide vapor: the spots
(4) Mercapto compoundsTo 1.5 g of Pantethine,
add 20 mL of water, shake, add 1 drop of ammonia TS
and 1 to 2 drops of sodium nitroprusside TS: a red color is not observed.
Water Between 18% and 22% (0.2 g, volumetric titration, direct titration).
Assay Weigh accurately about 0.3 g of Pantethine,
add water to make exactly 20 mL. Transfer exactly 5
mL of this solution in an iodine bottle and add exactly
25 mL of 0.05 mol/L bromine VS and 100 mL of water.
Add 5 mL of diluted sulfuric acid (1 in 5) rapidly, stopper tightly immediately and warm at 40 C to 50 C for
15 minutes with occasional shaking. After cooling,
carefully add 5 mL of a solution of potassium iodide (2
in 5), then immediately stopper tightly, shake, add 100
mL of water and titrate the liberated iodine with 0.1
Each mL of 0.05 mol/L bromine VS
= 5.547 mg of C22H42N4O8S2
tight containers. Store at a temperature not exceeding
10 C.
Papaverine Hydrochloride
N
CH2
OCH 3
OCH3
(3) Readily carbonizable substancesPerform the

test with 0.12 g of Papaverine Hydrochloride: the solution has no more color than Color Matching Fluid S or
P.
hours).
HCl

CH3O
OCH 3
C20H21NO4HCl: 375.85
Papaverine Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of papaverine hydrochloride (C20H21NO4HCl).
Description Papaverine Hydrochloride is a white
Papaverine Hydrochloride is sparingly soluble in water
or in glacial acetic acid, slightly soluble in ethanol and
practically insoluble in acetic anhydride or in ether.
pHThe pH of a solution of Papaverine Hydrochloride (1 in 50) is between 3.0 and 4.0.
Identification (1) Take 1 mg of Papaverine Hydrochloride and add 1 drop of formalin-sulfuric acid TS: a
colorless to a pale yellow-green color is observed and it
gradually changes to deep red, then to brown.
(2) Dissolve 20 mg of Papaverine Hydrochloride in
1 mL of water and add 3 drops of sodium acetate TS: a
white precipitate is produced.
(3) Dissolve 1 mg of Papaverine Hydrochloride in 3
mL of acetic anhydride and 5 drops of sulfuric acid,
heat in a water-bath for 1 minute and examine under ultraviolet light (main wavelength: 365 nm): the solution
shows a yellow-green fluorescence.
(4) Dissolve 0.1 g of Papaverine Hydrochloride in
10 mL of water, make alkaline with ammonia TS and
shake with 10 mL of ether. Draw off the ether layer,
wash with 5 mL of water and filter. Evaporate the filtrate on a water-bath and dry the residue at 105 C for 3
hours: the residue so obtained melts between 145 C
and 148 C.
(5) Alkalify a solution of Papaverine Hydrochloride
(1 in 50) with ammonia TS and filter the precipitate.
Acidify the filtrate with dilute nitric acid: the solution
0.10 g of Papaverine Hydrochloride in 10 mL of water:
(2) MorphineDissolve 10 mg of Papaverine Hydrochloride in 1 mL of water, add 5 mL of -nitroso-naphthol TS and 2 mL of a solution of potassium nitrate (1 in 10) and warm 40 C. Add 1 mL of solution
of sodium nitrate (1 in 5000) and warm at 40 C. After
cooling, shake the mixture with 10 mL of chloroform,
centrifuge and separate the aqueous layer: the solution
has no more color than a pale red color.
Assay Weigh accurately about 0.5 g of Papaverine

a mixture of acetic anhydride and glacial acetic acid
(7 : 3) by warming, cool and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
tight containers.
Papaverine Hydrochloride
Injection
Papaverine Hydrochloride Injection is an aqueous solution for injection. Papaverine Hydrochloride Injection
of the labeled amount of papaverine hydrochloride
(C20H21NO4-HCl: 375.85).
Method of Preparation Prepare as directed under Injections, with Papaverine Hydrochloride.
Description Papaverine Hydrochloride Injection is a
Identification (1) Take 1 mL of Papaverine Hydrochloride Injection and add 3 drops of sodium acetate TS:
a white precipitate is produced.
(2) Dilute a volume of Papaverine Hydrochloride
Injection, equivalent to 0.1 g of Papaverine Hydrochloride according to the labeled amount, with water to
make 10 mL, render the solution alkaline with ammonia TS and shake with 10 mL of ether. Draw off the
ether layer, wash with 5 mL of water and filter. Evaporate the filtrate in a water-bath to dryness and dry the
residue at 105 C for 3 hours: the residue so obtained
melts between 145 C and 148 C.
(3) Proceed with 1 mg each of the residue obtained
in (2) as directed in the Identification (1) and (3) under
Papaverine Hydrochloride.
(4) Alkalify 2 mL of Papaverine Hydrochloride Injection with ammonia TS, filter the precipitate off and
KP 9 733
acidify the filtrate with dilute nitric acid: the solution
Assay Take exactly a volume of Papaverine Hydrochloride Injection, equivalent to about 0.2 g of Papaverine
Hydrochloride (C20H21NO4.HCl), add water to make 10
mL, render the solution alkaline with ammonia TS and
extract with 20 mL, 15 mL, 10 mL and 10 mL of chloroform. Combine the extracts, wash with 10 mL of water and re-extract the washings with two 5 mL volumes
of chloroform. Combine all the chloroform extracts and
evaporate the chloroform in a water-bath. Dissolve the
residue in 30 mL of glacial acetic acid and titrate with
0.05 mol/L perchloric acid VS (indicator: 2 drops of
methylrosaniline chloride TS). Perform a blank determination and make any necessary correction.
Paraformaldehyde
warm slowly: a persistent, dark red color is produced.

0.20 g of Paraformaldehyde in 10 mL of ammonia TS:
(2) Acidity or alkalinityTo 0.5 g of Paraformaldehyde, add 10 mL of water, shake vigorously for 1
minute and filter: the filtrate is neutral.
(3) ChlorideDissolve 1.5 g of Paraformaldehyde
in 75 mL of water and 7.5 mL of sodium carbonate TS,
evaporate on a water-bath to dryness and ignite at about
500 C. Dissolve the residue in 15 mL of water, filter, if
necessary, neutralize with diluted nitric acid (3 in 10)
and add 6 mL of dilute nitric acid and water to make 50
mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: to 0.25 mL
of 0.01 mo1/L hydrochloric acid VS, add 7.5 mL of sodium carbonate TS, volume of diluted nitric acid (3 in
10) required for neutralization of the test, 6 mL of dilute nitric acid and water to make 50 mL (not more than
0.006%).
(4) SulfateDissolve 1.5 g of Paraformaldehyde in
45 mL of water and 4.5 mL of sodium carbonate TS,
evaporate on a water-bath to dryess and ignite at about
500 C. Dissolve the residue in 15 mL of water, filter, if
necessary, neutralize the diluted hydrochloric acid (3 in
5) and boil for 5 minutes. After cooling, add 1 mL of
dilute hydrochloric acid and water to make 50 mL. Perform the test using this solution as the test solution.
Prepare the control solution as follows: to 4.5 mL of
sodium carbonate TS, add an equal volume of diluted
hydrochloric acid (3 in 5) for the neutralization of the
test and 15 mL of water and boil for 15 minutes. After
cooling, add 0.35 mL of 0.005 mol/L sulfuric acid VS,
1 mL of dilute hydrochloric: acid and water to make 50
mL (not more than 0.011%).
Poly(oxymethylene)
(CH2O)n
Paraformaldehyde contains not less than 95.0% and not

more than 101.0% of formaldehyde (CH2O: 30.03).
Description Paraformaldehyde is a white powder and
has a slight odor of formaldehyde, but a very strong irritating odor is perceptible when it is heated.
Paraformaldehyde is practically insoluble in water, in
Paraformaldehyde dissolves in hot water, in hot dilute
hydrochloric acid, in sodium hydroxide TS or in ammonia TS.
Paraformaldehyde sublimes at about 100 C.
Identification (1) Dissolve 0.1 g of Paraformaldehyde in 5 mL of ammonia TS, add 5 mL of silver nitrate TS, shake and add 3 mL of a solution of sodium
hydroxide (1 in 10): a mirror of metallic silver is immediately formed on the sides of the container.
(2) Add a solution of 40 mg of salicylic acid in 5
mL of sulfuric acid to 20 mg of Paraformaldehyde and
Assay Dissolve about 50 mg of Paraformaldehyde,

accurately weighed, in 10 mL of potassium hydroxide
TS in an iodine flask. Add 40 mL of water and exactly
50 mL of 0.05 mol/L iodine VS, stopper and allow to
stand for 5 minutes. Then add 5 mL of dilute hydrochloric acid, stopper immediately, allow to stand for 15
minutes and titrate the excess iodine with 0.1 mol/L sodium thiosulfate VS (indicator: 1 mL of starch TS).
correction..
Each mL of 0.05 mol/L iodine VS
= 1.5013 mg of CH2O
Paroxetine Hydrochloride
Hydrate
F
H
HCl
O
NH
1/2H2O
H
O
C19H21ClFNO3H2O : 374.84
Paroxetine Hydrochloride Hydrate contains not less
than 97.5% and not more than 102.0% of paroxetine
hydrochloride (C19H21ClFNO3), calculated on the anhydrous basis.
Description Paroxetine Hydrochloride Hydrate is a
Paroxetine Hydrochloride Hydrate is freely soluble in
methanol, sparingly soluble in ethanol or in dichloromethane, and slightly insoluble in water.
Identification (1) To about 0.16 g of Paroxetine Hydrochloride Hydrate in a test tube, add 0.2 g of potassium dichromate and 1 mL of sulfuric acid and place a
filter paper wet with diphenylcarbazide TS: the color of
filter paper turns to reddish violet.
(2) Determine the infrared absorption spectra of Paroxetine Hydrochloride Hydrate and Paroxetine Hydrochloride Hydrate RS, as directed in the potassium
bromide disk method under lnfrared Spectrophotornetry : both spectra exhibit similar intensities of absorption at the same wavenumbers. If any difference appears in the absorption spectra, dissolve Paroxetine
Hydrochloride Hydrate and paroxetine hydrochloride
hydrate RS in a mixture of isopropanol and water (9 :
1) at the concentration of 10% and recrystalize, respectively. Perform the test with the residues in the same
manner.
(3) Perform the test with the test solution and the
standard solution (3) in the Related substance I as directed under the Liquid Chromatography, according to
the operating conditions: the retention times of the
principal peaks are similar to each other.
Purity (1) Heavy metalsProceed with 1.0 g of Paroxetine Hydrochloride Hydrate in a platinum crucible
according to Method 2, and perform the test. Prepare
the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm).
(2) Related substance IDissolve 0.1 g of Paroxetine Hydrochloride Hydrate, accurately weighed, in 20
mL of methanol, add the mobile phase to make exactly
100 mL and use this solution as the test solution. Pipet
1.0 mL of the test solution, add the mobile phase to
make exactly 100 mL, pipet 1.0 mL of this solution,

this solution as the standard solution (1). Separately,
dissolve 5 mg each of paroxetine related substance I
{(3S,4R)-3[1,3-benzodioxol-5-yloxy]methyl}-4-(4ethoxyphenyl)piperidine ((+)-trans-paroxtine)} and paroxetine hydrochloride hydrate RS in 2 mL of methanol,
dissolve 10 mg of Paroxetine Hydrochloride Hydrate
RS in 2 mL of methanol, add the mobile phase to make
exactly 10 mL and use this solution as the standard solution (3). Perform the test with 10 L each of the test
solution, the standard solution (1) and the standard solution (2) as directed under the Liquid Chromatography,
measure the areas of peaks: the area of peak corresponding to the related substance I obtained from the
test solution is not more than 2 times the area of the
principal peak from the standard solution (1). (not more
than 0.2%)
(main wavelength: 295 nm)
inside diameter and 10 cm in length, packed with silica
gel AGP for liquid chromatography (5 m in particle
diameter).
Mobile phase: A mixture of 0.58% sodium chloride
solution and methanol (8 : 2).
Flow rate: About 0.5 mL/minute
System suitability
with 10 L of the standard solution (2) according to the
above operating conditions, the resolution between the
related substance I and paroxetine is not less than 2.2.
as the retention time of paroxetine.
(3) Related substancesDissolve 50.0 mg of Paroxetine Hydrochloride Hydrate in a mixture of water
and tetrahydrofuran (9 : 1) to make exactly 50 mL and
use this solution as the test solution. To 5.0 mL of the
test solution, add a mixture of water and tetrahydrofuran (9 : 1) to make exactly 50 mL and use this solution
as the standard solution (1). Separately, dissolve 2 mg
of paroxetine related substance II RS {(3S,4R)-3-[(1,3benzodioxol-5-yloxy)methyl]-4-(4-ethoxyphenyl) piperidine} in a mixture of water and tetrahydrofuran (9 : 1)
standard solution (2). To 2.0 mL of the standard solution (1), add 2.0 mL of the standard solution (2) and a
mixture of water and tetrahydrofuran (9 : 1) to make
exactly 20 mL and use this solution as the standard solution (3). To 2.0 mL of the standard solution (1), add a
mixture of water and tetrahydrofuran (9 : 1) to make
exactly 200 mL and use this solution as the standard solution (4). Separately, dissolve 2 mg of paroxetine related substance III RS {(3S,4R)-3-[(1,3-benzodioxol-5yloxy)methyl]-4-phenypiperidien
(desfluoroparox-
KP 9 735
etine)} in a mixture of water and tetrahydrofuran (9 : 1)
standard solution (5). Perform the test with 10 L each
of the test solution, the standard solution (3), the standard solution (4) and the standard solution (5) as directed under the Liquid Chromatography, according to
the following operating conditions and measure the
areas of peaks: the area of the peak corresponding to
the related substance III from the test solution is not
more than 3 times the area of the principal peak from
the standard solution (4) (0.3%), area of each of any
other related substances is not more than the area of the
principal peak from the standard solution (4) (0.1%),
and the total area of those peaks is not more than 5
times the area of the principal peak from the standard
solution (4) (0.5%). The peaks with areas of less than
1/2 times the area of the principal peak from the standard solution (4) are disregarded.
Column: A stainless stcel column 4.6 mm in inside
diameter and 25 cm in length, packed with octylsilanized silica gel for liquid chromatography (5 m in particle diameter)
about 40 C.
Control the gradient by mixing the mobile phases
A and B as directed in the following table.
Mobile phase A: A mixture of water, tetrahydrofuran and trifluoroactic acid (900 : 100 : 5)
Mobile phase B: A mixture of acetonitrile, tetrahydrofuran and trifluoroactic acid (900 : 100 : 5)
0 to 30
Mobile
phase A
(vol%)
80
Mobile
phase B
(vol%)
20
30 to 50
80 20
20 80
50 to 60
20
80
60 to 65
20 80
80 20
65 to 70
80
20

(minutes)
Elution
condition
Isocratic
Linear
gradient
Isocratic
Linear
gradient
Isocratic

System suitability
System performance: Mix 2.0 mL of the standard solution (1) and 1.0 mL of the standard soluteon
(5), and add a mixture of water and tetrahydrofuran (9 :
1) to make exactly 20 mL. When the procedure is run
conditions, the relative retention time of the related
substance III peak to the paroxetine peak is about 0.8.
When the procedure is run with 20 L of the standard
solution (3) under the above operating conditions, the
resolution between the peaks of the related substance II
and paroxetine is not less than 3.5.
long as the retention time of paroxetine.
Assay Dissolve about 50 mg each of Paroxetine Hydrochloride Hydrate and Paroxetine Hydrochloride Hydrate RS in water to make exactly 100 mL and use
these solutions as the test solution and the standard solution, respectively. Perform the test with 10 L each
under the Liquid Chromatography, according to the following operating conditions, and measure the peak
areas, AT and AS, of paroxetine for the test solution and
the standard solution, respectivly.
Amount (mg) of paroxetine hydrochloride
(C19H21ClFNO3) = amount (mg) of paroxetine hydrochloride in Paroxetine Hydrochloride Hydrate RS, calcuAT
larated on the anhydrous basis A
S
(main wavelength: 295 nm).
Column: A stainless steel column, about 4.6 mm
in inside diameter and about 25 cm in length, packed
with trimethylsilyl silica gel for liquid chromatography
Mobile phase: Dissolve 3.85 g of ammonium acetate in 500 mL of water, adjust to pH 5.5 with glacial
acetic acid, add water to make 600 mL, add 400 mL of
acetonitrile slowly and 10 mL of triethylamine and adjust to pH 5.5 with glacial acetic acid.
System suitability
System performnace: Dissolve 5.0 mg each of
Paroxetine Hydrochloride Hydrate and paroxetine related substance III RS, accurately weighed, in water to
make exactly 10 mL. When the procedure is run with
10 L of this solution according to the above operating
conditions, the resolution between the peaks of paroxetine related substance III and paroxetine is not less
than 2.0.
as the retention time of paroxetine.
Penbutolol Sulfate
OH
OCH2
CH2NHC(CH3)3
H2SO4
layer Chromatography. Spot 10 L each of the test solution and standard solution on a plate of silica gel with
Develop the plate with a mixture of 2-propanol, ethanol
and ammonia solution (28) (85 : 12 : 3) to a distance of
about 10 cm, and air-dry the plate. Examine under
uhraviolet light (main wavelength: 254 nm): the spots
and enantiomer
(C18H29NO2)2H2SO4 : 680.94
Penbutolol Sulfate, when dried, contains not less than
98.5% and not more than 101.0% of penbutolol sulfate
[(C18H29NO2)2H2SO4].
Description Penbutolol Sulfate is a white crystalline
powder.
Penbutolol Sulfate is very soluble in glacial acetic acid,
freely soluble in methanol, sparingly soluble in ethanol,
slightly soluble in water, and practically insoluble in
acetic anhydride or in diethyl ether.
of solution of Penbutolol Sulfate and Penbutolol Sulfate RS in methanol (1 in 10000) as directed under the
Penbutolol Sulfate and Penbutolol Sulfate RS, previously dried, as directed in the paste method under
lnfrared Spectrophotornetry : both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) Dissolve 0.1 g of Penbutolol Sulfate in 25 mL of
water by warming, and cool: this solution responds to
the Qualitative Tests for sulfate.
Melting Point

[ ] 20
D

: Between -23 and
- 25 (after drying, 0.2 g, methanol, 20 mL, 100 mm).
Penbutolol Sulfate according to Method 2, and perform
Standard Lead Solution (not more than 10 ppm).
Penbutolol Sulfate according to Method 4, and perform
(3) Related substancesDissolve 0.8 g of Penbutolol Sulfate in 10 mL of methanol, and use this solution
as the test solution. Pipet exactly 1 mL of the sample
solution, add methanol to make exactly 200 mL, and
test with these solutions as directed under the Thin-

3 hours).
Assay Weigh accurately about 0.8 g of Penbutolol
Sulfate, previously dried, dissolve in 50 mL of a mixture of acetic anhydride and glacial acetic acid (7 : 3),
and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any
= 68.09 mg of (C18H29NO2)2H2SO4
Penicillin G Potassium
O
KO
H
O
N
CH3
CH3
N
H
S
H
C16H17N2KO4S: 372.48
Penicillin G Potassium is the potassium salt of a penicillin substance having antibacterial activity produced
by the growth of Penicillium species.
Penicillin G Potassium contains not less than 1350
units (potency) per mg of penicillin G (C16H18N2O4S:
Description Penicillin G Potassium is a white crystal
or crystalline powder, is odorless or has a little bit of a
characteristic odor.
Penicillin G Potassium is very soluble in water, sparingly soluble in ethanol, and practically insoluble in
ether.
Identification (1) To 2 mL of an aqueous solution of
Penicillin G Potassium (1 in 10), add diluted hydrochloric acid (1 in 10): a white precipitate develops. This
precipitate is dissolved in ethanol, in amylacetate, or in
KP 9 737
chloroform.
(2) Weigh 0.1 g of Penicillin G Potassium, dissolve
in 25 mL of water, take 1 mL of this solution, and add
water to make 20 mL. To this solution add 0.3 g of hydroxylamine hydrochloride and dissolve, add 3 mL of 1
mol/L sodium hydroxide TS, allow to stand for 5 minutes, and add 3 mL of 1 mol/L hydrochloric acid TS
and 5 mL of freshly prepared ferric (III) chloride solution (0.1 % as an iron): a brief lasting purple-brown
color develops.
(3) Ignite 20 mg of Penicillin G Potassium in platinum dish, add a few drop of water and one drop of hydrochloric acid and filter. The filtrate responds to the
Qualitative Tests (1) for potassium salt.
Crystalliity Test
pH The pH of a solution obtained by dissolving

10000 units (potency) of Penicillin G Potassium in 1
mL of water is between 5.0 and 7.5.
Heat Stability Test Weigh accurately about 50000
units (potency) [A unit] of Penicillin G Potassium, according to the result of assay, allow to stand at 100
1 C for 4 days, and determine a potency [B unit] by
reassay (loss in potency: not more than 10 %).
Ratio [%] of loss in potency
= {([A unit] - [B unit]) x 100}/ [A unit]
Sterility Test It meets the requirement, when Penicillin G Potassium is used in a sterile preparation.
Bacterial Endotoxins Less than 0.01 EU per 100
units of penicillin G, when Penicillin G Potassium is
used in a sterile preparation.
suction the precipitate through glass filter (G4, diameter about 10 mm), previously weighed the mass, and
wash with 1 mL of acetone TS (0 ~ 8 C) for penicillin
by using a syringe. Place the glass filter in the test tube,
dry in vacuum for 1 hour, and weigh the mass (not less
than 85.0 %). Calculate the ratio by using the following
equation.
Amount [%] of penicillin G potassium
Amount [mg] of the precipitate of
N - ethylpiperidine penicillin 116.53
=
Amount [mg] of Penicillin G Potassium taken
Assay Weigh accurately about 60 mg of Penicillin G
Potassium, dissolve in 1 % phosphate buffer solution,
pH 6.0 to make a solution so that each mL contains
2000 units (potency), and use this solution as the test
Penicillin G Potassium RS, dissolve in 1 % phosphate
buffer, pH 6.0 to make a solution so that each mL contains 2000 units (potency), and use this solution as the
standard solution. Pipet exactly 2 mL each of the test
solution and the standard solution, transfer into a 100
mL flask for iodine titration, add 2.0 mL of 1 mol/L sodium hydroxide TS, allow to stand for 15 minutes, add
2.0 mL of diluted hydrochloric acid (1 in 10) and 10.0
mL of 0.01 mol/L iodine VS and allow to stand for 15
minutes, if necessary, add about 5 mL of carbon tetrachloride and shake. Pipet exactly 2 mL each of the
test solution and the standard solution, add exactly 10.0
mL of 0.01 mol/L iodine VS, titrate each of these solutions in the same manner as the above except 15
minute-standing to perform a blank determination, and
make any necessary correction. Determine the consumed amounts (mL) of 0.01 mol/L iodine VS, VT and
VS, of the test solution and the standard solution, respectively.
Potency of Penicillin G Potassium

Content of Penicillin G Potassium (as by mass ratio)
Weigh accurately 60 ~ 70 mg of Penicillin G Potassium,
transfer into stoppered centrifuge tube, add 2.0 mL of
water to dissolve, allow to cool to 0 ~ 5 C, add 2.0 mL
of amylacetate TS for penicillin, previously cool to 0 ~
5 C, and 0.5 mL of diluted phosphoric acid (1 in 5),
shake vigorously to mix for 15 seconds, and centrigure
for 20 seconds to separate into two layers. Take the
amylacetate layer (about 1.7 ~ 1.8 mL) by using a 2 mL
syringe with needle, and filter through glass filter (diameter about 10 mm) with 0.1 g of sodium sulfate anhydrous. The filter unit is kept cool with ice. Pipet exactly 1.0 mL of this solution, add 0.5 mL of Nethylpiperidine TS for penicillin and 1.0 mL of acetone
TS for penicillin, and transfer into a 15 x 15 mm flatbotom test tube, previously weighed the mass. Perform
the prodcedure within 3 minutes from acidifying the
test solution to transferring the filtrate. Place the above
test tube in stoppered weighing bottle, close stopper,
and allow to stand at 0 ~ 8 Cfor 2 hours. Filter under
= Potency of Penicillin G Potassium RS
VT
VS
Penicillin G Sodium
O
NaO
H
O
N
CH3
CH3
N
H
S
H
C16H17N2NaO4S: 356.37
Penicillin G Sodium is the sodium salt of a penicillin
growth of Penicillium species.

Penicillin G Sodium contains not less than 1400 units
(potency) per mg of penicillin G (C16H18N2O4S:
Amount [mg] of the precipitate of

N - ethylpiperidine penicillin 159.3
=
Amount [mg] of Penicillin G Sodium taken
Description Penicillin G Sodium is a white crystal or

crystalline powder, is odorless or has a little bit of a
Penicillin G Sodium is very soluble in water, and
slightly soluble in acetone.
Penicillin G Sodium is very soluble in Isotonic Sodium
Chloride Injection and in Dextrose Injection Solution.
Assay Perform the test according to Assay under Penicillin G Potassium. Take exactly 2.0 mL of the solution, and use as the test solution.
Identification (1) To 2 mL of an aqueous solution of

Penicillin G Sodium (1 in 10), add diluted hydrochloric
acid (1 in 10): a white precipitate develops. This precipitate is dissolved in ethanol, in amylacetate, or in chloroform.
(2) Weigh 0.1 g of Penicillin G Sodium, dissolve in
25 mL of water, take 1 mL of this solution, and add water to make 20 mL. To this solution add 0.3 g of hydroxylamine hydrochloride and dissolve, add 3 mL of 1
mol/L sodium hydroxide TS, allow to stand for 5 minutes, and add 3 mL of 1 mol/L hydrochloric acid TS
and 5 mL of freshly prepared ferric (III) chloride solution (0.1 % as an iron): a brief lasting purple-brown
color develops.
(3) Ignite 20 mg of Penicillin G Sodium in platinum
dish, add a few drop of water and one drop of hydrochloric acid and filter. The filtrate responds to the Qualitative Tests 1) for sodium salt.
Crystalliity Test

10000 units (potency) of Penicillin G Sodium in 1 mL
of water is between 5.0 and 7.5.
Heat Stability Test Perform the test according to
Heat stability test under Penicillin G Potassium (loss in
potency: not more than 10 %).
Sterility Test It meets the requirement, when Penicillin G Sodium is used in a sterile preparation.
Bacterial Endotoxins Less than 0.01 EU per 100
units of penicillin G, when Penicillin G Sodium is used
in a sterile preparation.
Pentazocine
CH3
CH2CH
C
CH3
N
H
CH3
CH3
and enantiomer
HO
C19H27NO: 285.42
Pentazocine, when dried, contains not less than 99.0%
and not more than 101.0% of pentazocine (C19H27NO).
Description Pentazocine is a white to pale yellowish
Pentazocine is freely soluble in glacial acetic acid or in
chloroform, soluble in ethanol, sparingly soluble in
Identification (1) Take 1 mg of Pentazocine, add 0.5
mL of formalin-sulfuric acid TS: a deep red color is observed and it changes to grayish brown immediately.
(2) Dissolve 5 mg of Pentazocine in 5 mL of sulfuric acid, add 1 drop of ferric chloride TS and heat in a
water-bath for 2 minutes: the color of the solution
changes from pale yellow to deep yellow. Shake the solution with 1 drop of nitric acid: the solution remains
yellow in color.
Pentazocine and Pentazocine RS in 0.01 mol/L hydrochloric acid TS (1 in 10000) as directed under the
1%
Content of Penicillin G Sodium (as by mass ratio)

Perform the test according to Content of penicillin G
potassium under Penicillin G Potassium (not less than
85.0 %). Calculate a ratio by using the following equation.
Amount [%] of penicillin G sodium
Absorbance E1cm (278 nm): Between 67.5 and 71.5

(after drying, 0.1 g, 0.01 mol/L hydrochloric acid TS,
1000 mL).
Melting Point

0.10 g of Pentazocine in 20 mL of 0.1 mol/L hydrochloric acid TS: the solution is clear and colorless.
KP 9 739
(2) Heavy metalsProceed with 1.0 g of Pentazocine according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
Pentazocine according to Method 3 and perform the
test with a solution of magnesium nitrate in ethanol (1
in 10) (not more than 2 ppm).
(4) Related substancesDissolve 0.20 g of Pentazocine in 10 mL of chloroform and use this solution as
add chloroform to make exactly 100 mL and use this
plate with a mixture of chloroform, methanol and isopropylamine (94 : 3 : 3) to a distance of about 13 cm
and air-dry the plate. Allow to stand for 5 minutes in
iodine vapor: the spot other than the principal spot from
the test solution is not more intense than the spot from
P2O5, 60 C, 5 hours).
Assay Weigh accurately about 0.5 g of Pentazocine,

= 28.542 mg of C19H27NO
Packaging and Storage Preserve in well-close containers.
Pentobarbital Sodium
O
H
N
C2H5
ONa
CH3(CH2)2C
H
CH3 O
C11H17N2NaO3: 248.25
Pentobarbital Sodium contains not less than 98.5% and
not more than 101.0% of pentobarbital sodium
(C11H17N2NaO3), calculated on the dried basis.
Description Pentobarbital Sodium is a white crystalline granule or powder, is odorless or has a characteris-
tic odor and has a slightly bitter taste.

Pentobarbital Sodium is very soluble in water, soluble
in ethanol and practically insoluble in ether.
The solution of Pentobarbital Sodium is decomposed
on being allowed to stand and the decomposition is accelerated by heating.
of the test solution and the standard solution obtained
in Assay, as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities
(2) Ignite about 0.2 g of Pentobarbital Sodium and
dissolve the residue with acid: the solution responds to
the Qualitative Tests for sodium salt.
pH Dissolve 1.0 g of Pentobarbital Sodium in 100
11.0.
1.0 g of Pentobarbital Sodium in 10 mL of freshly
boiled and cooled water and allow to stand for 1
minute: the solution is clear and there is no insoluble
material.
(2) IsomerDissolve about 300 5 mg of Pentobarbital Sodium in 5 mL of water and 300 5 mg of pnitrobenzyl bromide in 10.0 mL of ethanol. Combine
the two solutions, mix by shaking, then reflux for 30
minutes, cool to 25 C and filter by suction. Wash the
residue with four 5 mL volumes of water, transfer as
completely as possible to a small flask, add 25.0 mL of
ethanol and reflux for 10 minutes: the solid dissolves
completely. Cool the solution and filter by suction: the
collected solid, after being dried at 105 C for 30 minutes, melts between 136 C and 146 C .
(3) Heavy metalsDissolve 2.0 g of Pentobarbital
Sodium in 50 mL of water. Add slowly, with vigorous
shaking, 5 mL of dilute hydrochloric acid and warm for
2 minute in a water-bath with occasional shaking. Cool,
add 25 mL of water with shaking and filter. Discard the
first 10 mL of the filtrate, take 40 mL of the subsequent
filtrate, add 1 drop of phenolphthalein TS, add ammonia TS drop-wise until a pale red color is observed, add
2 mL of dilute acetic acid, add water to make 50 mL
test. Prepare the control solution as follows: add 2.5 mL
of dilute acetic acid and 1 drop of phenolphthalein TS,
add ammonia TS drop-wise until a pale red color is observed, add 2 mL of dilute acetic acid, 3.0 mL of standard lead solution and water to make 50 mL (not more
than 30 ppm).
hours).
Assay Weigh accurately about 25 mg of Pentobarbital
Sodium, previously dried and add diluted ammonia solution (28) (1 in 200) to make exactly 50 mL. Pipet exactly 2 mL of this solution, add diluted ammonia solu-
tion (28) (1 in 200) to make exactly 100 mL and use

this solution as the test solution. Separately, weigh accurately about 0.1 g of Pentobarbital RS and dissolve in
diluted ammonia solution (28) (1 in 200), to make exactly 100 mL. Pipet exactly 1 mL of this solution, add
diluted ammonia solution (28) (1 in 200) to make exactly 100 mL, use this solution as a standard solution.
Determine the absorbances of the test solution and the
standard solution, AT and AS, at 240 nm as directed under the Ultraviolet-visible Spectrophotometry, using diluted ammonia solution (28) (1 in 200) as a blank.
Amount (mg) of pentobarbital sodium (C11H17N2NaO3)
1
AT
= amount (mg) of Pentobarbital RS A 1.097 4
S
Pentobarbital Sodium Capsules

Pentobarbital Sodium Capsules contain not less than
of pentobarbital sodium (C11H17N2NaO3: 248.25).
Capsules, with Pentobarbital Sodium.
Identification Dissolve a portion of Pentobarbital
Sodium Capsules equivalent to about 0.1 g of pentobarbital sodium according to the labeled amount, in 15
mL of water in a separatory funnel, add 2 mL of hydrochloric acid, shake well and extract the liberated
pentobarbital with five 25 mL volumes of chloroform.
Filter each extract through a suitable filter. Evaporate
the combined chloroform extract to dryness in a waterbath with the aid of a current of air, add 10 mL of ether
and evaporate to dryness again. Recrystallize from hot
ethanol and dry the residue at 105 C for 30 minutes.
With the residue so obtained, proceed as directed in the
Identification (1) under Pentobarbital Sodium.
Pentobarbital Sodium Capsules at 100 revolutions per
Test, using 900 mL of water. Take the dissolved solution after 45 minutes from starting of the test and filter.
Add freshly prepared diluted ammonia solution (28) (1
in 20) to obtain a solution having known concentration
of about 10 g of pentobarbital per mL and use this solution as the test solution. Separately, weigh accurately
a portion of Pentobarbital RS, dissolve in freshly prepared diluted ammonia solution (28) (1 in 20) to obtain
a solution having known concentration of about 10 g
of pentobarbital per mL and use this solution as the
standard solution. The concentration of the standard solution, multiplied by 1.097, represents the equivalent
amount of Pentobarbital Sodium. Determine the absorbances of the test solution and the standard solution at
240 nm as directed under the Ultraviolet-visible Spectrophotometry using diluted ammonia solution (28) (1
in 20) as the blank.
The dissolution rate of Pentobarbital Sodium Capsules
in 45 minutes is not less than 75%.
Uniformity of Dosage Units It meets the requirement when the content uniformity test is performed according to the following procedure.
Transfer the contents of 1 capsule of Pentobarbital Sodium Capsules with 5 mL of ethanol to a 250-mL volumetric flask, add 10 mL of freshly prepared diluted
ammonia solution (28) (1 in 200) and dilute with immediately the same solution to make 250 mL. Mix by
shaking and filter, if necessary. Discard the first 20 mL
of the filtrate and dilute the subsequent filtrate with diluted ammonia solution (28) (1 in 200) to obtain a solution having known concentration of 10 g of pentobarbital sodium per mL and use this solution as the test solution. Separately, weigh accurately a suitable amount
of Pentobarbital Sodium RS, dissolve in diluted ammonia solution (28) (1 in 200) to obtain a solution having
known concentration of 10 g of pentobarbital sodium
standard solution at 240 nm as directed under the Ultraviolet-visible Spectrophotometry using diluted ammonia solution (28) (1 in 20) as the blank.
Amount (mg) of pentobarbital sodium (C11H17N2NaO3)

in 1 capsule = labeled amount (mg) of Pentobarbital
CS
AT
Sodium in 1 capsule C A 1.097
T
S
CS : concentration (g/mL) of pentobarbital in the
standard solution
CT : concentration (g/mL) of pentobarbital sodium
in the test solution, calculated on the basis of the labeled quantity per capsule and the extent of dilution
20 Pentobarbital Sodium Capsules, mix uniformly the
contents and transfer accurately a portion of the powder,
equivalent to about 50 mg of Pentobarbital Sodium
(C11H17N2NaO3), to a separatory funnel. Add 15 mL of
water and 1 mL of hydrochloric acid, shake well and
extract with five 25 mL volumes of chloroform. Filter
the extracts through about 15 g of anhydrous sodium
sulfate that is supported on a funnel by a small pledget
of glass wool. Collect the combined filtrate in a volumetric flask, wash the sodium sulfate with 15 mL of
chloroform, collecting the washing with the filtrate and
add chloroform to make exactly 100 mL. Mix 2.0 mL
of this solution with 1.0 mL of the internal standard solution and use this solution as the test solution. Separately, weigh accurately about 45 mg of pentobarbital
RS, previously dried at 105 C for 2 hours, dissolve in
chloroform to make exactly 100 mL, mix 2.0 mL of
this solution with 1.0 mL of the internal standard solution and use this solution as the standard solution. Per-
KP 9 741
form the test with 10 L each of the test solution and

the standard solution as directed under the Gas Chromatography according to the following conditions and
calculate the ratios, QT and QS, of the peak area of pentobarbital to that of the internal standard for the test solution and the standard solution, respectively.
Amount (mg) of pentobarbital sodium
(C11H17N2NaO3) = amount (mg) of Pentobarbital
QT
RS Q 1.097
S
Internal standard solutionA solution of ntricosane in chloroform (4 in 10000).
Column: A glass column, about 4 mm in inside diameter and about 0.9 m in length, having polyamide
coated at the ratio of 3% on siliceous earth for gas
Column temperature: 200 10 C.
Injection point and detector temperature: About 225
C .
Flow rate: 60 to 80 mL/minute.
System suitability
above operating conditions, n-tricosane and pentobarbital are eluted in this order with the resolution between
their peaks being not less than 2.3 and with a symmetry
factor being not more than 2.0.
the above operating conditions: the relative standard
deviation of the ratios of the peak area is not more than
1.5%.
Pentoxifylline
O
CH3CO(CH 2)4
CH3
N
N
N
O
N
CH 3
C13H18N4O3: 278.31
Pentoxifylline, when dried, contains not less than
99.0% and not more than 101.0% of pentoxifylline
(C13H18N4O3).
Description Pentoxifylline is a white, crystalline
powder, has a characteristic odor and a bitter taste.
Pentoxifylline is freely soluble in glacial acetic acid,

soluble in water, in methanol, in ethanol or in acetic
anhydride and slightly soluble in ether.
Identification (1) Take 10 mg of Pentoxifylline, add
10 drops of hydrogen peroxide TS and 1 drop of hydrochloric acid and evaporate on a water-bath to dryness: a yellow-red color is observed in the residue.
Hold the residue over a vessel containing 2 to 3 drops
of ammonia TS: the color changes to red-purple and on
the addition of 2 to 3 drops of sodium hydroxide TS,
the color disappears.
(2) Dissolve 0.1 g of Pentoxifylline in 10 mL of 6
mol/L acetic acid TS by warming and add, while warming, a solution of 70 mg of 2,4-dinitrophenylhydrazine
in 10 mL of diluted acetic acid (1 in 2). After cooling,
filter the yellow precipitate produced, wash with water,
then with a small quantity of cold ethanol and dry at 80
C for 1 hour: it melts between 199 C and 201 C.
Pentoxifylline and Pentoxifylline RS (1 in 100000) as
Pentoxifylline and Pentoxifylline RS as directed in the
1%
Absorbance E1cm (274 nm): Between 360 and 376

(10 mg, water, 1000 mL).
Melting Point
pH The pH of a solution of Pentoxifylline (1 in 100)

Purity (1) ChlorideDissolve 2.0 g of Pentoxifylline in 80 mL of hot water, cool rapidly to 20 C, add
water to make 100 mL. To 40 mL of this solution, add 6
mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution.
0.01 mol/L hydrochloric acid VS, add 6 mL of dilute
nitric acid and water to make 50 mL (not more than
0.011%).
(2) SulfateTo 40 mL of the solution obtained in
(1), add 1 mL of dilute hydrochloric acid and water to
make 50 mL. Perform the test using this solution as the
test solution. Prepare the control solution as follows: to
0.40 mL of 0.005 mol/L sulfuric acid VS, add 1 mL of
dilute hydrochloric acid and water to make 50 mL (not
more than 0.024%).
(3) Heavy metalsProceed with 2.0 g of Pentoxifylline according to Method 1 and perform the test.
Pentoxifylline according to Method 3 and perform the

(5) Related substancesDissolve 0.10 g of Pentoxifylline in 5.0 mL of methanol and use this solution
as the test solution. Pipet exactly 1 mL of the test solution and add methanol to make exactly 100 mL. Pipet
exactly 3 mL of this solution, add methanol to make
Develop the plate with a mixture of ethyl acetate and
methanol (17 : 3) to a distance of about 10 cm and airdry the plate. Examine under ultraviolet light (main
P2O5, 60 C, 3 hours).
Assay Weigh accurately about 0.3 g of Pentoxifylline,
previously dried, dissolve in 40 mL of acetic anhydride
and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection method in Titrimetry). Perform a blank determination and make any

= 27.831 mg of C13H18N4O3
Pentoxyverine Citrate
CH2CO2H
O
C
OCH2CH2OCH2CH2N(CH2CH3)2
HO
CO2H
CH2CO2H
C20H31NO3C6H8O7: 525.60
Pentoxyverine Citrate, when dried, contains not less
than 98.5% and not more than 101.0% of pentoxyverine citrate (C20H31NO3C6H8O7).
Description Pentoxyverine Citrate is a white, crystalline powder.
Pentoxyverine Citrate is very soluble in glacial acetic
acid, freely soluble in water and in ethanol and practically insoluble in ether.
Identification
(1) Dissolve 0.1 g of Pentoxyverine
Citrate in 10 mL of water and add 10 mL of Reinecke

salt TS: a pale red precipitate is produced.
(2) Determine the infrared spectra of Pentoxyverine
Citrate and pentoxyverine citrate RS, previously dried,
as directed in the paste method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
(3) A solution of Pentoxyverine Citrate (1 in 10) responds to the Qualitative Tests (1) and (2) for citrate.
Melting Point

1.0 g of Pentoxyverine Citrate in 10 mL of water: the
(2) Heavy metalsProceed with 2.0 g of Pentoxyverine Citrate according to Method 2 and perform the
Pentoxyverine Citrate according to Method 3 and perform the test (not more than 2 ppm).
(4) Related substancesDissolve 0.20 g of Pentoxyverine Citrate in 10 mL of ethanol and use this solution as the test solution. Pipet 1.0 mL of the test solution, add ethanol to make exactly 200 mL and use this
of silica gel for thin-layer chromatography. Immediately after air-drying, develop the plate with a mixture of
chloroform, methanol, ethyl acetate and ammonia solution (28) (25 : 10 : 10 : 1) to a distance of about 10 cm
and air-dry the plate. Allow to stand in iodine vapor for
10 minutes: the spots other than the principal spot from
the test solution are not more intense than the spot from
P2O5, 60 C, 4 hours).
Assay Weigh accurately about 0.5 g of Pentoxyverine
Citrate, previously dried, dissolve in 30 mL of glacial
acetic acid, add 30 mL of acetic anhydride and titrate
with 0.1 mol/L of perchloric acid VS until the color of
the solution changes from purple through blue-green to
green (indicator: 3 drops of methylrosaniline chloride

= 52.56 mg of C20H31NO3C6H8O7
KP 9 743
Perphenazine
CH2CH2CH2
N
CH2CH2OH
Cl
C21H26ClN3OS: 403.97
Perphenazine, when dried, contains not less than 98.5%
and not more than 101.0% of perphenazine
(C21H26ClN3OS).
Description Perphenazine is a white to pale yellow
crystal or crystalline powder, is odorless and has a bitter taste.
Perphenazine is freely soluble in methanol or in ethanol,
soluble in glacial acetic acid, sparingly soluble in ether
Perphenazine dissolves in dilute hydrochloric acid.
Perphenazine is gradually colored by light.
Identification (1) Dissolve 5 mg of Perphenazine in
5 mL of sulfuric acid: a red color, changing to deep redpurple upon warming, is observed.
(2) Dissolve 0.2 g of Perphenazine in 2 mL of methanol, add this solution to 10 mL of a warm solution of
picric acid in methanol (1 in 25) and allow to stand for
4 hours. Collect the crystals, wash with a small volume
of methanol and dry at 105 C for 1 hour: the crystals
so obtained melt between 237 C and 244 C (with decomposition).
Perphenazine and Perphenazine RS in 0.1 mol/L hydrochloric acid VS (1 in 200000) as directed under the
Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths. Add 10 mL of water to another 10 mL each of
these solutions and determine the absorption spectra:
(4) Perform the test with Perphenazine as directed
under the Flame Coloration Test (2): a green color is
observed.
Melting Point
Purity (1) Heavy metalsProceed with 1.0 g of Perphenazine according to Method 2 and perform the test.
(2) Related substancesPerform the test in the
current of nitrogen in light-resistant containers under
the protection from sunlight. Dissolve 0.10 g of Perphenazine in 10 mL of ethanol and use this solution as
the test solution. Pipet exactly 1 mL of the test solution
and add ethanol to make exactly 10 mL. Pipet exactly 1
mL of this solution, add ethanol to make exactly 20 mL

10 L each of the test solution and the standard solution on a plate of silica gel with fluorescent indicator
mixture of n-butanol and 1 mol/L ammonia water (5 :
nm): any spot other than the principal spot from the test
solution is not more intense than that from the standard
solution.
P2O5, 65 C, 4 hours).
Assay Weigh accurately about 0.4 g of Perphenazine,
previously dried, dissolve in 50 mL of glacial acetic acid and titrate with 0.1 mol/L perchloric acid VS until
the color of the solution changes from purple through
blue-purple to blue-green (indicator: 3 drops of methylrosaniline chloride TS). Perform a blank determination

= 20.198 mg of C21H26ClN3OS
tight containers.
Perphenazine Tablets
Perphenazine Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of perphenazine(C21H26ClN3OS: 403.98).
Tablets, with Perphenazine.
Identification (1) Shake well a portion of powdered
Perphenazine Tablets, equivalent to 25 mg of Perphenazine according to the labeled amount, with 10 mL of
methanol and filter. Evaporate 2 mL of the filtrate in a
water-bath to dryness. With the residue, proceed as directed in the Identification (1) under Perphenazine.
(2) Add 5 mL of the filtrate obtained in the Identification (1) to 10 mL of a warm solution of picric acid in
methanol(1 in 25) and proceed as directed in the Identification (2) under Perphenazine.
(3) Determine the absorption spectrum of the filtrate obtained in the Assay as directed under the Ultraviolet-visible Spectrophotometry: it exhibits an absorption maximum between 309 nm and 313 nm. Add 30
mL of methanol to another 10 mL of the filtrate and determine the absorption spectrum: it exhibits an absorp-
tion maximum between 256 nm and 260 nm.

Perphenazine Tablets at 100 revolutions per minute according to Method 2 under the Dissolution Test, using
900 mL of diluted phosphate buffer solution, pH 6.8 (1
in 2). Take 30 mL or more of the dissolved solution after 90 minutes from start of the test and filter through a
membrane filter with pore size of not more than 0.8 m.
Discard the first 10 mL of the filtrate and use the subsequent filtrate as the test solution. Separately, weigh
accurately about 10 mg of Perphenazine RS, previously
dried in vacuum with P2O5 at 65 C for 4 hours, dissolve in 5 mL of 0.1 mol/L hydrochloric acid TS and
add diluted phosphate buffer solution, pH 6.8, (1 in 2)
to make exactly 250 mL. Pipet exactly 5 mL of this solution, add diluted phosphate buffer solution, pH 6.8, (1
in 2) to make exactly 50 mL and use this solution as the
standard solution. Determine the absorbances, AT and
AS, of the test solution and the standard solution, respectively, at 255 nm as directed under the Ultravioletvisible Spectrophotometry.
The dissolution rate of Perphenazine Tablets in 90 minutes is not less than 70%.

amount of Perphenazine (C21H26ClN3OS)
1
AT
= WS A C 36
S
WS: Amount (mg) of Perphenazine RS,
C: Labeled amount (mg) of Perphenazine
(C21H26ClN3OS) in 1 tablet.
Uniformity of Dosage Units It meets the requirement when the content uniformity test is performed according to the following procedure. Disintegrate 1 Tablet of Perphenazine Tablets by shaking with 5 mL of
water, shake well with 70 mL of methanol and add methanol to make exactly 100 mL. Centrifuge this solution, pipet exactly x mL of the supernatant liquid, add
methanol to make exactly V mL of a solution containing about 4 g of perphenazine (C21H26ClN3OS) in each
weigh accurately about 10 mg of Perphenazine RS,
hours, dissolve in methanol to make exactly 250 mL.
Pipet exactly 5 mL of this solution, add methanol to
make exactly 50 mL and use this solution as the standard solution. Determine the absorbances, AT and AS, of
Spectrophotometry.
Amount (mg) of Perphenazine (C21H26ClN3OS)

1
AT
V
= amount (mg) of Perphenazine RS A 25 x
S
powder, equivalent to about 5 mg of perphenazine

(C21H26ClN3OS), dissolve in methanol to make exactly
100 mL and filter. Discard the first 10 mL of the filtrate,
pipet exactly 10 mL of the subsequent filtrate and 5 mL
of the internal standard solution, add methanol to make
exactly 100 mL and use this solution as a test solution.
Separately, weigh accurately about 25 mg of Perphenazine RS previously dried in desiccator (in vaccume,
P2O5, 65 C) for 4 hours and dissolve in methanol to
make exactly 100 mL. Pipet exactly 2 mL of this solution and 5 mL of internal standard solution, add methanol to make exactly 100 mL and use this solution as the
under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS,
of the peak area of perphenazine to that of the internal
respectively.
Amount (mg) of perphenazine (C21H26ClN3OS)
1
QT
= amount (mg) of Perphenazine RS Q 5
S
Internal standard solutionDissolve 50 mg of anhydrous caffeine RS in methanol to make 50 mL.
(main wavelength: 254 nm)
with nitrilized silica gel for liquid chromatography (5
Mobile phase: Dissolve 0.65 g of ammonium acetic
acid in 84 mL of water, add 916 mL of methanol.
time of perpernazine is about 5.5 minutes.
Selection of column: Proceed with 20 L of this solution according to the above operating conditions, and
calculate the resolution. Use a column giving elution of
internal standard and Perpernazine in this order with
the resolution between their peaks being not less than
3.0.

tight containers.
Perphenazine Maleate
CH2CH2CH2
N
CH3
H
Cl
CO 2H
C
2
C

Perphenazine Tablets. Weigh accurately a portion of the
CO 2H
KP 9 745
C21H26ClN3OS2C4H4O4: 636.11
Perphenazine Maleate, when dried, contains not less
than 98.0% and not more than 101.0% of perphenazine
maleate (C21H26ClN3OS2C4H4O4).
Description Perphenazine Maleate is a white to pale
yellow powder and is odorless.
Perphenazine Maleate is sparingly soluble in glacial
acetic acid, slightly soluble in water or in ethanol and
practically insoluble in chloroform.
Perphenazine Maleate dissolves in dilute hydrochloric
acid.
Perphenazine Maleate is gradually colored by light.
Identification (1) Dissolve 8 mg of Perphenizine
Maleate in 5 mL of sulfuric acid: a red color is observed, which becomes deep red-purple on warming.
(2) Dissolve 0.3 g of Perphenazine Maleate in 3 mL
of dilute hydrochloric acid, add 2 mL of water and 3
mL of strong ammonia water, shake and extract with
three 10 mL volumes of chloroform. [Reserve the
aqueous layer and use for (5)]. Evaporate the combined
chloroform extracts on a water-bath to dryness, dissolve the residue in 20 mL of methanol and pour into
10 mL of a warm solution of picric acid in methanol (1
in 25). Allow to stand for 4 hours, collect the crystals,
wash with a small amount of methanol and dry at 105
C for 1 hour: the crystals melt between 237 C and
244 C (with decomposition).
Perphenazine Maleate and Perphenazine Maleate RS (1
(4) Perform the test with Perphenazine Maleate as
directed under the Flame Coloration Test (2): a green
color is observed.
(5) Evaporate the aqueous layer reserved in (2) to
dryness. To the residue, add 1 mL of dilute sulfuric acid
and 5 mL of water and extract with four 25 mL volumes of ether. Combine the ether extracts and evaporate on a water-bath at about 35 C with the aid of a
current of air: the residue melts between 128 C and
136 C.
Purity (1) Heavy metalsProceed with 2.0 g of Perphenazine Maleate according to Method 2 and perform
(2)ArsenicPrepare the test solution with 1.0 g of
Perphenazine Maleate according to Method 3 and perform the test (not more than 2 ppm).
hours).
Assay Weigh accurately about 0.5 g of Perphenazine

Maleate, previously dried, dissolve in 70 mL of glacial
VS until the color of the solution changes from purple
through blue to blue-green (indicator: 3 drops of methylrosaniline chloride TS). Perform a blank determination and make any necessary correction.

= 31.806 mg of C21H26ClN3OS2C4H4O4
Perphenazine Maleate Tablets

Perphenazine Maleate Tablets contain not less than
93.0% and not more than 107.0% of labeled amount of
perphenazine
maleate
(C21H26ClN3OS2C4H4O4:
636.11).
Tablets, with Perphaenazine Maleate.
Identification (1) Shake a portion of powdered Perphenazine Maleate Tablets, equivalent to 40 mg of perphenazine maleate according to the labeled amount,
with 3 mL of dilute hydrochloric acid and 30 mL of
water, centrifuge, filter the supernatant solution, add 3
mL of strong ammonia water to the filtrate and extract
with three 10 mL volumes of chloroform. [Reserve the
aqueous layer and use for (4)]. Wash the combined
chloroform extracts with two 5 mL volumes of water
and separate the chloroform layer. Evaporate 6 mL of
the chloroform solution in a water-bath to dryness. Proceed with the residue as directed in the Identification
(1) under Perphenazine Maleate.
(2) Evaporate 20 mL of the chloroform solution obtained in (1) in a water-bath to dryness, dissolve the residue in 20 mL of methanol and filter, if necessary.
Warm the filtrate, add 5 mL of a warm solution of picric acid in methanol (1 in 25), allow to stand for 4
hours and proceed as directed in the Identification (2)
under Perphenazine Maleate.
(3) Take 2 mL of the filtrate obtained in the Assay
and add water to make 50 mL. Determine the absorption spectrum of the solution as directed under the Ultraviolet-visible Spectrophotometry: it exhibits absorption maxima between 253 nm and 257 nm and between
303 nm and 313 nm.
(4) Filter, if necessary, the aqueous layer reserved
in (1), evaporate the filtrate to make about 5 mL, add 2
mL of dilute sulfuric acid and extract with two 10 mL
volumes of ether. Combine the ether extracts, evaporate
in a water-bath to dryness, dissolve the residue in 5 mL
of sulfuric acid TS and add 1 to 2 drops of potassium
permanganate TS: the red color of potassium permanganate TS fades immediately.

Disintegrate 1 tablet of Perphenazine Maleate Tablets
by shaking with 15 mL of 0.1 mol/L hydrochloric acid
TS, shake vigorously with 50 mL of methanol, add water to make exactly 100 mL and centrifuge. Pipet x mL
of the supernatant liquid, add water to make exactly V
mL of a solution containing about 6 g of perphenazine
maleate (C21H26ClN3OS2C4H4O4) in each mL and use
this solution as the test solution. Separately, weigh accurately 30 mg of Perphenazine Maleate RS, previously
dried at 105 C for 3 hours, dissolve in 15 mL of 0.1
mol/L hydrochloric acid TS and 50 mL of methanol and
add water to make exactly 100 mL. Pipet exactly 5 mL
of this solution, add 3 mL of 0.1 mol/L hydrochloric acid TS and 10 mL of methanol, add water to make exactly 250 mL and use this solution as the standard solution.
Determine the absorbance, AT and AS, of the test solution and the standard solution, respectively, at 255 nm
as directed under the Ultraviolet-visible Spectrophotometry, using water as the blank.
Amount (mg) of perphenazine maleate

(C21H26ClN3OS2C4H4O4: 636.12) = amount (mg) of
1
AT
V
Perphenazine Maleate RS A 50 x
S
Perphenazine Maleate Tablets. Weigh accurately a portion of the powder, equivalent to about 40 mg of perphenazine maleate (C21H26-ClN3OS2C4H4O4), shake
well with 15 mL of 1 mol/L hydrochloric acid TS and
50 mL of methanol, add water to make exactly 100 mL
and filter. Discard the first 20 mL of the filtrate, measure exactly 5 mL of the subsequent filtrate, add water to
solution. Separately, weigh accurately 40 mg of Perphenazine Maleate RS, previously dried at 105 C for 3
hours, dissolve in a mixture of 15 mL of 1 mol/L hydrochloric acid TS and 50 mL of methanol and add water to make exactly 250 mL and use this solution as the
standard solution. Determine the absorbance, AT and AS,
of the test solution and the standard solution, respectively, at 255 nm as directed under the Ultravioletvisible Spectrophotometry, using water as the blank.
Amount (mg) of perphenazine maleate

(C21H26ClN3OS2C4H4O4) = amount (mg) of
AT
Perphenazine Maleate RS A
S
tight containers.
Pethidine Hydrochloride
N
CH3
HCl
C2H5OOC
Operidine
C15H21NO2HCl: 283.79
Pethidine Hydrochloride, when dried, contains not less

than 98.0% and not more than 101.0% of pethidine hydrochloride (C15H21NO2HCl).
Description Pethidine Hydrochloride is a white, crystalline powder.
Pethidine Hydrochloride is very soluble in water or in
glacial acetic acid, freely soluble in ethanol, sparingly
soluble in acetic anhydride and practically insoluble in
ether.
pHThe pH of a solution dissolved 1.0 g of Pethidine Hydrochloride in 20 mL of water is between 3.8
and 5.8.
of solutions of Pethidine Hydrochloride and Pethidine
Hydrochloride RS (1 in 2000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Pethidine Hydrochloride and Pethidine Hydrochloride RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same
wavenumbers.
(3) A solution of Pethidine Hydrochloride (1 in 50)
Melting Point

1.0 g of Pethidine Hydrochloride in 10 mL of water: the
(2) SulfatePerform the test with 0.20 g of Pethidine Hydrochloride. Prepare the control solution with
1.0 mL of 0.005 mol/L sulfuric acid VS (not more than
0.240%).
(3) Related substancesDissolve 50 mg of Pethidine Hydrochloride in 20 mL of the mobile phase and
of the test solution, add the mobile phase to make exactly 100 mL and use this solution as the standard solution. Perform the test with 20 L each of the test solution and the standard solution as directed under the
Liquid Chromatography according to the following operating conditions. Determine each peak area obtained
from the test solution and the standard solution by the
automatic integration method: the total area of the
KP 9 747
peaks other than that of pethidine from the test solution

is not larger than the peak area of pethidine from the
standard solution.
(about 5 m in particle diameter).
about 40 C.
adjust the pH to 3.0 with sodium hydroxide TS and to
550 mL of this solution, add 450 mL of acetonitrile.
time of pethidine is about 7 minutes.
System suitability
System performance: Take 2 mL each of the test
solution and a solution of isoamyl parahydroxybenzoate in the mobile phase (1 in 50000) and add the mobile phase to make 10 mL. When the procedure is run
with 20 L of this solution according to the above operating conditions, pethidine and isoamyl parahydroxybenzoate are eluted in this order with the resolution
between their peaks being not less than 2.0.
deviation of the peak area of pethidine is not more than
2.0%.
as the retention time of pethidine after the solvent peak.
Pethidine Hydrochloride
Injection
Operidine Injection
Pethidine Hydrochloride Injection is an aqueous solution for injection. Pethidine Hydrochloride Injection
of the labeled amount of pethidine hydrochloride
(C15H21NO2HCl: 283.79).
Method of Preparation Prepare as directed under Injections, with Pethidine Hydrochloride.
Description Pethidine Hydrochloride Injection is a
Pethidine Hydrochloride Injection is affected by light.
Identification Take a volume of Pethidine Hydrochloride Injection, equivalent to 0.1 g of pethidine hydrochloride according to the labeled amount and add
water to make 200 mL. Determine the absorption spectrum of this solution as directed under the Ultravioletvisible Spectrophotometry: it exhibits absorption maxima between 250 nm and 254 nm, between 255 nm and
259 nm and between 261 nm and 265 nm.

hours).


Assay Weigh accurately about 0.5 g of Pethidine Hydrochloride, previously dried, dissolve in 50 mL of a

tight containers.
Assay Measure exactly a volume of Pethidine Hydrochloride Injection, equivalent to about 0.1 g of pethidine hydrochloride (C15H21NO2HCl) according to
the labeled amount, add exactly 10 mL of the internal
standard solution and add the mobile phase to make 50
mL. To 5 mL of this solution, add the mobile phase to
make exactly20 mL and use this solution as the test solution. Separately, weigh accurately about 0.1 g of Pethidine Hydrochloride RS, previously dried at 105 C
for 3 hours, add exactly 10 mL of the internal standard
solution and add the mobile phase to make exactly 50
mL. To 5 mL of this solution, add the mobile phase to
make 20 mL and use this solution as the standard solution. Perform the test with 20 L each of the test solution and the standard solution as directed under the
Liquid Chromatography according to the following operating conditions and calculate the ratios, QT and QS,
of the peak area of pethidine to that of the internal

respectively.
Amount (mg) of pethidine hydrochloride
(C15H21NO2HCl) = amount (mg) of Pethidine HyQT
drochloride RS Q
S
Internal standard solutionA solution of isoamyl
parahydroxybenzoate in the mobile phase (1 in 12500).
(about 5 m in particle diameter).
about 40 C.
adjust the pH to 3.0 with sodium hydroxide TS and to
550 mL of this solution, add 450 mL of acetonitrile.
time of pethidine is about 7 minutes.
System suitability
above operating conditions, pethidine and the internal
deviation of the ratios of the peak area of pethidine to
that of the internal standard material is not more than
1.0%.
Pethidine Hydrochloride Tablets

Pethidine Hydrochloride Tablets contain not less than
of pethidine hydrochloride (C15H21NO2HCl: 283.79).
Tablets, with Pethidine Hydrochloride.
Identification Transfer a portion of powdered Pethidine Hydrochloride Tablets, equivalent to about 50 mg
of Pethidine Hydrochloride, to a separatory funnel, add
10 mL of water and shake well. Add 5 mL of sodium
chloride TS and 1 mL of sodium hydroxide (1 in 25)
and extract the solution with three 20 mL volumes of
chloroform. Filter the chloroform extract through a absorbent cotton with anhydrous sodium sulfate, evapo-
rating the solvent from the filtrate by heating in waterbath. Dissolve the residue in 4 mL of carbon disulfide
transfer about 50 mg of Pethidine Hydrochloride RS,
accurately weighed, to a separatory funnel, proceed as
directed for the test solution and use this solution as the
standard solution. Determine the infrared spectra of the
test solution and the standard solution as directed in the
solution method (1 mm cell, wavelengths of 7 to 15
m) under the Infrared Spectrophotometry using carbon disulfide as a blank: both spectra exhibit similar intensities of absorption at same wavenumbers.
Dissolution Test Perform the test with a tablet of Pethidine Hydrochloride Tablets at 100 revolutions per
minute according to the Method 1 under the dissolution
test, using 500 mL of water. Filter the dissolved solution after 45 minutes from start of the test and use this
solution, or diluted, if necessary, as the test solution.
Separately, weigh accurately, a portion of Pethidine
Hydrochloride RS, dissolve in the dissolution solution
to make the same concentration as the test solution and
test with the test solution and standard solution as directed under the Ultraviolet-visible Spectrophotmetry.
standard solution of Pethidine Hydrochloride at the
wavelength of a maximum absorbance at about 257 nm.
The dissolution rate of Pethidine Hydrochloride Tablets
in 45 minutes is not less than 75%.
ment.
Assay Weigh accurately not less than 20 powdered

Pethidine Hydrochloride Tablets. Weigh accurately a
portion of the powder, equivalent to about 0.1 g of pethidine hydrochloride, add exactly 10 mL of the internal solution, and add the mobile phase to make exactly
50 mL. Filter this solution, discard the the first 10 mL
of the filtrate, take exactly 5 mL of the subsequent filtrate, add the mobile phase to make exactly 20 mL and
0.1 g of Pethidine Hydrochloride RS, previously dried
at 105 C for 3 hours, add exactly 10 mL of the internal
standard solution as directed in the Assay under Pethidine Hydrochloride Injection.
Amount (mg) of pethidine hydrochloride

(C15H21NO2HCl) = amount (mg) of Pethidine HyQT
drochloride RS Q
S
Internal standard solutionA solution of isoamyl
parahydroxybenzoate in the mobile phase (1 in 12500).
KP 9 749
Phenobarbital
O
H
N
C2H5
NH
C12H12N2O3: 232.24
Phenobarbital, when dried, contains not less than
99.0% and not more than 101.0% of phenobarbital
(C12H12N2O3).
Description Phenobarbital is a white crystal or crystalline powder, is odorless and has a bitter taste.
Phenobarbital is very soluble in dimethylformamide,
freely soluble in ethanol, in acetone or in pyridine, soluble in ether and very slightly soluble in water.
Phenobarbital dissolves in sodium hydroxide TS or in
ammonia TS.
pHThe pH of a saturated solution of Phenobarbital is between 5.0 and 6.0.
Identification (1) Heat 0.2 g of Phenobarbital in 10
mL of sodium hydroxide TS: the gas evolved changes
moistened red litmus paper to blue.
(2) Dissolve 0.1 g of Phenobarbital in 5 mL of diluted pyridine (1 in 10), shake the solution with 0.3 mL
of cupric sulfate TS and allow to stand for 5 minutes: a
pale red-purple precipitate is produced. Shake the mixture with 5 mL of chloroform: the chloroform layer remains colorless. Dissolve 0.1 g of Phenobarbital in a
mixture of 2 to 3 drops of ammonia-ammonium chloride buffer solution, pH 10.7 and 5 mL of diluted pyridine (1 in 10), then add 5 mL of chloroform and 0.3 mL
of cupric sulfate TS: a pale red-purple precipitate is
produced in the water layer. Shake again: the chloroform layer remains colorless.
(3) Shake 0.4 g of Phenobarbital with 0.1 g of anhydrous sodium carbonate and 4 mL of water and add a
solution of 0.3 g of p-nitrobenzyl chloride in 7 mL of
ethanol. Heat in a water-bath for 30 minutes under a
reflux condenser and allow, to stand for 1 hour. Filter
the crystals, wash with 7 mL of sodium hydroxide TS,
then with a small amount of water, recrystallize from a
mixture of ethanol and chloroform (1 : 1) and dry at
105 C for 30 minutes: the crystals melt between 181
C and 185 C.
(4) Dissolve 0.1 g of Phenobarbital in 2 mL of sulfuric acid, shake the solution with 5 mg to 6 mg of potassium nitrate and allow to stand for 10 minutes: a yellow to yellow-brown color is observed.
Melting Point
0.5 g of Phenobarbital in 5 mL of sodium hydroxide

(2) ChlorideDissolve 0.30 g of Phenobarbital in
20 mL of acetone and add 6 mL of dilute nitric acid and
control solution as follows: take 0.30 mL of 0.01 mol/L
hydrochloric acid VS, 20 mL of acetone and 6 mL of
dilute nitric acid and add water to make 50 mL (not
more than 0.035%).
(3) SulfateDissolve 0.40 g of Phenobarbital in 20
mL of acetone and add 1 mL of dilute hydrochloric acid
control solution as follows: take 0.40 mL of 0.005
mol/L sulfuric acid VS, 20 mL of acetone and 1 mL of
dilute hydrochloric acid and add water to make 50 mL
(4) Heavy metalsProceed with 1.0 g of Phenobarbital according to Method 2 and perform the test.
(5) Phenylbarbituric acidBoil 1.0 g of Phenobarbital with 5 mL of ethanol for 3 minutes: the solution is clear.
test with 0.5 g of Phenobarbital. The solution does not
have more color than Color Matching Fluid A.
hours).
Assay Weigh accurately about 0.5 g of Phenobarbital,
previously dried, dissolve in 50 mL of dimethylformamide and titrate with 0.1 mol/L potassium hydroxideethanol VS until the color of the solution change from
yellow to yellow-green (indicator: 1 mL of alizarin yellow GG-thymol-phthalein TS). Perform a blank determination using a mixture of 50 mL of dimethylformamide and 22 mL of ethanol and make any necessary
correction.

= 23.224 mg of C12H12N2O3
10% Phenobarbital Powder

Phenobarbital Powder contains not less than 9.3% and
not more than 10.7% of phenobarbital (C12H12N2O3:
232.24).
Phenobarbital
Starch, lactose hydrate,
or their mixture
100 g
To make 1000 g
Identification Shake thoroughly 5 g of 10% Phenobarbital Powder with 20 mL of hexane and filter. Collect the residue and dry in a water-bath, then extract
with four 30 mL volumes of chloroform. Filter the
combined chloroform extracts and evaporate the filtrate
to dryness. Dry the residue at 105 C for 1 hour: the residue so obtained melts between 174 C and 179 C.
With the residue, proceed as directed in the Identification (1) and (2) under Phenobarbital.
Particle Size Distribution Test for Preparations It
Uniformity of Dosage Units (divided) It meets the
requirement.
Assay Weigh accurately about 10 g of 10% Phenobarbital Powder, transfer to a glass-stoppered flask and
add exactly 100 mL of a mixture of chloroform and
ethanol (10 : 1). Stopper tightly, shake and allow to
stand for 30 minutes. Transfer the mixture to a glassstoppered centrifuge tube and centrifuge. Measure exactly 50 mL of the supernatant liquid, evaporate on a
water-bath to dryness, dissolve the residue in 50 mL of
dimethylformamide and proceed as directed in the Assay under Phenobarbital.

= 23.224 mg of C12H12N2O3
Phenobarbital Tablets
Phenobarbital Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of phenobarbital (C12H12N2O3: 232.24).
Tablets, with Phenobarbital.
Identification (1) Shake thoroughly a portion of
powdered Phenobarbital Tablets, equivalent to 60 mg
of phenobarbital according to the labeled amount, with
50 mL of chloroform and filter. Evaporate the filtrate to
dryness and dry at 105 C for 2 hours. Determine the
infrared spectra of the residue obtained above and Phenobarbital RS, respectively, as directed under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers. If any
difference appears in the absorption spectra, dissolve
the residue and phenobarbital RS in chloroform, re-
spectively, evaporate the ethyl acetate and perform the

test with the residues in the same manner.
of the standard solution, as obtained in the Assay.
Phenobarbital Tablets at 50 revolutions per minute according to Method 2 under the Dissolution Test, using
900 mL of water. Take the dissolved solution after 45
minutes from start of the test and filter. Dilute the filtrate to a appropriate concentration, using alkaline borate buffer solution, pH 9.6 and use this solution as the
test solution. Separately, weigh accurately a portion of
Phenobarbital RS, previously dried at 105 C for 2
hours, dissolve in alkaline borate buffer solution, pH
9.6 to make same concentration with the test solution
and use this solution as the standard solution. Determine the absorbances of the test solution and the standard solution at 240 nm as directed under the Ultraviolet-visible Spectrophotometry.
The dissolution rate of Phenobarbital Tablets in 45 minutes is not less than 75%.
ment.

Phenobarbital Tablets, weigh accurately a portion of the
powder, equivalent to about 20 mg of phenobarbital
(C12H12N2O3), add 15.0 mL of the internal standard solution, mix and shake for 15 minutes. Filter before use
and use this filtrate as the test solution. Separately,
weigh accurately 20 mg of Phenobarbital RS, previously dried at 105 C for 2 hours, dissolve in 15.0 mL of
the internal standard solution and use this solution as
the standard solution. If necessary, mix and dissolve by
sonication. Perform the test with 10 L each of the test
of the peak area of phenobarbital to that of the internal
respectively.
Amount (mg) of phenobarbital (C12H12N2O3)

QT
= amount (mg) of Phenobarbital RS Q
S
Internal standard solutionDissolve 12.5 mg of
caffeine in 100 mL of mixture of pH 4.5 buffer solution
inside diameter and about 25 cm in length, having octadecylsilanized silica gel for liquid chromatography (5
KP 9 751

System suitability
their peaks is not less than 1.2 and the symmetry factor
is not more than 2.0.
above operating conditions, the relative standard deviation of the ratios of the peak area of phenobarbital to
pH 4.5 buffer solutionTo 6.6 g of sodium acetate
and 3.3 mL of anyhydrous acetic acid, add water to
make 1000 mL. Adjust pH to 4.5 0.1 with anhydrous
acetic acid, if necessary.
Phenobarbital Sodium
O
H
N
C2H5
ONa
numbers.
(2) Ignite about 0.2 g of Phenobarbital Sodium and
dissolve the residue in 10 mL of water. This solution
changes red litmus paper to blue and responds to the
Qualitative Tests for sodium salt.
(3) The retention time of the principal peak of the
chromatogram obtained from the test solution corresponds to that from the standard soution, as obtained in
the Assay.
pH The pH of a solution of Phenobarbital Sodium (1
Purity (1) Clarity of color of solutionDissolve 1.0
g of Phenobarbital Sodium in 10 mL of freshly boiled
and cooled water: the solution is colorless and clear after 1 minute.
(2) Heavy metalsDissolve 2.0 g of Phenobarbital
Sodium in 52 mL of water. Add 8 mL of 1 mol/L hydrochloric acid with vigorous shaking and filter. Discarding the first 5 mL of the filtrate and dilute 20 mL of
the subsequent filtrate with water to make 25 mL. Perform the test with this solution as the test solution, according to Method 1. Prepare the control solution with
ppm).
hours).
C12H11N2NaO3: 254.22
Phenobarbital Sodium contains not less than 98.5% and
not more than 101.0% of phenobarbital sodium
Description Phenobarbital Sodium is a white crystal
or white powder, is odorless and has a slightly bitter
taste.
Phenobarbital Sodium is very soluble in water, soluble
in ethanol and practically insoluble in ether or in chloroform.
Phenobarbital Sodium is hygroscopic and gradually decomposed on being allowed to stand in the humid air.
Identification (1) Dissolve about 50 mg of Phenobarbital Sodium in 15 mL of water in a separatory funnel, add 2 mL of hydrochloric acid, shake and extract
with four 25 mL volumes of chloroform. Filter the
combined extracts, take 50 mL of filtrate and evaporate
on a water-bath with aid of a current air. Add 10 mL of
ether, again evaporate and dry the residue at 105 C for
2 hours. Determine the infrared spectra of the residue
obtained above and Phenobarbital RS, respectively, as
Assay Weigh accurately about 22 mg of Phenobarbital Sodium, add 15.0 mL of the internal standard solution and shake for 15 minutes using sonicator. Filter
through a membrane filter with the pore size of not
bigger than 0.5 m and use the filtrate as the test solution. Separately, weigh accurately 20 mg of Phenobarbital RS, previously dried at 105 C for 2 hours, dissolve in 15.0 mL of the internal standard solution and
use this solution as the standard solution. If necessary,
mix and dissolve by sonication. Perform the test with
10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions and calculate the ratios, QT and QS, of the peak area of phenobarbital to that of the internal standard for the test solution and the standard solution, respectively.
Amount (mg) of phenobarbital sodium (C12H11N2NaO3)

= amount (mg) of Phenobarbital RS
QT
Q 1.095
S
caffeine in 100 mL of a mixture of pH 4.5 buffer solution and methanol (1 : 1).

System suitability
their peaks of caffeine and phenobarbital is not less
than 1.2 and the symmetry factor is not more than 2.0.
deviation of the ratio of the peak area of phenobarbital
to that of internal standard is not more than 2.0%.
pH 4.5 buffer solutionTo 6.6 g of sodium acetate
and 3.0 mL of anhydrous acetic acid, add water to
make 1000 mL. Adjust pH to 4.5 0.1 with anhydrous
acetic acid, if necessary.
nal standard solution, mix, and sonicate for 15 minutes.

Filter, and use the filtrate as the test solution. Separately,
weigh accurately about 20 mg of Phenobarbital RS
(previously dried at 105 o C for 2 hours), dissolve in 15
mL of internal standard solution, and use this solution
as the standard solution. Proceed as directed in the Assay under Phenobarbital Sodium.
Amount (mg) of phenobarbital sodium (C12H11N2NaO3)
Q
= amount (mg) of Phenobarbital RS T 1.095
QS
caffeine in 100 mL of a mixture of methanol and pH
4.5 buffer solution (1:1).
Phenolsulfonphthalein
O2
S
O
OH
OH
Phenobarbital Sodium Tablets

Phenobarbital Sodium Tablets contain not less than
of phenobarbital sodium (C12H11N2NaO3: 254.22).
Tablets, with Phenobarbital Sodium.
Identification (1) Dissolve 0.2 g of residue, obtained
in the Assay, in 15 mL of diluted ethanol (1 in 4) in a
water-bath, filter with glass crucible filter when it is hot
and cool. Wash with small amount of diluted ethanol (1
in 4) ethanol, evaporate the filtrate in the cap-mounted
test tube and dry the residue at 105 C for 1 hour: Determine the infrared spectra of the residue obtained
above and Phenobarbital RS, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
(2) A powder of Phenobarbital Sodium Tablets responds to the Qualitative Tests for sodium salt.
ment.

Phenobarbital Sodium Tablets. Weigh accurately a portion of the powder, equivalent to 22 mg of phenobarbital sodium (C12H11N2NaO3), dissolve in 15 mL of inter-
C19H14O5S: 354.38
Phenolsulfonphthalein, when dried, contains not less
than 98.0% and not more than 101.0% of phenolsulfonphthalein (C19H14O5S).
Description Phenolsulfonphthalein is a vivid red to
dark red, crystalline powder.
Phenolsulfonphthalein is very slightly soluble in water
or in ethanol.
Phenolsulfonphthalein dissolves in sodium hydroxide
TS or in sodium carbonate TS.
Identification (1) Dissolve 5 mg of Phenolsulfonphthalein in 2 to 3 drops of sodium hydroxide TS, add 2
mL of 0.05 mol/L bromine VS and 1 mL of dilute sulfuric acid, shake well and allow to stand for 5 minutes.
Render the solution alkaline with sodium hydroxide
TS: a deep blue-purple color develops.
(2) Dissolve 10 mg each of Phenolsulfonphthalein
and Phenolsulfonphthalein RS in sodium carbonate solution (1 in 10) to make 200 mL. Take 5 mL of this solution and add sodium carbonate solution (1 in 10) to
make 100 mL. Determine the absorption spectra of
these solutions as directed under the Ultraviolet-visible
Spectrophotometry: both spectra exhibit similar intensities of absorption at same wavelengths.
Purity (1) Insoluble substancesTake about 1.0 g
of Phenolsulfonphthalein, accurately weighed, add 20
mL of a solution of sodium bicarbonate (1 in 40). Al-
KP 9 753
low the mixture to stand for 1 hour with frequent shaking, add water to make 100 mL and allow to stand for
24 hours. Collect the insoluble substances using a tared
glass filter (G4), wash with 25 mL of a solution of sodium bicarbonate (1 in 100) and wash with five 5 mL
volumes of water and dry at 105 C for 1 hour: the residue is not more than 0.2%.
(2) Relative substancesDissolve 0.10 g of Phenolsulfonphthalein in 5 mL of dilute sodium hydroxide
TS and use this solution as the test solution. Pipet exactly 0.5 mL of this solution, add dilute sodium hydroxide TS to make exactly 100 mL and use this solution as
Thin-layer Chromatography. Spot 10 L of each of the
test solution and the standard solution on a plate of silica gel with a fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of t-amyl
alcohol, anhydrous acetic acid and water (4 : 1 : 1) to
distance of about 15 cm and air-dry the plate. After
leaving in ammonia vapor, examine under Ultraviolet
light (main wavelength: 254 nm): the spot other than
the principal spot from the test solution are not more intense than the spot form the standard solution.
Phenolsulfonphthalein
6g
Sodium Chloride
9g
Sodium Bicarbonate
1.43 g
(or sodium hydroxide)
(0.68 g)
Water for Injection
To make 1000 mL
Description
Phenolsulfonphthalein Injection is a
clear, orange-yellow to red liquid.
Identification Take 1 mL of Phenolsulfonphthalein
Injection, add 2 to 3 drops of sodium hydroxide TS and
proceed as directed in the Identification (1) under Phenolsulfonphthalein.
Loss on Drying Not more than 1.0% (1 g, silica gel.

4 hours).
Sensitivity Take 1.0 mL of Phenolsulfonphthalein Injection and add 5 mL of water. To 0.20 mL of this solution, add 50 mL of freshly boiled and cooled water and
0.40 mL of 0.01 mol/L sodium hydroxide VS: a deep
red-purple color develops and it changes to pale yellow
on the addition of 0.40 mL of 0.005 mol/L sulfuric acid
VS.
Assay Weigh accurately about 0.15 g of Phenolsulfonphthalein, previously dried, transfer to an iodine
flask, dissolve in 30 mL of a solution of sodium hydroxide (1 in 250) and add water to make exactly 200
mL. Add exactly measured 50 mL of 0.05 mol/L bromine VS, add 10 mL of hydrochloric acid to the solution quickly and stopper immediately. Allow the mixture to stand for 5 minutes with occasional shaking, add
7 mL of potassium iodide TS, stopper again immediately and shake gently for 1 minute. Titrate the liberated
iodine with 0.1 mol/L sodium thiosulfate VS (indicator:
1 mL of starch TS). Perform a blank determination and

= 4.430 mg of C19H14O5S
Phenolsulfonphthalein Injection
Phenolsulfonphthalein Injection is an aqueous solution
for injection. Phenolsulfonphthalein Injection contains
not less than 0.54% and not more than 0.63% of phenolsulfonphthalein (C19H14O5S: 354.38).

Assay Pipet exactly 5 mL of Phenolsulfonphthalein
Injection and add a solution of anhydrous sodium carbonate (1 in 100) to make exactly 250 mL. Pipet exactly 5 mL of this solution, add a solution of anhydrous
sodium carbonate (1 in 100) to make exactly 200 mL
weigh accurately about 30 mg of Phenolsulfonphthalein
hours and dissolve in a solution of anhydrous sodium
carbonate (1 in 100) to make exactly 250 mL. Pipet exactly 5 mL of this solution, add a solution of anhydrous
sodium carbonate (1 in 100) to make exactly 200 mL
and use this solution as the standard solution. Determine the absorbances, AT and AS, of the test solution
and the standard solution, respectively, at 559 nm as directed under the Ultraviolet-visible Spectrophotometry.
Amount (mg) of phenolsulfonphthalein (C19H14O5S)

AT
= amount (mg) of Phenolsulfonphthalein RS A
S

Packaging and Storage Preserve in hermetic containers.
L-Phenylalanine
H
Phenovalin
CH 2
COOH
NH 2
Phenovalin is a mixture of equal quantities of isovalerylphenolphthalein and acetylphenolphthalein and contains not less than 71.0% and not more than 74.0% of
phenolphthalein (C20H14O4: 318.33).
Description Phenovalin is a white, crystalline powder,
is odorless and tasteless.
Phenovalin is freely soluble in acetone, sparingly soluble in ethanol or in ether and practically insoluble in
water.
Identification (1) Heat 0.2 g of Phenovalin with 1
mL of sodium hydroxide TS: a red color develops and
the color disappears on the addition of excess dilute
hydrochloric acid.
(2) Heat 0.2 g of Phenovalin with 3 mL of diluted
ethanol (7 in 10) and 4 drops of sulfuric acid: the odor
of ethyl acetate is perceptible.
(3) Heat 0.2 g of Phenovalin with 1 mL of a solution of sodium hydroxide (1 in 6), cool, acidify with
sulfuric acid, shake with ether, separate the ether layer
and evaporate the ether: an oily substance with the odor
of valeric acid is produced.
Purity (1) Heavy metalsDissolve 1.0 g of Phenovalin in 40 mL of acetone and add 2 mL of dilute acetic
acid and water to make 50 mL. Perform the test. Prepare the control solution as follows: to 2.0 mL of standard lead solution, add 40 mL of acetone and 2 mL of
dilute acetic acid and add water to make 50 mL (not
more than 20 ppm).
Phenovalin, according to Method 3 and perform the test
(3) Free phenolphthaleinShake 0.5 g of Phenovalin with 10 mL of sodium carbonate TS: no red color
develops immediately.
Assay Weigh accurately about 0.5 g of Phenovalin,
add 3 mL of potassium hydroxide-ethanol TS and 12
mL of ethanol, heat in a water-bath for 10 minutes, add
and evaporate almost to dryness. To the residue, add 10
mL of water and allow to stand for 30 minutes. Collect
the insoluble substances using a tared glass filter (G4),
wash with four times with 5mL volumes of water, dry
at 105 C for 4 hours and weigh as the weight of phenolphthalein (C20H14O4).
C9H11NO2: 165.19
L-Phenylalanine,
when dried, contains not less than

98.5% and not more than 101.0% of L-phenylalanine
(C9H11NO2).
Description L-Phenylalanine is a white crystal or
crystalline powder, is odorless or has a faint, characteristic odor, and has a slightly bitter taste.
L-Phenylalanine is freely soluble in formic acid, sparingly soluble in water and practically insoluble in
L-Phenylalanine dissolves in dilute hydrochloric acid.
Identification Determine the infrared spectra of LPhenylalanine and L-Phenylalanine RS, previously
wavenumbers.
pH Dissolve 0.20 g of L-Phenylalanine in 20 mL of
water by warming and cool: the pH of this solution is
D : Between -33.0
and -35.5 (after drying, 0.5 g, water, 25 mL, 100 mm).
0.5 g of L-Phenylalanine in 10 mL of 1 mol/L hydrochloric acid: the solution is clear and colorless.
(2) ChloridePerform the test with 0.5 g of LPhenylalanine. Prepare the control solution with 0.30
0.021%).
(3) SulfatePerform the test with 0.6 g of LPhenylalanine. Prepare the control solution with 0.35
0.028%).
(4) AmmoniumPerform the test with 0.25 g of LPhenylalanine. Prepare the control solution with 5.0 mL
of standard ammonium solution (not more than 0.02%).
(5) Heavy metalsDissolve 0.1 g of LPhenylalanine in 40 mL of water and 2 mL of dilute
acetic acid by warming, cool and add water to make 50
mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: to 2.0 mL
of standard lead solution, add 2 mL of dilute acetic acid
and water to make 50 mL (not more than 20 ppm).
(6) ArsenicDissolve 1.0 g of L-Phenylalanine in
3 mL of 1 mol/L hydrochloric acid TS and 2 mL of water by heating in a water-bath and perform the test (not
KP 9 755
more than 2 ppm).

(7) Related substancesDissolve 0.10 g of LPhenylalanine in 25 mL of water and use this solution
as the test solution. Pipet exactly 1 mL of the test solution and add water to make exactly 50 mL. Pipet exactly 5 mL of this solution, add water to make exactly 20
Spot 5 L each of the test solution and the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of n-butanol,
water and anhydrous acetic acid (3 : 1 : 1) to a distance
of about 10 cm and air-dry the plate. Spray evenly a solution of ninhydrin in acetone (1 in 50) on the plate and
heat at 80 C for 5 minutes: the spots other than the
hours).
Assay
Weigh accurately about 0.17 g of LPhenylalanine, previously dried, dissolve in 3 mL of
formic acid, add 50 mL of glacial acetic acid and titrate
with 0.1 mol/L perchloric acid VS until the color of the
solution changes from orange-yellow through yellowish green to green (potentiometric titration, Endpoint
Each mL of 0.1 mol/L perchioric acid VS

= 16.519 mg of C9H11NO2
Phenylephrine Hydrochloride
H
C
CH2NHCH3
HCl
drochloride (1 in 100) is between 4.5 and 5.5.

Identification (1) Take 1 mL of a solution of Phenylephrine Hydrochloride (1 in 100), add 1 drop of cupric
sulfate TS and 1 mL of a solution of sodium hydroxide
(1 in 5): a blue color is observed. To this solution, add 1
mL of ether and shake vigorously: no blue color is observed in the ether layer.
(2) Take 1 mL of a solution of Phenylephrine Hydrochloride (1 in 100) and add 1 drop of ferric chloride
TS: a persistent purple color is observed.
(3) Dissolve 0.3 g of Phenylephrine Hydrochloride
in 3 mL of water, add 1 mL of ammonia TS and rub the
inner side of the test tube with a glass rod: a precipitate
is produced. Collect the precipitate, wash with a few
drops of ice-cold water and dry at 105 C for 2 hours: it
(4) A solution of Phenylephrine Hydrochloride (1 in
Melting Point

D : Between -42.0
1.0 g of Phenylephrine Hydrochloride in 10 mL of water: the solution is clear and colorless.
(2) SulfateTake 0.5 g of Phenylephrine Hydrochloride and perform the test. Prepare the control solution
more than 0.048%).
(3) KetoneDissolve 0.20 g of Phenylephrine Hydrochloride in 1 mL of water and add 2 drops of sodium nitroprusside TS, 1 mL of sodium hydroxide TS
and then 0.6 mL of anhydrous acetic acid: the solution
has no more color than the following control solution.
Control solutionPrepare as directed above without Phenylephrine Hydrochloride.
hours).
OH
HO
C9H13NO2HCl: 203.67
Phenylephrine Hydrochloride, when dried, contains not
less than 98.0% and not more than 102.0% of phenylephrine hydrochloride (C9H13NO2HCl).
Description Phenylephrine Hydrochloride is a white
crystal or crystalline powder, is odorless and has a bitter taste.
Phenylephrine Hydrochloride is very soluble in water,
freely soluble in ethanol and practically insoluble in
ether.
pHThe pH of a solution of Phenylephrine Hy-
Assay Weigh accurately about 0.1 g of Phenylephrine

water contained in an iodine flask, add exactly measured 50 mL of 0.05 mol/L bromine VS, then add 5 mL
of hydrochloride acid and immediately stopper tightly.
Shake the mixture and allow to stand for 15 minutes.
To this solution, add 10 mL of potassium iodide TS
carefully, stopper tightly immediately, shake thoroughly,
allow to stand for 5 minutes and titrate with 0.1 mol/L
sodium thiosulfate VS (indicator: 1 mL of starch TS).
correction.


tight containers.
Phenytoin
H
N
NH
O
Diphenylhydantoin
C15H12N2O2: 252.27
Phenytoin, when dried, contains not less than 99.0%

and not more than 101.0% of phenytoin (C15H12N2O2).
Description Phenytoin is a white, crystalline powder
or granule, is odorless and tasteless.
Phenytoin is sparingly soluble in ethanol or in acetone,
Phenytoin dissolves in sodium hydroxide TS.
Identification (1) Dissolve 20 mg of Phenytoin in 2
mL of ammonia TS and add 5 mL of silver nitrate TS: a
white precipitate is produced.
(2) Boil a mixture of 10 mg of Phenytoin, 1 mL of
ammonia TS and 1 mL of water and add drop-wise 2
mL of a mixture prepared from 50 mL of a solution of
cupric sulfate (1 in 20) and 10 mL of ammonia TS: a
red, crystalline precipitate is produced.
(3) Heat 0.1 g of Phenytoin with 0.2 g of sodium
hydroxide and fuse: the gas evolved turns moistened
red litmus paper blue.
(4) Add 3 mL of chlorinated lime TS to 0.1 g of
Phenytoin, shake for 5 minutes and dissolve the oily
precipitate in 15 mL of hot water. After cooling, add 1
mL of dilute hydrochloric acid drop-wise, then add 4
mL of water. Filter the white precipitate thus obtained,
wash with water and press it with dry filter paper to
remove the accompanying water. Dissolve the precipitate with 1 mL of chloroform, add 5 mL of diluted
ethanol (9 in 10) and rub the inner surface of the flask
to produce a white, crystalline precipitate. Collect the
precipitate, wash with ethanol and dry: the melting
point is between 165 C and 169 C.
0.20 g of Phenytoin in 10 mL of 0.2 mol/L sodium hydroxide VS: the solution is clear and colorless. Then
heat the solution: no turbidity is produced. Cool and
mix the solution with 5 mL of acetone: the solution is
(2) Acid or alkaliShake 2.0 g of Phenytoin with

40 mL of water for 1 minute, filter and perform the following tests using this filtrate as the test solution. (i) To
10 mL of the test solution, add 2 drops of phenolphthalein TS: no color develops. Then add 0.15 mL of
0.01 mol/L sodium hydroxide VS: a red color develops.
(ii) To 10 mL of the test solution, add 0.30 mL of 0.01
mol/L hydrochloric acid VS and 5 drops of methyl red
TS: a red to orange color develops.
(3) ChlorideDissolve 0.30 g of Phenytoin in 30
mL of acetone and add 6 mL of dilute nitric acid and
water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution
from 0.60 mL of 0.01 mol/L hydrochloric acid VS, 30
mL of acetone and 6 mL of dilute nitric acid and add
water to make 50 mL (not more than 0.071%).
(4) Heavy metalsProceed with 1.0 g of Phenytoin
hours).
Assay Weigh accurately about 0.5 g of Phenytoin,
previously dried, dissolve in 40 mL of ethanol with the
aid of gentle heating, add 0.5 mL of thymolphthalein
TS immediately and titrate with 0.1 mol/L sodium hydroxide VS until a pale blue color develops. Then add 1
mL of pyridine, 5 drops of phenolphthalein TS and 25
mL of silver nitrate TS and titrate with 0.1 mol/L sodium hydroxide VS until a pale red color, which persists for 1 minute, develops.

= 25.227 mg of C15H12N2O2.
Phenytoin Powder
Diphenylhydantoin Powder
Phenytoin Powder contains not less than 95.0% and not
more than 105.0% of the labeled amount of phenytoin
(C15H12N2O2: 252.27).
Powders, with Phenytoin.
Identification Weigh a portion of Phenytoin Powder,

equivalent to 0.3 g of phenytoin according to the labeled amount, stir well with two 100 mL volumes of
ether and extract. Combine the ether extracts and filter.
Evaporate the filtrate on a water-bath to dryness and
KP 9 757
proceed with the residue as directed in the Identification under Phenytoin.

requirement.
Assay Weigh accurately Phenytoin Powder, equivalent to about 0.5 g of phenytoin (C15H11N2NaO2), add
exactly 100 mL of ethanol, stir for 30 minutes and centrifuge. Pipet exactly 50 mL of the supernatant liquid,
add 0.5 mL of thymolphthalein TS, titrate with 0.1
mol/L sodium hydroxide VS until a pale blue color develops, then add 1 mL of pyridine, 5 drops of phenolphthalein TS and 12.5 mL of silver nitrate TS and titrate with 0.1 mol/L sodium hydroxide VS until a pale
red color persists for 1 minute.
ly 5 mL of the subsequent filtrate, add 10.0 mL of the

internal standard solution, add the mobile phase to
make exactly 50 mL and use this solution as the test solution. Separately, weigh accurately about 25 mg of
Phenytoin RS (previously dry at 105 C for 2 hours and
measure the loss on drying), dissolve in the internal
standard solution to make exactly 25 mL. Pipet exactly
5 mL of this solution, add 10.0 mL of the internal standard solution, add the mobile phase to make exactly 50
mL and use this solution as the standard solution. Perform the test with 10 L each of the test solution and
conditions and calculate the ratios, QT and QS, of the
peak area of phenytoin to that of the internal standard

= 25.227 mg of C15H12N2O2
Amount (mg) of phenytoin (C15H12N2O2)

= amount (mg) of Phenytoin RS,
QT
calculated on the dried basis Q
S
Internal standard solutionA solution of butyl paraoxybenzoate in methanol (1 in 10,000).
Phenytoin Tablets
Diphenylhydantoin Tablets
Phenytoin Tablets contain not less than 95.0% and not
more than 105.0% of the labeled amount of phenytoin
(C15H12N2O2: 252.27).
Tablets, with Phenytoin.
Identification Weigh a portion of powdered Phenytoin Tablets, equivalent to about 0.3 g of Phenytoin, put
it in a seperatory funnel with 1 mL of dilute hydrochloric acid and 10 mL of water. Extract with one 100 mL
volume of ether, next four 25 mL volume of ether by
shaking well, combine the extracts and filter. Evaporate
the filtrate on a water-bath to dryness and perform the
test with the residue as directed in the Identification
under Phenytoin.
ment.

Phenytoin Tablets. Weigh accurately a portion of the
powder, equivalent to about 25 mg of phenytoin
(C15H12N2O2), shake with the mobile phase for 10 minutes, add the mobile phase to make exactly 25 mL and
filter. Discard the first 10 mL of the filtrate, take exact-
inside diameter and 15 cm to 30 cm in length, having
Mobile phase: A mixture of 0.005 mol/L ammonium hydrogen phosphate solution and methanol (50 :
50).
Flow rate: Adjust the retention time of phenytoin to
be about 5 minutes.
System suitability
above operating conditions, phenytoin and internal
deviation of the ratios of the peak area of phenitoin to
Phenytoin Sodium
H
N
ONa
N
O
Diphenylhydantoin Sodium
C15H11N2NaO2 : 274.25
Phenytoin Sodium contains not less than 98.0% and not

more
than
102.0%
of
phenytoin
sodium
Description Phenytoin Sodium is a white crystal or
crystalline powder, and is odorless.
Phenytoin Sodium is soluble in water or in ethanol and
practically insoluble in chloroform or in ether.
Phenytoin Sodium is hygroscopic.
A solution of Phenytoin Sodium absorbs carbon dioxide gradually when exposed to air and a crystalline
precipitate of phenytoin is produced.
pHThe pH of a solution of Phenytoin Sodium (1
in 20) is about 12.
Identification (1) Put 0.3 g of Phenytoin Sodium in a
separatory funnel, dissolve in 50 mL water and add 10
mL of dilute hydrochloric acid, extract with 100 mL of
ether. Next extract 4 times with 25 mL of ether and
combine the ether extracts and filter. Evaporate the filtrate on a water-bath to dryness and proceed with the
residue as directed in the Identification under Phenytoin.
(2) Ignite 0.5 g of Phenytoin Sodium, cool and dissolve the residue in 10 mL of water: the solution
changes red litmus paper to blue and responds to the
Qualitative Tests (1) for sodium salt.
1.0 g of Phenytoin Sodium in 20 mL of freshly boiled
and cooled water: the solution is clear and colorless. If
any turbidity is produced, add 4.0 mL of 0.1 mol/L sodium hydroxide VS: the solution becomes clear and colorless.
Sodium according to Method 2 and perform the test.
this solution, add 10 mL of the internal standard solution, add the mobile phase to make exactly 50 mL and
test with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions
and calculate the ratios, QT and QS, of the peak area of
phenytoin to that of the internal standard, for the test
Amount (mg) of phenytoin sodium (C15H12N2NaO2)
QT
calculated on the dried basis Q 1.087
S
Internal standard solutionA solution of butyl paraoxybenzoate in methanol (1 in 10000).
Mobile phase: A mixture of 0.005 mol/L dibasic
phosphate ammonium solution and methanol (50 : 50).
be about 5 minutes.
System suitability
above operating conditions, phenytoin and internal
deviation of the ratios of the peak area of phenytoin to
Phenytoin Sodium for Injection

H
N
ONa
Assay Weigh accurately about 25 mg of Phenytoin

Sodium and dissolve in the mobile phase to make exactly 25 mL. Pipet exactly 5 mL of this solution, add
10.0 mL of the internal standard solution, add the mobile phase to make exactly 50 mL and use this solution
as the test solution. Separately, weigh accurately about
25 mg of Phenytoin RS, dissolve in internal standard
solution to make exactly 25 mL. Pipet exactly 5 mL of
Diphenylhydantoin Sodium for Injection

C15H11N2NaO2 : 274.25
Phenytoin Sodium for Injection is a preparation for injection which is reconstituted before use.
KP 9 759
Phenytoin Sodium for Injection, when dried, contains

not less than 98.5% and not more than 101.0% of phenytoin sodium (C15H11N2NaO2) and contains not less
amount of Phenytoin Sodium (C15H11N2NaO2).
Method of Preparation Prepare as directed under Injections.
Description Phenytoin Sodium for Injection is a
white crystal or crystalline powder, and is odorless.
Phenytoin Sodium for Injection is soluble in water or in
ethanol and practically insoluble in chloroform or in
ether.
Phenytoin Sodium for Injection is hygroscopic.
A solution of Phenytoin Sodium for Injection absorbs
carbon dioxide gradually when exposed to air and a
crystalline precipitate of phenytoin is produced.
pHThe pH of a solution of Phenytoin Sodium for
Injection (1 in 20) is about 12.
Identification (1) Weigh a portion of Phenytoin Sodium for Injection, equivalent to 0.3 g of phenytoin according to the labeled amount, dissolve in 50 mL water
and add 10 mL of dilute hydrochloric acid, extract with
100 mL of ether. Next extract 4 times with 25 mL of
ether and combine the ether extracts and filter. Evaporate the filtrate on a water-bath to dryness and proceed
with the residue as directed in the Identification under
Phenytoin.
(2) Ignite 0.5 g of Phenytoin Sodium for Injection,
cool and dissolve the residue in 10 mL of water: the solution changes red litmus paper to blue and responds to
the Qualitative Tests (1) for sodium salt.
1.0 g of Phenytoin Sodium for Injection in 20 mL of
freshly boiled and cooled water: the solution is clear
and colorless. If any turbidity is produced, add 4.0 mL
of 0.1 mol/L sodium hydroxide VS: the solution becomes clear and colorless.
Sodium for Injection according to Method 2 and perform the test. Prepare the control solution with 2.0 mL
hours).
ment.
Assay Weigh accurately the content of not less than

10 samples of Phenytoin Sodium for Injection. Weigh
accurately about 25 mg of Phenytoin Sodium of Inhection and dissolve in the mobile phase to make exactly
25 mL. Pipet exactly 5 mL of this solution, add 10.0
mL of the internal standard solution, add the mobile
mg of Phenytoin RS, dissolve in internal standard solution to make exactly 25 mL. Pipet exactly 5 mL of this
solution, add 10 mL of the internal standard solution,
calculate the ratios, QT and QS, of the peak area of phenytoin to that of the internal standard, for the test solution and the standard solution, respectively.
Amount (mg) of phenytoin sodium (C15H12N2NaO2)

QT
calculated on the dried basis Q 1.087
S
Internal standard solutionA solution of butyl paraoxybenzoate in methanol (1 in 10000).
Mobile phase: A mixture of 0.005 mol/L dibasic
phosphate ammonium solution and methanol (50 : 50).
be about 5 minutes.
System suitability
above operating conditions, phenytoin and the internal
deviation of the ratios of the peak area of phenytoin to
tainers.
Physostigmine Salicylate
CH3
N
OH
O
CH3HN
CO2H
H
N
CH3
O
H3C
Eserine salicylate
C15H21N3O2C7H6O3: 413.47
Physostigmine Salicylate, when dried, contains not less

than 97.0% and not more than 102.0% of physostigmine salicylate (C15H21N3-O2C7H6O3).
Description Physostigmine Salicylate is a white to
pale yellow crystal or crystalline powder and is odorless.
Physostigmine Salicylate is freely soluble in chloroform, soluble in ethanol, sparingly soluble in water and
slightly soluble in ether.
pHThe pH of a solution of Physostigmine Salicylate (1 in 100) is between 5.0 and 6.0.
Physostigmine Salicylate gradually shows a red color
by air and by light.
Identification (1) Take 5 mL of a solution of Physostigmine Salicylate (1 in 100) and add 2 to 3 drops of
sodium hydroxide TS: the color of the solution changes
from orange to red.
(2) Take 5 mg of Physostigmine Salicylate and add
5 to 10 drops of ammonia TS and warm in a waterbath: a yellow-red color develops. Evaporate this solution on a water-bath: the residue shows a blue-purple
color. Divide this residue into two portions and perform
the following tests. Dissolve one residue in 1 mL of
ethanol: a blue-purple color develops. To the solution,
add 2 mL of acetic acid: a red fluorescence appears,
which is intensified on the addition of 4 mL of water.
And dissolve the other residue in 1 mL of sulfuric acid:
a green color develops. To the solution, add 3 mL of
ethanol slowly: the color of the solution changes to red.
Evaporate the ethanol solution: the color returns to
green.
(3) A solution of Physostigmine Salicylate (1 in
100) responds to the Qualitative Tests (3) for salicylate.
D : Between -91 and 94(after drying, 0.20 g, water, 20 mL, 200 mm).
Purity (1) SulfateDissolve 0.12 g of Physostigmine Salicylate in 10 mL of water, add 0.5 mL of dilute
hydrochloric acid and filter the precipitate. Add 5 drops
of barium chloride TS to the filtrate: no turbidity is
produced immediately.
(2) EseridineDissolve 50 mg of Physostigmine
Salicylate in 5 mL of water, add 5 drops of dilute hydrochloric acid, 1 mL of a solution of potassium iodate
(1 in 50) and 1 mL of chloroform and shake for 1
minute: the chloroform layer shows neither a purple
color nor a red color.
test with 0.10 g of Physostigmine Salicylate: after
standing for 5 minutes, the solution has no more color
than Color Matching Fluid I.
Loss on Drying Not more than 1.0% (0.5 g, silica gel,
24 hours).
Assay Weigh accurately about 0.16 g of Physostigmine Salicylate, previously dried, dissolve in 50 mL of
glacial acetic acid and titrate with 0.02 mol/L perchloric acid VS (potentiometic titration, Endpoint Detection
Method in Titrimetry). The end point is the first equivalent point. Perform a blank determination and make any

= 8.269 mg of C15H21N3O2C7H6O3
tight containers.
Physostigmine Sulfate
CH3
CH3
H
N
H2SO4
CH3NHCOO
CH3
2
Eserine sulfate
(C15H21N3O2)2H2SO4: 648.77
Physostigmine Sulfate, when dried, contains not less

than 97.0% and not more than 102.0% of physostigmine sulfate [(C15H21N3O2)2H2SO4].
Description Physostigmine Sulfate is a white to pale
yellowish white crystalline powder and is odorless.
Physostigmine Sulfate is very soluble in water or in
ethanol, soluble in chloroform and practically insoluble
in ether.
Physostigmine Sulfate is hygroscopic and the color
changes gradually to red by light or air
pHDissolve 1.0 g of Physostigmine Sulfate in
and 5.5.
KP 9 761
Identification (1) Take 5 mL of an aqueous solution
(1 in 100) of Physostigmine Sulfate and add 2 to 3
drops of sodium hydroxide TS: an orange color develops and then changes to red.
(2) Take 5 mg of Physostigmine Sulfate, add 5 to 10
drops of ammonium hydroxide TS and heat: a yellowish red color develops. Evaporate this solution on a
water-bath: a blue-violet develops. Divide the residue
into two and perform the following tests, respectively.
(i) Dissolve the residue in 1 mL of ethanol: a red fluorescent is observed. Add 4 mL of water again: the fluorescent becomes more intense.
(ii) Dissolve the residue in 1 mL of sulfuric acid: a
green color develops, add 3 mL of ethanol again: the
color changes to red and evaporate the ethanol: a green
color develops again.
(3) An aqueous solution of Physostigmine Sulfate
(1 in 100) responds to the Qualitative Tests for sulfate.
-120 (after drying, 0.25 g, water, 25 mL, 200 mm).
Purity Readily carbonizable substancesPerform the
test with 0.1 g of Physostigmine sulfate. The solution
has not more color than Color Matching Fluid I.
Loss on Drying Not more than 1.0% (0.3 g, silica gel,
24 hours).
Assay Weigh accurately about 0.2 g of Physostigmine
Sulfate, priviously dried, dissolve in 25 mL water, add
1 g of sodium bicarbonate, extract with 25 mL of chloroform and extract again with five 10 mL volumes of
chloroform with vigorous shaking. Filter each extracts
in order, combine the extracts, add 15 mL of glacial
correction.

= 6.488 mg of (C15H21N3O2)2H2SO4

tight containers.
Phytonadione
O
CH3
CH3
H
O
Phytomenadione
CH3
CH3
CH3
CH3
Vitamin K1
C31H46O2: 450.70
Phytonadione contains not less than 97.0% and not

more than 102.0% of phytonadione (C31H46O2).
Description
Phytonadione is a clear yellow to
orange-yellow, viscous liquid and is odorless.
Phytonadione is miscible with isooctane.
Phytonadione is soluble in dehydrated ethanol and
Phytonadione decomposes gradually and changes to
red-brown by light.
20
: About 0.967.
of solutions of Phytonadione and Phytonadione RS in
isooctane (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Phytonadione
and Phytonadione RS as directed in the potassium bromide disk method under Infrared Spectrophotometry,
and compare the spectrum with the standard spectrum:
Refractive Index
nD20 : Between 1.525 and 1.529.
Purity (1) Ratio of absorbances Determine the absorbances, A1 , A2 and A3 of a solution of Phytonadione in isooctane (1 in 100000) at 248.5 nm, 253.5
nm and 269.5 nm, respectively, as directed under Ultraviolet-visible Spectrophotometry: the ratio A2 / A1
is between 0.69 and 0.73, and the ratio A2 / A3 is
between 0.74 and 0.78. Determine the absorbances,
A4 and A5 of a solution of Phytonadione in isooctane (1 in 10000) at 284.5 nm and 326 nm, respectively: the ratio A4 / A5 is between 0.28 and 0.34.
(2) Heavy metalsCarbonize 1.0 g of Phytonadione by gentle heating. Cool, add 10 mL of a solution
of magnesium nitrate hexahydrate in dehydrated ethanol (1 in 10), and ignite the ethanol to burn. Cool, add 1
mL of sulfuric acid, proceed according to Method 4 and
(3) MenadioneDissolve 20 mg of Phytonadione
in 0.5 mL of a mixture of water and ethanol (1 : 1), add
1 drop of a solution of 3-methyl-1-phenyl-5-pyrazolone
in ethanol (1 in 20) and 1 drop of strong ammonia water, and allow to stand for 2 hours: no blue-purple color
develops.
Isomer ratio Perform this procedure rapidly without
exposure to light. Dissolve 30 mg of Phytonadione in
50 mL of the mobile phase. To 4 mL of this solution
add the mobile phase to make 25 mL. To 10 mL of this
solution add the mobile phase to make 25 mL, and use
this solution as the test solution. Perform the test with
50 L of the test solution as directed under Liquid

and determine the peak areas of Z-isomer and E-isomer,
ATZ and ATE : ATZ /( ATZ + ATE ) is between 0.05 and
0.18.
Proceed as directed in the operating conditions in
the Assay.
System suitability
above operating conditions, Z-body and E-body are
eluted in this order with the resolution between then being not less than 1.5.
deviation of the sum of peak areas of E-body peak and
Z-body peak is not more than 1.0%.
Assay Perform this procedure rapidly without exposure to light. Weigh accurately about 30 mg each of
Phytonadione and Phytonadione RS, and dissolve each
in the mobile phase to make exactly 50 mL. Pipet exactly 4 mL each of these solutions, and add the mobile
phase to make exactly 25 mL. To exactly 10 mL each
of these solutions add exactly 7 mL of the internal
standard solution and the mobile phase to make exactly
25 mL, and use these as the test solution and standard
of the test solution and standard solution as directed
under Liquid Chromatography according to the following conditions, and determine the ratios, QT and QS ,
of the total area of the peaks of Z-isomer and E-isomer
to the peak area of the internal standard.

above operating conditions, the internal standard substance, Z-body and E-body are eluted in this order with
the resolution of Z-body and E-body being not less than
1.5.
deviation of the sum of peak areas of E-body peak and
Z-body peak to the peak area of internal standard substance is not more than 1.0%.
tight containers. At a cold place.
Phytonadione Injection
Vitamin K1 Injection
Phytonadione Injection is an aqueous solution for injection. Phytonadione Injection contains not less than
of phytonadione (C31H46O2: 450.70).
Method of Preparation Prepare as directed under Injections, with Phytonadione. Phytonadione Injection
contains suitable solubilizing or dispersing agents.
Identification The retention time of principal peak in
the chromatogram of the Assay preparation corresponds
to that of the standard preparation, as obtained in the
assay.
pH
Amount (mg) of phytonadione (C31H46O2)

Q
= WS T
QS
Internal standard solutionThe mobile phase solution (1 in 400) of cholesterol benzoic acid.
(wavelength: 254nm).
octadecylsilanized silica gel for the Liquid Chromatography ( 5 m in particle diameter).
about 30 .
Mobile phase: A mixture of hexane and n-amyl alcohol (4000 : 3).
Flow rate: Adjust the retention time of peak eluted
next in two peaks of Phytonadione to be about 25 minutes.
System suitability

Bacterial Endotoxins Less than 14.0 EU /mg of Phytonadione.
Assay In case of Phytonadione Injection containing
10 mg or more of Phytonadione per mL, pipet accurately a volume of Phytonadione Injection, equivalent to 10
mg of phytonadione (C31H46O2), add mobile phase to
make exactly 10 mL and mix. Pipet 1.0 mL of this solution, dilute with mobile phase to make exactly 10 mL
and use this solution as the test solution. And in case of
KP 9 763
Phytonadione Injection containing less than 10 mg

Phytonadione per mL, pipet accurately a volume of
Phytonadione Injection, equivalent to 1 mg of phytonadione (C31H46O2), add mobile phase to make exactly 10
mL. Separately, weigh accurately a portion of Phytonadione RS, dissolve in mobile phase and dilute quantitatively to obtain a solution having a known concentration of about 1 mg per mL. Pipet 1.0 mL of this solution, dilute with mobile phase to make exactly 10 mL
standard solution as directed under the Liquid Chromatography according to the following operating conditions and determine the main peak areas, AT and AS
of Phytonadione for the test solution and the standard
Amount (mg/mL) of phytonadione (C31H46O2)
C A
= D T
V AS
D: 100 (in case of Phytonadione Injection containing 10 mg or more of Phytonadione per mL) or 10 (in
case of Phytonadione Injection containing less than 10
mg of Phytonadione per mL),
C: Concentration of Phytonadione in the standard
solution (mg/mL),
V: Amount (mL) of injection taken.
Mobile phase: A mixture of dehydrated ethanol and
water (95 : 5).
System suitability
deviation of the peak areas of Phytonadione is not more
than 1.5%.
Phytonadione Tablets
Vitamin K1 Tablets
Phytonadione Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of phytonadione (C31H46O2: 450.70).

Tablets, with Phytonadione.
Identification (1) Dissolve a portion of the powdered
Phytonadione Tablets, equivalent to about 10 mg of
Phytonadione according to the labeled amount, in 750
mL of dehydrated ethanol with shaking, add dehydrated
ethanol to make 1000 mL, mix and filter, use the filtrate as the test solution. Separately, proceed the same
manner used in the test solution with Phytonadione RS,
test with test solution and standard solution as directed
same wavelenghs.
(2) The retention time of the principal peak from
the test solution in the Assay is the same with the retention time of peak from the standard solution..
ment.

Phytonadione Tablets. Weigh accurately a portion of
the powder, equivalent to about 5 mg of phytonadione
(C31H46O2), add 20 mL of dehydrated ethanol, dissolve
with vigorous shaking for 15 minutes and add dehydrated ethanol to make exactly 50 mL. Filter this solution and use this filtrate as the test solution. Separately,
weigh accurately about 5 mg of Phytonadione RS, dissolve in dehydrated ethanol to make exactly 50 mL, use
according to the following operating conditions: determine the main peak areas, AT and AS , of Phytonadione for the test solution and the standard solution, respectively.
Amount (mg) of phytonadione (C31H46O2)

A
= amount (mg) of Phytonadione RS (mg) T
AS
Mobile phase: A mixture of anhydrous ethanol and
water (95 : 5).
System suitability

above operating conditions, a symmetry factor is not
more than 2.0.
deviation of the peak areas of Phytonadione is not more
than 2.0%.
tight containers.
Pilocarpine Hydrochloride
H
H
CH2
H5C2
NCH3
HCl
C11H16N2O2HCl: 244.72
Pilocarpine Hydrochloride, when dreid, contains not
less than 99.0% and not more than 101.0% of pilocarpine hydrochloride (C11H16N2O2HCl).
Description Pilocarpine Hydrochloride is a colorless
crystal or white powder, is odorless and has a slightly
bitter taste.
Pilocarpine Hydrochloride is very soluble in glacial
acetic acid, freely soluble in water, in methanol or in
ethanol, soluble in acetic anhydride and practically insoluble in ether.
pHThe pH of a solution of Pilocarpine Hydrochloride (1 in 10) is between 3.5 and 4.5.
Pilocarpine Hydrochloride is hygroscopic.
Pilocarpine Hydrochloride is affected by light.
Identification (1) Dissolve 0.1 g of Pilocarpine Hydrochloride in 5 mL of water, add 1 drop of dilute nitric
acid, 1 mL of hydrogen peroxide TS, 1 mL of chloroform and 1 drop of a potassium dichromate solution (1
in 300) and shake the mixture vigorously: a violet color
is observed in the chloroform layer, no color or a pale
yellow color is observed in the aqueous layer.
(2) Take 1 mL of a solution of Pilocarpine Hydrochloride (1 in 20), add 1 mL of dilute nitric acid and
2 to 3 drops of silver nitrate TS: a white precipitate or
opalescence is produced.
Purity (1) SulfateDissolve 0.5 g of Pilocarpine
Hydrochloride in 20 mL of water and use this solution
as the test solution. To 5.0 mL of the test solution, add
1 mL of dilute hydrochloric acid and 0.5 mL of barium
chloride TS: no turbidity is produced.
(2) NitrateTo 2.0 mL of the test solution obtained
in (1), add 2 mL of ferrous sulfate TS and superimpose
the mixture upon 4 mL of sulfuric acid: no dark brown

color is observed at the zone of contact.
(3) Related substancesDissolve 0.3 g of Pilocarpine Hydrochloride in 10 mL of methanol and use this
solution as the test solution. Pipet exactly 1 mL of the
10 L each of the test solution and the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chloroform,
methanol and ammonia water (85 : 14 : 2) to a distance
of about 13 cm and dry the plate at 105 C for 10 minutes. Cool and spray evenly bismuth potassium iodide
TS on the plate: the spots other than the principal spot
obtained from the standard solution.
of Pilocarpine Hydrochloride and perform the test: the
solution has no more color than Color Matching Fluid
B.
hours).
Assay Weigh accurately about 0.5 g of Pilocarpine
3) and titrate with 0.1 mol/L perchloric acid VS (potentiometic titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any

= 24.472 mg of C11H16N2O2HCl
tight containers.
Pimozide
HN
C28H29F2N3O : 461.55
KP 9 765
Pimozide contains not less than 98.0% and not more

than 102.0% of pimozide (C28H29F2N3O), calculated on
the dried basis.
Description Pimozide is a white, crystalline powder,
is odorless, and has bitter taste.
Pimozide is freely soluble in chloroform, slightly soluble in ethanol or in ether, and practically insoluble in
water.
Identification (1) Dissolve 35 mg each of Pimozide
and Pimozide RS in 0.1 mol/L hydrochloric acid methanol solution (1 in 10) to make 100 mL, pipet 5.0 mL
of this solution and add 0.1 mol/L hydrochloric acid
methanol solution (1 in 10) to make 50 mL. Determine
the absorption spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry: both
same wavelengths.
(2) Determine the infrared absorption spectra of Pimozide and Pimozide RS, as directed in the potassium
bromide disk method under lnfrared Spectrophotornetry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Purity (1) Heavy metalsProceed with l.0 g of Pimozide according to Method 2, and perform the test.
(2) Related substancesDissolve 0.10 g of Pimozide, accurately weighed, in 10 mL of chloroform and
use this solution as the test solution. Separately, dissolve a proper portion of Pimozide RS, accurately
weighed, to make solutions containing 0.01, 0.05, 0.1
and 0.2 mg per mL and use these solutions as the standard solutions. Perform the test with the test solution
and the standard solutions, as directed under Thin
Layer Chromatography. Spot 20 L each of the test solution and the standard solutions on silica gel plate with
Develop the plate with a mixture of acetone and cyclohexane (1 : 1) to a distance of about 12 cm, and air-dry
the plate. Examine under ultraviolet light (main wavelength: 254 nm) and expose to iodine vapor: the spots
from the test solution, except the principal spot, not
more intense than the spot from the standard solution
(1.0%).

= 46.155 mg of C28H29F2N3O
tight containers.
Pindolol
H
N
CH3
OCH2CCH2NHCH
OH
CH3
and enantiomer
C14H20N2O2: 248.32
Pindolol, when dried, contains not less than 98.5% and

not more than 101.0% of pindolol (C14H20N2O2).
Description Pindolol is a white, crystalline powder
and has a slight, characteristic odor.
Pindolol is sparingly soluble in methanol, slightly soluble in ethanol and practically insoluble in water or in
ether.
Pindolol dissolves in dilute sulfuric acid or in glacial
acetic acid.
Identification (1) Take 1 mL of a solution of Pindolol in methanol (1 in 10000), add 1 mL of a solution of
1-(4-pyridyl)-pyridinium chloride hydrochloride (1 in
1000) and 1 mL of sodium hydroxide TS, then add 1
mL of hydrochloric acid: a blue to blue-purple color,
changing to red-purple, develops.
(2) Dissolve 50 mg of Pindolol in 1 mL of dilute
sulfuric acid and add 1 mL of Reinecke salt TS: a pale
red precipitate is produced.
Pindolol and Pindolol RS in methanol (1 in 50000) as
(4) Determine the infrared spectra of Pindolol and
Pindolol RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
absorption at the same wave numbers.
Residue on Ignition Not more than 0.2% (2 g, platinum crucible).

Assay Weigh accurately about 0.5 g of Pimozide,
dissolve in 40 mL of glacial acetic acid, and titrate with
%
Absorbance E11cm
(10 mg, methanol, 500 mL).

0.5 g of Pindolol in 10 mL of glacial acetic acid and
observe immediately: the solution is clear and has no
more color than the following control solution.

Control solutionPipet 4 mL of Color Matching
Fluid A, add exactly 6 mL of water and mix.
(2) Heavy metalsProceed with 1.0 g of Pindolol

Pindolol according to Method 3 and perform the test
(4) Related substancesDissolve 0.10 g of Pindolol in 10 mL of methanol and use this solution as the
test solution. Pipet 2 mL of the test solution and add
methanol to make exactly 100 mL. Pipet 5 mL of this
solution, add methanol to make exactly 20 mL and use
plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chloroform, acetone
and isopropylamine (5 : 4 : 1) to a distance of about 12
cm and air-dry the plate. Spray evenly diluted sulfuric
acid (3 in 5) and a sodium nitrite solution (1 in 50) on
the plate: the spots other than the principal spot from
hours).
Assay Weigh accurately about 0.5 g of Pindolol, previously dried, dissolve in 80 mL of methanol and titrate
with 0.1 mol/L hydrochloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary
correction.

= 24.832 mg of C14H20N2O2
tight containers.
Pipemidic Acid Hydrate

C2H5
N
NH
3H2O
N
HOOC
O
C14H17N5O33H2O: 357.36
Pipemidic Acid Hydrate, when dried, contains not less

than 98.5% and not more than 101.0% of pipemidic acid (C14H17N5O3: 303.32).
Description Pipemidic Acid Hydrate is a pale yellow,
Pipemidic Acid Hydrate is freely soluble in glacial
acetic acid, very slightly soluble in water or in ethanol
Pipemidic Acid Hydrate dissolves in sodium hydroxide
TS.
Pipemidic Acid Hydrate is gradually colored by light.
Identification (1) Dissolve 0.1 g of Pipemidic Acid
Hydrate in 20 mL of sodium hydroxide TS, heat under
a reflux condenser in a water-bath for 1 hour and cool.
To 2 mL of this solution, add 1 drop of phenolphthalein
TS, neutralize with dilute acetic acid, add 1 mL of dilute acetic acid, then add 4 mL of a solution of pbenzoquinone in methanol (1 in 1000) and boil gently:
an orange-red color develops.
(2) Dissolve 0.1 g each of Pipemidic Acid Hydrate
and Pipemidic Acid Hydrate RS in 20 mL of sodium
hydroxide TS and add water to make 200 mL. To 1 mL
each of these solutions, add water to make 100 mL and
determine the absorption spectra of these solutions as
(3) Determine the infrared spectra of Pipemidic Acid Hydrate and Pipemidic Acid Hydrate RS as directed
in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wave numbers.
Purity (1) ChlorideDissolve 1.0 g of Pipemidic
Acid Hydrate in 35 mL of water and 10 mL of sodium
hydroxide TS, shake well with 15 mL of dilute nitric
acid and filter through a glass filter (G3). To 30 mL of
the filtrate, add 6 mL of dilute nitric acid and water to
make 50 mL. Perform the test. Prepare the control solution as follows: to 0.30 mL of 0.01 mol/L hydrochloric
acid VS, add 5 mL of sodium hydroxide TS, 13.5 mL of
dilute nitric acid and water to make 50 mL (not more
than 0.021%).
(2) SulfateDissolve 1.0 g of Pipemidic Acid Hydrate in 35 mL of water and 10 mL of sodium hydroxide TS, shake well with 15 mL of dilute hydrochloric
acid and filter through a glass filter (G3). To 30 mL of
the filtrate, add water to make 50 mL. Perform the test.
0.005 mol/L sulfuric acid VS, add 5 mL of sodium hydroxide TS, 7.5 mL of dilute hydrochloric acid and water to make 50 mL (not more than 0.048%).
(3) Heavy metalsProceed with 2.0 g of Pipemidic
Acid Hydrate according to Method 2 and perform the
KP 9 767

Pipemidic Acid Hydrate according to Method 3 and
(5) Related substancesDissolve 0.10 g of Pipemidic Acid Hydrate in 10 mL of diluted glacial acetic
acid (1 in 20) and use this solution as the test solution.
Pipet 1.0 mL of the test solution, add diluted glacial
acetic acid (1 in 20) to make exactly 200 mL and use
plate of silica gel with fluorescent indicator for thinlayer chromatography. Develop the plate with a mixture
of chloroform, methanol, formic acid and triethylamine
(25 : 15 : 5 : 1) to a distance of about 10 cm and air-dry
the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot
C, 3 hours).
Piperacillin Sodium is freely soluble in water or in methanol, sparingly soluble in ethanol, and practically insoluble in ether.
Identification (1) Dissolve 10 mg of Piperacillin Sodium in 2 mL of water, add 3 mL of hydroxylamine hydrochloride TS, allow to stand for 5 minutes, and add 1
mL of acidic ferric ammonium sulfate TS and shake: a
red-brown color develops.
(2) To 0.1 g of Piperacillin Sodium, add 4 mL of 2
mol/L sodium hydroxide TS, boil until the solution
turns to be turbid, allow to cool, add 10 mL of dilute
acetic acid, heat and add 1 mL of calcium chloride TS.
Filter the suspension with shaking, wash with 10 mL of
water twice and discard the filtrate. To the precipitate
on filter paper add 1 mL of 1 mol/L sulfuric acid TS
and dissolve the precipitate, and take the filtrate. To the
filtrate add about 10 mg of magnesium and dissolve.To
3 drops of this solution add 2 mL of 2,7dihydroxynaphthalene solution in sulfuric acid (1 in
10000), and heat for 10 minutes in water bath: a purplered color develops.
(3) Piperacillin Sodium responds to the Qualitative
Tests 1) for sodium salt.

Assay Weigh accurately about 0.3 g of Pipemidic Acid Hydrate, previously dried, dissolve in 40 mL of glacial acetic acid for non-aqueous titration and titrate
correction.

= 30.332 mg of C14H17N5O3

Piperacillin Sodium
N
H3C
O
N
O
O
H
ONa
O
N
NH
H
N
CH3
CH3
S
C23H26N5NaO7S: 539.54
Piperacillin Sodium contains not less than 863 g (potency) per mg of piperacillin (C23H27N5O7S: 517.56),
Description Piperacillin Sodium is a white powder, is
odorless, and has a little bit of a bitter taste.

g, water, 20 mL, 200 mm).
[ ] 20
D : +175 ~ +190 (0.8

of Piperacillin Sodium in 10 mL of water is between
5.0 and 7.0.
Purity (1) Clarity or color of solutionDissolve 1.0
g of Piperacillin Sodium in 4 mL of water: the solution
(2) Heavy metals Proceed with 2.0 g of Piperacillin Sodium according to Method 2 and perform the test.
(3) Arsenic Prepare the test solution with 2.0 g of
Piperacillin Sodium according to Method 3 and perform the test (not more than 1 ppm).
(4) Ampicillin contentPerform the test according
to Bioautograph Method.
() Developing solvent mixture- Mix n-butanol, water
and acetic acid (10:5:1) in a separating funnel with
shaking, allow to stand for 4 hours at room temperature,
and use the upper layer as the developing solvent mixture.
() Weigh an appropriate amount of Piperacillin Sodium, dissolve in water to make a solution so that each
mL contains 8 mg (potency), and use this solution as
the test solution. Separately, weigh an appropriate
amount of Ampicillin RS, dissolve in water to make a
solution so that each mL contains 40 g (potency), and
use this solution as the standard solution.
1 under
() Medium- Use the medium in I 2 1) (1)
Microbial Assay for Antibiotics. Adjust the pH of the
mediun so that it will be 5.8 to 6.0.
() Test organism- Bacillus subtilis ATCC 6633.

() Apparatus- Use an apparatus for closed thin-layer
chromatography. Add the developing solvent mixture to
about 10 mm high.
() Thin-layer plate- Use 50 x 200 mm glass plate
coated with microcrystalline cellulose (thickness: 0.2 ~
0.3 mm) and air-dried. Instead of glass plate, an appropriate plastic plate could be used.
() Procedure- Spot 1 L each of the test solution and
the standard solution with about 5 mm interval between
spots. A spot position should be 20 mm above from the
bottom of a plate and 10 mm from the both side of a
plate. Develop the plate in an apparatus for closed thinlayer chromatography to a distance of 10 cm from the
origin, and air-dry the plate until a smell of acetic acid
disappears. Contact the plate with the seeded agar medium in a box for 1 ~ 2 minutes. During contact between the plate and the medium microbial contamination is not permitted from outside environment. Incubate the box between 32 C and 37 C for 17 ~ 20
hours.
() Rf value- The Rf value of Piperacillin Hydrochloride is about 0.85 and the Rf value of ampicillin is
about 0.57.
() The diameter of inhibition zone for ampicillin obtained from the test solution is smaller than the diameter of inhibition zone for ampicillin obtained from the
diluted standard solution (not more than 0.5 %, mass vs
potency ratio).
(5) Related substance 1 contentPerform the test
according to the following the procedure and calculation (not more than 2.0 %).
Procedure and calculation- Weigh accurately about 0.2
mg of Piperacillin Sodium, transfer into 100 mL glassstoppered flask, add 25 mL of 0.1 mol/L phosphate buffer solution, pH 6.0 and dissolve, add immediately and
exactly 10 mL of 0.005 mol/L iodine solution, allow to
stand for 10 minutes, and titrate with 0.01 mol/L sodium thiosulfate VS. Use 1 mL of starch TS as an indicator. Perform a blank determination with 0.1 mol/L
phosphate buffer, pH 6.0, in the same manner, and
Amount [%]
amount[mL] consumed of
0.005 mol/L iodine solution 0.80
=
amount [mg] of Piperacillin Sodium taken 100
(6) Related substance 2 contentWeigh accurately
20 mg of Piperacillin Sodium, dissolve in 4 mL of water, and use this solution as the test solution. Perform
the test with this solution as directed under Thin-layer
Chromatography. Spot 2.5 L of the test solution on a
plate of silica gel for thin-layer chromatography. Develop the plate with the mixture of n-butylacetate, acetic acid, water and isopropanol (10:5:3:2) to a distance
of about 10 cm, and air-dry the plate. Then allow the
plate to expose in iodine vapor: the spot of piperacillin
sodium appears around Rf 0.5 and no pale browm spot

of the related substance 2 is detected around Rf 0.6.
Sterility Test It meets the requirement, when Piperacillin Sodium is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Piperacillin Sodium is used in a sterile preparation. Weigh an
appropriate amount of Piperacillin Sodium, dissolve in
water to make a solution so that each mL contains 40
mg (potency), and use the solution as the test solution.
The amount of injection is 1.0 mL of the test solution
per kg of body weight of rabbit.
Piperacillin Sodium and Piperacillin RS, dissolve each
in the mobile phase to make exactly 100 mL, and use
these solutions as the test solution and the standard solution. Perform the test with 20 L each of the test solution and the standard solution as directed under the
Liquid Chromatography according to the following operating conditions and obtain the peak areas, AT and AS,
of piperacillin.
Amount [g (potency)] of piperacillin (C23H27N5O7S)

A
= Amount [g (potency)] of Piperacillin RS T
AS
chromatography (5 ~ 10 m in particle diameter)
Mobile phase: A mixture of water, acetonitrile, 0.2
mol/L ammonium dihydrogenphosphate solution and
acetic acid (54:35:10:1)
Piperacillin Sodium
for Injection
Piperacillin Sodium for Injection is a preparation for injection which is dissolved before use, and contains not
less than 90.0 % and not more than 120 % of the labeled amount of piperacillin (C23H27N5O7S: 517.56).
Method of Preparation Prepare as directed under Injections, with Piperacillin Sodium.
Identification Proceed as directed under the Identifi-
KP 9 769
cation (1) and (2) in Piperacillin Sodium.

of Piperacillin Sodium for Injection in 10 mL of water
Sterility Test It meets the requirement, when Piperacillin Sodium for Injection is used in a sterile preparation.
Pyrogen Test Proceed as directed under the Pyrogen
in Piperacillin Sodium: it meets the requirement. The
of body weight of rabbit.
ment.

Assay Weigh accurately about 1.0 g (potency) of labeled amount of Piperacillin Sodium for Injection, dissolve in the mobile phase and dilute to make a solution
so that each mL contains 100 g, and use this solution
as the test solution. Perform the test according to the
Assay under Piperacillin Sodium.
Amount [g (potency)] of piperacillin (C23H27N5O7S)

A
= Amount [g (potency)] of Piperacillin RS T
AS
tainers.
Piperazine Adipate
H
N
HO 2CCH2CH2CH2CH2CO 2H
N
H
C4H10N2C6H10O4: 232.28
Piperazine Adipate, when dried, contains not less than
98.5% and not more than 101.0% of piperazine adipate
(C4H10N2C6H10O4).
Description Piperazine Adipate is a white, crystalline
powder, is odorless and has a slightly acid taste.
Piperazine Adipate is soluble in water or in glacial acetic acid and practically insoluble in ethanol, in acetone
or in ether.
Melting pointAbout 250 (with decomposition).
Identification (1) Dissolve 0.5 g of Piperazine Adipate in 10 mL of water, add 1 mL of hydrochloric acid
and extract with two 20 mL volumes of ether. Combine
the ether extracts, evaporate to dryness in a water-bath
and dry the residue at 105 for 1 hour: the melting
point of the residue is between 152 and 155 .
(2) Take 3 mL of a solution of Piperazine Adipate
(1 in 100) and add 3 drops of Reinecke salt TS: a pale
red precipitate is formed.
(3) Determine the infrared spectra of Piperazine
Adipate and Piperazine Adipate RS, previously dried,
the lnfrared Spectrophotometry: both spectra exhibit
pH The pH of a solution of Piperazine Adipate(1 in
1.0 g of Piperazine Adipate in 30 mL of water: the solution is clear and colorless.
(2) Heavy metalsProceed with 2.0 g of Piperazine Adipate according to Method 2 and perform the
hours).
Assay Weigh accurately about 0.2 g of Piperazine
Adipate, previously dried, dissolve in a mixture of 20
mL of glacial acetic acid and 40 mL of acetone for
nonaqueous titration and titrate with 0.1 mol/L perchloric acid VS until the red-purple color of the solution changes to blue-purple (indicator: 6 drops of bromocresol green-methylrosaniline chloride TS). Perform

= 11.614 mg of C4Hl0N2C6H10O4
Piperazine Citrate Hydrate

HO
O
HN
NH
xH2O
3
OH
HO
O
OH
O
2
(C4H10N2)32C6H8O7xH2O
Piperazine Citrate Hydrate contains not less than 98.0%
and not more than 100.5% of piperazine citrate
[(C4H10N2)32C6H8O7 :642.65], calculated on the anhydrous basis.
Description Piperazine Citrate Hydrate is a white
crystalline powder and has slight odor.
Piperazine Citrate Hydrate is soluble in water and very
slightly soluble in ethanol or in ether.
pHThe pH of a solution of Piperazine Citrate
Hydrate (1 in 10) is about 5.
Identification (1) Dissolve 0.2 g of Piperazine Citrate Hydrate in 5 mL of 3 mol/L hydrochloric acid and
add, with stirring, 1 mL of sodium nitrite VS (1 in 2).
Cool in a water-bath for 15 minutes, stirring, if necessary, to induce crystallization, filter the precipitate on a
sintered-glass funnel, wash with 10 mL of cold water
and dry at 105 C: the obtained N, N-dinitrosopipera
zine melts between 156 C and 160 C.
(2) Piperazine Citrate Hydrate responds to the Qualitative Tests for citrate.
Purity Primary amines and ammoniaDissolve 0.5
g of Piperazine Citrate Hydrate in 10 mL of water. Add
1 mL of 2.5 mol/L sodium hydroxide, 1 mL of acetone
and 1 mL of sodium nitropruside TS. Mix and allow to
stand for exactly 10 minutes. Determine, A1 and A2, the
absorbance of this solution at 520 nm and at 600 nm,
respectively, as directed under the Ultraviolet-visible
Spectrophotometry, using a blank consisting of the
same quantities of the same reagents, but substituting
water for the sodium hydroxide solution. The ratio,
A2/A1, is not more than 0.5 (not more than about 0.7%
of primary amines and ammonia).
Assay Weigh accurately about 0.2 g of Piperazine Citrate Hydrate and dissolve in 100 mL of glacial acetic
acid TS, warming slightly, if necessary to make a solution. Titrate with 0.1 mol/L perchloric acid VS (indicator: 3 drops of methylrosaniline cholride TS). Perform

= 10.71 mg of (C4H10N2)32C6H8O7
Piperazine Phosphate Hydrate

HN
NH
H3PO4
H2O
Piperazine monophosphate monohydrate

C4Hl0N2H3PO4H2O: 202.15
Piperazine Phosphate Hydrate contains not less than
98.5% and not more than 101.0% of piperazine phosphate (C4Hl0N2H3PO4: 184.13), calculated on the anhydrous basis.
Description Piperazine Phosphate Hydrate is a white
crystal or crystalline powder, is odorless and has a
slightly acid taste.
Piperazine phosphate Hydrate is soluble in formic acid,
sparingly soluble in water, very slightly soluble in glacial acetic acid and practically insoluble in methanol, in
Piperazine Phosphate Hydrate dissolves in dilute hydrochloric acid.
Identification (1) Take 3 mL of a solution of Piperazine Phosphate Hydrate (1 in 100) and add 3 drops of
Reinecke salt TS: a pale red precipitate is formed.
(2) Determine the infrared spectra of Piperazine
Phosphate Hydrate and Piperazine Phosphate Hydrate
RS as directed in the potassium bromide disk method
under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wave
numbers.
(3) A solution of Piperazine Phosphate Hydrate (1
in 100) responds to the Qualitative Tests (1) and (3) for
phosphate.
pH Dissolve 1.0 g of Piperazine Phosphate Hydrate
in 100 mL of water: the pH of the solution is between
6.0 and 6.5.
Purity (1) ChlorideTake 0.5 g of Piperazine Phosphate Hydrate, add 6 mL of dilute nitric acid and water
to make 50 mL. Use this solution as the test solution
0.25 mL of 0.01 mol/L hydrochloric acid (not more
than 0.018%).
(2) Heavy metalsTake 2.0 g of Piperazine Phosphate Hydrate, add 5 mL of dilute hydrochloric acid, 30
KP 9 771
mL of water and 2 mL of dilute acetic acid and dissolve.

Add sodium hydroxide TS, adjust the pH of the solution to 3.3 and add water to make 50 mL. Perform the
(3) ArsenicDissolve 2.0 g of Piperazine Phosphate Hydrate in 5 mL of dilute hydrochloric acid and
(4) Related substancesDissolve 50 mg of Piperazine Phosphate Hydrate in 10 mL of water and use this
solution as the test solution. Pipet 1.0 mL of the test solution, add water to make exactly 100 mL and use this
of cellulose for thin-layer chromatography. Develop the
plate with a mixture of ethyl acetate, acetone, strong
ammonia water and dehydrated ethanol (8 : 3 : 3 : 2) to
a distance of about 13 cm and air-dry the plate. Spray
evenly p-dimethylamino-cinnamaldehyde TS and allow
to stand for 15 minutes: the spots other than the principal spot and the spot on the starting line from the test
solution are not more intense than the spot from the
standard solution.
Assay Weigh accurately about 0.15 g of Piperazine
Phosphate, dissolve in 10 mL of formic acid, add 60
mL of glacial acetic acid and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.

= 9.207 mg of C4Hl0N2H3PO4
Piperazine Phosphate Tablets

Piperazine Phosphate Tablets contian not less than
of piperazine phosphate hydrate (C4Hl0N2H2H3PO4:
202.15).
the Tablets, with Piperazine Phosphate Hydrate.
Identification Take a portion of Piperazine Phosphate Tablets equivalent to 0.1 g of Piperazine Phosphate according to the labeled amount, previously
powdered, add 10 mL of water, shake while warming
for 10 minutes, allow to cool and filter. To 3 mL of the
filtrate, add 3 drops of Reinecke salt TS: a pale red precipitate is formed.
Disintegration Test It meets the requirement. The
disintegration time is 10 minutes.

ment.

Piperazine Phosphate Tablets. Weigh accurately a portion of the powder, equivalent to about 0.15 g of pipe-
razine phosphate hydrate (C4Hl0N2H2H3PO4.H2O) according to the labeled amount. Add 5 mL of formic acid,
shake for 5 minutes, centrifuge and collect the supernatant liquid. To the residue, add 5 mL of formic acid,
shake for 5 minutes, centrifuge and collect the supernatant liquid. Repeat twice the same procedure with 5 mL
each of glacial acetic acid, combine all the supernatant
liquids, add 50 mL of acetic anhydride and titrate with
= 10.107 mg of C4Hl0N2H3PO4H2O
Piracetam
O
N
NH2
O
C6H10N2O2 : 142.16
Piracetam contains not less than 98.0% and not more
than 102.0% of piracetam, calculated on the anhydrous
basis.
Description Piracetam is white powder.
Piracetam is freely soluble in water, and soluble in
ethanol.
Piracetam shows polymorphism.
Identification Determine the infrared spectra of Piracetam and Piracetam RS as directed in the potassium
bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers. If any differences
appear, dissolve Piracetam and Piracetam RS in ethanol,
evaporate in water-bath to dryness, respectively and
with the residues repeat the test.
Purity (1) Clarity and color of solutionA solution
of 2.0 g of Piracetam in 10 mL of water is clear and colorless.

(2) Heavy metalsProceed with 2.0 g of Piracetam
(3) Related substancesDissolve 50.0 mg of Piracetam in a mixture of water and acetonitrile (90 : 10) to
solution. Separately, dissolve 5 mg of Piracetam and 10
mg of piracetam related substance I RS {2pyrrolidone} in a mixture of water and acetonitrile (90 :
10) to make exactly 100 mL and use this solution as the
standard solution (1). To 1.0 mL of the test solution,
add a mixture of water and acetonitrile (90 : 10) to
make exactly 100 mL, to 5.0 mL of this solution, add a
mixture of water and acetonitrile (90 : 10) to make exactly 50 mL and use this solution as the standard solution (2). Perform the test with 20 L each of the test solution and the standard solutions as directed under the
Liquid Chromatography, according to the following
operating conditions: the areas of any peaks except the
principal peak obtained from the test solution are not
more than the area of the principal peak from the standard solution (2) (0.1%), and the total area of peaks except the principal peak from the test solution is not
more than 3 times the area of the principal peak from
the standard solution (2) (0.3%). The peaks with area of
less than 0.5 times the area of the principal peak from
the standard solution (2).
particle diameter)
Mobile phase: A mixture of the phosphate and acetonitrile (90 : 10)
System suitability
with the standard solution (1) under the above operating conditions, the resolution between the peaks of piracetam and piracetam related substance I is not less
than 3.0 and the symmetry factor of the piracetam peak
Phosphate bufferDissolve 1.0 g of potassium dihydrogen phosphate in water to make 1000 mL and adjust to pH 6.0 with dilute phosphoric acid.
constant mass).
Assay Weigh accurately about 0.75 g of Piracetam,
dissolve in 50 mL of water, add 20.0 mL of 1 mol/L so-
dium hydroxide VS, and heat to boil for 15 minutes.

Cool, add 20.0 mL of 1 mol/L hydrochloric acid VS,
and heat to boil for 2 minutes. Cool and and titrate with
0.1 mol/L sodium hydroxide VS (indicator: 2 drops of
phenolphthalein TS). Perform a blank determination in
the same manner, and make any necessary correction.
= 142.15 mg of C6H10N2O2.

Pirenzepine Hydrochloride
Hydrate
CH3
O
N
N
N
O
HN
2HCl H2O
C19H21N5O22HClH2O : 442.34
Pirenzepine Hydrochloride Hydrate contains not less
than 98.5% and not more than 101.0% of pirenzepine
hydrochloride (C19H21N5O22HCl : 424.32), calculated
Description Pirenzepine Hydrochloride Hydrate is a
white to pale yellow crystalline powder.
Pirenzepine Hydrochloride Hydrate is freely soluble in
water or in formic acid, slightly soluble in methanol,
and very slightly soluble in ethanol.
Pirenzepine Hydrochloride Hydrate is gradually colored by light.
Melting point About 245 C (with decomposition).
pH A solution of 1 g of Pirenzepine Hydrochloride
Hydrate in 10 mL of water is between 1.0 and 2.0.
of solution of Pirenzepine Hydrochloride Hydrate and
Pirenzepine Hydrochloride Hydrate RS (1 in 40000), as
directed under Ultraviolet-visible Spectrophotometry:
(2) Determine the infrared absorption spectra of Pirenzepine Hydrochloride Hydrate and Pirenzepine Hydrochloride Hydrate RS as directed in the potassium
chloride disk method under lnfrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) A solution of Pirenzepine Hydrochloride Hydrate
(1 in 50) responds to Qualitative Tests for chloride.
KP 9 773
of 1.0 g of Pirenzepine Hydrochloride Hydrate in 10
mL of water is clear and has no more color than that of
Control solution: To 1.2 ml. of Matching fluid for
color F, add 8.8 mL of diluted hydrochloric acid (1 in
40).
(2) Heavy metalsProceed with 2.0 g of Pirenzepine Hydrochloride Hydrate according to Method 2,
2.0 mL of Standard Lead Solution (not more than 10
ppm).
(3) Related substancesDissolve 0.3 g of Pirenzepine Hydrochloride Hydrate in 10 mL of water. To exactly 1 mL of this solution, add 5 mL of methanol and
the mobile phase A to make exactly 10 mL, and use this
test solution, and add 5 mL of methanol and the mobile
phase A to make exactly 10 mL. Pipet exactly 1 mL of
this solution, add 5 mL of methanol and the mobile
as the standard solution. Perform the test with 10 L
each of the test solution and the standard solution as directed under Liquid Chromatography according to the
following conditions, and determine each peak area by
the automatic integration method: the area of the peak
other than pirenzepine is not more than 0.3 times the
peak area of pirenzepine from the standard solution,
and the total area of the peaks other than pirenzepine is
riot more than 0.6 times the peak area of pirenzepine
particle diameter)
about 40 C.
Control the gradient by mixing the mobile phases A,
B and C as directed in the following table.
Mobile phase A: Dissolve 2 g of sodium lauryl sulfate in 900 mL of water, adjust the pH to 3.2 with glacial acetic acid and add water to make l000 mL.
Mobile phase C: Acetonitrile
(minutes)
0 to 15
After 15
Mobile
phase A
(vol%)
55 25
25
Mobile
phase B
(vol%)
30
30
Mobile
phase C
(vol%)
15 45
45

time of pirenzepine is about 8 minutes.
System suitability
Test for required detectability: Pipet 1 mL or the
standard solution, and add 5 mL of methanol and the
mobile phase A to make exactly 10 mL. Confirm that
the peak area of pirenzepine obtained from 10 L of
this solution is equivalent to 7% to 13% of that from l0
L of the standard solution.
System performance: Dissolve 0.1 g of phenylpiperazine hydrochloride in 10 mL of methanol. Mix 1
mL of this solution and 1 mL of the test solution, and
add 5 mL of methanol and the mobile phase A to make
solution under the above operating conditions, pirenzepine and phenylpiperazine are eluted in this order with
the resolution between these peaks being not less than 5.
System repeatability: When the procedure is repeated 6 times with l0 L of the standard solution under the above operating conditions, the relative standard deviation of the peak area of pirenzepine is not
more than 2.0%.
long as the retention time of pirenzepine beginning after the solvent peak.
Assay Weigh accurately about 0.2 g of Pirenzepine
Hydrochloride Hydrate, dissolve in 2 mL of formic acid,
add 60 mL of acetic anhydride, and titrate with 0.1
Endpiont Detection Method in Titrimetry). Perform a
blank determination in the same manner, and make any

= 14.14 mg of C19H21N5O22HCl
Piroxicam
O
O
S
CH3
N
CONH
OH
C15H13N3O4S: 331.35
Piroxicam contains not less than 97.0% and not more
than 103.0% of piroxicam (C15H13N3O4S), calculated
Description
Piroxicam is a grayish white to pale
brown or pale yellow powder and is odorless.

Piroxicam is sparingly soluble in acetic anhydride,
slightly soluble in acetonitrile, methanol or dehydrated
ethanol, very slightly soluble in glacial acetic acid, and

main peak areas, AT and AS , of the test solution and
Identification (1) Weigh 0.1 g of Piroxicam, dissolve

in a mixture of chloroform and methanol (1 : 1) to
Separately, weigh 0.1 g of Piroxicam RS, follow the
procedure for the preparation of the test solution and
on a plate (thickness: 0.25 mm) of silica gel for thinlayer chromatography. Develop the plate with a mixture
of toluene and glacial acetic acid (95 : 5) to a distance
of about 15 cm, air-dry the plate, develop again the
plate in the above solution as before, mark the solvent
front and air-dry the plate. Examine under ultraviolet
light (main wavelength: 254 nm): the principal spot
from the test solution shows the same Rf value as the
principal spot from the standard solution.
(2) Determine the absorption spectra of solutions of Piroxicam and Piroxicam RS, respectively, in methanolic
hydrochloric acid (1 in 1200) solution (1 in 100000):
both spectra exhibit maximum and minimum at the
same wavenumbers.
(3) Determine the infrared spectra of Piroxicam and Piroxicam RS, as directed in the paste method under the
Amount (mg) of piroxicam (C15H13N3O4S)

A
= amount (mg) of Piroxicam RS T
AS
Purity Heavy metalsProceed with about 1.0 g of

Piroxicam according to the Method 2 and perform the
Mobile phase: A mixture of buffer solution and methanol (55 : 45).
System suitability
above operating conditions, the symmetry factor of the
peak is not more than 1.5.
deviation of the peak areas of Piroxicam is not more
than 2.0%.
Buffer solutionDissolve 7.72 g of anhydrous citric acid in 400 mL of water and separately dissolve
5.35 g of dibasic sodium phosphate in 100 mL of water.
Add the phosphate solution to the citric acid solution,
dilute with water to make 1000 mL and mix.
tight containers.
Water Not more than 0.5%. (1 g, volumetric titration,

direct titration)
Assay Dissolve about 50 mg of Piroxicam, accurately
weighed, in 0.01 mol/L methanolic hydrochloric acid to
make 100 mL exactly. Transfer 10.0 mL of the solution
to the 100 mL volumetric flask, add 50 mL of 0.01
mol/L methanolic hydrochloric acid, 20.0 mL of water
and add 0.01 mol/L methanolic hydrochloric acid to
Piroxicam RS, dissolve in 0.01 mol/L methanolic hydrochloric acid to make exactly 100 mL. Transfer 10.0
mL of this solution to the 100 mL volumetric flask, add
50 mL of 0.01 mol/L methanolic hydrochloric acid,
20.0 mL of water and add 0.01 mol/L methanolic hydrochloric acid to make exactly 50 mL, and use this solution as the standard solution. Perform the test with 25
Piroxicam Capsules
Piroxicam Capsules contain not less than 92.5% and
not more than 107.5% of the labeled amount of piroxicam (C15H13N3O4S: 331.35).
Capsules, with Piroxicam.
Identification Powder the contents of the Piroxicam
Capsules, weigh a portion of the powder, equivalent to
20 mg of Piroxicam according to the labeled amount,
add 20 mL of a mixture of chloroform and methanol
(1 : 1), shake for 10 minutes, filter and use the filtrate
as the test solution. Proceed as directed in the Identification (3) under Piroxicam.
KP 9 775
Water Not more than 8.0%. (0.3 g, volumetric titration, direct titration)
O
CH3
O
H
Dissolution Test Perform the test with 1 tablet of Piroxicam Capsules at 50 revolutions per minute according to Method 1 under the Dissolution Test, using 900
mL of the first fluid of the Disintegration Test as a dissolution solution. Take the dissolved solution after 45
minutes from the start of the test, filter, dilute properly
with a dissolution solution, if necessary, and use this
solution as the test solution. Separately, weigh accurately a portion of Piroxicam RS, add methanol to obtain a solution having a known concentration of about
0.5 mg per mL and use this solution as the stock solution. Take a proper portion of the stock solution exactly,
dilute exactly with a dissolution solution to make a
known concentration and use this solution as the standard solution. Determine the absorbances of the test solution and the standard solution at the wavelength of a
maximum absorbance at about 333 nm.
The dissolution rate of Piroxicam Capsules in 45 minutes is not less than 75%.
ment.
Assay Transfer, as completely as possible, the contents of not less than 20 Proxicam Capsules to a suitable container and determine the average weight per
capsule. Mix the combined contents and transfer an accurately weighed portion, equivalent to about 50 mg of
piroxicam (C15H13N3O4S) according to labeled amount,
to 100 mL of a volumetric flask. Add 70 mL of 0.01
mol/L methanolic hydrochloric acid and mix with sonicator for 30 minutes. Dilute with 0.01 mol/L methanolic hydrochloric acid to make 100 mL and mix. Centrifuge this solution to obtain a clear solution. Transfer
10.0 mL of the solution so obtained to a volumetric
flask, add 50 mL of 0.01 mol/L methanolic hydrochloric acid and 20.0 mL of water and add 0.01 mol/L methanolic hydrochloric acid to make 100 mL, mix and
use this solution as the test solution. Proceed as directed in the Assay under Piroxicam.
Amount (mg) of piroxicam (C15H13N3O4S)

A
= amount (mg) of Piroxicam RS T
AS
tight containers.
Pivmecillinam Hydrochloride
CH3
CH3
CH3
CH3
HCl
S
H
C21H33N3O5SHCl: 476.03
Pivmecillinam Hydrochloride contains not less than
615 g (potency) per mg of mecillinam (C15H23N3O3S:
Description Pivmecillinam Hydrochloride is a white
to yellowish white crystalline powder, is odorless or
has a little bit of a characteristic odor.
Pivmecillinam Hydrochloride is very soluble in methanol, in glacial acetic acid, and in chloroform, freely soluble in water and in ethanol anhydrous, soluble in acetonitrile, slightly soluble in acetone, and practically insoluble in ether or in benzene.
Identification (1) Weigh 30 mg of Pivmecillinam
Hydrochloride, dissolve in 15 mL of water, add 2 mL of
hydroxylamine hydrochloride TS and 2 mL of 1 mol/L
sodium hydroxide TS, allow to stand for 5 minutes, and
add 3 mL of 1 mol/L hydrochloric acid TS and 1 mL of
ferric chloride TS and mix with shaking: a red-purple
color develops.
(2) To 1 mL of a solution of Pivmecillinam Hydrochloride (1 in 1000), add 10 mL of chromotrofic acid TS, heat for 3 minutes in water bath: a deep purple
color develops.
(3) Dissolve 50 mg of Pivmecillinam Hydrochloride in 10 mL of water, and add 1 mL of dilute nitric acid and one drop of silver nitrate TS: a white precipitate
develops.
D : +200 ~ +220 (1.0
g calculated on the anhydrous basis, water, 100 mL,
100 mm).
of Pivmecillinam Hydrochloride in 10 mL of water is
Assay Weigh accurately about 75 mg of Pivmecillinam Hydrochloride, dissolve in ethanol anhydrous to
make exactly 100 mL, pipet exactly 4 mL of this solution, and use as the test solution. Separately, weigh accurately about 75 mg of Pivmecillinam Hydrochloride
RS, dissolve in ethanol anhydrous to make exactly 100
mL, pipet exactly 4 mL of this solution, and use as the
standard solution. Perform the test with these solutions
as follows.
Transfer each of the test solution and the standard solu-
tion into two 100 mL glass-stoppered flasks, add 5.0

mL of 1 mol/L sodium hydroxide and allow to stand for
60 minutes, and add 5 mL of 1 mol/L hydrochloric acid
and 10 mL of 0.4 mol/L acetate buffer solution, pH 4.5.
To this solution add exactly 10.0 mL of 0.01 mol/L
iodine VS, stopper the flask, and allow to stand for exactly 40 minutes in the dark place, and titrate this solution with 0.01 mol/L sodium thiosulfate VS (indicator:
0.5 mL of starch TS), VT, VS. Separately, transfer each
of the test solution and the standard solution into a separate 100 mL glass-stoppered flasks, add 10 mL of 0.4
mol/L acetate buffer solution, pH 4.5. To this solution
add exactly 10.0 mL of 0.01 mol/L iodine VS, stopper
the flask, and allow to stand for exactly 40 minutes in
the dark place. To these solutions add 5 mL of of carbon tetrachloride, shake occasionly, titrate with 0.01
mol/L sodium thiosulfate VS, perform a blank determination, and make any necessary correction. Use 0.5 mL
of starch TS as an indicator and the end point is when
carbon tetrachloride layer and aqueous layer become
colorless.
Amount [g (potency)] of Pivmecillinam Hydrochloride
= Amount [g (potency)] of Pivmecillinam HydrochloV
ride RS T
VS
Polymyxin B Sulfate
R1
a
L-R2
L-Thr
L-R2
L-R2
D-Phe
L-Thr
L-R2
xH2SO4
L-R2
Polymyxin B1 R1 = 6-Methyloctanoic acid

R2 = L---Diaminobutyric acid
Polymyxin B2 R1 = 6-Methylheptanoic acid
R2 = L---Diaminobutyric acid
Thr: Threonine

500000 units of Poymyxin B Sulfate in 10 mL of water is between 5.0 and 7.5.
Sterility Test It meets the requirement, when Poymyxin B Sulfate is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Poymyxin B Sulfate is used in a sterile preparation,. Weigh
an appropriate amount of Poymyxin B Sulfate, dissolve
in Isotonic Sodium Chloride Injection to make a solution so that each mL contains 20000 units, and use the
solution as the test solution. The amount of injection is
1.0 mL of the test solution per kg of body weight of
rabbit.
L-Leu
a
Identification (1) To 5 mL of a solution of Poymyxin

B Sulfate (1 in 10) add 5 mL of sodium hydroxide solution (1 in10), add dropwisely 5 drops of a solution of
copper (II) sulfate (1 in 100) while shaking: a purple
color develops.
(2) Dissolve 2 mg of Poymyxin B Sulfate in 5 mL
of water, add 0.5 mL of ninhydrin solution (1 in 1000)
and 2 drops of pyridine and boil for 1 minute: a blue
color develops.
(3) Poymyxin B Sulfate responds to the Qualitative
Tests for sulfate.
a
L-R2
Poymyxin B Sulfate is freely soluble in water, very

slightly soluble in ethanol, and practically insoluble in
ether.
Phe: Phenylalanine
Leu: Leucine
Poymyxin B Sulfate is the sulfate of a mixture of peptide substances having antibacterial activity produced
by the growth of Bacillus polymyxa.
Poymyxin B Sulfate contains not less than 6000 units
(potency) per mg of polymyxin B (C55~56H96~98N16O13),
calculated on the dried basis
Description Poymyxin B Sulfate is a white to yellow-brown powder.

for seed and base layer- Use the medium in I 2 1) (5)
(2) Test organism- Esherichia coli NIHJ.

(3) Weigh accurately about 200000 units (potency)
of Poymyxin B Sulfate, and dissolve in 1 % phosphate
buffer solution, pH 6.0 to make a solution so that each
mL contains 10000 units (potency), take exactly a suitable amount of the solution, add 1 % phosphate buffer
solution, pH 6.0 to make solutions so that each mL contains 4000 units (potency) and 1000 units (potency),
and use these solutions as the high concentration test
solution and the low concentration test solution, respectively. Separately, weigh accurately about 200000 units
(potency) of Poymyxin B Sulfate, and dissolve in 1 %
phosphate buffer solution, pH 6.0 to make a solution so
that each mL contains 10000 units (potency), and use
the solution as the standard stock solution. Keep the
standard stock solution at not exceeding 5 C and use
within 14 days. Take exactly a suitable amount of the
standard stock solution before use, add 1 % phosphate
buffer solution, pH 6.0 to make solutions so that each
mL contains 4000 units (potency) and 1000 units (po-
KP 9 777
tency), and use these solutions as the high concentration standard solution and the low concentration standard solution, respectively. Perform the test with these
solutions according to the Cylinder-plate method (I 8)
tight containers.
Potassium Bromide
KBr: 119.00
Potassium Bromide, when dried, contains not less than
99.0% and not more than 101.0% of potassium bromide (KBr).
Description Potassium Bromide is colorless or white
crystal granules or crystalline powder and is odorless.
Potassium Bromide is freely soluble in water or glycerin, soluble in hot ethanol and slightly soluble in ethanol.
Identification A solution of Potassium Bromide (1 in
10) responds to the Qualitative Tests for potassium salt
and for bromide.
1.0 g of Potassium Bromide in 3 mL of water: the solution is clear and colorless.

hours).
Assay Weigh accurately about 0.4 g of Potassium
Bromide, previously dried and dissolve in 50 mL of
water. Add 10 mL of dilute nitric acid and exactly
measured 50 mL of 0.1 mol/L silver nitrate VS and titrate the excess silver nitrate with 0.1 mol/L ammonium
thiocyanate VS (indicator: 2 mL of ferric ammonium
sulfate TS). Perform a blank determination and make

= 11.900 mg of KBr
Potassium Canrenoate
H3C
(2) AlkaliDissolve 1.0 g of Potassium Bromide

in 10 mL of water, add 0.10 mL of 0.05 mol/L sulfuric
acid VS and 1 drop of phenolphthalein TS, heat to boiling and cool: no color develops.
(3) ChlorideMake a calculation from the result
obtained in the Assay: not more than 84.5 mL of 0.1
mol/L silver nitrate VS is consumed for 1 g of Potassium Bromide.
(4) SulfateProceed with 2.0 g of Potassium Bromide and perform the test. Prepare the control solution
than 0.024%).
(5) IodideDissolve 0.5 g of Potassium Bromide
in 10 mL of water, add 2 to 3 drops of ferric chloride
TS and 1 mL of chloroform and shake: no red-purple to
purple color develops in the chloroform layer.
(6) BromateDissolve 1.0 g of Potassium Bromide in 10 mL of freshly boiled and cooled water and
add 0.1 mL of potassium iodide TS, 1 mL of starch TS
and 3 drops of dilute sulfuric acid. Shake the mixture
gently and allow to stand for 5 minutes: no blue color
develops.
(7) Heavy metalsProceed with 2.0 g of Potassium Bromide according to Method 1 and perform the
(8) BariumDissolve 0.5 g of Potassium Bromide
in 10 mL of water, add 0.5 mL of dilute hydrochloric
acid and 1 mL of potassium sulfate TS and allow to
stand for 10 minutes: no turbidity is produced.
Potassium Bromide according to Method 1 and perform
H3C
OH
CH2CH2CO2K
C22H29KO4: 396.56
Potassium Canrenoate, when dried, contains not less
than 98.0% and not more than 102.0% of potassium
canrenoate (C22H29KO4).
Description Potassium Canrenoate occurs as a pale
yellowish white to pale yellow-brown, crystalline
powder.
Potassium Canrenoate is freely soluble in water, soluble in methanol, sparingly soluble in ethanol and
practically insoluble in chloroform or ether.
Identification (1) Dissolve 2 mg of Potassium Canrenoate in 2 drops of sulfuric acid: an orange color
develops. observe under ultraviolet light (main wavelength: 365 nm): the solution shows a yellow-green
fluorescence. Add 1 drop of acetic anhydride to this solution: the color of the solution changes to red.
Potassium Canrenoate and Potassium Canrenoate RS in
methanol (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(3) Determine the infrared spectra of Potassium
Canrenoate and Potassium Canrenoate RS, previously
wavenumbers.
KP 9 779
(4) The solution of Potassium Canrenoate (1 in 10)

responds to the Qualitative Tests (1) for potassium salt.
pH Dissolve 1.0 g of Potassium Canrenoate in 20 mL
D : Between -71 and 76 (after drying, 0.2 g, methanol, 20 mL, 100 mm).
0.5 g of Potassium Canrenoate in 5 mL of water: the
solution is clear and shows a pale yellow to light yellow color.
(2) Heavy metalsProceed with 2.0 g of Potassium
Canrenoate according to Method 2 and perform the test.
Potassium Canrenoate according to Method 3 and perform the test (not more than 2 ppm).
(4) CanrenonePlace 0.40 g of Potassium Canrenoate in a glass-stoppered centrifuge tube, cool in icewater to a temperature not higher than 5C, add 6 mL
of boric acid-potassium chloride-sodium hydroxide
buffer solution, pH 10.0, being cooled to a temperature
not higher than 5 C to dissolve and add 8 mL of water
being cooled to a temperature not higher than 5 C.
Add exactly 10 mL of chloroform, allow to stand for 3
minutes at a temperature not higher than 5 C, shake
vigorously for 2 minutes and contrifuge. Drain of the
water layer, collect 5 mL of the chloroform layer, transfer to a glass-stoppered centrifuge tube containing 3
mL of boric acid-potassium chloride-sodium hydroxide
buffer solution, pH 10.0, cooled to a temperaturenot
higher than 5 C and 4 mL of water cooled to a temperature not higher than 5 C, shake for 1 minute and contrifuge. Drain off the water layer, pipet 2.0 mL of the
chloroform layer and add chloroform to make exactly
10 mL. Determine the absorbance of this solution at
283 nm as directed under the Ultraviolet-visible Spectrophotometry: it is not more than 0.67.
hours).
Canrenoate, previously dried, dissolve in 75 mL of glacial acetic acid and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Use a solution of saturated potassium chloride-glacial acetic acid as the internal liquid.
correction.

= 39.656 mg of C22H29KO4
Potassium Chloride
KCl: 74.55
Potassium Chloride, when dried, contains not less than
99.0% and not more than 101.0% of potassium chloride
(KCl).
Description Potassium Chloride is a colorless or
white crystal or crystalline powder, is odorless and has
a saline taste.
Potassium Chloride is freely soluble in water, and practically insoluble in ethanol or ether.
A solution of Potassium Chloride (1 in 10) is neutral.
Identification A solution of Potassium Chloride (1 in
and for chloride.
1.0 g of Potassium Chloride in 5 mL of water: the solution is clear and colorless.
(2) Acid and alkaliDissolve 5.0 g of Potassium
Chloride in 50 mL of freshly boiled and cooled water
and add 3 drops of phenolphthalein TS: no red color is
observed. Then add 0.50 mL of 0.01 mol/L sodium hydroxide VS: a red color is observed.
(3) BromideDissolve 1.0 g of Potassium Chloride in water to make 100 mL. To 5 mL of the solution,
add 3 drops of dilute hydrochloric acid and 1 mL of
chloroform and add 3 drops of chloramine TS dropwise
while shaking: no yellow to yellow-red color is observed in the chloroform layer.
(4) IodideDissolve 0.5 g of Potassium Chloride
in 10 mL of water, add 3 drops of ferric chloride TS
and 1 mL of chloroform, shake, allow to stand for 30
minutes and shake again: no red-purple to purple color
is observed in the chloroform layer.
Chloride according to Method 1 and perform the test.
(6) Calcium and magnesiumDissolve 0.20 g of
Potassium Chloride in 20 mL of water, add 2 mL of
ammonia TS, 2 mL of ammonium oxalate TS and 2 mL
of dibasic sodium phosphate TS and then allow to stand
for 5 minutes: no turbidity is produced.
(7) SodiumDissolve 1.0 g of Potassium Chloride
in 20 mL of water and perform the Flame Coloration
Test (1): no persistent, yellow color is observed.
Potassium Chloride according to Method 1 and perform
hours).

Chloride, previously dried, dissolve in 50 mL of water
and titrate with 0.1 mol/L silver nitrate VS while shaking vigorously (indicator: 1 mL of potassium chromate
TS).

= 7.455 mg of KCl
Potassium Guaiacolsulfonate
SO 3K
OCH 3
OH
C7H7KO5S: 242.29
Potassium Guaiacolsulfonate contains not less than
98.5% and not more than 101.0% of potassium guaiacolsulfonate (C7H7KO5S), calculated on the anhydrous
basis.
Description Potassium Guaiacolsulfonate is a crystal
or crystalline powder and is odorless or has a slight,
characteristic odor and a slightly bitter taste.
Potassium Guaiacolsulfonate is freely soluble in water
or in formic acid, slightly soluble in methanol and practically insoluble in ethanol, in ether or in acetic anhydride.
Identification (1) Take 10 mL of a solution of Potassium Guaiacolsulfonate (1 in 100) and add 2 drops of
ferric chloride TS: a blue-purple color is observed.
(2) Dissolve separately 0.25 g of Potassium Guaiacolsulfonate and Potassium Guaiacolsulfonate RS in
water to make 500 mL each, to 10 mL each of these solutions, add phosphate buffer solution, pH 7.0, to make
100 mL each and use these solution as the test solution
and the standard solution, respectively. Determine the
absorption spectra of the test and the standard solutions
(3) A solution of Potassium Guaiacolsulfonate (1 in
10) responds to Qualitative Tests for potassium salt.
pH Dissolve 1.0 g of Potassium Guaiacolsulfonate in
20 mL of water: the pH of the solution is between 4.0
and 5.5.
1.0 g of Potassium Guaiacolsulfonate in 20 mL of water: the solution is clear and colorless.
(2) SulfatePerform the test with 0.8 g of Potassium Guaiacolsulfonate. Prepare the control solution
more than 0.030%).
Guaiacolsulfonate according to Method 1 and perform
Potassium Guaiacolsulfonate according to Method 1
(5) Related substancesDissolve 0.20 g of Potassium Guaiacolsulfonate in 200 mL of mobile phase and
test solution, add the mobile phase to make exactly 100
mL and use this solution as the standard solution. Perform the test with 5L each of the test solution and the
standard solution as directed under the Liquid Chromatography according to the following conditions. Determine each peak area obtained from the test solution and
the standard solution by the automatic integration method: the total area of peaks other than the peak of Potassium Guaiacolsulfonate from the test solution is not
larger than the peak area of Potassium Guaiacolsulfonate from the standard solution.
with dimethylaminopropylsilanized silica gel (5 m to
10 m in particle diameter).
about 30 C.
Mobile phase: A mixture of 0.05 mol/L monobasic
potassium phosphate VS and methanol (20 : 1).
time of Potassium Guaiacolsulfonate is about 10 minutes.
System suitability
System performance: Weigh 50 mg each of Potassium Guaiacolsulfonate and guaiacol and dissolve in
50 mL of the mobile phase. When the procedure is run
conditions, guaiacol and Potassium Guaiacolsulfonate
are eluted in this order with the resolution of their
Detection sensitivity: Adjust the sensitivity so
that the peak height of Potassium Guaiacolsulfonate
from 5 L of the standard solution is not less than 10
mm.
as the retention time of Potassium Guaiacolsulfonate.
Water Between 3.0% and 4.5% (0.3 g, direct titration).
Assay
Weigh accurately about 0.3 g of Potassium
KP 9 781
Guaiacolsulfonate, dissolve in 2.0 mL of formic acid,

add 50 mL of acetic anhydride and titrate with 0.1
= 24.229 mg of C7H7KO5S
Potassium Iodide
KI: 166.00
Potassium Iodide, when dried, contains not less than
99.0% and not more than 101.0% of potassium iodide
(KI).
Description Potassium Iodide is a colorless or white
crystal or a white crystalline powder.
Potassium Iodide is very soluble in water, soluble in
Potassium Iodide is slightly deliquescent in moist air.
Identification A solution of Potassium Iodide (1 in
and for iodide.
1.0 g of Potassium Iodide in 2 mL of water: the solution is clear and colorless.
(2) AlkaliDissolve 1.0 g of Potassium Iodide in
10 mL of freshly boiled and cooled water and add 0.50
mL of 0.005 mol/L sulfuric acid and 1 drop of phenolphthalein TS: no color is observed.
(3) Chloride, bromide and thiosulfateDissolve
0.20 g of Potassium Iodide in 5 mL of ammonia TS,
add 15.0 mL of 0.1 mol/L silver nitrate VS, shake for 2
minutes to 3 minutes and filter. To 10 mL of the filtrate,
add 15 mL of dilute nitric acid: no brown color is observed. The solution has no more turbidity than that of
Control solutionTake 0.30 mL of 0.01 mol/L hydrochloric acid VS, add 2.5 mL of ammonia TS and 7.5
mL of 0.1 mol/L silver nitrate VS and 15 mL of dilute
nitric acid.
(4) Nitrate, nitrite and ammoniumPlace 1.0 g of

Potassium Iodide in a test tube and add 5 mL of water,
5 mL of sodium hydroxide TS and 0.2 g of aluminum
wire. Insert the absorbent cotton in the mouth of the
test tube and place a piece of moistened red litmus paper on it. Heat the test tube carefully in a water-bath for
15 minutes: the gas evolved does not turn red litmus
paper to blue.
(5) CyanideDissolve 0.5 g of Potassium Iodide in

10 mL of water. To 5 mL of this solution, add 1 drop of
ferrous sulfate TS and 2 mL of sodium hydroxide TS,
warm and then add 4 mL of hydrochloric acid: no green
color is observed.
(6) IodateDissolve 0.5 g of Potassium Iodide in
10 mL of freshly boiled and cooled water and add 2
drops of dilute sulfuric acid and 1 drop of starch TS: no
blue color is observed immediately.
Iodide according to Method 1 and perform the test.
(8) BariumDissolve 0.5 g of Potassium Iodide in
10 mL of water, add 1 mL of dilute sulfuric acid and allow to stand for 5 minutes: no turbidity is produced.
(9) SodiumDissolve 1.0 g of Potassium Iodide in
10 mL of water and perform the Flame Coloration Test
(1): a yellow color is observed, but does not persist.
of Potassium Iodide according to Method 1 and perform the test (not more than 5 ppm).
hours).
Iodide, previously dried, in an iodine flask, dissolve in
10 mL of water, add 35 mL of hydrochloric acid and 5
mL of chloroform and titrate with 0.05 mol/L potassium iodate VS with shaking vigorously until the redpurple color of the chloroform layer disappears. The
end point is reached when the red-purple color does not
reappear in the chloroform layer within 5 minutes after
the layer has been decolorized.
Each mL of 0.05 mol/L potassium iodate VS

= 16.600 mg of KI
tight containers.
Potassium Permanganate
KMnO4: 158.03
Potassium Permanganate, when dried, contains not less
than 99.0% and not more than 101.0% of potassium
permanganate (KMnO4).
Description Potassium Permanganate, a dark purple
crystal, has a metallic luster.
Potassium Permanganate is soluble in water.
A solution of Potassium Permanganate (1 in 1000) has
a slightly sweet taste, astringent.
Identification A solution of Potassium Permanganate
(1 in 100) responds to the Qualitative Tests for permanganate.

Purity (1) Water-insoluble substancesDissolve 2.0
g of Potassium Permanganate, previously powdered, in
200 mL of water. Filter the insoluble substances
through a tared glass filter (G4), wash with water until
the last washing shows no color and dry at 105 for 2
hours: the residue is not more than 4 mg.
(2) ArsenicDissolve 0.40 g of Potassium Permanganate in 10 mL of water, add 1 mL of sulfuric acid,
add a strong Hydrogen Peroxide Solution until the solution remains colorless and evaporate on a sand-bath
nearly to dryness. Dissolve the residue in 5 mL of water
and perform the test with this solution as the test solution: the color produced is not more intense than the
following standard color (not more than 5 ppm).
Standard color To 10 mL of water, add 1 mL of
sulfuric acid and the same volume of strong Hydrogen
Peroxide Solution as used for the preparation of the test
solution. Evaporate the solution on a sand-bath nearly
to dryness, add 2.0 mL of standard arsenic solution and
water to make 5 mL and perform the test with this solution in the same manner as the test solution.
Loss on Drying Not more than 0.5% (1 g, silica gel,
18 hours).
Permanganate, previously dried, dissolve in water to
solution. Pipet 25.0 mL of 0.05 mol/L oxalic acid VS
into a Erlenmeyer flask, add 200 mL of diluted sulfuric
acid (1 in 20) and keep at a temperature between 30
and 35 . Transfer the test solution to a buret. Add
quickly 23 mL of the test solution from the buret to the
flask while shaking gently and then allow the flask to
stand until the red color disappears. Warm the mixture
to a temperature between 55 and 60 and continue
the titration slowly until the red color persists for 30
seconds.
Each mL of 0.05 mol/L oxalic acid VS

= 3.1607 mg of KMnO4
Povidone Iodine
N
Description Povidone Iodine is a dark red-brown

powder and has a characteristic odor.
Povidone Iodine is freely soluble in water or in dehydrated ethanol.
pHA solution of Povidone Iodine (1 in 100) is
Identification (1) To 10 mL of diluted starch TS (1 in
10), add 1 drop of a solution of Povidone Iodine (1 in
10): a deep blue color develops.
(2) To 1 mL of a solution of Povidone Iodine (1 in
100), add 1 mL of sodium thiosulfate TS and add 1 mL
of ammonium thiocyanate-cobaltous nitrate TS and 2
drops of 1 mol/L hydrochloric acid TS: a blue color develops and a blue precipitate is gradually produced.
0.30 g of Povidone Iodine in 100 mL of water: the solution is clear and brown.
(2) Heavy metalsProceed with 1.0 g of Povidone
Iodine according to Method 2 and perform the test.
Povidone Iodine according to Method 4 and perform
the test (not more than 2ppm).
(4) Iodide ionWeigh 0.5 g of Povidone Iodine,
dissolve in 100 mL of water and add sodium bisulfite
TS until the color of iodine completely disappears. To
this solution, add exactly 25 mL of 0.1 mol/L silver nitrate VS, shake well with 10 mL of nitric acid, titrate
the excess silver nitrate with 0.1 mol/L ammonium thiocyanate VS until a red-brown color develops and calculate the total amount of iodine (indicator: 1 mL of
ferric ammonium sulfate TS). Perform a blank determination and make any necessary correction.
Each mL of 0.1 mol/L ammonium thiocyanate VS

= 12.690 mg of I
Obtain the amount of iodide ion, calculated on the dried
basis, by deducting the amount (%) of available iodine
from the total amount (%) of iodine: it is not more than
6.6%.
hours).
CHCH2
O
Povidone Iodine is a complex of iodine with 1-vinyl-2pyrrolidone polymer. Povidone Iodine contains not less
than 9.0% and not more than 12.0% of available iodine
(I: 126.90) and not less than 9.5% and not more than
11.5% of nitrogen (N: 14.01), calculated on the dried
basis.
xI
(C6H9NO)nxI
Assay (1) Available iodineWeigh accurately about

0.5 g of Povidone Iodine, dissolve in 30 mL of water
and titrate with 0.02 mol/L sodium thiosulfate VS (in-
KP 9 783
dicator: 2 mL of starch TS).

= 2.5381 mg of I
(2) NitrogenWeigh accurately about 1.0 g of Povidone Iodine, dissolve in water to make exactly 50 mL
and use this solution as the test solution. Pipet exactly 1
mL of the test solution and perform the test as directed
under the Nitrogen Determination.
= 0.14007 mg of N
Pralidoxime Chloride
CH3
N
CH
NOH
Cl
C7H9ClN2O: 172.61
Pralidoxime Chloride contains not less than 97.0% and

not more than 102.0% of pralidoxime chloride
(C7H9ClN2O), calculated on the dried basis.
Povidone Iodine Topical

Solution
Description Pralidoxime Chloride is a white and pale

yellow crystalline powder and has no odor.
Pralidoxime Chloride is very soluble in water.
Pralidoxime Chloride is stable on the exposure to air.
Povidone Iodine Topical Solution is a solution of Povidone Iodine for external use. Povidone Iodine Topical
Solution contains not less than 85.0% and not more
than 120.0% of the labeled amount of iodine (I: 126.90).
Solutions, with Povidone Iodine.
Identification (1) Take a portion of Povidone Iodine
Topical Solution, equivalent to 50 mg of iodine according to the labeled amount, add water to make 100 mL.
Pipet 1 mL of this solution and add 1 mL of starch TS
and 9 mL of water: a deep blue color develops.
(2) Transfer 10 mL of Povidone Iodine Topical Solution to an Erlenmeyer flask, avoiding contact with the
neck of the flask. Cover the mouth of the flask with a
small disk of filter paper and wet it with 1 drop of
starch TS: no blue color develops within 60 seconds.
Alcohol Content According to Method 2 under the
Alcohol Number Determination Test, Povidone Iodine
Topical Solution contains not less than 90.0% and not
more than 110.0% of the labeled amount of alcohol.
pH
Assay Transfer an accurate volume of Povidone

Iodine Topical Solution, equivalent to about 50 mg of
iodine, to a glass-stoppered flask, add water to make 30
mL and titrate with 0.02 mol/L sodium thiosulfate VS
(indicator: 3 mL of starch TS). Perform a blank determination and make any necessary correction.

= 2.5380 mg of I
Identification (1) The retention time of the principal

peak from the test solution corresponds to that from the
standard solution, under the Assay.
(2) Determine the infrared spectra of Pralidoxime
Chloride and Pralidoxime Chloride RS, previously
dried, as directed in the paste method unter the Infrared
(3) A solution (1 in 10) responds to the Qualitative
Tests for chlorides.
Purity Heavy metalsProceed with 1.0 g of Pralidoxime Chloride according to Method 1 and perform
hours).
Assay Transfer about 62.5 mg of Pralidoxime Chloride, accurately weighed, to a flask, dissolve in water,
dilute with water to make 50 mL, mix and filter. Pipet
exactly 2 mL of the filtrate, add the mobile phase to
solution. Separately, dissolve a portion of Pralidoxime
Chloride RS, accurately weighed, in water to obtain a
known concentration of 1.25 mg per mL. Pipet exactly
2 mL of this solution, add the mobile phase to make
exactly 100 mL and use this solution as the standard solution. Perform the test with 15 L each of the test solution and the standard solution, according the following operating conditions as directed under the Liquid
Chromatography. Measure the peak areas, AT and AS, of
pralidoxime chloride for the test solution and the standard solution, respectivly.
Amount (mg) of pralidoxime chloride (C7H9ClN2O)
AT
= 2.5 C A
S
C: Concentration of pralidoxime chloride in the
standard solution (g/mL).
Column: A stainless steel column, about 3 mm to 5
mm, in inside diameter and about 25 cm in length,
packed with octadecylated silica gel for liquid chromatography (5 m in particle diameter).
Mobile phase: A mixture of acetonitrile and tetraethyl ammonium chloride (52 : 48).
System suitability
System performnace: Dissolve 0.65 mg of pyridine-2-aldoxime in 1 mL of water. To 2 mL of this solution, add 2 mL of a solution of pralidoxime chloride
RS containing 1.25 mg per mL and the mobile phase to
of this solution according to the above operating conditions, pyridine-2-aldoxime and pralidoxime chloride
their peaks being not less than 4.0, the number of theoretical plates being not less than 4000 and the symmetry factor being not more than 2.5.
above operating conditions, the relative standard deviation of the peak areas of pralidoxime is not more than
2.0%.
Tetraethylammonium chloride solutionDilute 3.4
mL of phosphoric acid (10 in 100), dissolve 0.17 g of
tetraethylammonium chloride, add water to make 1000
mL.
Dissolution Test Perform the test with 1 tablet of Pralidoxime Chloride Tablets at 100 revolutions per
Test, using 900 mL of water. Take the dissolved solution after 60 minutes from start of the test, filter, dilute
with the water, if necessary and use the solution as the
test solution. Separately, weigh accurately a portion of
Pralidoxime Chloride RS, dilute with the water to make
the same concentration as the test solution and use this
test solution and standard solution, using water as the
blank, to determin the absorbances at the wavelength of
a maximum absorption near 293 nm as directed under
the Ultraviolet-visible Spectrophtometry.
The dissolution rate of Pralidoxime Chloride Tablets in
60 minutes is not less than 55%.
ment.
Assay Weigh accurately not less than 20 Pralidoxime

Chloride Tablets and finely powder. Take an accurately
weighed portion of the powder, equivalent to about
0.25 g of pralidoxime chloride, add 150 mL of water
and mechanically swirl for 30 minutes. Add water to
make exactly 200 mL, centrifuge, pipet exactly 2 mL of
the supernatant and add the mobile phase to make exactly 100 mL and use this solution as the test solution.
Separately, weigh accurately about 50 mg of Pralidoxime Chloride RS and dissolve with water to make exactly 100 mL. Pipet exactly 5 mL of this solution, add
the standard solution. Proceed with the test solution and
the standard solution as directed in the Assay under
Pralidoxime Chloride.
Amount (mg) of pralidoxime chloride (C7H9ClN2O)

AT
= amount (mg) of Pralidoxime Chloride RS A 5
S
Pranoprofen
Pralidoxime Chloride Tablets
CH3
CCO 2H
Pralidoxime Chloride Tablets contain not less than

of pralidoxime chloride (C7H9ClN2OHCl: 172.61).
Tablets, with Pralidoxime Chloride.
Identification The retention time of the principal
peak from the test solution corresponds to that from the
standard solution, as directed in the Assay.
H
N
and enantiomer
C15H13NO3: 255.27
Pranoprofen, when dried, contains not less than 98.5%

and not less than 101.0% of pranoprofen (C15H13NO3).
Description Pranoprofen is a white to pale yellowish
KP 9 785
white crystalline powder.

Pranoprofen is freely soluble in dimethylformamide,
soluble in glacial acetic acid, sparingly soluble in methanol, slightly soluble in acetonitrile, in ethanol or in
acetic anhydride, very slightly soluble in ether and
A solution of Pranoprofen in dimethylformamide (1 in
Identification (1) Dissolve 20 mg of Pranoprofen
and Pranoprofen RS in 1 mol/L hydrochloric acid TS to
make 100 mL. Pipet 10 mL each of these solutions and
add water to make 100 mL. Determine the absorption
spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry using 0.1 mol/L hydrochloric acid TS as the blank: both spectra exhibit
similar intensities of absorption at the same wavelength.
(2) Determine the infrared spectra of Pranoprofen
and Pranoprofen RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Purity (1) ChlorideDissolve 0.5 g of Pranoprofen
in 40 mL of methanol and 6 mL of dilute nitric acid and
add water to make 50 mL. Perform the test using this
solution as the test solution. Prepare the control solution as follows: to 0.30 mL of 0.01 mol/L hydrochloric
acid, add 40 mL of methanol, 6 mL of dilute nitric acid
and water to make 50 mL (not more than 0.021%).
(2) Heavy metalsProceed with 2.0 g of Pranoprofen according to Method 4 and perform the test. Prepare the control solution with 2.0 mL of the standard
(3) Related SubstancesDissolve 50 mg of Pranoprofen in 50 mL of the mobile phase and use this solution as the test solution. Pipet exactly 1 mL of the test
standard solution as directed under the Liquid Chromatography according to the following operating conditions. Determine each peak area from both solutions by
the automatic integration method: the each area of the
peaks other than the principal peak from the test solution is not larger than peak area of the principal peak
from the standard solution and the total peak area of
them is not larger than twice of the peak area of the
principal peak from the standard solution.
about 25 C.
Mobile phase: Dissolve 7.02 g of sodium perchlorate in 1000 mL of water and adjust the pH to 2.5 with
perchloric acid. To 2 volumes of this solution, add 1
volume of acetonitrile.
time of pranoprofen is about 10 minutes.
System suitability
System performance: Dissolve 4 mg each of Pranoprofen and ethyl parahydroxybenzoate in 200 mL of
the mobile phase. When the procedure is run with 10
conditions pranoprofen and ethyl parahydroxybenzoate
Detection sensitivity: Adjust the detection sensitivity so that the peak height of pranoprofen from 10
L of the standard solution is between 10 mm and 20
mm.
Time span of measurement: About three times as
long as the retention time of pranoprofen.
P2O5, 4 hours).
Assay Weigh accurately about 0.4 g of Pranoprofen,
previously dried, dissolve in 70 mL of a mixture of
acetic anhydride and glacial acetic acid (7 : 3) and titrate with 0.1 mol/L perchloric acid VS (potentiometric
correction.

= 25.527 mg of C15H13NO3

tight containers.
Pravastatin Sodium
CO2Na
CH3
OH
OH
H
H
O
H
CH3
H3C
HO
C23H35NaO7 : 446.51
Pravastatin Sodium contains not less than 98.5% and
not more than 101.0% of pravastatin sodium
(C23H35NaO7), calculated on the anhydrous and solvent-free basis.

Description Pravastatin Sodium is a white to yellowish white, powder or crystalline powder.
Pravastatin Sodium is freely soluble in water or in methanol, and soluble in ethanol.
Pravastatin Sodium is hygroscopic.
of solutions of Pravastatin Sodium and Pravastatin Sodium RS (1 in 100,000) as directed under the Ultraviolet-visible Spectrophotometry : both spectra exhibit
(2) Determine the infrared absorption spectra of Pravastatin Sodium as directed in the potassium bromide
disk method under the Infrared Spectrophotometry: it
exhibits absorption at the wavenumbers of about 2970
cm-1, 2880 cm-1, 1727 cm-1 and 1578 cm-1.
(3) A solution of Pravastatin Sodium (1 in 10) responds to the Qualitative Tests (1) for sodium salt.
D : Between +153
and +159 (0.1 g calculated on the anhydrous and solvent-free basis, water, 20 mL, 100 mm).
of Pravastatin Sodium in 20 mL of freshly boiled and
cooled water is between 7.2 and 8.2.
Purity (1) Heavy metalsProceed with 1.0 g of Pravastatin Sodium according to Method 2, and perform
Standard Lead Solution (not more than 10 ppm).
(2) Related substancesDissolve 0.10 g of Pravastatin Sodium in 100 mnL of a mixture of water and methanol (11 : 9), and use this solution as the test solution.
Pipet 10 mL of the test solution, add the mixture of water and methanol (11 : 9) to make exactly 100 mL. Pipet 5 mL of this solution, add the mixture of water arid
methanol (11:9) to make exactly 100 mL, and use this
solution as the standard solution. Perfom the test with
10 L each of the test solution and standard solution as
directed under Liquid Chromatography according to the
the automatic integration method: the area of the peak
other than pravastatin form the test solution is not larger than 0.2 times the peak area of pravastatin from the
standard solution, and the total area of the peaks other
than pravastatin form the test solution is not larger than
the peak area of pravastatin from the standard solution.
Keep the test solution and the standard solution at not
over than 15 C.
Operating condition
System suitability
of the standard solution add a mixture of water and me-
thanol (11 : 9) to make exactly 50 mL. Confirm that the

peak area of pravastatin obtained with 10 L of this solution is equivalent to 7% to 13% of that with 10 L of
System performance: Dissolve 5 mg of Pravastatin Sodium in 50 mL of the mixture of water and methanol (11 : 9). When the procedure is run with 10 L
the number of theoretical plates and the symmetry factor of the peak of pravastatin are not less than 3500 and
not more than 1 .6, respectively.
above operating conditions, the relative standard deviation of the peak area of pravastatin is not more than
2.0%.
long as the retention time of pravastatin beginning after
the solvent peak.
Assay Weigh accurately about 0.1 g of Pravastatin
Sodium and dissolve in a mixture of water and methanol (11 : 9) to make exactly 100 mL. Pipet exactly 10
mL of this solution, add exactly 10 mL of the internal
standard solution and the mixture of water and methanol (11 : 9) to make exactly 100 mL and use this solution as the test solution. Separately, weigh accurately
about 30 mg of Pravastatin 1,1,3,3-Tetramethylbutyl
amine RS (previously determine the water with 0.5 g
by direct titration in volumetric titration), dissolve in
the mixture of water and methanol (1 1 : 9) to make exactly 25 mL. Proceed with exactly 10 L of this solution in the same manner for the preparation of the test
solution, and use the solution so obtained as the standard solution. Perform the test with 10 L each of the
test solution and standard solution as directed under
conditions, and determine the ratios, QT and QS, of the
peak area of pravastatin to that of the internal standard.
Amount (mg) of pravastatin sodium (C23H35NaO7)

QT
= WS Q 4 1.0518
S
WS: Amount (mg) of Pravasiatin 1,1,3,3Tetramethylbutylamine RS, calculated on the anhydrous basis
Internal sandard solutionA solution of ethyl parahydroxybenoate in the mixture of water and methanol
(11 : 9) (3 in 4000).
(wavelength: 238 tim).
diameter and 15 cm in length, packed with octadecylsi-
KP 9 787
lanized silica gel for liquid chromatography (5 m in

particle diameter).
about 25 C.
Mobile phase: A mixture of water, methanol, glacial
acetic acid and triethylamine (550 : 450 : 1 : 1).
time of pravastatin is about 21 minutes.
System suitability
operating condition, the internal standard and pravastatin are eluted in this order with the resolution between
times with l0 L of the standard solution under the
above operating conditions, the relative standard deviation of the ratio of the peak area of pravastatin to that of
Prazepam
CH2
O
N
Cl
C19H17ClN2O: 324.80
Prazepam, when dried, contains not less than 98.5%
and not more than 101.0% of prazepam (C19H17ClN2O).
Description Prazepam is a white to pale yellow crystal or crystalline powder and is odorless.
Prazepam is freely soluble in acetone, soluble in acetic
anhydride, sparingly soluble in dehydrated ethanol or in
Identification (1) Dissolve 10 mg of Prazepam in 3
mL of sulfuric acid and observe under ultraviolet light
(main wavelength: 365 nm): the solution shows a
grayish blue fluorescence.
(2) Dissolve 10 mg each of Prazepam and Prazepam RS in 1000 mL of a solution of sulfuric acid in dehydrated ethanol (3 in 1000) and determine the absorption spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(3) Determine the infrared spectra of Prazepam and
Prazepam RS, previously dried, as directed in the po-
tassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
(4) Perform the Flame Coloration Test (2) with Prazepam: a green color develops.
Melting Point
Purity (1) ChlorideTake 1.0 g of Prazepam, add

50 mL of water, allow to stand for 1 hour with occasional shaking and filter. To 20 mL of the filtrate, add 6
mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution.
Prepare the control solution with 40 mL of 0.0l mol/L
hydrochloric acid VS (not more than 0.036%).
(2) SulfateTo 20 mL of the filtrate obtained in (1),
add 1 mL of dilute hydrochloric acid and water to make
50 mL. Perform the test using this solution as the test
(3) Heavy metalsProceed with 2.0 g of Prazepam
Prazepam according to Method 3 and perform the test
(5) Related substancesDissolve 0.40 g of Prazepam in 10 mL of acetone and use this solution as the
test solution. Pipet exactly 1 mL of the test solution and
add acetone to make exactly 20 mL. Pipet exactly 1 mL
of this solution, add acetone to make exactly 25 mL and
mixture of chloroform and acetone (9 : 1) to a distance
of about 10 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots
hours).
Assay Weigh accurately about 0.4 g of Prazepam,

= 32.480 mg of C19H17ClN2O

Prazepam Tablets
Prazepam Tablets contain not less than 93.0% and not
more than 107.0% of the labeled amount of prazepam
(C19H17ClN2O: 324.80).
the Tablets, with Prazepam.
Identification (1) Take a portion of powdered Prazepam Tablets, equivalent to 50 mg of Prazepam according to the labeled amount, add 25 mL of acetone, shake
well and filter. Take 5 mL of the filtrate, evaporate on a
water-bath to dryness and dissolve the residue in 3 mL
of sulfuric acid. With this solution, proceed as directed
in the Identification (1) under Prazepam.
(2) Take a portion of powdered Prazepam Tablets,
equivalent to 20 mg of prazepam according to the labeled amount, add 200 mL of a solution of sulfuric acid
in dehydrated ethanol (3 in 1000), shake well and filter.
To 5 mL of the filtrate and add a solution of sulfuric acid in dehydrated ethanol (3 in 1000) to make 50 mL,
and determine the absorption spectrum of this solution
as directed under the Ultraviolet-visible Spectrophotometry: it exhibits maxima between 241 nm and 245 nm,
between 283 nm and 287 nm and between 363 nm and
367 nm and minima between 263 nm and 267 nm and
between 334 nm and 338 nm.
Dissolution Test Proceed with 1 tablet of Prazepam
Tablets according to Method 1 in the Dissolution Test
and perform the test, using 900 mL of 0.1 mol/L hydrochloric acid TS at 100 rotations per minute. After 30
minutes from the start of the test, separate 20 mL or
more of the dissolved solution and filter with a membrane filter with pore size not more than 0.8 m. Discard the first 10 mL of the filtrate, measure exactly the
subsequent V mL of the filtrate, add 0.1 mol/L hydrochloric acid TS to make exactly V mL so that each mL of
this solution might contain about 5 g of Prazepam
(C19H17ClN2O) according to the labeled amount and
accurately about 5 mg of Prazepam RS, previously
dried at 105 C for 2 hours, add 200 mL of 0.1 mol/L
hydrochloric acid TS and dissolve with shaking, or by
ultrasonication, if necessary, add 0.1 mol/L hydrochloric acid TS to make exactly 1000 mL and use this solution as the standard solution. Determine the absorbances, AT and AS, of the test solution and the standard
The dissolution rate of Prazepam Tablets in 30 minutes
Dissolution rate (%) of prazepam (C19H17ClN2O) to the

90
AT
V'
labeled amount = WS A V C
S
WS: Amount (mg) of Prazepam RS,

C: Labeled amount (mg) of
(C19H17ClN2O) in each tablet.
ment.
prazepam

Prazepam Tablets. Weigh accurately a portion of the
powder, equivalent to about 50 mg of prazepam
(C19H17ClN2O), add 30 mL of acetone, shake well, centrifuge and separate the supernatant. Repeat the same
procedure twice with 30 mL each of acetone, combine
all the supernatants and evaporate on a water-bath to
dryness. Dissolve the residue in 50 mL of a mixture of
acetic anhydride and anhydrous acetic acid (7 : 3) and
correction.

= 6.496 mg of C19H17ClN2O
Precipitated Calcium
Carbonate
CaCO3: 100.09
Precipitated Calcium Carbonate, when dried, contains
not less than 98.5% and not more than 101.0 % of calcium carbonate (CaCO3).
Description Precipitated Calcium Carbonate occurs
as a white, fine crystalline powder, is odorless and
tasteless.
Precipitated Calcium Carbonate is practically insoluble
in water (but its solubility in water increased in the
presence of carbon dioxide),and practically insoluble in
Precipitated Calcium Carbonate dissolves with effervescence in dilute acetic acid, in dilute hydrochloric acid or in dilute nitric acid.
Identification (1) Dissolve 0.5 g of Precipitated Calcium Carbonate in 10 mL of dilute hydrochloric acid,
boil, then cool and neutralize with ammonia TS: the solution responds to the Qualitative Tests for calcium salt.
(2) Precipitated Calcium Carbonate responds to the
Qualitative Tests (1) for carbonate.
Purity (1) Acid-insoluble substancesTo 5.0 g of
Precipitated Calcium Carbonate, add 50 mL of water,
then add 20 mL of hydrochloric acid drop-wise with
KP 9 789
stirring, boil for 5 minutes, cool, add water to make 200

mL and filter through filter paper for Assay. Wash the
residue until the last washing shows no turbidity with
silver nitrate TS and ignite the residue together with the
filter paper: the weight of the residue is not more than
10.0 mg.
(2) Heavy metalsMix 2.0 g of Precipitated Calcium Carbonate with 5 mL of water, add slowly 6 mL
of dilute hydrochloric acid and evaporate on a waterbath to dryness. Dissolve the residue in 50 mL of water
and filter. To 25 mL of the filtrate, add 2 mL of dilute
acetic acid, 1 drop of ammonia TS and water to make
50 mL and perform the test using this solution as the
test solution. Prepare the control solution as follows:
evaporate 3 mL of hydrochloric acid on a water-bath to
dryness and add 2 mL of dilute acetic acid, 2.0 mL of
standard lead solution and water to make 50 mL (not
more than 20 ppm).
(3) BariumMix 1.0 g of Precipitated Calcium
Carbonate with 10 mL of water, add drop-wise 4 mL of
hydrochloric acid with stirring, boil for 5 minutes, cool,
add water to make 40 mL and filter. With the filtrate,
perform the test as directed under Flame Coloration
Test (1): no green color appears.
(4) Magnesium and alkali metalsDissolve 1.0 g
of Precipitated Calcium Carbonate in a mixture of 20
mL of water and 10 mL of dilute hydrochloric acid,
boil, neutralize with ammonia TS and add ammonium
oxalate TS until precipitation of calcium oxalate is
completed. Heat the mixture in a water-bath for 1 hour,
cool, dilute with water to make 100 mL, shake well and
filter. To 50 mL of the filtrate, add 0.5 mL of sulfuric
acid, evaporate to dryness and ignite at 600 C to a
constant mass: the weight of the residue is not more
than 5.0 mg.
(5) ArsenicMoisten 0.40 g of Precipitated Calcium Carbonate with 1 mL of water, then dissolve in 4
mL of dilute hydrochloric acid, use this solution as the
test solution and perform the test (not more than 5 ppm).
hours).
Assay Weigh accurately about 0.12 g of Precipitated
Calcium Carbonate, previously dried and dissolve in 20
mL of water and 3 mL of dilute hydrochloric acid. Add
80 mL of water, 15 mL of a solution of potassium hydroxide (1 in 10) and 50 mg of NN indicator and titrate
immediately with 0.05 mol/L disodium ethylenediaminetetraacetate VS until the color of the solution changes
from red-purple to blue.
Each mL of 0.05 mol/L disodium ethylenediaminetetraacetate VS = 5.004 mg of CaCO3

Prednisolone
O
H
H3C
HO
CH2OH
OH
H3C
C21H28O5: 360.44
Prednisolone, when dried, contains not less than 97.0%
and not more than 102.0% of prednisolone (C21H28O5).
Description Prednisolone is a white, crystalline
Prednisolone is soluble in methanol or ethanol, slightly
soluble in ethyl acetate or chloroform and very slightly
soluble in water.
Identification (1) Take 2 mg of Prednisolone, add 2
mL of sulfuric acid and allow to stand for 2 to 3 minutes: a deep red color, without fluorescence, develops.
To this solution, add 10 mL of water cautiously: the
color disappears and a gray, flocculent precipitate is
produced.
(2) Determine the infrared spectra of Prednisolone
and Prednisolone RS, previously dried, as directed in
Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers. If any difference appears, dissolve each in ethyl acetate, evaporate to dryness and repeat the test on the residues.
D : Between +113
and +119 (after drying, 0.2g, ethanol, 20 mL, 100 mm).
Purity (1) SeleniumTo about 0.10 g of Prednisolone add 0.5 mL of a mixture of perchloric acid and
sulfuric acd (1 : 1) and 2 mL of nitric acid and heat on a
water bath until no more brown gas evolves and the solution becomes to be a pale yellow clear solution. After
cooling, add 4 mL of nitric acid to this solution, then
as the test solution. Separatly, pipet exactly 3 mL of selenium standard solution, add 0.5 mL of a mixture of
perchloric acid and sulfuric acid (1 : 1) and 6 mL of nitric acid, then add water to make exactly 50 mL and use
this solution as the stndard solution. Perform the test
with the test solution and the standard solution as directed under the Atomic Absorption Spectrophotometry
according to the following operating conditions and determine constant absorbances, AT and AS, obtained on a
recorder after rapid increasing of the absorption: AT is
smaller than AS (not more than 30 ppm). Perform the

test by using a hydride generating system and a thermal
absorption cell.
Lamp: A selenium hollow cathode lamp
Temperature of sample atomizer: When an electric
furnace is used, about 1000 C
Carrier gas: Nitorgen or Argon.
(2) Related substancesDissolve about 20 mg of
Prednisolone, dissolve in exactly 2 mL of a mixture of
methanol and chloroform (1 : 1) and use this solution as
the test solution. Separately, dissolve 20 mg of Hydrocortisone RS and 10 mg of Prednisolone Acetate RS
each in a mixture of methanol and chloroform (1 : 1) to
make exactly 100 mL and use these solutions as the
standard solution (1) and the standard solution (2). Perform the test with the test solution and the standard solutions (1) and (2) as directed under the Thin-layer
Chromatography. Spot 5 L each of the test solution,
the standard solutions (1) and (2) on a plate of silica gel
mixture of acetone, toluene and diethylamine (55 : 45 :
2) to a distance of about 15 cm and air-dry the plate (do
not dip the filter paper in the developing vessel). Spray
evenly alkaline blue tetrazolium TS on the plate: the
spots from the test solution corresponding to those
from the standard solutions (1) and (2) are not more intense than the spots from the standard solutions (1) and
(2) and no spots other than the principal spot, hydrocortisone and prednisolone acetate appear from the test solution.
3 hours).
Assay Dissolve about 25 mg each of Prednisolone
and Prednisolone RS, previously dried and accurately
weighed, in 50 mL of methanol, add 25.0 mL of the internal standard solution to each and add methanol to
make exactly 100 mL. To 1.0 mL each of these solution
of the peak area of prednisolone to that of the internal
standard, for the test solution and the standard solution,
respectively.
Amount (mg) of prednisolone(C21H28O5)

QT
= amount (mg) of Prednisolone RS Q
S
Internal standard solutionA solution of methyl
parahydroxybenzoate in methanol (1 in 2000).
fluorosilanized silica gel for liquid chromatography (5
about 40 C.
Mobile phase: A mixture of water and methanol
(13 : 7).
time of prednisolone is about 15 minutes.
System suitability
System performance: Dissolve 25 mg of Prednisolone and 25 mg of hydrocortisone in 100 mL of methanol. To 1 mL of this solution add the mobile phase to
this solution under the above operating conditions, hydrocortisone and prednisolone are eluted in this order
with the resolution between these peaks being not less
than 1.5.
above operating conditions, the relative standard deviation of the ratios of the peak area of prednesolone to
that of the internal standard is not more than 1.0 %.
Prednisolone Tablets
Prednisolone Tablets contain not less than 90.0% and
not more than 110.0% of the labeled amount of prednisolone (C21H28O5: 360.45).
Tablets, with Prednisolone.
Identification (1) Weigh a portion of powdered
Prednisolone Tablets, equivalent to 50 mg of prednisolone according to the labeled amount, add 10 mL of
chloroform, shake for 15 minutes, and filter. Evaporate
the filtrate on a water-bath to dryness. Dry the residue
at 105C for 1 hour, and proceed with the residue as directed in the Identification (1) under Prednisolone.
(2) Determine the infrared spectra of the residue in
(1) and Prednisolone RS, previously dried, as directed
in the potassium brimide disk method under Infrared
Spectrophotometry : both spectra exhibit similar intensities of absorption at the same wavenumbers. If any
difference appears, dissolve the residue and Prednisolone RS in ethyl acetate, evaporate to dryness, and repeat the test on the residues.
Dissolution Test Take 1 tablet of Prednisolone Tablets, perform the test as directed in Method 2 under the
Dissolution Test at 100 revolutions per minute, using
KP 9 791
900 mL of water as the dissoution solution. After 20

minutes from stat of the test, take 20 mL or more of the
dissolved solution, and filter through a membrane filter
with a pore size of 0.8 m or less. Discard the first 10
mL of the filtrate, and use the subsequent filtrate as the
test solution. Weigh accurately about 10 mg of Prednisolone RS, previously dried at 105 C for 3 hours, and
dissolve in ethanol to make exactly 100 mL. Pipet exactly 5 mL of this solution, add water to make exactly
Determine the absorbances, AT and AS, of the test solution and the standard solution, respectively, at the wavelength of maximum absorption at about 242 nm as
directed under the Ultraviolet-visible Spectrophotometry.
The dissolution rate of Prednisolone Tablets in 20 minutes is not less than 70%.
first 3 mL of the filtrte, and use the subsequent filtrate

25 mg of Prednisolone RS, previously dried at 105 C
for 3 hours, dissolve in 50 mL of methanol, add 25.0
mL of the internal standard solution, and add methanol
to make exactly 100 mL. To 1.0 mL of this solution add
the mobile phase to make exactly 10 mL, and use this
solution as the standard solution. Proceed as directed in
the Assay under Prednisolone.
Amount (mg) of prednisolone (C21H28O5)
1
QT
= amount (mg) of Prednisolone RS Q 5
S
Prednisolone Acetate

45
AT
of Prednisolone (C21H28O5) = WS A C
S
H3C
WS: Amount (mg) of Prednisolone RS,

C: Labeled amount (mg) of prednisolone (C21H28O5) in each tablet.
HO
H3C

1
AT
V
= amount (mg) of Prednisolone RS A 10 x
S
Prednisolone Tablets using an agate mortar. Weigh accurately a portion of the powder, equivalent to about 5
mg of prednisolone (C21H28O5), add 1 mL of water, and
shake gently. Add 5.0 mL of the internal standard solution and 15 mL of methanol, and shake vigorously for
20 minutes. To 1.0 mL of this solution add the mobile
phase to make exactlty 10 mL, and filter through a
membrane filter with pore size of 0.45 m. Discard the
CH2O
OH
CH3
Uniformity of Dosage Units It meets the requirement when the content uniformity test is performed according to the following procedure. Take 1 tablet of
Prednisolone Tablets, and shake with 10 mL of water
until the tablet is disintegrated. Add 50 mL of methanol,
shake for 30 minutes, add methanol to make exactly
100 mL, and centrifuge this solution. Pipet x mL of the
supernatant liquid, add methanol to make exactly V mL
to provide a solution that contains about 10 g of prednisolone (C21H28O5) per mL, and use this solution as
mg of Prednisolone RS, previously dried at 105 C for
3 hours, dissolve in 10 mL of water and 50 mL of methanol, and add methanol to make exactly 100 mL. Pipet exactly 5 mL of this solution, add methanol to make
exactly 50 mL, and use this solution as the standard solution. Determine the absorbances, AT and AS, of the
242 nm as directed under the Ultraviolet-visible Spectrophotometry.
C23H30O6: 402.48
Prednisolone Acetate, when dried, contains not less
than 96.0% and not more than 102.0% of prednisolone
acetate (C23H30O6).
Description Prednisolone Acetate is a white, crystalline powder.
Prednisolone Acetate is slightly soluble in methanol, in
ethanol, in dehydrated ethanol or in chloroform and
Identification (1) Take 2 mg of Prednisolone, add 2
mL of sulfuric acid and allow to stand for 2 to 3 minutes: a deep red color, without fluorescence, develops.
To this solution, add 10 mL of water cautiously: the
color disappears and a gray, flocculent precipitate is
produced.
Acetate and Prednisolone Acetate RS, previously dried,
similar intensities of absorption at the same wavenumbers. If any difference appears, dissolve each in
ethanol, evaporate the anhydrous ethanol to dryness
and repeat the test on the residues.
D : Between +128
and +137 (after drying, 70 mg, methanol, 20 mL, 100
mm).

Purity
Related substancesDissolve 0.20 g of
Prednisolone Acetate in exactly 10 mL of a mixture of
chloroform and methanol (9 : 1) and use this solution as
the test solution. Separately, dissolve 20 mg each of
prednisolone, cortisone acetate and hydrocortisone acetate in a mixture of chloroform and methanol (9 : 1) to
make exactly 10 mL and use this solution as the standard solution. Perform the test with the the test solution
and the standard solution as directed under the Thinlayer Chromatography. Spot 5 L each of the test solution and the standard solution on plate of silica gel with
a fluorescent indicator for thin-layer chromatography.
Develop the plate with a mixture of dichloromethane,
ether, methanol and water (385 : 75 : 40 : 6) to a distance of about 15 cm and air-dry the plate. Examine
under ultraviolet light (wavelength: 254 mm): the spots
from the test solution corresponding to those from the
standard solution are not more intense than the spots
from the standard solution and any spot other than the
principal spot, prednisolone, cortisone acetate and hydrocortisone acetate from the test solution do not appear.

time of prednisolone acetate is about 10 minutes.
System suitability
operating conditions, prednisolone acetate and the internal standard are eluted in this order with a resolution
between their peaks being not less than 10.0.
above operating conditions, the relative standard deviation of the ratios of the peak height of Prednisolone
Acetate to that of the internal standard is not more than
1.0 %.
Packing and Storage Preserve in tight containers.
Prednisolone Sodium Succinate

for Injection
O

3 hours).
H3C
HO
O
CH2O
CH2CH2CO2Na
OH
H
H3C

H
Assay Dissolve about 10 mg each of Prednisolone

Acetate and Prednisolone Acetate RS, previously dried
and accurately weighed, in 60 mL each of methanol,
add exactly 2 mL each of the internal standard solution,
then add methanol to make 100 mL and use these solutions as the test solution and the standard solution, respectively. Perform the test with 10 L each of the test
peak height of prednisolone acetate to that of the internal standard, for the test solution and the standard solution, respectively.
Amount (mg) of prednisolone acetate (C23H30O6)

QT
= amount (mg) of Prednisolone Acetate RS Q
S
Internal standard solutionA solution of butyl phydrosybenzoate in methanol (3 in 1000).
octadecylsilanized silica gel (5 m in particle diameter).
about 25 C.
(3 : 2).
C25H31NaO8: 482.50
Prednisolone Sodium Succinate for Injection is a preparation for injection which is reconstituted before use.
Prednisolone Sodium Succinate for Injection contains
not less than 72.4% and not more than 83.2% of prednisolone sodium succinate (C25H31NaO8: 482.51) and
the equivalent of not less than 90.0% and not more than
110.0% of the labeled amount of prednisolone
(C21H28O5: 360.44). The amount of Prednisolone Sodium Succinate for Injection is labeled as the amount of
prednisolone (C21H28O5).
Method of Preparation Prepare as directed under Injections, with Prednisolone Succinate and Dried Sodium Carbonate or Sodium Hydroxide. Prednisolone
Sodium Succinate for Injection contains a suitable buffering agent.
Description Prednisolone Sodium Succinate for Injection is a white powder or porous, friable mass.
Prednisolone Sodium Succinate for Injection is freely
soluble in water.
Prednisolone Sodium Succinate for Injection is hygroscopic.
Identification (1) Take 2 mg of Prednisolone Sodium
Succinate for Injection add 2 mL of sulfuric acid and
allow to stand for 2 to 3 minutes: a deep red color,
without fluorescence, develops. To this solution add 10
KP 9 793
mL of water cautiously: the color disappears and a gray,

flocculent precipitate is formed.
(2) Dissolve 10 mg of Prednisolone Sodium Succinate for Injection in 1 mL methanol and add Fehlings
TS and heat: an orange to red precipitate is formed.
(3) Dissolve 0.1 g of Prednisoione Sodium Succinate for Injection in 2 mL of sodium hydroxide TS, allow to stand for 10 minutes and filter. Add 1 mL of dilute hydrochloric acid to the shake, filtrate, if necessary.
Adjust the solution with diluted ammonia TS (1 in 10)
to a pH of about 6 and add 2 to 3 drops of ferric chloride TS: a brown precipitate is formed.
(4) Prednisolone Sodium Succinate for Injection responds to the Qualitative Tests (1) for sodium salt.
pH Dissolve 1.0 g of Prednisolone Sodium Succinate
for Injection in 40 mL of water: the pH of the solution
Purity Clarity and color of solutionDissolve 0.25
g of Prednisolone Sodium Succinate for Injection in 10
mL of water: the solution is clear and colorless.
Uniformity of Dosage Units It meets the requirement.
Assay Take a number of sealed containers of Prednisolone Sodium Succinate for Injection, equivalent to
about 0.10 g of prednisolone (C21H28O5) and dissolve
the contents in a suitable amount of diluted methanol (1
in 2) and transfer to a volumetric flask. Wash each container with diluted methanol (1 in 2), collect the washings in the volumetric flask and add diluted methanol
(1 in 2) to make exactly 100 mL. Pipet exactly 4 mL of
this solution, add diluted methanol (1 in 2) to make exactly 50 mL. Pipet exactly 5 mL of this solution, add
exactly 5 mL of the internal standard solution, mix by
shaking and use this solution as the test solution. Separately, weigh accurately about 25 mg of Prednisolone
Succinate RS, previously dried in a desiccator for 6
hours (in vacuum, P2O5, 60 C), dissolve in methanol to
make exactly 25 mL. Pipet exactly 5 mL of this solution. add diluted methanol (1 in 2) to make exactly 50
mL. Pipet exactly 5 mL of this solution, add exactly 5
mL of the internal standard solution, mix by shaking
the test with 10 L of the test solution and the standard
calculate the ratios, QT and QS, of the peak area of
prednisolone succinate to that of the internal standard
Amount (mg) of prednisolone sodium succinate

(C25H31NaO8) = amount (mg) of Prednisolone
QT
Succinate RS Q 5 1.0477
S

= amount (mg) of prednisolone sodium succinate
(C25H31NaO8) 0.7470
Internal standard solutionA solution of propyl phydroxybenzoate in diluted methanol (1 in 2) (1 in
25000).
about 25 C.
Mobile phase: Dissolve 0.32 g of tetra nbutylammonium bromide, 3.22 g of sodium dibasic
phosphoric acid and 6.94 g of potassium monobasic
phosphoric acid in 1000 mL of water. To 840 mL of this
solution, add 1160 mL of methanol.
time of prednisolone succinate is about 15 minutes.
System suitanility
System performace: When the procedure is run
operating conditions, prednisolone succinate and the internal standard are eluted in this order with the resolution between their peaks being not less than 6.0.
above operating conditions, the relative standard deviation of the ratios of the peak area of Prednisolone Succinate to that of the internal standard is not more than
1.0 %.
tainers.
Prednisolone Succinate
O
H
H3C
HO
O
CH2O
CH2CH2CO2H
OH
H
H3C
C25H32O8: 460.52
Prednisolone Succinate, when dried, contains not less
than 97.0% and not more than 103.0% of prednisolone
succinate (C25H32O8).

Description Prednisolone Succinate is a white, fine,
Prednisolone Succinate is freely soluble in methanol,
soluble in ethanol and very slightly soluble in water or
in ether.
Identification (1) Take 2 mg of Prednisolone Succinate add 2 mL of sulfuric acid and allow to stand for 2
to 3 minutes: a deep red color, without fluorescence,
develops. To this solution add 10 mL of water cautiously: the color disappears and a gray, flocculent precipitate is formed.
Succinate and Prednisolone Succinate RS as directed in
D : Between +114
and +120 (after drying, 67 mg, methanol, 10 mL, 100
mm).
Purity
Related substancesDissolve 0.10 g of
Prednisolone Succinate in methanol to make exactly 10
dissolve 30 mg of prednisolone in methanol to make
exactly 10 mL. Pipet 1.0 mL of the solution, add methanol to make exactly 10 mL and use this solution as
Thin-layer Chromatography. Spot 5 L of the test solution and the standard solution on a plate of silica gel
with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate
and ethanol (2 : 1) to a distance of about 10 cm and airdry the plate. Examine the plate under ultraviolet light
P2O5, 60 C, 6 hours).
Assay Weigh accurately about 10 mg each of Prednisolone Succinate and Prednisolone Succinate RS, previously dried and dissolve each in methanol to make
exactly 100 mL. Pipet exactly 5 mL each of these solutions, add methanol to make exactly 50 mL and use
these solutions as the test solution and the standard solution, respectively. Determine the absorbances, AT and
Amount (mg) of prednisolone succinate (C25H32O8)
AT
= amount (mg) of Prednisolone Succinate RS A
S
Primidone
H
Cl
HCl
Cl
Cl
H
Cl
Cl
Cl
Cl
ClH
ClH
ClH
HCl
ClH
Cl
ClH
C12H14N2O2: 218.25
Primidone, when dried, contains not less than 98.5%
and not more than 101.0% of primidone (C12H14N2O2).
Description Primidone is a white, crystalline powder
or granule, is odorless and has a slightly bitter taste.
Primidone is soluble in dimethylformamide, sparingly
soluble in pyridine, slightly soluble in ethanol, very
ether.
Identification (1) Heat 0.5 g of Primidone with 5 mL
of diluted sulfuric acid (1 in 2): the odor of formaldehyde is perceptible.
(2) Mix 0.2 g of Primidone with 0.2 g of anhydrous
sodium carbonate and heat: the gas evolved changes
0.10 g of Primidone in 10 mL of dimethylformamide:
(2) Heavy metalsProceed with 2.0 g of Primidone according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
(3)
2-Ethyl-2-phenylmalonediamideDissolve
0.10 g of Primidone in 2 mL of pyridine, add 2.0 mL of
the internal standard solution, then add 1 mL of bistrimethylsilyl acetamide, shake well and heat at 100 o C
for 5 minutes. Cool, add pyridine to make 10 mL and
use this solution as the test solution. Separately, dissolve 50 mg of 2-ethyl-2-phenylmalonediamide in pyridine to make exactly 100 mL. Pipet 2.0 mL of this solution, add 2.0 mL of the internal standard solution,
proceed in the same manner as Primidone and use this
2 L of the test solution and the standard solution as directed under the Gas Chromatography according to the
following operating conditions and calculate the ratios,
KP 9 795
QT and QS , of the peak area of 2-ethyl-2phenylmalonediamide to that of the internal standard
for the test solution and the standard solution, respectively: QT is not more than QS .
lution.
Internal standard solutionA solution of stearyl

alcohol in pyridine (1 in 2000).
Primidone Tablets
and about 1.5 m in length, packed with 3% of 50% methylphenyl silicon polymer supported on 125 m to 150
m siliceous earth for gas chromatography.
about 195 C.
time of stearyl alcohol is 8 to 9 minutes.
System suitability
with 2 L of the standard solution under the above operating conditions, 2-ethyl-2-phenyl-malonediamide
and the internal standard are eluted in this order with
the resolution between their peaks being not less than
3.0.
above operating conditions, the relative standard deviation of the ratios of the peak area of 2-ethyl-2phenylmalonediamide to that of the internal standard is
not more than 1.5%.
Primidone Tablets contain not less than 95.0% and not

more than 105.0% of the labeled amount of primidone
(C12H14N2O2: 218.25).

hours).
Residue on Ignition
Tablets, with Primidone.
Identification The retention time of the principal

peak in the chromatogram of the test solution corresponds to that of the standard solution, as obtained in the
Assay.
Primidone Tablets at 50 revolutions per minute according to Method 2 under the Dissolution Test, using 900
mL of water. Take the dissolved solution after 60 minutes from start of the test, filter, dilute with the test solution, if necessary and use this solution as the test solution. Separately, weigh accurately a portion of Primidone RS, previously dried at 105 C for 2 hours, add
the water to make the same concentration with the test
solution and use this solution as the standard solution.
standard solution at 257 nm as directed under the Ultraviolet-visible Spectrophotometry using the water as
the blank.
The dissolution rate of Primidone Tablets in 60 minutes
Assay Weigh accurately about 20 mg each of Primidone and Primidone RS, previously dried, dissolve
each in 20 mL of ethanol by warming and after cooling,
add ethanol to make exactly 25 mL and use these solutions as the test solution and the standard solution, respectively. Determine the absorbance, A1 , of the test
solution and the standard solution at the wavelength of
a maximum absorption at about 257 nm and the absorbances, A2 and A3 , at the wavelength of minimum
absorption at about 254 nm and at about 261 nm, respectively, as directed under the Ultraviolet-visible
Spectrophotometry, using ethanol as the blank.
Amount (mg) of primidone (C12H14N2O2)

(2 A1 A2 A3 )T
= amount (mg) of Primidone RS
(2 A1 A2 A3 ) S
where ( 2 A1 A2 A3 )T is the value from the test solution and (2 A1 A2 A3 ) S is from the standard so-

ment.

Primidone Tablets. Weigh accurately a portion of the
powder, equivalent to about 50 mg of primidone
(C12H14N2O2), add 35 mL of ethanol and boil for 1 hour.
Cool to room temperature, add 5.0 mL of the internal
standard solution, add ethanol to make exactly 50 mL,
filter and use this solution as the test solution. Separately, weigh accurately about 50 mg of Primidone RS,
previously dried at 105 C for 2 hours, add 35 mL of
ethanol and boil for 1 hour. Cool to room temperature,
add 5.0 mL of the internal standard solution, add ethanol to make exactly 50 mL and use this solution as the
under Gas Chromatography according to the following
operating conditions and calculate the ratios, QT and
QS , of the peak area of Primidone to that of the internal
respectively.

Amount (mg) of primidone (C12H14N2O2)
Q
= amount (mg) of Primidone RS T
QS
Internal standard solutionA solution of androsterone in ethanol (1 in 100).
diameter and about 120 cm in length, having 50%
phenyl and 50% methylpolysiloxane coated at the ratio
of 10% on siliceous earth.
Column temperature: About 260 C.
Injector and detector temperature: About 310 C.
System suitability
their peaks is not less than 1.5.
deviation of the ratios of the peak area of Primidone to
Purity (1) AcidTake 2.0 g of Probenecid, add 100

mL of water, heat in a water-bath with occasional shaking for 30 minutes, cool and filter. To the filtrate, add 1
drop of phenolphthalein TS and 0.50 mL of 0.1 mol/L
sodium hydroxide VS: a red color develops.
(2) ChlorideTake 1.0 g of Probenecid, add 100
mL of water and 1 mL of nitric acid and heat in a water-bath with occasional shaking for 30 minutes. After
cooling, add, if necessary, water to make 100 mL and
filter. Perform the test with 50 mL of the filtrate as the
test solution. Prepare the control solution with 0.30 mL
0.021%).
(3) SulfateTake 1.0 g of Probenecid, add 100 mL
of water and 1 mL of hydrochloric acid and heat in a
water-bath with occasional shaking for 30 minutes. After cooling, add, if necessary, water to make 100 mL
and filter. Perform the test using 50 mL of the filtrate as
the test solution. Prepare the control solution with 0.40
0.038%).
(4) Heavy metalsProceed with 2.0 g of Probenecid according to Method 2 and perform the test. Prepare
Probenecid according to Method 3 and perform the test

hours).
Probenecid
CH2CH2CH3
HOOC
SO2N
CH2CH2CH3
C13H19NO4S: 285.36
Probenecid, when dried, contains not less than 98.0%
and not more than 101.0% of probenecid (C13H19NO4S).
Description Probenecid is a white crystal or crystalline powder, is odorless and has a slightly bitter taste,
followed by unpleasant bitter taste.
Probenecid is sparingly soluble in ethanol, slightly soluble in ether and practically insoluble in water.
Probenecid dissolves in sodium hydroxide TS or in
ammonia TS.
Melting pointBetween 198 C and 200 C
Identification (1) Heat Probenecid strongly: the odor
of sulfur dioxide is perceptible.
(2) Determine the absorption spectra of a solution
of Probenecid and Probenecid RS in ethanol (1 in

Assay Weigh accurately about 0.5 g of Probenecid,
previously dried and dissolve in 50 mL of neutralized
ethanol. Titrate with 0.1 mol/L sodium hydroxide VS
(indicator: 3 drops of phenolphthalein TS).

= 28.536 mg of C13H19NO4S
Probenecid Tablets
Probenecid Tablets contain not less than 95.0% and not
more than 105.0% of the labeled amount of probenecid
(C13H19NO4S: 285.36).
Tablets, with Probenecid.
Identification (1) Weigh a portion of powdered Probenecid Tablets, equivalent to 0.5 g of probenecid ac-
KP 9 797
cording to the labeled amount, add 50 mL of ethanol

and 1 mL of 1 mol/L hydrochloric acid TS, shake and
filter. Evaporate the filtrate in a water-bath to about 20
mL. After cooling, collect the produced crystals, recrystallize from 50 mL of dilute ethanol and dry at 105 C
for 4 hours: it melts between 198 C and 200 C. With
the crystals so obtained, proceed as directed in the
Identification (1) under Probenecid.
of the dried crystals obtained in Identification (1) in
ethanol (1 in 50000) as directed under the Ultravioletvisible Spectrophotometry: it exhibits maxima between
224 nm and 226 nm and between 247nm and 249 nm
and a minimum between 234 nm and 236 nm.
Probenecid Tablets at 50 revolutions per minute according to Method 2 under the Dissolution Test, using 900
mL of the dissolution medium (2). Take 30 mL or more
of the dissolved solution after 30 minutes from start of
the test and filter through a membrane filter with a pore
size of not more than 0.8 m. Discard the first 10 mL
of the filtrate, pipet the subsequent V mL, add diluted
phosphate buffer solution, pH 6.8 (1 in 2), to make exactly V' mL so that each mL contains about 14 g of
probenecid (C13H19NO4S) according to the labeled
amount and use this solution as the test solution. Separately, weigh accurately about 70 mg of Probenecid RS,
previously dried at 105 C for 4 hours and add the dissolution medium (2) to make exactly 100 mL. Pipet exactly 1 mL of this solution, add the dissolution medium
(2) to make exactly 50 mL and use this solution as the
The dissolution rate of Probenecid Tablets in 30 minutes is not less than 80%.

amount of probenecid (C13H19NO4S)
1
AT
V'
= WS A V C 18
S
WS: Amount (mg) of Probenecid RS,
C: Labeled amount (mg) of
(C13H19NO4S) in 1 tablet.
ment.
probenecid
It meets the repuire-

Probenecid Tablets. Weigh accurately a portion of the
powder, equivalent to about 0.15 g of probenecid
(C13H19NO4S) according to the labeled amount, add
200 mL of ethanol and 5 mL of 1 mol/L hydrochloric
acid TS and heat in a water-bath at 70 C for 30 minutes with occasional shaking. After cooling, add ethanol to make exactly 250 mL and filter. Discard the first
20 mL of the filtrate. To 5 mL of the subsequent filtrate,
exactly measured, add 5 mL of 0.1 mol/L hydrochloric

acid TS, dilute with ethanol to exactly 250 mL and use
this solution as the test solution. Separately, weigh accurately about 0.15 g of Probenecid RS, previously
dried at 105 C for 4 hours, dissolve in 5 mL of 1 mol/L
hydrochloric acid TS and add ethanol to make exactly
250 mL. Pipet exactly 5 mL of the solution, add 5.0 mL
of 0.1 mol/L hydrochloric acid TS and ethanol to make
exactly 250 mL and use this solution as the standard solution. Determine the absorbances, AT and AS, of the
248 nm as directed under the Ultraviolet-visible Spectrophotometry, using a solution prepared with 5 mL of
0.1 mol/L hydrochloric acid TS and ethanol to make
exactly 250 mL as the blank.
Amount (mg) of probenecid (C13H19NO4S)
AT
= amount (mg) of Probenecid RS A
S
Procainamide Hydrochloride
C2H5
H2N
CONHCH2CH2N
HCl
C2H5
C13H21N3OHCl: 271.79
Procainamide Hydrochloride, when dried, contains not
less than 98.0% and not more than 101.0% of procainamide hydrochloride (C13H21N3OHCl).
Description Procainamide Hydrochloride is a white
to pale yellow, crystalline powder and is odorless.
Procainamide Hydrochloride is very soluble in water,
freely soluble in methanol, in glacial acetic acid or in
ethanol, slightly soluble in acetic anhydride and practically insoluble in ether.
Procainamide Hydrochloride is hygroscopic.
Identification (1) Dissolve 1 g of Procainamide Hydrochloride in 10 mL of water, add 10 mL of sodium
hydroxide TS and extract with two 10 mL volumes of a
mixture of ether and chloroform (1 : 1). Combine the
extracts, add calcium chloride for drying and dry the
extracts for 30 minutes. Decant the solution into a small
flask by tilting, add 5 mL of pyridine and add slowly 1
mL of benzoyl chloride drop-wise. Heat the mixture in
a water-bath for 30 minutes, add 20 mL of a mixture of
diethyl ether and chloroform (1 : 1), shake, and pour
the mixture into 100 mL of sodium hydroxide TS, then
shake. Separate the organic solvent layer, wash it with
20 mL of water, cool to 10 C and allow the crystals to
separate. Collect the separated crystals by filtration, recrystallize from 10 mL of dilute ethanol and dry at 105
C for 1 hour: the crystals so obtained melt between
180 C and 187 C.

(2) Dissolve 10 mg of Procainamide Hydrochloride
in 1 mL of dilute hydrochloric acid and 4 mL of water:
the solution responds to the Qualitative Tests for primary aromatic amines.
(3) A solution of Procainamide Hydrochloride (1 in
pH Dissolve 1.0 g of Procainamide Hydrochloride in
and 6.5.
1.0 g of Procainamide Hydrochloride in 10 mL of water: the solution is clear.
(2) Heavy metalsProceed with 2.0 g of Procainamide Hydrochloride according to Method 2 and perform the test. Prepare the control solution with 2.0 mL
Procainamide Hydrochloride according to Method 1
(4) Related substancesDissolve 0.20 g of Procainamide Hydrochloride in 10 mL of methanol and use
10 L each of the test solution and the standard solution on a plate of silica gel for thin-layer chromatography. Then spot 10 L each of a solution of ammonia
solution (28) in methanol (11 in 50) on each of the
above spots. Develop the plate with a mixture of chloroform, methanol and strong ammonia water (700 :
plate. Spray evenly p-dimethylaminobenzaldehyde TS
for spray on the plate: the spots other than the principal
hours).
Assay Weigh accurately about 0.5 g of Procainamide

Injection
Procainamide Hydrochloride Injection is an aqueous
solution for injection. Procainamide Hydrochloride Injection contains not less than 95.0% and not more than
105.0% of the labeled amount of procainamide hydrochloride (C13H21N3OHCl: 271.79).
Method of Preparation Prepare as directed under Injections, with Procainamide Hydrochloride.
Description Procainamide Hydrochloride Injection is
a clear, colorless or pale yellow liquid.
Identification (1) Proceed with a volume of Procainamide Hydrochloride Injection, equivalent to 1 g of
procainamide hydrochloride according to the labeled
amount, as directed in the Identification (1) under Procainamide Hydrochloride.
(2) Dilute a volume of Procainamide Hydrochloride
Injection, equivalent to 10 mg of procainamide hydrochloride according to the labeled amount, with 1 mL
of dilute hydrochloric acid and water to make 5 mL: the
solution responds to the Qualitative Tests for primary
aromatic amines.
(3) Procainamide Hydrochloride Injection responds
to the Qualitative Tests (2) for chloride.
Assay Dilute an exactly measured volume of Procainamide Hydrochloride Injection, equivalent to about
0.5 g of procainamide hydrochloride (C13H21N3OHCl),
with 5 mL of hydrochloric acid and water to make 50
mL, cool to 15 C and titrate with 0.1 mol/L sodium nitrite VS (potentiometric titration or amperometric titration, Endpoint Detection Method in Titrimetry).
Each mL of 0.1 mol/L sodium nitrite VS

tainers.
KP 9 799
Tablets
Procainamide Hydrochloride Tablets contain not less
amount
of
procainamide
hydrochloride
(C13H21N3OHCl: 271.79).
Tablets, with Procainamide Hydrochloride.
Identification (1) Shake a portion of powdered Procainamide Hydrochloride Tablets, equivalent to 1.5 g of
procainamide hydrochloride according to the labeled
amount, with 30 mL of water, filter and use the filtrate
as the test solution. To 20 mL of the test solution, add
10 mL of sodium hydroxide TS and proceed as directed
in the Identification (1) under Procainamide Hydrochloride.
(2) Take 0.2 mL of the test solution obtained in (1),
add 1 mL of dilute hydrochloric acid and 4 mL of water: the solution responds to the Qualitative Tests for
Procainamide Hydrochloride Tablets at 50 revolutions
per minute according to Method 2 under the Dissolution Test, using 900 mL of water. Take 30 mL or more
the test and filter through a membrane filter with pore
of the filtrate, pipet the subsequent V mL, add diluted
phosphate buffer solution, pH 6.8, (1 in 2) to make exactly V mL so that each mL contains about 7 g of
procainamide hydrochloride (C13H21N3OHCl) according to the labeled amount and use this solution as the
test solution. Separately, weigh 0.125 g of Procainamide Hydrochloride RS, previously dried at 105 C for
4 hours and dissolve in water to make exactly 1000 mL.
Pipet 5.0 mL of this solution, add diluted phosphate
buffer solution, pH 6.8, (1 in 2) to make exactly 100
mL and use this solution as the standard solution. Determine the absorbances, AT and AS, of the test solution
The dissolution rate of Procainamide Hydrochloride
Tablets in 30 minutes should be not less than 80.0%.

of procainamide hydrochloride (C13H21N3OHCl)
1
AT
V
= WS A V C 4.5
S
RS,
WS: Amount (mg) of Procainamide Hydrochloride
C: Labeled amount (mg) of procainamide hydrochloride (C13H21N3OHCl) in 1 tablet.

Procainamide Hydrochloride Tablets. Weigh accurately
a portion of the powder, equivalent to about 0.5 g of
procainamide hydrochloride (C13H21N3OHCl), stir well
with 25 mL of 1 mol/L hydrochloric acid TS, centrifuge
and separate the supernatant liquid. Wash the residue
with two 10 mL portions of 1 mol/L hydrochloric acid
VS in the same manner. Add 10 mL of a solution of potassium bromide (3 in 10) to the combined supernatant
liquid, cool to below 15 C and titrate with 0.1 mol/L
sodium nitrite VS. (potentiometric titration or amperometric titration, Endpoint Detection Method in Titrimetry)

Procaine Hydrochloride
C2H5
H2N
HCl
COOCH2CH2N
C2H5
C13H20N2O2HCl: 272.77
Procaine Hydrochloride, when dried, contains not less
than 99.0% and not more than 101.0% of procaine hydrochloride (C13H20N2O2HCl).
Description Procaine Hydrochloride is a white crystal or crystalline powder.
Procaine Hydrochloride is very soluble in water, soluble in ethanol and practically insoluble in ether.
of a solution of Procaine Hydrochloride and Procaine
Hydrochloride RS (1 in 100000) as directed under the
(2) Determine the infrared spectra of Procaine Hydrochloride and Procaine Hydrochloride RS, previously
dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry,: both spectra exhibit similar intensities of absorption at the same
wavenumbers.
(3) A solution of Procaine Hydrochloride (1 in 10)
Melting Point
pH Dissolve 1.0 g of Procaine Hydrochloride in 20

6.0.
1.0 g of Procaine Hydrochloride in 10 mL of water: the

(2) Heavy metalsProceed with 1.0 g of Procaine
(3) Related substancesTake 1.0 g of Procaine
Hydrochloride, add 5 mL of ethanol, dissolve by mixing well, add water to make exactly 10 mL and use this
solution as the test solution. Separately, dissolve 10 mg
of p-aminobenzoic acid in ethanol to make exactly 20
mL, then pipet exactly 1 mL of this solution, add 4 mL
of ethanol and water to make exactly 10 mL and use
mixture of dibutyl ether, n-hexane and glacial acetic acid (20 : 4 : 1) to a distance of about 10 cm and air-dry
the plate. After drying the plate at 105 C for 10 minutes, examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot
from the test solution are not more dense than the spot
from the standard solution. The principal spot from the
test solution stays at the origin.
4 hours).
Assay Weigh accurately about 0.4 g of Procaine Hydrochloride, previously dried, dissolve in 5 mL of hydrochloric acid and 60 mL of water, add 10 mL of a solution of potassium bromide (3 in 10), cool to below 15
C and titrate with 0.1 mol/L sodium nitrite VS (potentiometric titration or amperometric titration, Endpoint
Detection Method in Titrimetry).

= 27.277 mg of C13H20N2O2HCl
Procaine Hydrochloride
Injection
Procaine Hydrochloride Injection is an aqueous solution for injection. Procaine Hydrochloride Injection
of the labeled amount of procaine hydrochloride
(C13H20N2O2HCl: 272.77).
Method of Preparation Prepare as directed under In-
jections, with Procaine Hydrochloride.

Description Procaine Hydrochloride Injection is a
Identification (1) Take a volume of Procaine Hydrochloride Injection, equivalent to 10 mg of Procaine
Hydrochloride according to the labeled amount and add
water to make 1000 mL. Determine the absorption
spectrum of this solution as directed under the Ultraviolet-visible Spectrophotometry: it exhibits maxima between 219 nm and 223 nm and between 289 nm and
293 nm.
(2) Procaine Hydrochloride Injection responds to
the Qualitative Tests (2) for chloride.
pH

Assay Take an exactly measured volume of Procaine
Hydrochloride Injection, equivalent to about 20 mg of
procaine hydrochloride (C13H20N2O2HCl), add the mobile phase to make exactly 20 mL. Pipet exactly 5 mL
of this solution, add exactly 5 mL of the internal standard solution and the mobile phase to make exactly 20
weigh accurately about 50 mg of Procaine Hydrochloride RS, previously dried in a desiccator (silica gel) for
4 hours and dissolve in the mobile phase to make exactly 50 mL. Pipet exactly 5 mL of this solution, add exactly 5 mL of the internal standard solution and the
mobile phase to make exactly 20 mL and use this solution as the standard solution. Perform the test with 5 L
the following operating conditions and calculate the ratios, QT and QS, of the peak area of procaine to that of
the internal standard for the test solution and the standard solution, respectively.
Amount (mg) of procaine hydrochloride

(C13H20N2O2HCl) = amount (mg) of Procaine HyQT
drochloride RS Q
S
Internal standard solutionA solution of caffeine
in the mobile phase (1 in 1000).
KP 9 801

about 40 C.
Mobile phase: Adjust the pH of 0.05 mol/L potassium dihydrogen phosphate to 3.0 with phosphoric acid
and add an amount of sodium-1-heptanesulfonate to
make a solution of 0.1%. Add 200 mL of methanol to
800 mL of this solution.
time of procaine hydrochloride is about 10 minutes.
System suitability
with 5 L of the standard solution under the above operating conditions, procaine and the internal standard
above operating conditions, the relative standard deviation of the ratios of the peak area of pracaine to that of
the internal standard is not more than 1.0 %.
tainers.
Procarbazine Hydrochloride
CH3
CH3NHNHCH2
HCl
CONHCH
CH3
C12H19N3OHCl: 257.76
Procarbazine Hydrochloride, when dried, contains not
less than 98.5% and note more than 101.0% of procarbazine hydrochloride (C12H19N3OHCl).
Description Procarbazine Hydrochloride is a white to
pale yellowish white crystal or crystalline powder.
Procarbazine Hydrochloride is freely soluble in water,
soluble in methanol, slightly soluble in ethanol and
Identification (1) Dissolve 10 mg of Procarbazine
Hydrochloride in 1 mL of diluted cupric sulfate TS (1
in 10) and add 4 drops of sodium hydroxide TS: a
green precipitate is produced immediately and the color
changes from green through yellow to orange.
(2) Determine the absorption spectra of solution of
Procarbazine Hydrochloride and Procarbazine Hydrochloride RS in 0.1 mol/L hydrochloric acid TS (1 in
(3) Determine the infrared spectra of Procarbazine

Hydrochloride and Procarbazine Hydrochloride RS,
(4) A solution of Procarbazine Hydrochloride (1 in
pH Dissolve 0.10 g of Procarbazine Hydrochloride in
and 5.0.
Purity (1) Heavy metalsProceed with 1.0 g of Procarbazine Hydrochloride according to Method 4 and
(2) Related substancesDissolve 50 mg of Procarbazine Hydrochloride in 5 mL of a solution of Lcysteine hydrochloride in diluted methanol (7 in 10) (1
in 200) and use this solution as the test solution. Pipet
exactly 1 mL of the test solution, add a solution of Lcysteine hydrochloride in diluted methanol (7 in 10) (1
in 200) to make exactly 50 mL and use this solution as
Thin-layer Chromatography. Immerse slowly, by inclining, a plate of silica gel with fluorescent indicator
for thin-layer chromatography in a solution of Lcysteine hydrochloride in diluted methanol (7 in 10) (1
in 200), allow to stand for 1 minute, lift the plate from
the solution, dry in cold wind for 10 minutes, then in
warm wind for 5 minutes and then dry at 60 C for 5
minutes. After cooling, spot 5 L each of the test solution and the standard solution on the plate. Develop the
plate with a mixture of methanol and ethyl acetate (1 :
nm): not more than 1 spot other than the principal spot
and the spot of the starting point from the test solution
appears and is not more dense than the spot from the
standard solution.
hours).
Assay Weigh accurately about 0.15 g of Procarbazine
Hydrochloride, previously dried, place in a stoppered
flask, dissolve in 25 mL of water, add 25 mL of hydrochloric acid and cool to room temperature. To this
solution, add 5 mL of chloroform and titrate, while
shaking, titrate with 0.05 mol/L potassium iodate VS
until the purple color of the chloroform layer disappears. The end point is reached when the red-purple
color of the chloroform layer no more reappears within
5 minutes after the purple color disappeared.
Procaterol Hydrochloride
Hydrate
OH
H
N
HCl
C
HO
H
1/2 H2O
CH2CH3
C
NHCH(CH3)2
H
C16H22N2O3HCl1/2H2O: 335.83
Procaterol Hydrochloride Hydrate contains not less
than 98.5% and not more than 101.0% of procaterol
hydrochloride (C16H22N2O3HCl: 326.82), calculated on
Description Procaterol Hydrochloride Hydrate is a
white pale yellowish white crystal or crystalline powder.
Procaterol Hydrochloride Hydrate is soluble in water,
in formic acid or in methanol, slightly soluble in ethanol and practically insoluble in ether.
Procaterol Hydrochloride Hydrate is gradually affected
by light.
The solution of Procaterol Hydrochloride Hydrate (1 in
pHThe pH of a solution of Procaterol Hydrochloride Hydrate (1 in 100) is between 4.0 and 5.0.
of solutions of Procaterol Hydrochloride Hydrate and
Procaterol Hydrochloride Hydrate RS (7 in 1000000)
(2) Determine the infrared spectra of Procaterol
Hydrochloride Hydrate and Procaterol Hydrochloride
same wavenumbers.
(3) A solution of Procaterol Hydrochloride Hydrate
1.0 g of Procaterol Hydrochloride Hydrate in 30 mL of
water: the solution is clear and has no more color than
Control solutionTake 3.0 mL of ferric chloride
stock CS, add water to make 50 mL.

(2) Heavy metalsProceed with 2.0 g of Procaterol
Hydrochloride Hydrate according to Method 2 and perform the test. Prepare the control solution with 2.0 mL
(3) Related substancesDissolve 0.10 g of Procaterol Hydrochloride Hydrate in 100 mL of diluted methanol (1 in 2) and use this solution as the test solution.
Pipet 1.0 mL of the test solution, add diluted methanol
(1 in 2) to make exactly 100 mL and use this solution
the following operating conditions. Determine each
peak area of the test solution and the standard solution
by the automatic integration method: the total area of
the peaks other than procaterol from the test solution is
not larger than the peak area of procaterol from the
standard solution.
inside diameter and about 25 cm in length packed with
about 40 C.
Mobile phase: Dissolve 0.87 g of sodium-1heptanesulfonate in 1000 mL of water. To 760 mL of
this solution, add 230 mL of methanol and 10 mL of
anhydrous acetic acid.
time of procaterol is about 15 minutes.
System suitability
Procaterol Hydrochloride Hydrate and threoprocaterol
hydrochloride in 100 mL of diluted methanol (1 in 2).
To 15 mL of this solution, add diluted methanol (1 in 2)
to make 100 mL. When the procedure is run with 2 L
of this solution according to the above operating conditions, procaterol and threoprocaterol are eluted in this
order with the resolution between their peaks being not
less than 3.0.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of procaterol obtained
from 2 L of the standard solution is not less than 10
mm.
Time span of measurement: 2.5 times as long as
the retention time of procaterol after the solvent peak.
Assay Weigh accurately about 0.25 g of Procaterol
Hydrochloride Hydrate, add 2 mL of formic acid, dis-
KP 9 803
solve by warming and add exactly 15 mL of 0.1 mol/L

perchloric acid VS. Add 1 mL of acetic anhydride, heat
on a water-bath for 30 minutes, cool, add 60 mL of
acetic anhydride and titrate the excess perchloric acid
with 0.1 mol/L sodium acetate VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary
correction.
= 32.682 mg of C16H22N2O3HCl

Prochlorperazine Maleate
CH2CH2CH2
N
CH2CH2OH
H
Cl
CO 2H
C
2
C
S
between 252 C and 258 C (with decomposition).

(3) Boil 0.5 g of Prochlorperazine Maleate with 10
mL of hydrobromic acid under a reflux condenser for
10 minutes. After cooling, add 100 mL of water and filter through glass filter (G4). Wash the residue with
three 10 mL volumes of water and dry at 105 C for 1
hour: it melts between 195 C and 198 C (with decomposition).
(4) To the aqueous layer reserved in (2), add boiling
chips and heat on a water-bath for 10 minutes. Cool,
add 2 mL of bromine TS, heat on a water-bath for 10
minutes and heat the solution to boil. After cooling, add
2 drops of this solution to 3 mL of a solution of resorcin in sulfuric acid (1 in 300) and heat on a water-bath
for 15 minutes: a red-purple color is observed.
Purity Heavy metalsProceed with 1.0 g of Prochlorperazine Maleate according to Method 2 and perform the test. Prepare the control solution with 1.0 mL
hours).
CO 2H
C20H24ClN3S2C4H4O4: 606.09
Prochlorperazine Maleate, when dried, contains not less
than 98.0% and not more than 101.0% of prochlorperazine maleate (C20H24ClN3S2C4H4O4).
Description Prochlorperazine Maleate is a white to
pale yellow powder, is odorless and has a slightly bitter
taste.
Prochlorperazine Maleate is slightly soluble in glacial
acetic acid, very slightly soluble in water or in ethanol
Prochlorperazine Maleate is gradually colored a red-tint
by light.
decomposition).
Identification (1) Dissolve 5 mg of Prochlorperazine
Maleate in 5 mL of sulfuric acid: a red color is observed, which darkens slowly on standing. Warm a half
of the solution: the color changes to red-purple. To the
remainder, add 1 drop of potassium dichromate TS: a
green-brown color is observed, which changes to
brown on standing.
(2) Dissolve 0.2 g of Prochlorperazine Maleate in 5
mL of a solution of sodium hydroxide (1 in 10) and extract with three 3 mL volumes of ether [reserve the
aqueous layer and use for (4)]. Evoporate the combined
ether extracts on a water-bath to dryness, dissolve the
residue in 10 mL of methanol by warming and pour into 30 mL of a solution of picric acid in methanol (1 in
75), previously warmed to 50 C. Allow to stand for 1
hour, collect the crystals, wash with a small amount of
methanol and dry at 105 C for 1 hour: the crystals melt
Assay Weigh accurately about 0.3 g of Prochlorperazine Maleate, previously dried and dissolve in 60 mL of
anhydrous acetic acid, while stirring and warming.
Cool and titrate with 0.05 mol/L perchloric acid VS until the color of the solution changes from orange to
green (indicator: 0.5 mL of -naphtholbenzeine TS).
correction.

= 15.152 mg of C20H24ClN3S2C4H4O4
tight containers.
Prochlorperazine Maleate
Tablets
Prochlorperazine Maleate Tablets contain not less than
of prochlorperazine maleate (C20H24ClN3S2C4H4O4:
606.09).
Tablets with Prochlorperazine Maleate.
Identification (1) Weigh a quantity of powdered
Prochlorperazine Maleate Tablets, equivalent to 5 mg
of prochlorperazine maleate according to the labeled
amount, add 15 mL of glacial acetic acid, shake and filter. To 5 mL of the filtrate, add 3 mL of sulfuric acid
and shake: a pale red color is observed. To this solution,
add 1 drop of potassium dichromate TS: a green-brown

color is observed and changes to brown on standing.
(2) Weigh a portion of powdered Prochlorperazine
Maleate Tablets, equivalent to 80 mg of prochlorperazine maleate according to the labeled amount, add 15
mL of methanol and 1 mL of dimethylamine, shake,
centrifuge and use the supernatant liquid as the test solution. Separately, dissolve 80 mg of prochlorperazine
maleate RS in 16 mL of a mixture of methanol and dimethylamine (15 : 1) and use this solution as the standard solution. Perform the test with the test solution
mixture of n-butanol and ammonia TS (15 : 2) to a distance of about 10 cm and air-dry the plate. Spray evenly palladium chloride TS on the plate: the spots obtained from the test solution and the standard solution
show a red-purple color and has the same Rf value.
(3) Take a portion of powdered Prochlorperazine
Maleate Tablets, equivalent to 40 mg of prochlorperazine maleate according to the labeled amount, add 10
mL of 1 mol/L hydrochloric acid TS and 20 mL of ether,
shake and centrifuge. Transfer the ether layer to a separatory funnel, wash with 5 mL of 0.05 mol/L sulfuric
acid TS and evaporate on a water-bath to dryness. Dissolve the residue in 5 mL of sulfuric acid TS, filter, if
necessary and add 1 to 2 drops of potassium permanganate TS: the red color of the test solution is discharged
immediately.
mide, stopper tightly and centrifuge after shaking vigorously for 15 minutes. Determine the absorbances, AT
and AS, of the water layers obtained from the test solution and the standard solution, respectively, at 495 nm
as directed under the Ultraviolet-visible Spectrophotometry, using palladium chloride TS as the blank.
Description Progesterone is a white crystal or crystalline powder and is odorless.

Progesterone is soluble in methanol, in ethanol, in dehydrated ethanol or in dioxane, sparingly soluble in

ment.

Prochlorperazine Maleate Tablets using an agate mortar.
Weigh accurately a portion of the powder, equivalent to
about 16 mg of prochlorperazine maleate (C20H24ClN3S
2C4H4O4), transfer to a stoppered centrifuge tube, add
exactly 25 mL of a mixture of dimethylformamide and
dimethylamine (100 : 1), stopper tightly, shake vigorously for 15 minutes and centrifuge. Use the supernatant liquid as the test solution. Separately, weigh accurately about 64 mg of Prochlorperazine Maleate RS,
previously dried in a desiccator (in vacuum, silica gel)
for 4 hours, dissolve in a mixture of dimethylformamide and dimethylamine (100 : 1) to make exactly 100
exactly 4 mL each of the test solution and the standard
solution into stoppered centrifuge tubes, add exactly 10
mL of boric acid-potassium chloride-sodium hydroxide
buffer solution, pH 9.0 and 20 mL of cyclohexane,
stopper tightly and centrifuge after shaking vigorously
for 5 minutes. Pipet exactly 10 mL each of the cyclohexane layer of the test solution and the standard solution into stoppered centrifuge tubes, add exactly 20 mL
of palladium chloride TS and 5 mL of dimethylforma-
Amount (mg) of prochlorperazine maleate

(C20H24ClN3S2C4H4O4) = amount (mg) of
1
AT
Prochlorperazine Maleate RS A 4
S

tight containers.
Progesterone
O
H3C
H3C
CH3
H
C21H30O2: 314.46
Progesterone, when dried, contains not less than 97.0%
and not more than 103.0% of progesterone (C21H30O2).
Identification (1) Take 50 mg of Progesterone and

add a solution of 50 mg of hydroxylamine hydrochloride and 50 mg of anhydrous sodium acetate in 5 mL of
ethanol. Boil for 2 hours under a reflux condenser, evaporate the ethanol to 3 mL and add 10 mL of water. Filter by suction and wash the precipitate on the filter with
a small amount of water. Recrystallize from dilute
ethanol and dry at 105 C for 1 hour: the dried crystals
melt between 235 C and 240 C.
(2) Determine the infrared spectra of Progesterone
and Progesterone RS, previously dried, as directed in
Spectrophotometry,: both spectra exhibit similar intensities of absorption at the same wavenumbers. If any
difference appears, dissolve each in ethanol, evaporate
to dryness and repeat the test on the residues.
Melting Point Between 128 C and 133 C or between 120 C and 122 C
D : Between +174
and +182 (after drying, 0.2 g, dioxane, 10 mL, 100
KP 9 805
mm).
Purity Related substancesDissolve 80 mg of
Progesterone in 2 mL of methanol and use this solution
as the test solution. Pipet exactly 1 mL of this solution,
add methanol to make exactly 100 mL and use this solution as the standard solution. Perform the test with
chloroform and diethylamine (19 : 1) to a distance of
Loss on Drying Not more than 0.5% (0.5 g, in vacuum, P2O5, 4 hours)
Assay Weigh accurately about 10 mg of Progesterone,
previously dried and dissolve in dehydrated ethanol to
make exactly 100 mL. To 5 mL of this solution, exactly
measured, add dehydrated ethanol to make exactly 50
mL and determine the absorbance, A, at the wavelength
of a maximum absorption at about 241 nm as directed
under the Ultraviolet-visible Spectrophotometry.
Amount (mg) of Progesterone (C21H30O2)

A
= 540 10000
tight containers.
Progesterone Injection
Progesterone Injection is an oily solution for injection.
Progesterone Injection contains not less than 90.0% and
not more than 110.0% of the labeled amount of progesterone (C21H30O2: 314.46).
Add 75 mg of 2,4-dinitrophenylhydrazine and 30 mL of

ethanol to the residue and boil for 15 minutes under a
reflux condenser. Add 1 mL of hydrochloric acid and
heat for 15 minutes. Cool and collect the precipitate on
a glass filter (G4). Wash the precipitate with five 10 mL
volumes of hexane and three 5 mL volumes of ethanol.
Then wash with diluted hydrochloric acid (1 in 20) until the washings become colorless and dry at 105 C for
3 hours: the residue melts between 269 C and 275 C.
Assay Measure exactly a volume of Progesterone Injection, equivalent to about 50 mg of progesterone
(C21H30O2) and dissolve in chloroform to make exactly
100 mL. To exactly 3 mL of this solution, add chloroform to make exactly 50 mL and use this solution as the
test solution. Separately, weigh accurately 50 mg of
Progesterone RS, previously dried in a desiccator (in
vacuum, P2O5) for 4 hours and prepare the standard solution in the same manner as directed for the preparation of the test solution. Pipet exactly 5 mL each of the
test solution and the standard solution, add exactly 10
mL of isoniazid TS and methanol to make exactly 20
mL, respectively. Allow to stand for 45 minutes and
perform the test with the test solution and the standard
solution as directed under the Ultraviolet-visible Spectrophotometry, using a solution, prepared with 5 mL of
chloroform in the same manner, as the blank. Determine the absorbances, AT and AS, of the subsequent solutions of the test solution and the standard solution at
380 nm, respectively.
Amount (mg) of progesterone (C21H30O2)

AT
= amount (mg) of Progesterone RS A
S
Method of Preparation Prepare as directed under Injections, with Progesterone.

Description Progesterone Injection is a clear, colorless to pale yellow, oily liquid.
Identification Transfer a volume of Progesterone Injection, equivalent to 20 mg of progesterone according
to the labeled amount, to a separatory funnel. Add 40
mL of hexane and mix thoroughly, then extract with
three 20 mL volumes of diluted ethanol (9 in 10). Evaporate the combined extracts on a water-bath to dryness.
Proglumide
(CH3CH2CH2)2N
NH
CCH 2CH2CO2H
H
cyclohexane, ethyl acetate, glacial acetic acid and methanol (50 : 18 : 5 : 4) to a distance of about 10 cm and
and enantiomer
Cl8H26N2O4: 334.41
Proglumide, when dried, contains not less than 98.5%

and not more than 101.0% of proglumide (Cl8H26N2O4).
Description Proglumide is a white crystal or crystalline powder.
Proglumide is freely soluble in methanol, soluble in
ethanol, sparingly soluble in ether and very slightly soluble in water.
A solution of Proglumide in methanol (1 in 10) shows
Identification (1) Put 0.5 g of Proglumide in a
round-bottomed tube, add 5 mL of hydrochloric acid,
seal the tube and heat the tube carefully at 120 C for 3
hours. After cooling, open the tube, collect crystals separated out, wash the crystals with 50 mL of water and
dry at 100 C for 1 hour: the melting point of the crystals is between 121 C and 124 C.
(2) Determine the infrared spectra of Proglumide
and Proglumide RS, previously dried, as directed in the
1%
Absorbance E1cm (225 nm): Between 384 and 414

(after drying, 4 mg, methanol, 250 mL)
Melting Point

Proglumide according to Method 2 and perform the test.
(2) ArsenicTake 1.0 g of Proglumide, add 10 mL
of a solution of magnesium nitrate in ethanol (1 in 10)
and 1.5 mL of hydrogen peroxide solution, burn the
ethanol and prepare the test solution according to Method 3 and perform the test (not more than 2 ppm).
(3) Related substancesDissolve 0.10 g of Proglumide in 5 mL of methanol and use this solution as the
test solution. Pipet exactly 1 mL of the test solution,
add methanol to make exactly 200 mL and use this solution as the standard solution. Perform the test with
Loss on Drying Not more than 0.10% (1 g, in vaccum, P2O5, 60 C, 3 hours).

Assay Weigh accurately about 0.16 g of Proglumide,
previously dried, dissolve in 40 mL of methanol, add
10 mL of water and titrate with 0.1 mol/L sodium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.

= 33.441 mg of Cl8H26N2O4
Promazine Hydrochloride
CH3
CH2CH2CH2N
N
CH3
HCl
C17H20N2SHCl: 320.88
Promazine Hydrochloride, when dried, contains not
less than 98.0% and not more than 102.0% of promazine hydrochloride (C17H20N2SHCl).
Description Promazine Hydrochloride is a white and
pale yellow crystalline powder and is odorless.
Promazine Hydrochloride is very soluble in water or in
chloroform.
Promazine Hydrochloride is oxidized by contact with
air and changes its color blue or pale red.
Identification (1) The infrared spectra of Promazine
Hydrochloride and Promazine Hydrochloride RS, previously dried, as directed in the potassium bromide disk
same wavenumbers.
(2) Determine the absorbance of the test solution in
the Assay at 301 nm, using 0.1 mol/L hydrochloric acid
as the blank, as directed under the Ultraviolet-visible
Spectrophotometry. Then, dilute 1 mL of the test solution with 0.1 mol/L hydrochloric acid TS to make 10
mL and determine the absorbance of this solution at the
KP 9 807
wavelength of a maximum absorbance at about 252

nm: the ratio, 10 (A252/A301), is between 7.1 and 7.9.
(3) The solution of Promazine (1 in 20) responds to
the Qualititive Tests for chloride
Melting Point Between 172 C and 182 C (the
range between beginning and the end of melting does
not exceed 3 C).
pH Dissolve 1.0 g of Promazine Hydrochloride in 20
5.2.
Purity (1) Clarity and color of solutionDissove
1.0 g of Promazine Hydrochloride in 20 mL of water
and chloroform (1 in 10) is clear and not more intense
than pale yellow.
(2) Heavy metalsProceed with 1.0 g of Promazine Hydrochloride according to Method 2 and perform
(3) SeleniumWeigh 0.1 g of Promazine Hydrochloride, transfer to a combustion flask and add 0.2 g of
magnesium oxide and 25 mL of diluted nitric acid (1 in
30). Perform the test of Oxygen-Flask Combustion Method, rinse the platinum basket with 10 mL of water
and transfer the rinsate to a beaker. Rinse the wall of
the flask with the above solution. Boil the solution for
10 minutes and use this solution as the test stock solution after cooling. Separately, transfer 3.0 mL of selenium standard solution to a beaker, add 25 mL of water
and use this solution as the standard stock solution. To
each the test stock solution, the standard stock solution
and water, add 25 mL of nitric acid (1 in 30) and 25 mL
of water, titrate the solutions with ammonium hydroxide (1 in 2) to the pH of 2.0, add water to make 60 mL.
Transfer the solution to a separating funnel and combine with 10 mL of water with which the beaker was
rinsed. Add 0.2 g of hydroxylamine to each solution,
shake well to dissolve and add 5.0 mL of diaminonaphthylene reagent. After thorough mixing, allow the solution to stand for 100 minutes. Then, add 5.0 mL of cyclohexane, shake for 2 minutes and let the layers of the
solution being separated. Pipet the cyclohexane layer
and centrifuge. Use these solutions as the test solution,
the standard solution and the blank solution, respectively. Perform the test with the test solution and the standard solution as directed under the Spectrophotometry
and determine the absorbances, AT and AS, at 380 nm.
AT is not be greater than AS (not more than 0.003%).
(4) Related substancesWeigh accurately a portion of Promazine Hydrochloride, dissolve in methanol
at the concentration of 20 mg/mL and use this solution
as the test solution. Separately, weigh accurately a portion of Promazine Hydrochloride RS, previously dried
at 105 C for 2 hours and add methanol to make a solution having a known concentration of 0.4 mg per mL.
Dilute quantitatively with methanol to obtain standard
preparation having the following compositions:
Standard
preparation
Dilution
Concentration
(g reference
standard per
mL)
(1)
(2)
(3)
(4)
undiluted
(1 in 2)
(3 in 10)
(1 in 10)
400
200
120
40
Percentage
(% for
comparison
with test
sample)
2.0
1.0
0.6
0.2
solutions as directed under the Thin-layer Chromatography. Spot each 10 L of the test solution and each
standard solution on a plate of silica gel for thin-layer
toluene, ethanol and strong ammonia water (95 : 15 : 1)
to a distance of about 15 cm and air-dry the plate. Examine the plate under ultraviolet light (254 nm). Compare the intensities of any secondary spots observed in
the chromatogram of the test solution with those of the
principal spots in the chromatograms of the standard
solution: the sum of the intensities of secondary spots
obtained from the test solution corresponds to not more
than 2.0% of related compounds, with no single impurity corresponding to more than 1.0%.
hours).
Assay Weigh accurately about 50 mg of Promazine
Hydrochloride, previously dried, add 0.1 mol/L hydrochloric acid to make exactly 1000 mL and use this
solution as the test solution. Separately weigh accurately 50 mg for Promazine Hydrochloride RS, previuosly
dried and add 0.l mol/L hydrochloric acid to make exactly 100 mL. Pipet exactly 10 mL of this solution, add
0.l mol/L hydrochloric acid to make exactly 100 mL
and use this solution as the standard solution. Determine the absorbances, AT and AS of the test solution
and standard solution of maximum absorbance at about
301 nm, respectively, as directed under the Ultravioletvisible Spectrophotometry, using 0.1 mol/L hydrochloric acid as a blank.
Amount (mg) of promazine hydrochloride

(C17H20N2SHCl) = amount (mg) of Promazine HyAT
drochloride RS A
S
tight containers.
Promazine Hydrochloride
Tablets
Promazine Hydrochloride Tablets contain not less than

of promazine hydrochloride (C17H20N2SHCl: 320.88).
Tablets, with Promazine Hydrochloride.
Identification (1) Weigh a portion of powdered Promazine Hydrochloride Tablets, equivalent to 50 mg of
Promazine Hydrochloride according to the labeled
amount, add 25 mL of 0.01 mol/L hydrochloric acid TS
and filter after shaking well to mix for 5 minutes.
Transfer the filtrate to a separatory funnel, add 2 mL of
1 mol/L sodium hydroxide and 4 mL of carbon disulfide and shake well to mix for 2 minutes. Take the carbon disulfide extract, centrifuge, if necessary, filter
through a dry filter paper and use this solution as the
test solution. Separately, weigh accurately 50 mg of
Promazine Hydrochloride RS, proceed as directed with
the test solution and use this solution as the standard
solution. Determine the infrared spectra of the test solution and the standard solution as directed in the solution
same wavenumbers.
(2) It responds to the Identification (2) for Promazine Hydrochloride.
ment.

Promazine Hydrochloride Tablets. Weigh accurately a
portion of the powder, equivalent to about 50 mg of
promazine hydrochloride (C17H20N2SHCl). Add 50 mL
of 0.1 mol/L hydrochloric acid, shake for about 1 hour,
add 0.1 mol/L hydrochloric acid to make exactly 100
mL, mix and centrifuge. Pipet exactly 10 mL of the supernatant liquid to a separatory funnel, add 20 mL of
water and ammonia TS to make alkali and extract with
four 25 mL volumes of ether. Extract combined ether
extract with five 15 mL volumes of 0.1 mol/L hydrochloric acid TS, collect the hydrochloric acid extracts to a
volumetric flask, evaporate the remaining ether by aeration, add 0.1 mol/L hydrochloric acid TS to make exactly 100 mL and shake. Use this solution as the test
solution. Separately, weigh accurately a quantity of
Promazine Hydrochloride RS, previously dried, add 0.1
mol/L hydrochloric acid TS to make the solution containing 50 g per mL and use this solution as the standard solution. Determine the absorbances, AT and AS, of
of a maximum absorbance at about 301 nm as directed
under the Ultraviolet-visible Spectrophotometry using
0.1 mol/L hydrochloric acid TS as the blank.
Amount (mg) of promazine hydrochlride

AT
(C17H20N2SHCl) = C A
S
C: Concentration of Promazine Hydrochlride RS in
the standard solution (g/mL).
Package and Storage Preserve in light resistant, tight
containers.
Promethazine Hydrochloride
CH3 H
CH2CN
N
CH3
CH3
HCl
and enantiomer
C17H20N2SHCl: 320.88
Promethazine Hydrochloride, when dried, contains not

less than 98.0% and not more than 101.0% of promethazine hydrochloride (C17H20N2SHCl).
Description Promethazine Hydrochloride is a white
to pale yellow powder.
Promethazine Hydrochloride is very soluble in water,
freely soluble in ethanol or in glacial acetic acid, sparingly soluble in acetic anhydride and practically insoluble in ether.
Promethazine Hydrochloride is gradually colored by
light.
A solution of Promethazine Hydrochloride (1 in 25)
of solutions of Promethazine Hydrochloride and Promethazine Hydrochloride RS (1 in 100000) as directed
same wavelengths.
(2) Determine the infrared spectra of Promethazine
Hydrochloride and Promethazine Hydrochloride RS,
(3) Dissolve 0.5 g of Promethazine Hydrochloride
in 5 mL of water, add 2 mL of ammonia TS and filter.
To 5 mL of the filtrate, add dilute nitric acid to make
acidic: the solution responds to the Qualitative Tests (2)
for chloride.
pH Dissolve 1 g of Promethazine Hydrochloride in
and 5.5.
KP 9 809
1.0 g of Promethazine Hydrochloride in 10 mL of water,

protecting form direct sunlight: the solution is clear and
colorless.
(2) Heavy metalsProceed with 1.0 g of Promethazine Hydrochloride according to Method 2 and perform the test. Prepare the control solution with 2.0 mL
(3) Related substancesPerform the test under the
protection from sunlight. Dissolve 0.10 g of Promethazine Hydrochloride in exactly 5 mL of ethanol and use
this solution as the test solution. Pipet exactly 1 mL of
the test solution, add ethanol to make exactly 200 mL
and use this solution as the standard solution (1). Separately, dissolve 20 mg of isopromethazine hydrochloride RS in ethanol to make exactly 100 mL and use this
solution as the standard solution (2). Perform the test
with the test solution and the standard solutions (1) and
(2) as directed under the Thin-layer Chromatography.
solutions (1) and (2) on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of methanol and diethylamine (19 : 1) to a distance of about 12 cm and air-dry
the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots from the test solution corresponding to the spots from the standard solution (2)
are not more intense than the spot from the standard solution (2) and any spot other than the principal spot
from the test solution is not more intense than the spot
from the standard solution (1).
hours).
Assay Weigh accurately about 0.5 g of Promethazine
mixture of acetic anhydride and glacial acetic acid (7
3 ) and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any

= 32.088 mg of C17H20N2SHCl
tight containers.
Propafenone Hydrochloride
OH
H
N
CH3
O
C21H27NO3HCl : 377.91
Propafenone Hydrochloride contains not less than
98.0% and not more than 102.0% of propafenone hydrochloride (C21H27NO3HCl), calculated on the dried
basis.
Description Propafenone Hydrochloride is a white
powder.
Propafenone Hydrochloride is soluble in methanol or in
hot water, slightly soluble in chloroform, very slightly
soluble in acetone and practically insoluble in ether or
in toluene.
spectra of Propafenone Hydrochloride and Propafenone
Hydrochloride RS, as directed in the potassiumn bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) Dissolve 0.5 g of Propafenone Hydrochloride in
50 mL of water by heating and adjust with 0.1 mol/L
sodium hydroxide TS to a pH of 9.5 to 10.0: a precipitate is formed. Cool the mixture, and filter. Add 1 mL
of 6 mol/L nitric acid TS and 2 to 3 drops of 0.1 mol/L
silver nitrate TS to the filtrate: a precipitate is formed.
It dissolves upon the addition of 2 to 3 drops of strong
ammonia solution.
pH Dissolve 0.5 g of Propafenone Hydrochloride in
and 6.2.
1.0 g of Propafenone Hydrochloride in 30 mL of hot
water: the solution is clear.
(2) Heavy metalsProceed with l.0 g of Propafenone Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL
of Standard Lead Solution (not more than 20 ppm).
(3) Methanol and acetoneDissolve a portion of
Propafenone Hydrochloride to make a solution containing 20 mg per 1 mL and use this solution as the test solution. Separately, dissolve methanol and acetone, accurately weighed, to make a solution containing 2.0 g
and 20.0 g per 1 mL, respectively and use this solution as the standard solution. Perform the test with 1.0
directed under the Gas Chromatography according to
the following conditions. Measure the areas of methanol and acetone peaks of each solution and calculate
the amounts of methanol and acetone: not more than
100 ppm of methanol and 1000 ppm of acetone are
found.
HCl
Column: A column, about 0.53 mm in inside diameter and about 30 m in length, coated with 6% cyanopropylphenyl-94% dimethylpolysiloxane for gas chromatography with a thickness of 3.0 m. A silica column
deactivated with phenylmethylsiloxane, about 0.53 mm
in inside diameter and 5 m in length is used as a guard
column.
Column temperature: Maintain the temperature at
40 C for 20 minutes after injection, increase the temperature rapidly to 240 C and maintaine that temperature for 20 minutes.
Inlet temperature: A constant temperature at about
140 C.
Detector temperature: A constant temperature at
about 260 C .
Flow rate: about 35 cm/sec.
System suitability
with 1.0 L of the standard solution according to the
above operating conditions, the resolution between methanol and acetone peaks is not less than 3.0.
times with 1.0 L of the standard solution according to
deviation of each area of methanol and acetone peaks is
not more than 15%.
(4) Related substancesDissolve 0.1 g of Propafenone Hydrochloride in 5.0 mL of methanol and use this
solution as the test solution. Separately, dissolve 0.1 g
of propafenone RS in 5.0 mL of methanol and use this
solution as the standard stock solution. Pipet proper
portions of the standard stock solution, add methanol to
make solutions containing 0.1 and 0.05 mg per 1 mL
and use these solutions as the standard solution (1) and
the standard solution (2), respectively. Perform the test
with the test solution and the standard solution (1) and
the standard solution (2), as directed under Thin Layer
and the standard solution (1) and the standard solution
(2) on silica gel plate with fluorescent indicator for
mixture of 1-propanol, water and glacial acetic acid (4 :
2 : 1) to a distance of about 15 cm, and air-dry the plate.
nm): the relative intensity of each spot from the test solution, except the principal spot, compared to that of
each standard solution is not more than 0.5% and the
total intensity of the spots is not more than 1.0%.
constant mass).
Assay Weigh accurately about 0.25 g of Propafenone
Hydrochloride, dissolve in 30 mL of methanol, add 15
mL of mercuric acetate, and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint De-
tection Method in Titrimetry). Perform a blank determination and make any necessary correction.
tight containers.
Propantheline Bromide
O
C
CH(CH3)2
OCH2CH2
CH3
CH(CH3)2
Br
C23H30BrNO3: 448.39
Propantheline Bromide, when dried, contains not less
than 98.0% and not more than 102.0% of propantheline
bromide (C23H30BrNO3).
Description Propantheline Bromide is a white to yellowish white, crystalline powder, is odorless and has a
very bitter taste.
Propantheline Bromide is very soluble in water, in
ethanol, in glacial acetic acid or in chloroform, soluble
in acetic anhydride and practically insoluble in ether.
pHThe pH of a solution of Propantheline Bromide (1 in 50) is between 5.0 and 6.0.
Melting pointAbout 161 C (with decomposition,
after drying).
Identification (1) Take 5 mL of a solution of Propantheline Bromide (1 in 20), add 10 mL of sodium hydroxide TS, heat to boil for 2 minutes. Cool to 60 C
and add 5 mL of dilute hydrochloric acid. After cooling,
collect the precipitates and wash with water. Recrystallize from dilute ethanol and dry at 105 C for 1 hour:
the crystals melt between 217 C and 222 C.
(2) Dissolve 10 mg of the crystals obtained in (1) in
5 mL of sulfuric acid: a vivid yellow to yellow-red color develops.
(3) Take 5 mL of a solution of Propantheline Bromide (1 in 10), add 2 mL of dilute nitric acid: this solution responds to the Qualitative Tests (1) for bromide.
60 mg of Propantheline Bromide and dissolve in the
mobile phase to make exactly 200 mL and use this solution as the test solution. Separately, weigh accurately
a portion of each 9-bromohydroxypropantheline RS,
xanthantanoic acid RS and xanthon RS, add mobile
phase to make the solution to contain 6.0 g of 9bromo-hydroxypropantheline, 1.5 g each of xanthan-
KP 9 811
tanoic acid and xanthon per mL and use this solution as

the standard solution. Perform the test with each 50 L
under the Liquid Chromatography according to the following operating conditions. Determine the peak areas,
AT and AS, for the test solution and the standard solution, respectively: xanthantinoic acid and xanthone are
not more than 0.5% and 9-bromohydroxyproprntheline
is not more than 2.0%. the total peak area of peaks of
not less than 0.1% except the solvent peak and the
principal peak is not more than 3.0%.
C
AT
Amount (mg) of related substance = 100 C A
x
S
C: Each concentration of 9-bromohydroxypropantheline, xanthantanoic acid and xanthon in the standard
solution (g/mL),
Cx: Concentration of Propantheline Bromide in the
test solution (g/mL)
Amount (%) of all of unidentified related compounds

Ai
of not less than 0.1% = 100 A
t
Ai: Peak area of an unidentified peak
At: Peak area of all peaks
Mobile phase: A mixture of acetonitrile and pH 3.5
buffer (55 : 45).
System suitability
operating conditions, the resolution between their peaks
is not less than 1.2.
times with 50 L of the standard solution as directed
under the above operating conditions, the relative standard deviation of the peak area of propantheline bromide is not more than 2.0%. If the Assay is performed
concomitantly, when the test is repeated 6 times with
50 L of the standard solution obtained in the Assay,
the relative standard deviation of the peak areas of propantheline bromide is not more than 2.0%.
pH 3.5 buffer solutionPrepare as directed in the
Assay under Propantheline Bromide Tablets.
hours).

Assay Weigh accurately about 1.0 g of Propantheline
Bromide, previously dried, dissolve in 50 mL of a mixture of acetic anhydride and glacial acetic acid (7 : 3)

= 44.84 mg of C23H30BrNO3.
Propantheline Bromide Tablets

Propantheline Bromide Tablets contain not less than
of propantheline bromide (C23H30BrNO3: 448.39).
Tablets, with Propantheline Bromide.
Identification Take a portion of powdered Propantheline Bromide Tablets, equivalent to about 0.5 g of
Propantheline Bromide according to the labeled amount,
add 20 mL of chloroform, shake, filter and use the filtrate. Evaporate the filtrate to dryness, add 10 mL of
ether with the residue, shake, evaporate the ether and
proceed with this residue as directed in the Identification under Propantheline Bromide.
Purity Related substanceProceed not less than 20
Propantheline Bromide Tablets as directed in the preparation of the test solution in the Assay and use this solution as the test solution. Separately, weigh accurately a
portion of each 9-bromohydroxypropantheline RS, xanthantanoic acid RS and xanthon RS, add the mobile
phase to make the solution to contain 12.0 g of 9bromo-hydroxypropantheline, 3.0 g each of xanthantanoic acid and xanthon per mL and use this solution as
under the Liquid Chromatography according to the following operating conditions. Determine the peak areas,
AT and AS, for the test solution and the standard solution, respectively: xanthantinoic acid and xanthone are
not more than 1.0% and 9-bromohydroxyproprntheline
C
AT
Amount (mg) of related substance = 100 C A
x
S
C: Each concentration of 9-bromohydroxypropantheline, xanthantanoic acid and xanthon in the standard
solution (g/mL),
Cx: Concentration of Propantheline Bromide in the
test solution (g/mL)
buffer (55 : 45).
System suitability
operating conditions, the resolution between their peaks
times with 50 L of the standard solution as directed
under the above operating conditions, the relative standard deviation of the peak area of Propantheline Bromide is not more than 2.0%. If the Assay is performed
concomitantly, when the test is repeated 6 times with
50 L of the standard solution obtained in the Assay,
the relative standard deviation of the peak areas of propantheline bromide is not more than 2.0%.
Propantheline Bromide Tablets at 50 revolution per
minute, according to Method 2 under the Dissolution
Test, using 500 mL of pH 4.5 acetate buffer, dissolve
1.64 g of anhydrous sodium acetate and 1.25 mL of anhydrous acetic acid in 500 mL of water, add water to
make 1000mL and adjust pH to 4.50 0.05. Take the
dissolved solution after 45 minutes from start of the test
and filter and use this filtrate as the test solution. Separately, weigh exactly a sufficient portion of Propantheline Bromide RS, previously dried at 105 C for 4
hours, dissolve in the dissolution solution, make the
same concentration of the test solution, use this solution as the standard solution. Pipet each 50 L of the
test solution and the standard solution and perform the
test as directed under Assay.
The dissolution rate of Propantheline Bromide Tablets
in 45 minutes is no less than 75%.
ment.

Propantheline Bromide Tablets. Weigh accurately a
portion of the powder, equivalent to about 15 mg of
propantheline bromide (C23H30BrNO3), dissolve in mobile phase, add mobile phase to make exactly 50 mL,
filter and use this filtrate as the test solution. Separately,
weigh exactly 15 mg of Propantheline Bromide RS,
previously dried at 105 C for 4 hours, add mobile

the standard solution. Perform the test with each 50 L
of the test solution and the standard solution, as directed under the Liquid Chromatography according to
peak areas, AT and AS of propantheline bromide for the
Amount (mg) of propantheline bromide (C23H30BrNO3)
= amount (mg) of Propantheline
AT
Bromide RS A
S
buffer (55 : 45).
System suitability
pH 3.5 buffer solutionDissolve 17.3 g of sodium
dodecylsulfate in 1000 mL of water contains 10 mL of
phosphoric acid, add 250 mL of 0.5 mol/L of sodium
hydroxide, stir, adjust pH 3.5 0.05 with 0.5 mol/L sodium hydroxide TS and add water to make 2000 mL.
Propofol
CH3
H3C
OH
CH 3
CH 3
C12H18O : 178.27
Propofol contains not less than 98.0% and not more
than 102.0% of propofol (C12H18O).
Description Propofol is a colorless or pale yellow,
clear liquid.
Propopol is very soluble in methanol or in ethanol,
slightly soluble in cyclohexane or in isopropanol, and
KP 9 813
Identification Determine the infrared spectra of Propopol and Propopol RS, as directed in the liquid film
same wavenumbers.
Refractive index
nD20 : Between 1.5125 and 1.5145.
Purity (1) Related substance IDissolve 0.5 g of

Propofol, accurately weighed, in hexane to make exactly 10 mL and use this solution as the test solution. Separately, dissolve 5 mg of propofol related substance I
{2,6-bis(1-methylethyl)-1,4-benzoquinone}, accurately
weighed, in hexane to make exactly 100 mL and use
this solution as the standard solution. Perfom the test
solution according to the operating conditions in the
Assay as directed under the Liquid Chromatography:
the area of the related substance I peak from the test solution is not more than 5 times the area of the the related substance I peak from the standard solution.

the retention time of propopol.
(2) Related substancesDissolve 1.0 g of Propofol,
accurately weighed, in hexane to make exactly 10 mL
of the test solution, dilute with hexane to make exactly
100 mL. Pipet 1.0 mL of this solution, dilute with hexane to make exactly 10 mL and use this solution as the
standard solution. Perfom the test with 10 L each of
the test solution and the standard solution according to
the operating conditions in the Assay as directed under
the Liquid Chromatography: the area of any peak due
to propopol related substance II {2-(1-methylethoxy)1,3-bis(1-methylethyl)benzene} is not more than 0.4
times the area of the peak due to propopol obtained
from the standard solution (0.2% taking into account a
response factor of 0.2), and the area of any peak due to
propopol related substance III {3,3,5,5-tetrakis(1methylethyl)biphenyl-4-4-diol} is not more than 0.4
times the area of the peak due to propopol obtained
from the standard solution (0.01% taking into account a
response factor of 4.0). The area of any other peak except peaks of propopol and the two related substances
is not more than 0.5 times the area of the peak due to
propopol obtained from the standard solution (0.5%).
The sum of all related substances including the related
substance II and the related substance III is not more
than 0.3%. Disregard any peak with an area less than
0.25 times the area of the peak due to propopol obtained from the standard solution.
Assay Dissolve about 0.24 g of Propopol, accurately
weighed, in hexane to make exactly 100 mL and use
this solution as the test solution. Separately, dissolve
about 0.24 g of Propopol RS, accurately weighed, in
hexane to make exactly 100 mL and use this solution as

under the Liquid Chromatography according to the following conditions, and measure the areas of propopol
obtained from each solutions, AT and AS.
Amount (mg) of propopol (C12H18O)
A
= amount (mg) of Propopol RS T
AS
Column: A stainless steel column about 5 mm in
silica gel for liquid chromatography (5 m in particle
diameter).
Mobile phase: A mixture of ethanol, acetonitrile
and hexane (1 : 7.5 : 990).
System suitability
with 10 L of the system suitability solution (1) under
the above operating conditions, the related substance I
(the retention time is about 2.5 minutes) and the propopol are eluted in this order, and the resolution between
them is not less than 4.0. When the procedure is run
with 10 L of the system suitability solution (2) under
the above operating conditions, the relative retention
times of peaks due to the related substance II and the
related substance III to that of propopol are about 0.5
and about 5, respectively.
as the retention time of propopol.
System suitability solution (1)Dissolve 5 mg of
Propopol RS and 15 mg of the related substance I RS in
hexane to make 15 mL.
System suitability solution (2)Dissolve 1.0 g of
Propopol RS in hexane to make 10 mL.
tight containers filled with an inert atmosphere of gas.
Propranolol Hydrochloride
OH
CH3
OCH2CCH2NHCH
CH3
HCl
C16H21NO2HCl: 295.80
Propranolol Hydrochloride, when dried, contains not
less than 99.0% and not more than 101.0% of propranolol hydrochloride (C16H21NO2HCl).

Description Propranolol Hydrochloride is a white,
Propranolol Hydrochloride is freely soluble in methanol, soluble in water, in ethanol or in glacial acetic acid,
sparingly soluble in chloroform and practically insoluble in ether.
Propranolol Hydrochloride is colored by light.
of solutions of Propranolol Hydrochloride and Propranolol Hydrochloride RS in methanol (1 in 50000) as directed under the Ultraviolet-visible Spectrophotometry:
(2) Determine the infrared spectra of Propranolol
Hydrochloride and Propranolol Hydrochloride RS, previously dried, as directed in the potassium chloride disk
same wavenumbers.
(3) A solution of Propranolol Hydrochloride (1 in
1.0 g of Propranolol Hydrochloride in 20 mL of water:
(2) Heavy metalsProceed with 1.0 g of Propranolol Hydrochloride according to Method 4 and perform
(3) Related substancesDissolve 20 mg of Propranolol Hydrochloride in 10 mL of the mobile phase,
mL of the test solution, and add the mobile phase to
make exactly 100 mL. Pipet exactly 1 mL of this solution, add the mobile phase to make exactly 10 ml, and
standard solution as directed under Liquid Chromatorraphy according to the following conditions, and determine each peak area by the automatic integration
method: the area of the peak other than propranolol is
not larger than 1/2 times the peak area of propranolol
from the standard solution, and the total area of the
peaks other than the peak of propranolol is not larger
than 2 times the peak area of propranolol from the
standard solution.
(wavelength: 292 jmm).
particle diameter)
about 25 C.
Mobile phase: Dissolve 1.6 g of sodium lauryl sul-
fate and 0.31 g of tetrabutylammonium phosphate in

450 mL of water, add 1 mL of sulfuric acid and 550 mL
of acetonitrile for liquid chromatography, and adjust to
pH 3.3 with 2 mol/L sodium hydroxide TS.
time of propranolol is about 4 minutes.
System suitability
Test for required detectability: Measure exactly 5
mL of the standard solution, and add the mobile phase
to make exactly 20 mL. Confirm that the peak area of
propranolol obtained with 20 L of this solution is
equivalent to 17 to 33% of that with 20 L of the standard solution.
operating conditions, the number of theoretical plates
and the symmetry factor of the peak of propranolol is
not less than 3000 and not more than 2.0, respectively.
above operating conditions, the relative standard deviation of the peak area of propranolol is not more than
2.0%.
long as the retention time of propranolol.
hours).
Assay Weigh accurately about 0.5 g of Propranolol
correction.

Propylthiouracil
CH3CH2CH2
H
N
NH
C7H10N2OS: 170.23
Propylthiouracil, when dried, contains not less than
KP 9 815
98.0% and not more than 101.0% of propylthiouracil

(C7H10N2OS).
Description Propylthiouracil is a white powder, odorless and has a bitter taste.
Propylthiouracil is sparingly soluble in ethanol and
very slightly soluble in water or in ether.
Propylthiouracil dissolves in sodium hydroxide TS or
in ammonia TS.
Identification (1) Shake well 20 mg of Propylthiouracil with 7 mL of bromine TS for 1 minute and heat
until the color of bromine TS disappears. Cool, filter
and add 10 mL of barium hydroxide TS to the filtrate: a
white precipitate is produced. The color of the precipitate does not turn purple within 1 minute.
(2) Take 5 mL of a hot saturated solution of Propylthiouracil, add 2 mL of a solution of sodium pentacyanoammine ferroate (1 in 100): a green color develops.
Purity (1) SulfateTriturate Propylthiouracil to the
finely powder, to 0.75 g of the powder, add 25 mL of
water, heat for 10 minutes in a water-bath, cool, filter
and wash the residue with water until the volume of the
filtrate becomes 30 mL. To 10 mL of the filtrate, add 1
mL and perform the test with this solution as the test
(2) ThioureaDissolve 0.3 g of Propylthiouracil in
50 mL of water by heating under a reflux condenser for
5 minutes, cool and filter. To 10 mL of the filtrate, add
3 mL of ammonia TS, shake well and add 2 mL of silver nitrate TS: the solution has no more color than the
Control solutionWeigh exactly 60 mg of thiourea
and dissolve in water to make exactly 100 mL. Pipet
1.0 mL of this solution, add water to make exactly 100
mL and proceed with 10 mL of this solution in the
same manner.
hours).
Assay Weigh accurately about 0.3 g of Propylthiouracil, previously dried and add 30 mL of water. Add 30
mL of 0.1 mol/L sodium hydroxide VS, heat to boil and
dissolve by stirring. Wash down the solid adhering to
the wall of the flask with a small volume of water and
add 50 mL of 0.1 mol/L silver nitrate VS with stirring.
Boil gently for 5 minutes, add 1 to 2 mL of bromothymol blue TS and titrate with 0.1 mol/L sodium hydroxide VS until a persistent blue-green color develops. Determine the total volume of 0.1 mol/L sodium hydroxide VS consumed.

= 8.512 mg of C7H10N2OS
Propylthiouracil Tablets
Propylthiouracil Tablets contain not less than 93.0%
propylthiouracil (C7H10N2OS: 170.23).
Tablets, with Propylthiouracil.
Identification Take a portion of powdered Propylthiouracil Tablets, equivalent to 0.3 g of Propylthiouracil according to the labeled amount, add 5 mL of ammonia TS, allow to stand for 5 minutes with occasional
shaking, add 10 mL of water and centrifuge. To the supernatant liquid, add acetic acid, collect the precipitate
produced, recrystallize from water and dry at 105 C
for 1 hour: it melts between 218 C and 221 C. Proceed with the residue as directed in the Identification
under Propylthiouracil.
Propylthiouracil Tablets at 75 revolutions per minute
according to Method 2 under the Dissolution Test, using 900 mL of diluted phosphate buffer solution, pH
6.8 (1 in 2). Take 20 mL or more of the dissolved solution after 30 minutes from the starting of the test and
more than 0.8 m. Discard the first 10 mL of the filtrate and use the subsequent as the test solution. Separately, weigh accurately about 50 mg of Propylthiouracil RS, previously dried at 105 C for 3 hours, dissolve
in diluted phosphate buffer solution, pH 6.8 (1 in 2), to
make exactly 1000 mL and use this solution as the
AS , of the test solution and the standard solution, respectively, at 274 nm as directed under the Ultravioletvisible Spectrophotometry.
The dissolution rate of Propylthiouracil Tablets in 30

A
1
of Propylthiouracil (C7H10N2OS) = W S T 90
AS C
WS : Amount (mg) of Propylthiouracil RS,
C: Labeled amount (mg) of propylthiouracil
(C7H10N2OS) in each tablet.

ment.

Propylthiouracil Tablets. Weigh accurately a portion of
the powder, equivalent to about 0.3 g of propylthiouracil (C7H10N2OS), transfer to a Soxhlet extractor and extract with 100 mL of acetone for 4 hours. Evaporate the
acetone extract by warming in a water-bath to dryness.
To the residue, add 30 mL of water and proceed as directed in the Assay under Propylthiouracil.

= 8.512 mg of C7H10N2OS
Protamine Sulfate
Protamine Sulfate is the sulfate of protamine prepared
from the mature spermary of fish belonging to the
family Salmonidae and others.
Description Protamine Sulfate is a white to pale
grayish yellow powder.
Protamine Sulfate is slightly soluble in water and practically insoluble in ethanol or in ether.
pHThe pH of a solution of Protamine Sulfate (1
Identification (1) Dissolve 1 mg of Protamine Sulfate in 2 mL of water, add 5 drops of a solution prepared by dissolving 0.1 g of -naphthol in 100 mL of
diluted ethanol (7 in 10) and 5 drops of sodium hypochlorite TS, then add sodium hydroxide TS until the
solution becomes alkaline: a vivid red color develops.
(2) Dissolve 5 mg of Protamine Sulfate in 1 mL of
water by warming, add 1 drop of a solution of sodium
hydroxide (1 in 10) and 2 drops of cupric sulfate TS: a
red-purple color develops.
(3) The solution of Protamine Sulfate (1 in 20) responds to the Qualitative Tests for sulfate.
0.10 g of Protamine Sulfate in 10 mL of water: the solution is clear and colorless.
(2) NitrogenWeigh accurately 10 mg of Protamine Sulfate, previously dried at 105 C to constant
mass and perform the test as directed under the Nitrogen Determination: not more than 0.255 mg of nitrogen
(N: 14.01) is found for each mg of Protamine Sulfate.
Potency as Antiheparin (1) Test solutionDissolve
20.0 mg of Protamine Sulfate in isotonic sodium chloride injection to make exactly 20 mL.
(2) Heparin sodium standard solutionDissolve

10.0 mg of Heparin Sodium RS in isotonic sodium
chloride injection to make a standard solution containing exactly 0.7 mg per mL.
(3) Sulfated whole bloodPlace 250 mL of fresh
bovine blood in a wide-mouthed stoppered polyethylene bottle containing 50 mL of a solution of sodium
sulfate decahydrate (9 in 50), and store between 1 C
and 4 C. Remove any clotted substance before use.
(4) Thrombokinase extractTo 1.5 g of acetonedried cattle brain add 60 mL of water, extract at 50 C
for 10 to 15 minutes, and centrifuge for 2 minutes at
1500 revolutions per minute. To the supernatant add
cresol to make 0.3% as a preservative, and store between 1 C and 4 C. The potency of this solution is
maintained for several days.
(5) ProcedureTo one of 10 clean, stoppered test
tubes, 13 mm in inside diameter and 150 mm in length,
transfer 1.30 mL of isotonic sodium chloride injection
and 0.20 mL of thrombokinase extract, then add exactly
1 mL of sulfated whole blood, stopper the tube, mix the
contents by inverting once and note the time on a stopwatch. When the solid clot which is formed at the bottom of the tube does not fall on inverting the tube, designate this time as the control clotting time. Adjust appropriately the volume of thrombokinase extract so that
the control clotting time is between 2 and 3 minutes. To
the nine remaining tubes, add 0.50 mL of the test solution and the same volume of thrombokinase extract as
was used in the previous measurement of the control
clotting time, pipet into the tubes 0.43 mL, 0.45 mL,
0.47 mL, 0.49 mL, 0.50 mL, 0.51 mL, 0.53 mL, 0.55
mL and 0.57 mL of the heparin sodium standard injection solution, respectively and make the volume in each
tube up to 1.50 mL by adding Isotonic Sodium Chloride Injection. Add finally 1.0 mL of sulfated whole
blood, stopper, mix the contents by inverting once and
determine the clotting times with a stop-watch, The estimated ratio, /V, is between 0.85 and 1.15, where is
the volume of the heparin sodium standard solution and
V is the volume of the test solution in that tube in
which the clotting time is most nearly the same as the
control clotting time.
Protamine Sulfate Injection

Protamine Sulfate Injection is an aqueous solution for
injection. The amount of Protamine Sulfate should be
labeled.
Method of Preparation Prepare as directed under Injections, with Protamine Sulfate.
Description Protamine Sulfate Injection is a colorless
liquid, is odorless or has the odor of preservatives.
KP 9 817
Identification (1) Dilute a volume of Protamine Sulfate Injection, equivalent to 1 mg of protamine sulfate
according to the labeled amount, with water to make 2
mL and proceed as directed on the Identification (1)
under Protamine Sulfate.
(2) Dilute a volume of Protamine Sulfate Injection,
equivalent to 5 mg of protamine sulfate according to
the labeled amount, with water to make 1 mL and proceed as directed in the Identification (2) under Protamine Sulfate.
(3) Protamine Sulfate Injection responds to the Qualitative Tests for sulfate.
Purity NitrogenTransfer an exactly measured volume of Protamine Sulfate Injection, equivalent to
about 10 mg of Protamine Sulfate according to the labeled amount, to a Kjeldahl flask and evaporate on a
water-bath with the aid of a current of air to dryness.
Perform the test as directed under the Nitrogen Determination: 0.225 mg to 0.255 mg of nitrogen (N: 14.01)
is found for each mg of the labeled amount of Protamine Sulfate.
Potency as Antiheparin Proceed as directed in the
Potency as antiheparin under Protamine Sulfate, but use
the following test solution.
Test solutionDilute an exactly measured volume
of Protamine Sulfate Injection, equivalent to 20.0 mg of
Protamine Sulfate according to the labeled amount,
with Isotonic Sodium Chloride Injection to make exactly 20 mL.
tainers.
Prothionamide
N
CH2CH2CH3
Prothionamide, when dried, contains not less than

98.0% and not more than 101.0% of prothionamide
(C9H12N2S).
Description Prothionamide is a yellow crystal or
crystalline powder and has a slight, characteristic odor.
Prothionamide is freely soluble in methanol or in glacial acetic acid, soluble in ethanol, slightly soluble in
Prothionamide dissolves in dilute hydrochloric acid or
in dilute sulfuric acid.
Identification (1) Mix 50 mg of Prothionamide with
0.1 g of 2,4-dinitrochlorobenzene, transfer about 10 mg
of this mixture to a test tube and heat for several
seconds over a small flame until the mixture is fused.
Cool and add 3 mL of potassium hydroxide-ethanol TS:
a red to orange-red color develops.
(2) Place 0.5 g of Prothionamide in a beaker and
dissolve in 20 mL of sodium hydroxide TS by heating
while shaking occasionally: the gas evolved turns a
moistened red litmus paper to blue. Boil gently and
evaporate the solution to 3 to 5 mL. After cooling, add
gradually 20 mL of glacial acetic acid and heat in a water-bath: the gas evolved the moistened red lithmus paper to blue. Evaporate the solution in a water-bath to 3
mL to 5 mL with the aid of a current of air, cool, add 10
mL of water and mix well. Filter the crystals by suction,
recrystallize from water immediately and dry in a desiccator (in vacuum, silica gel) for 6 hours: the crystals
melt between 198 C and 203 C (with decomposition).
0.5 g of Prothionamide in 20 mL of ethanol: the solution is clear and shows a yellow color.
(2) AcidDissolve 3.0 g of Prothionamide in 20
mL of methanol with warming. Add 100 mL of water to
the solution, cool in an ice water-bath with agitation
and remove any precipitate by filtration. Allow 80 mL
of the filtrate to cool to room temperature and add 0.8
mL of cresol red TS and 0.20 mL of 0.1 mol/L sodium
hydroxide VS: a red color develops.
(3) Heavy metalsProceed with 1.0 g of Prothionamide according to Method 2 and perform the test.
Prothionamide according to Method 3 and perform the
test. To the test solution, add 10 mL of a solution of
magnesium nitrate in ethanol (1 in 50), then add 1.5 mL
of strong hydrogen peroxide and ignite to burn (not
more than 3.3 ppm).
hours).
CSNH2
C9H12N2S: 180.27

Assay Weigh accurately about 0.3 g of Prothionamide,
previously dried, dissolve in 50 mL of glacial acetic acid and titrate with 0.1 mol/L perchloric acid VS until
the color of the solution changes from orange-red to
dark orange-brown (indicator: 2 mL of naphtholbenzeine TS). Perform a blank determination

= 18.027 mg of C9H12N2S
Protirelin
NH
N
O
O
H
N
O
H
CH2
C
H
NH2
N
N
H
C
O
C16H22N6O4: 362.38
Protirelin contains not less than 98.5% and not more
than 101.0% of protirelin (C16H22N6O4), calculated on
Description Protirelin is a white powder.
Protirelin is freely soluble in water, in methanol, in
ethanol or in glacial acetic acid.
Protirelin is hygroscopic.
Identification (1) Take 10 mg of Protirelin in a test
tube made of hard glass, add 0.5 mL of 6 mol/L hydrochloric acid TS, seal the upper part of the tube and
heat carefully at 110 C for 5 hours. After cooling, open
the seal, transfer the contents into a beaker and evaporate on a water-bath to dryness. Dissolve the residue in
1 mL of water and use this solution as the test solution.
Separately, dissolve 80 mg of L-glutamic acid, 0.12 g
of L-histidine hydrochloride and 60 mg of L-proline in
20 mL of water and use this solution as the standard solution. Perform the test with the test solution and the
mixture of n-butanol, water, glacial acetic acid and pyridine (4 : 1 : 1 : 1) to a distance of about 12 cm and dry
the plate at 100 C for 30 minutes. Spray evenly a solution of ninhydrin in acetone (1 in 50) on the plate and
heat at 80 C for 5 minutes: the three spots obtained
from the test solution show the same color and the
same Rf value as each corresponding spots obtained
(2) Determine the infrared spectra of Protirelin and
Protirelin RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
pH Dissolve 0.2 g of Protirelin in 10 mL of water: the
D : Between -66.0
and -69.0 (calculated on the anhydrous basis, 0.1 g,
water, 20 mL, 100 mm).
0.1 g of Protirelin in 10 mL of water: the solution is
(2) Heavy metalsProceed with 1.0 g of Protirelin
(3) Related substancesDissolve 0.20 g of Protirelin in 10 mL of water and use this solution as the test
solution. Pipet exactly 1 mL of this solution, add water
and the standard solution as directed under the Thinlayer Chromatography. Spot 5 L each of the test solution and the standard solution on a plate (1) of silica gel
for thin-layer chromatography and spot 5 L of the test
solution on a plate (2) of silica gel for thin-layer chromatography. Develop the plates with a mixture of nbutanol, water, pyridine and glacial acetic acid (4 : 2 :
1 : 1) to a distance of about 12 cm and dry the plates at
100 C for 30 minutes. Spray evenly a mixture of a solution of sulfanilic acid in 1 mol/L hydrochloric acid
TS (1 in 200) and a solution of sodium nitrite (1 in 20)
(1 : 1) on the plate (1) and air-dry the plates. Successively spray evenly a solution of sodium carbonate (1
in 10): the spots other than the principal spot from the
standard solution. Spray evenly a solution of ninhydrin
in acetone (1 in 50) on the plate (2) and heat at 80 C
for 5 minutes: no colored spot appears.
Water Not more than 5.0% (0.1g, volumetric titration,
direct titration).
Assay Weigh accurately about 70 mg of Protirelin
dissolve in 50 mL of glacial acetic acid and titrate with

= 7.248 mg of C16H22N6O4
KP 9 819
Protirelin Tartrate Hydrate

D : Between -50.0
and -53.0 (0.5 g, calculated on the anhydrous basis,
water, 25 mL, 100 mm).
H
N
O
N
C
H
O
O
H2O
N
CHOH
CO2H
N
H
H
CO2H
CHOH
CH2
H
N
NH2
and 4.0.
Cl6H22N6O4C4H6O6H2O : 530. 49
Protirelin Tartrate Hydrate contains not less than 98.5%
and not more than 101.0% of protirelin tartrate
(Cl6H22N6O4C4H6O6: 512.47), calculated on the anhydrous basis.
Description Protirelin Tartrate Hydrate is a white to
pale, yellowish white crystal or crystalline powder.
Protirelin Tartrate Hydrate is freely soluble in water,
sparingly soluble in glacial acetic acid and practically
insoluble in ethanol or in ether.
Identification (1) Take 1 mL of a solution of Protirelin Tartrate Hydrate (1 in 1000), add 2 mL of a solution
of p-nitrobenzene diazonium fluoroborate (1 in 2000)
and 2 mL of boric acid potassium chloride-sodium hydroxide buffer solution, pH 9.0: a red color develops.
(2) Dissolve 30 mg of Protirelin Tartrate Hydrate in
5 mL of sodium hydroxide TS, add 1 drop of cupric
sulfate TS: a purple color develops.
(3) To 0.20 g of Protirelin Tartrate Hydrate, add 5.0
mL of 6 mol/L hydrochloric acid TS and boil for 7
hours under a reflux condenser. After cooling, evaporate 2.0 mL of this solution in a water-bath to dryness,
dissolve the residue in 2.0 mL of water and use this solution as the test solution Separately, dissolve 22 mg of
L-glutamic acid, 32 mg of L-histidine hydrochloride
monohydrate and 17 mg of L-proline in 2.0 mL of 0.1
mol/L hydrochloric acid TS by heating and use this solution as the standard solution. Perform the test with
plate with a mixture of n-butanol, water, glacial acetic
acid and pyridine (4 : 1 : 1 : 1) to a distance of about 12
cm and dry at 100 C for 30 minutes. Spray evenly a
solution of ninhydrin in acetone (1 in 50) on the plate
and dry at 80 C for 5 minutes: the three spots obtained
from the test solution show, respectively, the same color and the same Rf value as the corresponding spot from
(4) A solution of Protirelin Tartrate Hydrate (1 in
40) responds to the Qualitative Tests for tartrate.
pH Dissolve 1.0 g of Protirelin Tartrate Hydrate in

0.10 g of Protirelin Tartrate Hydrate in 10 mL of water:
(2) Heavy metalsProceed with 1.0 g of Protirelin
Tartrate Hydrate according to Method 2 and perform
standard lead aolution (not more than 20 ppm).
(3) ArsenicTake 1.0 g of Protirelin Tartrate Hydrate in a porcelain crucible. Add 10 mL of a solution
of magnesium nitrate in ethanol (1 in 10), ignite ethanol
and heat gradually to incinerate. If a carbonized material still remains in this method, moisten with a small
quantity of nitric acid and ignite to incinerate. After
cooling, add 10 mL of dilute hydrochloric acid, heat in
a waterbath to dissolve the residue, use this solution as
the test solution and perform the test (not more than 2
ppm).
(4) Related SubstancesDissolve 0.60 g of Protirelin Tartrate Hydrate in 10 mL of water and use this
test solution, add water to make exactly 200 mL and
on a plate (1) of silica gel for thin-layer chromatography. Spot 5 L of the test solution on a plate (2) of silica gel for thin-layer chromatography. Develop the
plates with a mixture of chloroform, methanol and
strong ammonia water (6 : 4 : 1) to a distance of about
10 cm and dry at 100 C for 30 minutes. Spray evenly a
mixture of a solution of sulfanilic acid in 1 mol/L hydrochloric acid TS (1 in 200) and a solution of sodium
nitrite (1 in 20) (1:1) on the plate (1) and air-dry the
plate. Then, spray evenly a solution of sodium carbonate (1 in 10) on the plate: the spots other than the principal spot from the test solution are not more intense
than those from the standard solution in color. On the
other hand, spray evenly a solution of ninhydrin in acetone (1 in 50) on the plate (2) and dry at 80 C for 5
minutes: no colored spot is obtained.
Assay Weigh accurately about 0.5 g of Protirelin Tartrate Hydrate, dissolve in 80 mL of glacial acetic acid
by warming, cool and titrate with 0.1 mol/L perchloric
acid VS (potentiometric titration, Endpoint Detection
Method in Titrimetry). Perform a blank determination

= 51.25 mg of Cl6H22N6O4C4H6O6
KP 9 821
Pseudoephedrine Hydrochloride
H
OH
H
N
CH3
H3C
HCl
spots, excluding the principal spot, from the test solution with the intensity of the spots from the standard
solutions: the sum of all related substances is not more
than 2.0%.
Loss on Drying Not more than 0.5% (1 g, 105 o C , 3
hours).
C10H15NOHCl : 201.69
Pseudoephedrine Hydrochloride contains not less than
98.0% and not more than 100.5% of pseudoephedrine
hydrochloride (C10H15NOHCl), calculated on the dried
basis.
Description Pseudoephedrine Hydrochloride is a fine
white crystal or powder with a slightly characteristic
ordor.
Pseudoephedrine Hydrochloride is very soluble in water, freely soluble in ethanol, and slightly insoluble in
chloroform.
spectra of Pseudoephedrine Hydrochloride and Pseudoephedrine Hydrochloride RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
(2) The solution of Pseudoephedrine Hydrochloride
in water (1 in 50) responds to the Qualitative Tests for
chloride (the Flame Coloration Test 2).
of Pseudoephedrine Hydrochloride in 20 mL of water is
D : Between +61.0
and +62.5 (0.5 g, water, 10 mL, 100 mm).
Purity Related substancesDissolve 0.1 g of Pseudoephedrine Hydrochloride, accurately weighed, in
ethanol to make exactly 10 mL, and use this solution as
the test solution. Separately, dissolve 1.0, 5.0, 10.0 and
20.0 mg each of Pseudoephedrine Hydrochloride RS in
ethanol to make exactly 100 mL. Use these solutions as
the standard solutions (1), (2), (3) and (4), respectively.
Perform the test with these solutions as directed under
test solution and the standard solutions on a plate of silica gel with fluorescent indicator for thin-layer chromatography, develop with a mixture of ethanol, glacial
acetic acid, and water (10:3:1) to a distance of about 15
cm, and dry the plate for 2 hours with a current from a
hot air dryer. Expose the plate to iodine vapors for not
less than 30 minutes. Compare the intensity of all the
Assay Dissolve about 0.4 g of Pseudoephedrine Hydrochloride, accurately weighed, in a mixture of 50 mL

of glacial acetic acid and 10 mL of mercuric acetate TS,
and titrate with 0.1 mol/L perchloric acid VS (indicator:
1 drop of methylrosaniline chloride). Perform a blank
determination and make any necessary correction.

= 20.17 mg of C10H15NOHCl.
tight containers.
Pyrantel Pamoate
COOH
CH3
H
N
OH
S
C
N
C
H
CH2
OH
COOH
C11H14N2SC23Hl6O6: 594.68
Pyrantel Pamoate, when dried, contains not less than
98.0% and not more than 101.0% of pyrantel pamoate
(C11H14N2-SC23Hl6O6).
Description Pyrantel Pamoate is a pale yellow to yellow, crystalline powder, is odorless and tasteless.
Pyrantel Pamoate is sparingly soluble in dimethylformamide, very slightly soluble in methanol or ethanol,
and practically insolubale in water, ethyl acetate, ether
or chloroform.
decomposition).
Identification (1) Take 50 mg of Pyrantel Pamoate,
add 10 mL of methanol and 1 mL of a mixture of hydrochloric acid and methanol (1 : 1) and shake vigorously: a yellow precipitate is produced. Filter the solution and use filtrate as the test solution, Use the precipitate for Identification (2). To 0.5 mL of the test solution,
add 1 mL of a solution of Isatin in sulfuric acid (1 in
1000): a red color develops.
(2) Collect the precipitate obtained in (1), wash

with methanol and dry at 105 C for 1 hour. To 10 mg
of the dried precipitate, add 10 mL of methanol, shake
well and filter. To 5 mL of the filtrate, add 1 drop of
ferric chloride TS: a green color develops.
(3) Dissolve 0.1 g each of Pyrantel Pamoate and
Pyrantel Pamoate RS in 50 mL of dimethylformamide
and add methanol to make 200 mL, respectively. To 2
mL each of these solutions, add a solution of hydrochloric acid in methanol (9 in 1000) to make 100 mL, respectively. Determine the absorption spectra of these
solutions as directed under Ultraviolet-visible Spectrophotometry, respectively: both spectra exhibit similar
(4) Determine the infrared spectra of Pyrantel Pamoate and Pyrante Pamotate RS, previously dried, as
same wavenumbers.
Purity (1) ChlorideTake 1.0 g of Pyrantel Pamoate,
add 10 mL of dilute nitric acid and 40 mL of water and
heat on a water-bath with shaking for 5 minutes. After
cooling, add water to make 50 mL and filter. To 20 mL
of the filtrate, add 2 mL of dilute nitric acid and water
to make 50 mL. Perform the test using this solution as
0.036%).
(2) SulfateTake 0.75 g of Pyrantel Pamoate, add
5 mL of dilute hydrochloric acid and water to make 100
mL and heat on a water-bath for 5 minutes with shaking.
After cooling, add water to make 100 mL and filter. To
20 mL of the filtrate, add water to make 50 mL. Perform the test using this solution as the test solution.
mol/L sulfuric acid VS (not more than 0.144%).
(3) Heavy metalsProceed with 1.0 g of Pyrantel
Pamoate according to Method 2 and perform the test.
Pyrantel Pamoate according to Method 3 and perform
(5) Related substancesPerform the test under
protection from direct sunlight in light-resistant vessels.
Dissolve 0.10 g of Pyrantel Pamoate in l0 mL of dimethylformamide and use this solution as the test solution.
Pipet exactly 1 mL of the test solution, add dimethylformamide to make exactly 100 mL and use this solution as the standard solution. Perform the test with the
test solution and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, water and glacial acetic acid (3 : 1 : 1) to a distance of about 10 cm and air-dry the plate. Examine
under ultraviolet light (main wavelength: 254 nm): any
spot other than the spot of pyrantel and pamoic acid

of pyrantel (Rf value: about 0.3) from the standard solultion.
hours)
Assay Weigh accurately about 0.5 g of Pyrantel Pamoate, previously dried, add 25 mL of chloroform and
25 mL of sodium hydroxide TS, shake for 15 minutes
and extract. Extract further with two 25 mL volumes of
chloroform. Filter each extract through 5 g of anhydrous sodium sulfate on a pad of absorbent cotton. Combine the chloroform extracts, add 30 mL of glacial acetic acid and titrate with 0.1 mol/L perchloric acid VS
(indicator: 2 drops of methylrosaniline chloride TS).
correction.

= 59.47 mg of C11H14N2SC23Hl6O6
Pyrazinamide
N
CONH2
C5H5N3O: 123.11
Pyrazinamide, when dried, contains not less than 99.0%
and not more than 101.0% of pyrazinamide (C5H5N3O).
Description Pyrazinamide is a white crystal or crystalline powder, is odorless and has a slightly bitter taste.
Pyrazinamide is sparingly soluble in water, slightly soluble in ethanol or acetic anhydride.
of solutions of Pyrazinamide and Pyrazinamide RS, respectively, in 0.1 mol/L hydrochloric acid TS (1 in
100000) as directed under Ultraviolet-visible Spectrophotometry : both spectra exhibit similar intensities of
(2) Determine the infrared spectra of Pyrazinamide
and Pyrazinamide RS, previously dried, as directed in
Spectrophotometry, respectively: both spectra exhibit
KP 9 823
Purity (1) Heavy metalsProceed with 1.0 g of Pyrazinamide according to Method 2 and perform the test.
(2) Related substancesDissolve 0.10 g of Pyrazinamide in 10 mL of methanol, and use this solution as the
add methanol to make exactly 200 mL, and use this solution as the standard solution. Perform the test with
these solutions as directed under Thin-layer Chromatography. Spot 20 L each of the test solution and standard solution on a plate of silica gel with fluorescent
plate with a mixture of 1-butanol, water and glacial
acetic acid (3 : 1 : 1) to a distance of about 10cm, and
wavelength: 254 nm): any spot other than the principal
spot from the test solution is not more intense than the
spot from the standard solution .
Assay Weigh accurately about 0.1 g of Pyrazinamide,
previously dried, in 50 mL of acetic anhydride, and titrate with 0.1 mol/L perchloric acid VS (potentiometric
Perform a blank determination in the same manner, and

= 12.31 mg of C5H5N3O
Pyrazinamide Tablets
Pyrazinamide Tablets contain not less than 93.0% and
not more than 107.0% of the labeled amount of pyrazinamide (C5H5N3O: 123.11).
mide RS at the wavelength of maximum absorption at

about 268 nm, respectively: the difference is not more
than 3.0%.
(2) Take 20 mg of the crystals obtained in Identification
(1), add 5 mL of 5 mol/L sodium hydroxide and heat
gently: the odor of ammonia is perceptible.
Dissolution Test Perform the test with 1 tablet of Pyrazinamide Tablets at 50 revolutions per minute according to Method 2 under the Dissolution Test, using 900
mL of water. Take the dissolved solution after 45 minutes from start of the test, filter, dilute with water, if
necessary and use this solution as the test solution.
Separately, weigh accurately a portion of Pyrazinamide
RS, add water to make constant concentration and use
this solution as the standard solution. Determine the absorbances of the test solution and the standard solution
Spectrophotometry using the water as the blank.
The dissolution rate of Pyrazinamide Tablets in 45 minutes is not less than 75%.
ment.

Pyrazinamide Tablets. Weigh accurately a portion of
the powder, equivalent to about 0.1 g of pyrazinamide
(C5H5N3O) and transfer with the aid of 300 mL of water to a volumetric flask. After sonication for 10 minutes, add water to make exactly 500 mL and mix. Filter this solution, discard the first portion of the filtrate,
take exactly 20 mL of the subsequent filtrate, add water
to make 100 mL and use this solution as the test solution. Separately, weigh accurately about 0.1 g of Pyrazinamide RS, add water to make exactly 500 mL, pipet
exactly 20 mL of this solution, add water to make exactly 100 mL and use this solution as the standard solution. Perform the test with 20 L each of the test solution and the standard solution as directed under the
Liquid Chromatography according to the following operating conditions and determine the peak areas, AT
and AS , of Pyrazinamide from the test solution and

Tablets, with Pyrazinamide.
Amount (mg) of pyrazinamide (C5H5N3O)

A
= amount (mg) of Pyrazinamide RS T
AS
Identification (1) Take a portion of powdered Pyrazinamide Tablets, equivalent to about 1 g of Pyrazinamide, add about 75 mL of isopropanol, heat in the water-bath and filter when it is hot. Allow to cool, filter
the crystals that form and dry at 105 C for 1 hour. Determine the absorption spectra of the aqueous solutions
(1 in 100000) of the crystals so obtained and Pyrazinamide RS, respectively, under the Ultraviolet-visible
Spectrophotometry: both spectra exhibit maximum and
minimum at the same wavenumbers. Determine the absorption spectra of the crystal solution and Pyrazina-
Mobile phase: Add phosphoric acid to phosphate
buffer, pH 8.0 and adjust pH to 3.0. To 1000 mL of this
solution add 10 mL of acetonitrile, shake and filter.

more than 1.3, the number of theoretical plate is not
less than 2500. To 1 mL of hydrochloric acid, add the
standard solution to make 5 mL, allow to stand in the
boiling water-bath for 5 minutes, cool and proceed under the above operation conditions, pyrazinoic acid and
Pyrazinamide are eluted in this order with the resolution between their peaks being not less than 6.0.
Pyridostigmine Bromide
CH3
N
Br
O
O
N(CH3)2
C9H13BrN2O2: 261.12
Pyridostigmine Bromide, when dried, contains not less
than 98.5% and not more than 101.0% of pyridostigmine bromide (C9H13BrN2O2).
Description Pyridostigmine Bromide is as a white,
crystalline powder, is odorless or has a slightly characteristic odor.
Pyridostigmine Bromide is very soluble in water, freely
soluble in ethanol or glacial acetic acid, and practically
insoluble in ether.
Pyridostigmine Bromide is deliquescent.
pHThe pH of a solution of Pyridostiginine Bromide (1 in 10) is between 4.0 and 6.0.
Identificatlon (1) Dissolve 20 mg of Pyridostigmine
Bromide in 10 mL of water, add 5 mL of Reinecke salt
(2) Take 0.1 g of Pyridostigmine Bromide, add 0.6
mL of sodium hydroxide TS: the unpleasant odor of
dimethylamine is perceptible.
Pyridostigmine Bromide and Pyridostigmine Bromide
RS, respectively, in 0.1 mol/L hydrochloric acid TS (1
(4) A solution of Pyridostigmine Bromide (1 in 50)
responds to the Qualitative Tests for bromide.
1.0 g of Pyridostigmine Bromide in 10 mL of water: the

(2) Heavy metalsProceed with 1.0 g of Pyridostigmine Bromide according to Method 1 and perform
Pyridostigmine Bromide according to Method 1 and
(4) Related substancesDissolve 0.10 g of Pyridostigmine Bromide in 10 mL of ethanol and use this
test solution and add ethanol to make exactly 10 mL.
Pipet exactly 1 mL of this solution, add ethanol to make
and the standard solution on a plate of silica gel with
Develop the plate with a mixture of methanol, chloroform and ammonium chloride TS (5 : 4 : 1) to a distance of about 12 cm and air-dry the plate. Examine
under ultraviolet light (main wavelength: 254 nm): any
spot other than the principal spot from the test solution
is not more intense than the spot from the standard solution.
P2O5, 100 C, 5 hours).
Assay Weigh accurately about 0.3 g of Pyridostigmine Bromide, previously dried, dissolve in 10 mL of
titrate with 0.1 mol/ L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry).
correction.

= 26.112 mg of C9H13BrN2O2

tainers.
Pyridoxine Hydrochloride
N
CH3
HCl
HOH2C
OH
CH2OH
Vitamin B6 Hydrochloride
C8H11NO3HCl: 205.64
Pyridoxine Hydrochloride, when dried, contains not

less than 98.0% and not more than 101.0% of pyridoxine hydrochloride (C8H11NO3HCl).
KP 9 825

Description Pyridoxine Hydrochloride is a white to
pale yellow, crystalline powder.
Pyridoxine Hydrochloride is freely soluble in water,
slightly soluble in dehydrated ethanol and practically
insoluble in glacial acetic acid or acetic anhydride.
Pyridoxine Hydrochloride is gradually colored by light.
of solutions of Pyridoxine Hydrochloride and Pyridoxine Hydrochloride RS, respectively, in 0.1 mol/L hydrochloric acid TS (1 in 100000) as directed under Ultraviolet-visible Spectrophotometry : both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Pyridoxine
Hydrochloride and Pyridoxine Hydrochloride RS, previously dried, as directed in the potassium bromide disk
method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) An aqueous solution of Pyridoxine Hydrochloride (1 in 10) responds to the Qualitative Tests for chloride.
pH The pH of a solution prepared by dissolving 1.0 g
of Pyridoxine Hydrochloride in 50 mL of water is between 2.5 and 3.5.
1.0 g of Pyridoxine Hydrochloride in 20 mL of water:
(2) Heavy metalsProceed with 1.0 g of Pyridoxine Hydrochloride according to Method 1 and perform
(3) Related substancesDissolve 1.0 g of Pyridoxine Hydrochloride in 10 mL of water, and use this solution as the test solution. Pipet exactly 2.5 mL of the test
solution, and add water to make exactly 100 mL. Pipet
exactly 1 mL of this solution, add water to make exactly 10 mL, and use this solution as the standard solution.
solution and standard solution on a plate of silica gel
for thin-layer chromatography, and air-dry the plate.
Develop the plate with a mixture of acetone, tetrahydrofuran, n-hexane and strong ammonia water (65 : 13 :
13 : 9) to a distance of about 10 cm, and air-dry the
plate. Spray evenly a solution of sodium carbonate in
diluted dehydrated ethanol (3 in 10) (1 in 20) on the
plate. After air-drying, spray evenly a solution of 2,6dibromo-N-chloro-1,4-benzoquinone monoimine in dehydrated ethanol (1 in 1000) on the plate, and air-dry:
any spot other than the principal spot from the test solution is not more intense than the spot from the standard
solution.

Assay Weigh accurately about 0.2 g of Pyridoxine
Hydrochloride, previously dried, add 5 mL of glacial
acetic acid and 5 mL of acetic anhydride, dissolve by
gentle boiling, cool, add 30 mL of acetic anhydride and
correction.

tight containers.
Injection
Vitamin B6 Hydrochloride Injection
Pyridoxine Hydrochloride Injection is an aqueous solution for injection. Pyridoxine Hydrochloride Injection
of the labeled amount of pyridoxine hydrochloride
(C8H11NO3HCl: 205.64).
Method of Preparation Prepare as directed under Injections, with Pyridoxine Hydrochloride.
Description Pyridoxine Hydrochloride Injection is a
colorless or pale yellow, clear liquid.
Pyridoxine Hydrochloride Injection is gradually affected by light.
Identification (1) Take a volume of Pyridoxine Hydrochloride Injection, equivalent to 50 mg of Pyridoxine Hydrochloride according to the labeled amount, add
0.1 mol/L hydrochloric acid TS to make 100 mL. Pipet
2 mL of this solution and add 0.1 mol/L hydrochloric
acid TS to make 100 mL. Determine the absorption
spectrum of this solution as directed under Ultravioletvisible Spectrophotometry: it exhibits a maximum between 288 nm and 292 nm.
(2) To a volume of Pyridoxine Hydrochloride Injection, equivalent to 10 mg of pyridoxine hydrochloride
according to the labeled amount, add water to make 10
mL, and use this solution as the test solution. Separately, dissolve 10 mg of Pyridoxine Hydrochloride RS in
10 mL of water, and use this solution as the standard
solution. Perform the test with these solutions as directed under Thin-layer Chromatography. Spot 2 L
each of the test solution and standard solution on a
plate of silica gel for thin layer chromatography, and

air-dry plate. Develop the plate with a mixture of acetone, tetrahydrofuran, n-hexane and strong ammonia
water (65 : 13 : 13 : 9) to a distance of about 10 cm,
and air-dry the plate. Spray evenly a solution of sodium
carbonate in diluted dehydrated ethanol (3 in 10) (1 in
20) on the plate. After air-drying, spray evenly a solution of 2,6-dibromo-N-chloro-1,4-benzoquinone monoimine in dehydrated ethanol (1 in 1000) on the plate:
the spots obtained from the test solution and the standard solution are blue in color and have the same Rf
value.
Sterility Test It meets the requirement
Bacterial Endotoxins Less than 3.0 EU/mg of Pyridoxine Hydrochloride
Assay Measure exactly a volume of Pyridoxine Hydrochloride Injection, equivalent to about 40 mg of pyridoxine hydrochloride (C8H11NO3HCl), dilute with
water, if necessary and add water to make exactly 100
mL. Pipet exactly 5 mL of this solution, add exactly 5
mL of internal standard solution and dilute with water
Pyridoxine Hydrochloride RS, previously dried in a desiccator (in vacuum, silica gel) for 4 hours, dissolve in
and dilute with water to make exactly 100 mL. Pipet
exactly 5 mL of this solution, add exactly 5 mL of internal standard solution and dilute with water to make
exactly 100 mL and use this solution as the standard solution. Perform the test with exactly 20 L each of the
test and the standard solutions as directed in Assay under Pyridoxine Hydrochloride Tablets.
Amounts (mg) of pyridoxine hydrochloride

(C8H11NO3HCl) = amounts (mg) of Pyridoxine HyQ
drochloride RS T
QS
Internal standard solutionDissolve 50 mg of Anhydrous Caffeine RS in and dilute with water to make
100 mL.
hermetic containers, and colored containers may be
used.
Tablets
Pyridoxine Hydrochloride Tablets contain not less than
of pyridoxine hydrochloride (C8H11NO3HCl: 205.64).
Tablets, with Pyridoxine Hydrochloride.
Identification Take a quantity of powdered Tablets,
equivalent to about 0.1 g of Pyridoxine Hydrochloride
according to the labeled amount, add about 5 mL of
water. Shake the mixture well, filter into a test tube and
add 2 or 3 drops of ferric chloride: an orange to deep
Dissolution Test Perform the test with 1 tablet of Pyridoxine Hydrochloride Tablets at 50 revolutions per
Test, using 900 mL of water. Take 20 mL or more of the
dissolved solution 45 minutes after starting the test and
more than 0.8 m. Discard the first 10 mL of the filtrate, use subsequent filtrate as the test solution. Dilute
properly with test solution if it is needed. Separately,
weigh accurately about 10 mg of Pyridoxine Hydrochloride RS, previously dried, dissolve in water to make
exactly 100 mL, then pipet exactly 5 mL of this solution and add water to make exactly 50 mL and use this
10 L each of the test solution and the standard solution according to the following operating conditions as
directed in the Liquid Chromatography and determine
the peak areas of pyridoxine, QT and QS , from the
test solution and the standard solution, respectively: the
dissolution rate of Pyridoxine Hydrochloride Tablets in

of Pyridoxine Hydrochloride (C8H11NO3HCl) =
Q 90
WS T
QS C
WS : Amount of Pyridoxine Hydrochloride RS (mg)
C : labeled amount of pyridoxine hydrochloride
(C8H11NO3HCl) in each Tablet (mg)
diameter and 30 cm in length, packed with octadecylsilanized silica gel for Liquid Chromatography (3 m to
KP 9 827
Mobile phase: Dissolve 0.14 g of sodium 1hexanesulfonate in 100 mL of a mixture of water, methanol and glacial acetic acid (73 : 27 : 1)
System suitability
System performance: Weigh 20 mg of Pyridoxine
Hydrochloride RS and 20 mg of Riboflavin RS, dissolve in the mixture of water, acetonitrile and glacial
acetic acid (94 : 5 : 1) at 65 C to 70 C with occasional
shaking, cool and dilute with the mixture of water, acetonitrile and glacial acetic acid (94 : 5 : 1) to 200 mL.
under the above operating condition, pyridoxine and riboflavin are eluted in this order.
times with 10 L of the upper solution under the above
the peak area of pyridoxine is not more than 3.0%.
Uniformity of Dosage Units It meets the requirement of the Content uniformity test when the test is
performed as the following method. Transfer 1 tablet of
Pyridoxine Hydrochloride Tablets, previously finely
powdered, to a 500 mL volumetric flask containing
about 300 mL of water, shake for about 30 minutes, and
dilute with water to volume. Filter a portion of the mixture, discarding the first 25 mL of the filtrate. Dilute a
suitable aliquot of the subsequent filtrate quantitatively
and stepwise with diluted hydrochloric acid (1 in 100)
so that the concentration of pyridoxine hydrochloride is
about 10 g per mL and use this solutionas test solution.
Dissolve about 10 mg of Pyridoxine Hydrochloride RS,
accurately weighed, in and dilute with diluted hydrochloric acid (1 in 100) to make exactly 100 mL. Pipet exactly 5.0 mL of this solution and dilute with diluted hydrochloric acid (1 in 100) to make exactly 50 mL and
standard solution, respectively, at the wavelength of
maximum absorbance at about 290 nm, as directed under Ultraviolet-visible Spectrophotometry.
Amount (mg) of Pyridoxine Hydrochloride

A
T
(C8H11NO3HCl) = C T
D
AS
T: the labeled quantity of pyridoxine hydrochloride
in the Pyridoxine Hydrochloride Tablets (mg).
D: the dilution factor
C: the concentration of Pyridoxine Hydrochloride
RS in the standard solution (g/ mL)
Assay Weigh accurately and finely powder not less
than 20 Pyridoxine Hydrochloride Tablets. Weigh accurately a portion of the powder, equivalent to about 40
mg of pyridoxine hydrochloride (C8H11NO3HCl), add
water and shake to mix for 15 minutes. Extract with
water to make the volume exactly 100 mL. Filter the
extract and discard the first 10 mL of the filtrate. Com-
bine the subsequent 5 mL of filtrate with exactly 5 mL

of the internal standard solution, dilute with water to
Pyridoxine Hydrochloride RS, previously dried in desiccator (in vacuum with silica gel) for 4 hours, and
dissolve in and dilute with water to make exactly 100
mL. Pipet exactly 5 mL of the solution, add exactly 5
mL of the internal standard solution, dilute with water
under the Liquid Chromatography according to the following operating conditions. Calculate the ratios of the
peak areas of Pyridoxine Hydrochloride, QT and QS ,
to that of the internal standard for the test solution and
Amount (mg) of Pyridoxine Hydrochloride
(C8H11NO3HCl) = amount (mg) of Pyridoxine
Q
Hydrochloride RS T
QS
Internal standard solutionDissolve about 50 mg of
Anhydrous Caffeine RS in and dilute with water to
make 100mL.
Detector : An ultraviolet absorption photometer
(wavelength ;280 nm)
Column : A stainless steel column, about 4 mm in
Column temperature : A room temperature.
Mobile phase : Dissolve about 1.0 g of sodium 1hexansulfonate in 750 mL of water and add 250 mL of
methanol and 10 ml of acetic acid.
Flow rate : Adjust the flow rate so that the retention
time of Pyridoxine Hydrochloride is about 5 minutes.
operating conditions, Pyridoxine Hydrochloride and the
internal standard are eluted in this order with the resolution between their peaks being not less than 3.0.
tight containers.
add methanol to make exactly 500 mL and use these

solutions as the test solution and the standard solution,
respectively. Determine the absorbances, AT and AS
of the test solution and the standard solution, respectively, at 505 nm as directed under the Ultravioletvisible Spectrophotometry, using methanol as the blank.
Pyrvinium Pamoate
H3C
Amount (mg) of pyrvinium pamoate (C75H70N6O6)

A
= amount (mg) of Pyrvinium Pamoate RS T
AS
CH3
CH3
N
H
C
H3C
CH

tight containers.
N
H3C
2
O
O
OH
HO
CH2
Pyrvinium Pamoate Syrup

Pyrvinium Pamoate Syrup contains, in each 100 mL, an
amount of Pyrvinium Pamoate equivalent to not less
than 0.90w/v% and not more than 1.10w/v% of pyrvinium (C26H28N3+: 382.52).
C75H70N6O6: 1151.40
Pyrvinium Pamoate contains not less than 96.0% and
not more than 104.0% of pyrvinium pamoate
(C75H70N6O6), calculated on the anhydrous basis.
Description Pyrvinium Pamoate is a bright orange or
blackish orange-red, crystalline powder.
Pyrvinium Pamoate is very soluble in glacial acetic acid, slightly soluble in chloroform or methoxyethanol,
very slightly soluble in ethanol, and practically insoluble in water or ether.
of the test solution of glacial acetic acid in methanol (1
in 200), prepared as directed in the Assay, as directed
under the Ultraviolet-visible Spectrophotometry: it exhibits maxima at about 358 nm and at about 505 nm
and the ratio, A505/A358, is between 1.93 and 2.07.
(2) Determine the infrared spectra of Pyrvinium
Pamoate and Pyrvinium Pamoate RS, respectively, as
the same intensities of absorption at the same wavenumbers.
Water Not more than 6.0% [0.2 g, volumetric titration, direct titration, a mixture of methanol and chloroform (1 : 1) instead of water measurement methanol].
Assay Weigh accurately about 0.25 g each of Pyrvinium Pamoate and Pyrvinium Pamoate RS, dissolve in
125 mL of glacial acetic acid in a 250 mL volumetric
flask and add methanol to make exactly 250 mL, respectively. Pipet exactly 5 mL each of these solutions,

Syrups, with Pyrvinium Pamoate.
Description Pyrvinium Pamoate Syrup is a dark reddish opaque suspension.
Identification Determine the absorption spectra, between 300 nm and 600 nm, of the test solution and the
standard solution obtained in the Assay, respectively, as
directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibits maxima and minima at the
same wavelengths.
Assay Transfer 50 mg of Pyrvinium Pamoate Syrup
(about 5 mL), freshly mixed and free from air bubbles,
to a 250 mL volumetric flask. Complete the transfer by
rinsing the pipet with 10 mL of methanol, add 100 mL
of glacial acetic acid, mix to dissolve the Pyrvinium
Pamoate, add methanol to make exactly 250 mL and
mix. Pipet 3.0 mL of this solution in a 100 mL volumetric flask, dilute with methanol to make exactly 100 mL
dissolve accurately weighed a portion of Pyrvinium
Pamoate RS (determined formerly water contents as directed under water determination assay) in glacial acetic acid, using 4 mL for each 3 mg taken and dilute with
methanol to obtain a standard solution having a known
concentration of about 9 g per mL. Determine the absorbances, AT and AS , of the test solution and the
standard solution, respectively, at 505 nm as directed
under the Ultraviolet-visible Spectrophotometry, using
methanol as the blank.
Amount (w/v%) of pyrvinium (C26H28N3+)
KP 9 829
= 0.1677 C
AT
0.6644
AS
C: Concentration of Pyrvinium Pamoate RS in the

standard solution (g/mL)
tight containers.
tight containers.
Quinidine Sulfate Hydrate

N
CH3O
H
Pyrvinium Pamoate Tablets
H2SO4
HO
H
HC
Pyrvinium Pamoate Tablets contain not less than 92.0%

pyrvinium (C26H28N3+: 382.52).
Tablets, with Pyrvinium Pamoate.
Identification Proceed as directed in the Identification under Pyrvinium Pamoate Syrup.
ment.
Assay Perform the test without exposure to daylight,

using light-resistant vessels. Take a number of Pyrvinium Pamoate Tablets, equivalent to about 0.5 g of
pyrvinium (C26H28N3+), place in a volumetric flask and
add 25 mL of water and 25 mL of acetone. Completely
disintegrate the tablets by heating in a water-bath for 10
minutes with frequent mixing. To the hot mixture, add
250 mL of glacial acetic acid, heat for additional 5 minutes and add methanol to make exactly 500 mL at
room temperature. Centrifuge a portion of the mixture
until a clear solution is obtained. Pipet exactly 3 mL of
the supernatant solution, add methanol to make exactly
500 mL and use this solution as the test solution. Dissolve accurately weighed a portion of Pyrvinium Pamoate RS (determined formerly water contents as directed under water determination assay) in glacial acetic acid, using 1 mL for each 3 mg taken and dilute with
methanol to obtain a standard solution having a known
concentration of about 9 g per mL. Determine the absorbances, AT and AS , of the test solution and the
standard solution, respectively, at 505 nm as directed
methanol as the blank.
Amount (w/w%) of pyrvinium (C26H28N3+)

A
= 83 .3 C T 0.6644
AS
C: Concentration of the standard solution (g/mL),
2 H2O
CH2
Quinidine Sulfate
(C20H24N2O2)2H2SO42H2O: 782. 94
Quinidine Sulfate Hydrate, when dried, contains not
less than 98.5% and not more than 101.0% of quinidine
sulfate [(C20H24N2O2)22H2SO4: 746.91]
Description Quinidine Sulfate Hydrate is a white
crystal, is odorless and has a very bitter taste.
Quinidine Sulfate Hydrate is freely soluble in ethanol
or in boiling water, sparingly soluble in water and practically insoluble in ether.
Quinidine Sulfate Hydrate, previously dried, is freely
soluble in chloroform.
Quinidine Sulfate Hydrate gradually darkens by light.
Specific oprical rotation [ ]20
D : Between +275
and +287 (after drying, 0.5 g. 0.1 mol/L hydrochloric
acid VS, 25 mL, 100 mm).
Identification (1) Dissolve 10 mg of Quinidine Sulfate Hydrate in 10 mL of water and 2 to 3 drops of dilute sulfuric acid: a blue fluorescence is produced.
(2) Take 5 mL of a solution of Quinidine Sulfate
Hydrate (1 in 1000), add 1 to 2 drops of bromine TS,
then add 1 mL of ammonia TS: a green color develops.
(3) Take 5 mL of a solution of Quinidine Sulfate
Hydrate (1 in 100), add 1 mL of silver nitrate TS, stir
with a glass rod and allow to stand for a short interval:
a white precipitate is produced and it dissolves on dropwise addition of nitric acid.
(4) Dissolve 0.4 g of Quinidine Sulfate Hydrate in
20 mL of water and 1 mL of dilute hydrochloric acid:
the solution responds to the Qualitative Tests for sulfate.
pH Dissolve 1.0 g of Quinidine Sulfate Hydrate in
100 mL of freshly boiled and cooled water: the pH of
Purity (1) Chloroform-ethanol-insoluble substances
Warm 2.0 g of Quinidine Sulfate Hydrate with 15
mL of a mixture of chloroform and dehydrated ethanol
(2 : 1) at about 50 C for 10 minutes. After cooling, filter through a tared glass filter (G4) by gentle suction.
Wash the residue with five 10 mL volumes of a mixture
of chloroform and dehydrated ethanol (2 : 1) and dry at

105 C for 1 hour: the weight of the residue is not more
than 2.0 mg.
(2) Related substancesDissolve 20 mg of Quinidine Sulfate Hydrate in the mobile phase to make exactly 100 mL and use this solution as the test solution.
Separately, dissolve 25 mg of Cinchonine RS in the
mobile phase to make exactly 100 mL. Pipet 2.0 mL of
this solution, add the mobile phase to make exactly 100
conditions. Determine each peak area of the test solution by the automatic integration method and calculate
their amount by the area percentage method: the
amount of dihydroquinine sulfate are not more than
15.0% and each amount of quinidine sulfate and dihydroquinine is not more than 1.0%. The total area of the
peaks other than the principal peak and the above peaks
is not larger than the peak area of cinchonine from the
standard solution.
and about 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 m in
particle diameter).
Temperature: A room temperature.
Mobile phase: A mixture of water, acetonitrile, methanesulfonic acid TS and a solution of diethylamine (1
in 10) (43 : 5 : 1 : 1).
time of quinidine is about 10 minutes.
System suitability
Quinidine Sulfate Hydrate and quinine sulfate in 5 mL
of methanol and add the mobile phase to make exactly
solution under the above operating conditions, quinidine, quinine, dihydroquinidine and dihydroquinine are
eluted in this order with the resolution between quinidine and quinine and that between quinine and dihydroquinidine being not less than 1.2, respectively.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of cinchonine obtained
from 50 L of the standard solution is between 5 mm
and 10 mm.
the retention time of quinidine after the solvent peak.

of Quinidine Sulfate Hydrate and perform the test: the
M.
hours).

Assay Weigh accurately about 0.5 g of Quinidine
Sulfate Hydrate, previously dried, dissolve in 20 mL of
glacial acetic acid and add 80 mL of acetic anhydride
and titrate with 0.1 mol/L perchloric acid VS until the
color of the solution changes from purple through blue
to blue-green (indicator: 3 drops of methylrosaniline
chloride TS). Perform a blank determination and make

= 24.897 mg of (C20H24N2O2)2H2SO4
Quinine Hydrochloride Hydrate

N
CH3O
HCl
HO
2 H2O
H
N
H
H
CH
CH2
C20H24N2O2.HCl2H2O: 396.91
Quinine Hydrochloride Hydrate, when dried, contains
not less than 98.5% and not more than 101.0% of quinine hydrochloride (C20H24N2O2HCl).
Description Quinine Hydrochloride Hydrate is a
white crystal, is odorless and has a very bitter taste.
Quinine Hydrochloride Hydrate gradually changes to
brown by light.
Quinine Hydrochloride Hydrate is very soluble in dehydrated ethanol, freely soluble in glacial acetic acid, in
acetic anhydride or in ethanol, soluble in water and
Quinine Hydrochloride Hydrate, previously dried, is
freely soluble in chloroform.
D : Between 245
and 255 (after drying, 0.5 g, 0.1 mol/L hydrochloric
acid VS, 25 mL, 100 mm).
Identification (1) A solution of Quinine Hydrochloride Hydrate (1 in 50) shows no fluorescence. To 1 mL
of the solution, add 100 mL of water and 1 drop of dilute sulfuric acid: a blue fluorescence is observed.
(2) Take 5 mL of a solution of Quinine Hydrochloride Hydrate (1 in 1000) and add 1 to 2 drops of bromine TS and 1 mL of ammonia TS: a green color develops.
(3) Take 5 mL of a solution of Quinine Hydrochloride Hydrate (1 in 50) and add 1 mL of dilute nitric acid
KP 9 831
and 1 mL of silver nitrate TS: a white precipitate is

produced. Collect the precipitate and add an excess of
ammonia TS: it dissolves.
pH Dissolve 1.0 g of Quinine Hydrochloride Hydrate
in 100 mL of freshly boiled and cooled water: the pH of
Purity (1) SulfatePerform the test with 1.0 g of
Quinine Hydrochloride Hydrate. Prepare the control solution with 1.0 mL of 0.005 mol/L sulfuric acid VS (not
more than 0.048%).
(2) BariumDissolve 0.5 g of Quinine hydrochloride Hydrate in 10 mL of water by warming and add 1
mL of dilute sulfuric acid: no turbidity is produced.
(3) Chloroform-ethanol-insoluble substances
Warm 2.0 g of Quinine Hydrochloride Hydrate with 15
mL of a mixture of chloroform and dehydrated ethanol
(2 : 1) at 50 C for 10 minutes. After cooling, filter
through a tared glass filter (G4) by gentle suction.
Wash the residue with five times with 10 mL volumes
of a mixture of chloroform and dehydrated ethanol (2 :
1), dry at 105 C for 1 hour and weigh: the weight of
the residue so obtained is not more than 2.0 mg.
(4) Related substancesDissolve 20 mg of Quinine Hydrochloride Hydrate in the mobile phase to
solution. Separately, dissolve 25 mg of cinchonidine in
the mobile phase to make exactly 100 mL. Pipet 2.0
mL of this solution, add the mobile phase to make exactly 100 mL and use this solution as the standard solution. Perform the test with 50 L each of the test solution and the standard solution as directed under the
Liquid Chromatography according to the following operating conditions. Determine each peak area of the test
solution by the automatic integration method and calculate the amount of dihydroquinine hydrochloride by the
area percentage method: it is not more than 10.0%. The
total area of the peaks other than the principal peak and
the above peaks is not larger than the peak area of cinchonidine from the standard solution.
in 10) (43 : 5 : 1 : 1).
time of quinine is about 10 minutes.
System suitability
Quinine Hydrochloride Hydrate and quinidine sulfate
in 5 mL of methanol and add the mobile phase to make
exactly 50 mL. When the procedure is run with 50 L

quinidine, quinine , dihydroquinidine and dihydroquinine are eluted in this order with the resolution between
quinidine and quinine and that between quinine and dihydroquinidine being not less than 1.2.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of cinchonidine from 50
L of the standard solution is between 5 mm and 10
mm.
the retention time of quinine after the solvent peak.
test with 0.25 g of Quinine Hydrochloride Hydrate. The
M.
hours).
Assay Weigh accurately about 0.4 g of Quinine Hydrochloride Hydrate, previously dried, dissolve in 100
mL of a mixture of acetic acid anhydride and glacial
acetic acid (7 : 3) by warming, cool and titrate with 0.1

= 18.044 mg of C20H24N2O2HCl
Quinine Sulfate Hydrate

N
CH3O
HO
H2SO4
2 H2O
H
H
HC
Quinine Sulfate
CH2
(C20H24N2O2)2H2SO42H2O: 782.94
Quinine Sulfate Hydrate contains not less than 98.5%

and not more than 101.0% of quinine sulfate
[(C20H24N2O2)2H2SO4:746.91], calculated on the dried
basis.
Description Quinine Sulfate Hydrate is a white crystal or crystalline powder, is odorless and has a very bitter taste.
Quinine Sulfate Hydrate is freely soluble in glacial
acetic acid, soluble in hot ethanol, sparingly soluble in

hot water, slightly soluble in water, in ethanol, in dehydrated ethanol or in chloroform and practically insoluble in ether.
Quinine Sulfate Hydrate gradually changes to brown by
light.
of solutions of Quinine Sulfate Hydrate and Quinine
Sulfate Hydrate RS (1 in 20000) as directed under the
(2) Determine the infrared spectra of Quinine Sulfate Hydrate and Quinine Sulfate Hydrate RS, previously dried, as directed in the potassium bromide disk
same wavenumbers.
-245 (after drying, 0.75 g, 0.1 mol/L hydrochioric acid
VS, 25 mL, 100 mm).
pH Shake 2.0 g of Quinine Sulfate Hydrate in 20 mL
of freshly boiled and cooled water and filter: the pH of
this filtrate is between 5.5 and 7.0.
Quinine Sulfate Hydrate according to Method 2 and
(2) Chloroformethanol-insoluble substances
Warm 2.0 g of Quinine Sulfate Hydrate with 15 mL of
a mixture of chloroform and dehydrated ethanol (2 : 1)
at 50 C for 10 minutes. After cooling, filter through a
tared glass filter (G4) by gentle suction. Wash the residue with five 10 mL volumes of a mixture of chloroform and dehydrated ethanol (2 : 1), dry at 105 C for 1
hour and weigh: the weight of the residue is not more
than 2.0 mg.
(3) Related substancesDissolve 20 mg of Quinine Sulfate Hydrate in the mobile phase to make exactly 100 mL and use this solution as the test solution.
Separately, dissolve 25 mg of cinchonidine in the mobile phase to make exactly 100 mL. Pipet 2.0 mL of
this solution, add the mobile phase to make exactly 100
conditions. Determine each peak area from the test solution by the automatic integration method and calculate the amount of dihydroquinine sulfate by the area
percentage method: it is not more than 5%. The total
area of the peaks other than the principal peak and the
above peak is not larger than the peak area of cinchonidine from the standard solution.
and about 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 m in
particle diameter).
Temperature: A room temperature.
in 10) (43 : 5 : 1 : 1).
time of quinine is about 10 minutes.
System suitability
Quinine Sulfate Hydrate and quinidine sulfate in 5 mL
of methanol and add the mobile phase to make exactly
solution under the above operating conditions, quinidine, quinine, dihydroquinidine and dihydroquinine are
eluted in this order with the resolution between quinidine and quinine and that between quinine and dihydroquinidine being not less than 1.2.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of cinchonidine obtained
and 10 mm.
the retention time of quinindine after the solvent peak.
hours).
Assay Weigh accurately about 0.5 g of Quinine Sulfate Hydrate, dissolve in 20 mL of glacial acetic acid,
add 80 mL of acetic anhydride and titrate with 0.1
mol/L perchloric acid VS (indicator: 2 drops of methylrosaniline chloride TS). Perform a blank determination

= 24.897 mg of (C20H24N2O2)2H2SO4
Ramipril
H3C
COOH
O
O
H
H H3C
H
H
N
N
H
O
KP 9 833
C23H32N2O5: 416.51
Ramipril contains not less than 98.0% and not more
than 101.0% of ramipil (C23H32N2O5), calculated on the
dried basis.
Description Ramipril is a white, crystalline powder.
Ramipril is freely soluble in methanol and sparingly soluble in water.
Identification Determine the infrared spectra of Ramipril and Ramipril RS as directed in the potassium
bile phase B to make exactly 100 mL and use this solution as the standard solution. Perform the test with 10
the following operating conditions, determine the areas
of peaks in the test solution and the standard solution,
and calculate the content of related substances according to the following equation: not more than 0.5% each
for ramipril related substance I, ramipril related substance II, ramipril related substance III or ramipril related substance IV, not more than 0.1% for any other
related substance and not more than 1.0% for total related substances.
Content (%) of related substance
C
A
= 100 F S T
CT AS

D : Between +32 and
+38 (0.25 g, after drying, methanolic hydrochloric acid TS, 25 mL, 100 mm).
Purity (1) PalladiumWeigh accurately about 0.2 g
of Ramipril, dissolve in a mixture of water and nitric
acid (997:3) to make exactly 100 mL and use this solution as the test solution. Separately, weigh accurately
about 50 mg of palladium, add 9 mL of hydrochloric
acid to dissolve and add water to make exactly 100 mL.
Pipet three suitable portions of this solution, add a mixture of water and nitric acid (997:3) to render the concentration of the resulting solutions having 0.02, 0.03
and 0.05 g per mL, respectively, and use these solutions as the standard solutions. Separately, weigh accurately about 0.15 g of magnesium nitrate, add a mixture
of water and nitric acid (997:3) to make exactly 100
mL and use this solution as the blank solution. Perform
the test with 20 L of the test solution, 20 L each of
the standard solutions and 10 L of the blank solution
as directed in the calibration curve method under the
Atomic Absorption Spectrophotometry according to the
following conditions and calculate the content of palladium in the test solution not more than 0.002%.
Content (%) of palladium

= 0.1 Concentration (g/mL) of palladium in the test
solution Concentration (mg/mL) of Ramipril in the
test solution
Gas: Combustible gasAcetylene or hydrogen
Supporting gasAir
Lamp: A palladium hollow cathode lamp
25 mg of Ramipril, dissolve in the mobile phase A to
Ramipril RS, dissolve in the mobile phase B to make
exactly 50 mL. To 1.0 mL of this solution, add the mo-
F: Relative response factor for related substance

(2.4 for ramipril related substance III and 1.0 for any
other related substance)
CS: Concentration (mg/mL) of ramipril in the test
solution
CT: Concentration (mg/mL) of ramipril in the standard solution
AT: Area of each peak obtained from the test solution
AS: Area of ramipril peak obtained from the standard solution
about 65 C.
Mobile phase A: Dissolve 2.0 g of sodium perchlorate in a mixture of 800 mL of water and 0.5 mL of
triethylamine, adjust the pH of the solution to 3.6 0.1
with phosphoric acid, add 200 mL of acetonitrile and
mix.
Mobile phase B: Dissolve 2.0 g of sodium perchlorate in a mixture of 300 mL of water and 0.5 mL of
triethylamine, adjust the pH of the solution to 2.6 0.1
with phosphoric acid, add 700 mL of acetonitrile and
mix.
0-6
Mobile
phase A
(vol%)
90
Mobile
phase B
(vol%)
10
6-7
9075
1025
7-20
7565
2535
Time (min)
Elution
condition
Isocratic
Linear gradient
Linear gradient
20-30
6525
3575
30-40
25
75
40-45
2590
7510
45-55
90
10
Linear gradient
Isocratic
Linear gradient
Isocratic

System suitability
System performance: Proceed with 10 L of the
standard solution under the above operating conditions
and adjust the conditions so that the retention time for
ramipil is between 16 and 19 minutes at the 75:25 stage.
Separately, weigh 5.0 mg each of Ramipril RS, ramipril
related substance I RS, ramipril related substance II RS,
ramipril related substance III RS and ramipril related
substance IV RS, and dissolve in 10 mL of the mobile
phase B. When the procedure is run with 10 L of this
solution under the above operating conditions, the relative retention times are about 0.8, 1.0, 1.3 and 1.5 for
ramipril related substance I, ramipril related substance
II, ramipril related substance III and ramipril related
substance IV, respectively, with the resolution between
the ramipril peak and the ramipril related substance I
peak being not less than 3.0. In addition, when the procedure is run with 10 L of the test solution under the
above operating conditions, the retention time for ramipril is between 16 and 19 minutes with the symmetry
factor being between 0.8 and 2.0.
above operating conditions, the relative standard deviation of the areas of ramipril peak is not more than 5.0%.
Loss on Drying
60 C, 6 hours).
Not more than 0.2% (1 g, in vacuum,

Assay Weigh accurately about 0.3 g of Ramipril, dissolve in 25 mL of methanol, add 25 mL of water and titrate with 0.1 mol/L sodium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any

= 41.65 mg of C23H32N2O5
Ranitidine Hydrochloride
H
N
H
N
O
S
H3C
CHNO2
CH3
N
CH3
HCl
C13H22N4O3SHCl: 350.87
Ranitidine Hydrochloride contains not less than 97.5%
and not more than 102.0% of ranitidine hydrochloride
(C13H22N4O3SHCl), calculated on the dried basis.
Description Ranitidine Hydrochloride is a white to
pale yellow crystalline powder and is odorless.
Ranitidine Hydrochloride is very soluble in water, and
sparingly soluble in ethanol or in chloroform.
Ranitidine Hydrochloride is sensitive to light and moisture.
Identification (1) Dissolve separately a portion of
Ranitidine Hydrochloride and Rantidine Hydrochloride
RS, accurately weighed, in water to render the concentration of 10 g per mL each. Determine the absorption
spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit
(2) Determine the infrared spectra of Ranitidine
Hydrochloride and Ranitidine Hydrochloride RS, previously dried, as directed in the paste method under the
Infrared Spectrophotometry: both spectra exhibit similar intensity of absorption at the same wavenumbers.
(3) A solution of Ranitidine Hydrochloride (1 in
pH Dissolve 1.0 g of Ranitidine Hydrochloride in
and 6.0.
Purity Related substancesDissolve about 0.2 g of
Ranitidine Hydrochloride, accurately weighed, in 10
mL of methanol, and use this solution as the test solution. Dissolve about 20 mg of Ranitidine Hydrochloride RS, accurately weighed, in 10 mL of methanol. Pipet 1.0 mL of this solution, dilute with methanol to
make exactly 10mL, and use this solution as the standard solution (1). Dilute the standard solution (1) with
methanol to obtain the standard solutions (2), (3) and
(4), having known concentrations of 0.1 mg/mL, 60
g/mL and 10 g/mL, respectively. Separately, dissolve
a suitable quantity of Ranitidine related compound I RS
in methanol to obtain a solution containing 1.3 mg per
mL, and use this solution as the resolution solution.
And dissolve a suitable quantity of Ranitidine related
compound II RS in methanol to obtain a solution having a known concentration of about 1 mg/mL, and use
this solution as the identification solution. Perform the
test with these solutions as directed under the Thinlayer Chromatography. Spot 10 L each of the test solution, the standard solutions (1), (2), (3), (4) and the
identification solution, on a plate of silica gel with a
Separately, spot 10 L of the test solution on the same
plate, and on top of this spot, spot 10 L of the resolution solution. Then, develop the plate with a mixture
KP 9 835
containing ethyl acetate, isopropyl alcohol, strong ammonia water and water (25 : 15 : 5 : 1) to a distance of
about 15 cm, and air-dry the plate. Expose the plate to
iodine vapor: any spots from the test solution corresponding to the Rf values of the principal spot obtained
from the identification solution are not greater in size
or intensity than the principal spots obtained from the
standard solutions (2) (not more than 0.5%). The spots
other than the principal spot are not greater in size or
intensity, as compared to the principal spot obtained
from the standard solution (3) (not more than 0.3%).
The sum of spots other than the principal spot, obtained
from the test solution, is not more than 1.0% of total.
The spot is observed in the chromatogram of standard
solution (4), and there is complete resolution between
the principal spots in the chromatogram of the combined test solution and resolution solution.
Loss on Drying Not more than 0.75% (1 g, 60 C, in
vacuum, 3 hours).
Assay Transfer about 0.1 g of Ranitidine Hydrochloride, accurately weighed, to a 100 mL volumetric flask.
Dissolve in and dilute with a mobile phase to volume.
Transfer 1.0 mL of this solution to a 10 mL volumetric
flask, dilute with the mobile phase to the volume, and
use this as the test solution. Dissolve an accurately
weighed quantity of Ranitidine Hydrochloride RS in
the mobile phase to obtain a solution containing 0.1 mg
per mL, and use this as the standard solution. Perform
standard solution as directed under the Liquid Chromatography according to the following operating conditions, and determine the peak areas, AT and AS, of ranitidine hydrochloride for the test solution and the standard solution, respectively.
Amount (mg) of ranitidine hydrochloride

AT
(C13H22N4O3SHCl) = C A 1000
S
C: Concentration of ranitidine hydrochloride in the
standard solution (mg/mL).
diameter and 20 cm to 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (3
Mobile phase: A degassesd and filtered mixture of
methanol and 0.1 mol/L aqueous ammonium acetate
(85 : 15).
System suitability
System performance: Dissolve an accurately
weighed quantity of Ranitidine Hydrochloride RS and
Ranitidine related compound III RS in a mobile phase

to obtain a solution containing 0.1 mg and 0.01 mg per
mL, respectively. When the procedure is run with 10
L each of these solutions under the above operating
conditions, the resolution between their peaks is not
less than 1.5, and the symmetry factor of Ranitidine
Hydrochloride peak is not more than 2.0. The column
efficiency determined from Ranitidine Hydrochloride
peak is not less than 700 theoretical plates.
deviation of the peak areas of Ranitidine Hydrochloride
tight containers.
Ranitidine Hydrochloride
Tablets
Ranitidine Hydrochloride Tablets contain not less than
of ranitidine (C13H22N4O3S: 314.40).
Tablets, with Ranitidine Hydrochloride.
Identification (1) The principal spots from the test
solution and the standard solution as directed in the Related substances under the Purity show the same Rf
value.
of the standard solution as obtained in the Assay.
(3) Take a portion of powdered Ranitidine Hydrochloride Tablets, equivalent to 0.1 g Ranitidine Hydrochloride according to the labeled amount, add 2 mL
of water, shake well, and filter. The filtrate responds to
the Qualitative Tests for chloride.
Purity Related substancesShake an appropriate
number of Ranitidine Hydrochloride Tablets in a suitable volume of methanol until the tablets have disintegrated completely, and filter. Pipet a suitable volume of
the filtrate, dilute with methanol to obtain a solution
containing 20 mg of Ranitidine per mL (equivalent to
22.4 mg of Ranitidine Hydrochloride per mL), and use
this as the test solution. Dissolve Ranitidine Hydrochloride RS in methanol to obtain a solution having a
known concentration of 0.22 mg/mL, and use this solution as the standard stock solution. Dilute portions of
the standard stock solution with methanol to obtain the
standard solutions (1), (2), (3) and (4), having known
concentrations of about 110 g/mL, 66 g/mL, 22
g/mL and 11 g/mL, respectively. Dissolve a suitable
quantity of Ranitidine Hydrochloride related compound
I RS, accurately weighed, in methanol to obtain a solution having a known concentration of about 1.27
mg/mL, and use this solution as the resolution solution.
test solution, the standard stock solution, the standard
solutions (1), (2), (3) and (4) on a plate of silica gel for
thin-layer chromatography. Then, develop the plate
with a mixture containing ethyl acetate, isopropyl alcohol, strong ammonia water, and water (25 : 15 : 5 : 1) to
a distance of about 15 cm, and air-dry the plate. Expose
the plate to iodine vapor: the spots other than the principal spot from the test solution are not more intense
than the principal spot obtained from the standard solution (1). No single secondary spot exhibits intensity
greater than that of the standard solution (1) (not more
than 0.5%), and no other secondary spot exhibits intensity greater than that of the standard solution (2) (0.3%).
The sum of the intensities of all secondary spots obtained from the test solution corresponds to not more
than 2.0%. A spot is observed in the chromatogram of
the standard solution (4), and there is complete resolution between the principal spots in the chromatogram of
the combined test solution and resolution solution.
Dissolution Test Perform the test with 1 tablet of Ranitidine Hydrochloride Tablets at 50 revolutions per
Test, using 900 mL of water. Take 20 mL of the dissolved solution after 45 minutes from start of the test,
and filter through a membrane filter with pore size of
not more than 0.8 m. Discard the first 10 mL of the
filtrate, and use the subsequent as the test solution.
Separately, take about 0.22 g of Ranitidine Hydrochloride RS, accurately weighed, and add water to make
exactly 100 mL. Pipet 1.0 mL of this solution, transfer
this to a 100 mL volumetric flask, dilute with water to
volume. Pipet 1.0 mL of this solution, transfer this to a
100 mL volumetric flask, dilute with water to volume,
and use this as the standard solution. Determine the absorbances, AT and AS, of the test solution and the standard solution at the maximum absorption wavelength
about 314 nm as directed under the Ultraviolet-visible
Spectrophotometry, using the dissolution test solution
as the blank.
The dissolution rate of Ranitidine Hydrochloride Tablets in 45 minutes is not less than 80%.
Uniformity of Dosage Units It meets the requirement when the content uniformity test is performed according to the procedure as directed in the Assay under
Ranitidine Hydrochloride Tablets for the uniformity of
the content.
Ranitidine Hydrochloride Tablets. Weigh accurately a
portion of the powder, equivalent to 10 Ranitidine Hydrochloride Tablets, add in excess of 250 mL of the
mobile phase and mix until the mixture is completely
dispersed. Filter the mixture and dilute a suitable por-
tion of the filtrate with the mobile phase to render the

concentration identical to the standard solution. Use
this solution as the test solution. Separately, weigh accurately Ranitidine Hydrochloride RS, dissolve in the
mobile phase to render the concentration of the solution
to be 0.12 mg in 1 mL. Use this solution as the standard
solution. Perform the test with the operating condition
directed in the Assay under Ranitidine Hydrochloride
and the Liquid Chromatography. Measure AT for the
peak area of ranitidine in the test solution and AS for
the peak area of Ranitidine in the standard solution.
Amount (mg) of ranitidine (C13H22N4O3S)
A 314.40 L
= C T
AS 350.87 D
C: Concentration of the standard solution (mg/mL)
L: Labeled amount of Ranitidine in one tablet (mg)
D: Concentration of Ranitidine in the test solution
according to the labeled amount of ranitidine in one
tablet (mg/mL)
tight containers.
Repaglinide
CH3
H 3C
N
H
OH
CH3
C27H36N2O4: 452.59
Repaglinide contains not less than 98.0% and not more
than 101.0% of repaglinide (C27H36N2O4), calculated
on the dried basis.
Description Repaglinide is a white solid.
Repaglinide is soluble in methanol.
Melting pointBetween 132 C and 136 C
of solutions of Repaglinide and Repaglinide RS in methanol (1 in 40000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared spectra of Repaglinide
and Repaglinide RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorp-
KP 9 837
tion at the same wavenumbers.

D : Between +6.3
and +7.3 (0.5 g, methanol, 10 mL, 100 mm).
Purity (1) Heavy metalsProceed with 1.0 g of Repaglinide according to Method 2, and perform the test.
0.1 g of Repaglinide, dissolve in methanol to make exactly 10 mL and use this solution as the test solution.
To 1.0 mL of the test solution, add methanol to make
exactly 10 mL and use this solution as the standard solution. Perform the test with 3 L each of the test solution and the standard solution as directed under the
Liquid Chromatography according to the following operating conditions and determine the areas of peaks
other than the principal peaks by the automatic integration method: not more than 0.1% for each related substance and not more than 0.5% for total related substances. Multiply the equation by a response factor of 2
for the repaglinide related substance I {(S)-3-methyl-1[2-(1-piperidinyl)phenyl]butylamine,
N-acetyl-Lglutamate salt}.
A
Content (%) of each related substance = i
AS
Ai : Area of each related substance peak obtained

from the test solution
AS : Area of the repaglinide peak obtained from the
standard solution
about 45 C.
Mobile phase A: Dissolve 3 g of potassium dihydrogen phosphate in 1000 mL of water and adjust the
pH of the solution to 7.0 by the addition of 1 mol/L sodium hydroxide TS.
Mobile
phase A
(vol%)
50
Mobile
phase B
(vol%)
50
0-2
5030
5070
Time (min)
Elution condition
Equilibration
Linear gradient
2-8
30
70
8-12
305
7095
12-15
95
Isocratic
Linear gradient
Isocratic

System suitability
System performance: Weigh 0.1 g of Repaglinide
RS, 1 mg each of repaglinide related substance I RS,
repaglinide related substance II (3-ethoxy-4ethoxycarbonylphenylacetate) RS and repaglinide related substance III {(S)-2-ethoxy-4-[2-[[2-phenyl-1-[2(1-piperidinyl)phenyl]ethyl]amino]-2-oxoethyl] benzoate} RS, dissolve in methanol to make 10 mL and
use this solution as the test solution for system performance. When the procedure is run with 20 L of the
test solution for system performance under the above
operating conditions, the relative retention times are 0.3,
0.6 and 1.6 for the related substance II, III and I, respectively.
times with 3 L each of the standard solution under the
above operating conditions, the relative standard deviation of the areas of repaglinide peak is not more than
10%.
Loss on Drying Not more than 0.7%. Weigh accurately 30 mg of Repaglinide, perform the test as directed in the thermogravimetry method under the
Thermal Analysis. Heat the test specimen at the rate of
10 C per minute between 30 C and 210 C with introduction of nitrogen at the flow rate of 200 mL per
minute and determine the accumulated loss in weight.
Assay Weigh accurately about 25 mg each of Repaglinide and Repaglinide RS, dissolve in methanol to
make exactly 50 mL each and use these solutions as the
conditions and determine the area of repaglinide peak
in test solution, AT , and in the standard solution, AS .
Amount (mg) of repaglinide (C27H36N2O4)

A
= amount (mg) of Repaglinide RS T
AS
about 45 C.
Mobile phase: A mixture of methanol and phosphate buffer (800:200)

Flow rate: 1.0 mL/min
System suitability
System performance: Dissolve 25 mg of Repaglinide RS and 2 mg of repaglinide related substance II
RS in methanol to make 50 mL. When the procedure is
run with 10 L of this solution under the above operating conditions, the relative retention times are about 1.0
and about 0.4 for repaglinide peak and the related substance II peak, respectively.
deviation of the areas of repaglinide peak is not more
than 2.0%.
Phosphate bufferTo the solution of potassium dihydrogen phosphate (1 in 1000), add phosphoric acid to
adjust the pH of the solution to 2.5.
Reserpine
CH3O
N
N
H
OCH3
OCH3
H
CH3O
C
O
OCH3
O
H
H OCH
3
C33H40N2O9: 608.68
Reserpine, when dried, contains not less than 96.0%
and not more than 101.0% of reserpine (C33H40N2O9).
Description Reserpine is a white to pale yellow crystal or crystalline powder and is odorless.
Reserpine is freely soluble in glacial acetic acid or in
chloroform, slightly soluble in acetonitrile, very
water or in ether.
Reserpine is affected by light.
Identification (1) Take 1 mg of Reserpine, add 1 mL
of vanillin-hydrochloric acid TS and warm: a vivid redpurple color is observed.
Reserpine and Reserpine RS in acetonitrile (1 in 50000)
(3) Determine the infrared spectra of Reserpine and
Reserpine RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
of absorption at the same wavenumbers

-127 (after drying, 0.25 g, chloroform, 25 mL, 100
mm).
Purity Related substancesPerform the test without
exposure to daylight, using light-resistant vessels. Dissolve 50 mg of Reserpine in 50 mL of acetonitrile and
test solution, add acetonitrile to make exactly 100 mL
standard solution as directed under the Liquid Chromatography according to the following operating conditions. Determine each peak area from test solution and
the standard solution by the automatic integration method: the total area of peaks other than reserpine peak
from the test solution is not larger than the peak area of
reserpine from the standard solution.
about 40 C.
potassium phosphate, pH 3.0 and acetonitrile (13 : 7).
time of reserpine is about 20 minutes.
System suitability
System performance: Dissolve 10 mg of Reserpine and 4 mg of butyl paraoxybenzoate in 100 mL of
acetonitrile. To 5 mL of this solution, add acetonitrile to
make exactly 50 mL. When the procedure is run with
20 L of this solution according to above operating
conditions, reserpine and butyl parahydroxybenzoate
Detection sensitivity: Adjust the detection sensitivity so that the peak height of reserpine from 10 L of
the standard solution is about 20 mm.
as the retention time of reserpine.
using light-resistant vessels. Weigh accurately about 10
mg each of Reserpine and Reserpine RS, previously
dried and dissolve each in acetonitrile to make exactly
100 mL. Pipet 5.0 mL each of these solutions, add ex-
KP 9 839
actly 10 mL of the internal standard solution, 5 mL of

acetonitrile and water to make exactly 50 mL and use
these solutions as the test solution and the standard solution, respectively. Perform the test with 20 L each
under the Liquid Chromatography according to the following operating conditions and calculate the ratios, QT
and Qs, of the peak area of reserpine to that of the internal standard for the test solution and the standard solution, respectively,
Amount (mg) of reserpine (C33H40N2O9)
Q
= amount (mg) of Reserpine RS T
QS
Internal standard solutionA solution of butyl paraoxybenzoate in acetonitrile (1 in 50000).
about 40 C.
potassium phosphate, pH 3.0 and acetonitrile (11 : 9).
time of reserpine is about 10 minutes.
System suitability
with 20 L of the standard solution according to above
operating conditions, reserpine and the internal standard are eluted in this order with the resolution between
deviation of the ratios of peak area of reserpine to that
tight containers.
Reserpine Injection
Reserpine Injection is an aqueous solution for injection.
Reserpine Injection contains not less than 90.0% and
not more than 110.0% of the labeled amount of reserpine (C33H40N2O9: 608.68).
Method of Preparation Prepare as directed under Injections, with Reserpine.
Description Reserpine Injection is a clear, colorless
or pale yellow liquid.

Identification Measure a volume of Reserpine Injection, equivalent to 1.5 mg of Reserpine according to the
labeled amount, add 10 mL of ether, shake for 10 minutes and take the aqueous layer. If necessary, add
10mL of ether to the aqueous layer and shake for
10minutes to repeat the process. To the aqueous layer
add water to make 50mL and determine the absorption
spectrum of this solution as directed under the Ultraviolet-visible Spectrophotometry : it exhibits a maximum
between 265nm and 269nm.
Assay Measure exactly a volume of Reserpine Injection, equivalent to about 4 mg of reserpine
(C33H40N2O9). Separately, weigh accurately about 4 mg
of Reserpine RS, previously dried in vacuum at 60 C
for 3 hours. Transfer them to a separatory funnel, add
10 mL each of water and 5 mL each of ammonia TS
and extract with one 20 mL volumes of chloroform,
then with three 10 mL volumes of chloroform with
shaking vigorously. Combine the chloroform extracts,
wash with two 50 mL volumes of diluted hydrochloric
acid (1 in 1000) and combine the washings. Extract the
combined washing with two times with 10 mL volumes
of chloroform and combine the washings with the former chloroform extract. Transfer the chloroform solution to a volumetric flask through a pledget of absorbent cotton previously wetted with chloroform, wash
with a small amount of chloroform, dilute with chloroform to make exactly 100 mL and use these solutions
as the test solution and the standard solution, respectively. Determine the absorbances, AT and AS, of the

A
AS
hermetic containers and colored containers may be
used.
Reserpine Powder
Reserpine Tablets
0.1% Reserpine Powder

Reserpine Powder contains not less than 0.09% and not
more than 0.11% of reserpine (C33H40N2O9: 608.68).
Reserpine
1g
Lactose Hydrate
To make 1000 g
Identification Take 0.4 g of Reserpine Powder, add
20 mL of acetonitrile, shake for 30 minutes and centrifuge. Determine the absorption spectrum of the supernatant liquid as directed under the Ultraviolet-visible
nm and 269 nm and between 294 nm and 298 nm.
Particle size distribution test for preparations
It

requirement.
using light-resistant vessels. Weigh accurately a portion
of Reserpine Powder, equivalent to about 0.5 mg of reserpine (C33H40-N2O9), disperse in 12 mL of water, add
10.0 mL of the internal standard solution and 10 mL of
acetonitrile and dissolve by warming at 50 C for 15
minutes, then add water to make exactly 50 mL and use
this solution as the test solution. Separately, weigh accurately about 10 mg of Reserpine RS, previously dried
at 60 C in vacuum for 3 hours, dissolve in acetonitrile
to make exactly 100 mL. Pipet 5.0 mL of this solution,
add 10.0 mL of the internal standard solution, 5 mL of
acetonitrile and water to make exactly 50 mL and use
this solution as the standard solution. Proceed with the
test solution and the standard solution as directed in the
Assay under Reserpine.

1
Q
= amount (mg) of Reserpine RS T 20
QS
Reserpine Tablets contain not less than 90.0% and not

more than 110.0% of the labeled amount of reserpine
(C33H40N2O9: 608.68).
Tablets, with Reserpine.
Identification Take a portion of powdered Reserpine

Tablets, equivalent to 0.4 mg of Reserpine according to
the labeled amount, add 20 mL of acetonitrile, shake
for 30 minute and centrifuge. Determine the absorption
spectrum of the supernatant liquid as directed under the
Ultraviolet-visible Spectrophotometry: it exhibits maxima between 265 nm and 269 nm and between 294 nm
and 298 nm.
Dissolution Test Take 1 tablet of Reserpine Tablets
and perform the test at 100 revolutions per minute with
500 mL of a solution of polysorbate 80 (1 in 20000) in
diluted dilute acetic acid (1 in 200) according to Method 2 under the Dissolution Test. Take 20 mL or more
the dissolution test, filter through a filter laminated
with polyester fibers, discard the first 10 mL of the filtrate and use the subsequent filtrate as the test solution.
Separately, weigh accurately an amount of 100 times
the labeled amount of Reserpine RS, previously dried
at 60 C in vacuum for 3 hours, and add a solution of
polysorbate 80 in diluted dilute acetic acid (1 in 200) (1
in 2000) to make exactly 200 mL. Pipet 1.0 mL of this
solution, add a solution of polysorbate 80 in diluted dilute acetic acid (1 in 200) (1 in 2000) to make exactly
Pipet 5.0 mL each of the test solution and the standard
solution, transfer to glass-stoppered brown test tubes T
and S, respectively, add exactly 5 mL each of dehydrated ethanol, shake well, add exactly 1 mL each of
diluted vanadium pentoxide (1 in 2), shake vigorously
and allow to stand for 30 minutes. Perform the test with
under the Fluorometry and determine the intensity of
fluorescence, FT and FS , at the wavelength of excitation at 400 nm and at the wavelength of fluorescence
at 500 nm for the test solution and the standard solution,
respectively.
Dissolution rate of Reserpine Tablets in 30 minutes is
not less than 70%.

F
1
of reserpine (C33H40N2O9) = WS T
FS C
WS: Amount (mg) of Reserpine RS,
C: Labeled amount (mg) of reserpine (C33H40-N2O9)
in each tablet.
KP 9 841
Uniformity of Dosage Units It meets the requirement when the content uniformity test is performed according to the following procedure. Perform the test
without exposure to daylight, using light-resistant vessels. To 1 tablet of Reserpine Tablets, add 2 mL of water, disintegrate by warming at 50 C for 15 minutes
while shaking. After cooling, add 2.0 mL of the internal
standard solution per 0.1 mg of Reserpine according to
the labeled amount, add 2 mL of acetonitrile, warm at
50 C for 15 minutes while shaking and after cooling,
add water to make 10 mL. Centrifuge the solution and
use the supernatant liquid as the test solution. Separately, weigh accurately about 10 mg of Reserpine RS, previously dried at 60 C in vacuum for 3 hours and dissolve in acetonitrile to make exactly 100 mL. Pipet 5.0
mL of this solution, add 10.0 mL of the internal standard solution, 5 mL of acetonitrile and water to make
Proceed with the test solution and the standard solution
as directed in the Assay under Reserpine.

Q
QS
labeled amount (mg) of Reserpine in each tablet
10
using light-resistant vessels. Weigh accurately and
powder not less than 20 Reserpine Tablets. Weigh accurately a portion of the powder, equivalent to about 0.5
mg of reserpine (C33H40N2O9), add 3 mL of water and
warm at 50 C for 15 minutes while shaking. After
cooling, add 10.0 mL of the internal standard solution
and 10 mL of acetonitrile and warm at 50 C for 15 minutes while shaking. After cooling, add water to make
exactly 50 mL, centrifuge and use the supernatant liquid as the test solution. Separately, weigh accurately
about 10 mg of Reserpine RS, previously dried at 60C
in vacuum for 3 hours and dissolve in acetonitrile to
add 10.0 mL of the internal standard solution and 5 mL
of acetonitrile and water to make exactly 50 mL and
use this solution as the standard solution. Proceed with
the test solution and the standard solution as directed in
the Assay under Reserpine.

1
Q
= amount (mg) of Reserpine RS T 20
QS
Retinol Acetate
CH3
H3C
CH3
CH3
CH2O
CH3
CH3
Vitamin A Acetate
C22H32O2: 328.49
Retinol Acetate is synthetic retinol acetate or synthetic

retinol acetate diluted with fixed oil. Retinol Acetate
contains not less than 2500000 vitamin A units per
gram. A suitable antioxidant may be added. Retinol
Acetate contains not less than 95.0% and not more than
105.0% of the labeled units.
Description Retinol Acetate is a pale yellow to yellow-red crystal or an ointment-like substance and has a
faint, characteristic odor, but has no rancid odor.
When powdered, Retinol Acetate is very soluble in
chloroform or in ether, freely soluble in petroleum ether,
soluble in isopropanol or in ethanol and practically insoluble in water.
Retinol Acetate is affected by air and by light
Identification Dissolve separately Retinol Acetate
and Retinol Acetate RS, equivalent to 15000 Units each,
in 5 mL each of petroleum ether, and use these solutions as the test solution and standard solution, respectively. Perform the test with these solutions as directed
of the test solution and standard solution on a plate of
silica gel for thin-layer chromatography. Develop with
a mixture of cyclohexane and ether (12:1) to a distance
of about 10 cm, and air-dry the plate. Spray evenly antimony (III) chloride TS: the principal spot obtained
from the test solution is the same in color tone and Rf
value with the blue spot from the standard solution.
Purity (1) Acid valueTake exactly 5.0 g of Retinol
Acetate, and perform the test : not more than 2.0.
(2) PeroxideWeigh accurately about 5 g of Retinol Acetate, transfer in a 250 mL glass-stoppered conical flask, add 50 mL of a mixture of glacial acetic acid
and isooctane (3:2), and gently mix to dissolve. Replace the air of the inside gradually with about 600 mL
of Nitrogen, then add 0.1 mL of saturated potassium
iodide TS under a current of Nitrogen. Immediately
stopper tightly, and mix with a swirling motion for 1
minute. Add 30 mL of water, stopper tightly, and shake
vigorously for 5 to 10 seconds. Titrate this solution
with 0.01 mol/L sodium thiosulfate VS until the blue
color of the solution disappears after addition of 0.5 mL
of starch TS near the end point where the solution is a
pale yellow color. Calculate the amount of peroxide by
the following formula: not more than 10 meq/kg.
Amount (meq/kg) of peroxide = (V/W) 10
V: Volume (mL) of 0.01 mol/L sodium thiosulfate

VS consumed
W: Amount (g) of the test specimen
Assay Proceed as directed for Method 1 under the Vitamin A Assay.
tight containers and almost well-filled, or under nitrogen atmosphere in a cold place.
Retinol Palmitate
H3C
CH3
CH3
CH3
Amount (meq/kg) of peroxide = (V/W) 10 mol/L

O
CH2O
(CH2)14CH3
CH3
Vitamin A Palmitate
Retinol Palmitinic Acid
Replace the air of the inside gradually with about 600

mL of Nitrogen, then add 0.1 mL of saturated potassium iodide TS under a current of Nitrogen. Immediately stopper tightly, and mix with a swirling motion
for 1 minute. Add 30 mL of water, stopper tightly, and
shake vigorously for 5 to 10 seconds. Titrate this solution with 0.01 mol/L sodium thiosulfate VS until the
blue color of the solution disappears after addition of
0.5 mL of starch TS near the end point where the solution is a pale yellow color . Calculate the amount of peroxide by the following formula: not more than 10
meq/kg.
V: Volume (mL) of 0.01 mol/L sodium thiosulfate

VS consumed
W: Amount (g) of the test specimen
Assay Proceed as directed in Method 1 under the Vitamin A Assay.
C36H60O2: 524.86
Retinol Palmitate is a synthetic retinol palmitate or a

synthetic retinol palmitate diluted with fixed oil and
contains not less than 1500000 vitamin A units in each
gram. Retinol Palmitate may contain a suitable antioxidant. Retinol Palmitate contains not less than 95.0%
and not more than 105.0% of the labeled units.
Description Retinol Palmitate is a pale yellow to yellow-red, ointment-like or an oily substance. Retinol
Palmitate has a faint, characteristic odor, but has no
rancid odor.
Retinol Palmitate is very soluble in petroleum ether,
water.
Retinol Palmitate is affected by air and by light.
Identification Dissolve separately Retinol Palmitate
and Retinol Palmitate RS, equivalent to 15000 Units
each, in 5 mL each of petroleum ether, and use these
solutions as the test solution and standard solution, respectively. Perform the test with these solutions as directed under the Thin-layer Chromatography. Spot 5
L each of the test solution and standard solution on a
plate of silica gel for thin-layer chromatography. Develop with a mixture of cyclohexane and ether (12:1) to
a distance of about 10 cm, and air-dry the plate. Spray
evenly antimony (III) chloride TS: the principal spot
obtained from the test solution is the same in color tone
and Rf value with the blue spot from the standard solution.
Purity (1) Acid valueTake exactly 5.0 g of Retinol
Acetate, and perform the test : not more than 2.0.
(2) PeroxideWeigh accurately about 5 g of Retinol Palmitate, transfer in a 250 mL glass-stoppered
conical flask, add 50 mL of a mixture of glacial acetic
acid and isooctane (3:2), and gently mix to dissolve.
Packaging and Storage Preserve in well-closed,

light-resistant and well-filled, tight containers. Store at
a cold place under nitrogen atmosphere.
Riboflavin
CH2
CH2OH
OH OH OH
H3C
H3C
NH
Vitamin B2
C17H20N4O6: 376.36
Riboflavin, when dried, contains not less than 98.0%

and not more than 101.0% of riboflavin (C17H20N4O6).
Description Riboflavin is a yellow to orange-yellow
crystal and has a slight odor.
Riboflavin is very slightly soluble in water, practically
insoluble in ethanol, in ether or in glacial acetic acid.
Riboflavin dissolves in sodium hydroxide TS.
A saturated solution of Riboflavin is neutral.
Riboflavin is decomposed by light.
Identification (1) The solution of Riboflavin (1 in
100000) is pale yellow-green in color and has an intense yellow-green fluorescence. The color and fluorescence of the solution disappear upon the addition of
20 mg of sodium hydrosulfite to 5 mL of the solution
and reappear on shaking the mixture in air. This fluo-
KP 9 843
rescence disappears upon the addition of dilute hydrochloric acid or sodium hydroxide TS.
(2) Take 10 mL of a solution of Riboflavin (1 in
100000), place in a glass-stoppered test tube, add 1 mL
of sodium hydroxide TS and after illumination with a
fluorescence lamp of 10 to 30 watts at 20 cm distance
for 30 minutes between 20 C and 40 C, acidify with
0.5 mL of acetic acid and shake with 5 mL of chloroform: the chloroform layer shows a yellow-green fluorescence.
Riboflavin and Riboflavin RS in phosphate buffer solution, pH 7.0 (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit
-142. Weigh accurately about 0.1 g of Riboflavin, previously dried, dissolve in 4.0 mL of dilute sodium hydroxide TS. Add 10 mL of freshly boiled and cooled
water and 4.0 mL of aldehyde-free alcohol while shaking, add freshly boiled and cooled water to make exactly 20 mL and determine the optical rotation in a 100
mm cell within 30 minutes after preparing the solution.
Purity LumiflavinShake 25 mg of Riboflavin with
10 mL of ethanol-free chloroform for 5 minutes and filter: the filtrate has no more color than the following
control solution.
Control solutionTake 2.0 mL of 0.0167 mol/L
potassium bichromate VS, add water to make exactly
1000 mL.
2 hours).
mg of Riboflavin, previously dried, dissolve in 800 mL
of diluted glacial acetic acid (1 in 400) by warming,
cool, add water to make exactly 1000 mL and use this
solution as the test solution. Weigh accurately about 15
mg of Riboflavin RS, previously dried at 105 C for 2
hours, dissolve in 800 mL of diluted glacial acetic acid
(1 in 400) by warming, cool, add water to make exactly
solution as directed under the Ultraviolet-visible Spectrophotometry, using water as the blank and determine
the absorbances, AT and AS , at 445 nm for the test
solution and the standard solution, respectively,. Add
20 mg of sodium hydrosulfite to 5 mL of each solution,
shake until decolorized and immediately measure the
Amount (mg) of riboflavin (C17H20N4O6)

A AT
= amount (mg) of Riboflavin RS T
AS AS
tight containers.
Riboflavin Powder
Vitamin B2 Powder
Riboflavin Powder contains not less than 95.0% and
not more than 115.0% of the labeled amount of riboflavin (C17H20N4O6: 376.36).
powders, with Riboflavin.
Identification Shake a portion of Riboflavin Powder,
equivalent to 1 mg of Riboflavin according to the labeled amount, with 100 mL of water, filter and proceed
with the filtrate as directed in the Identification (1) and
(2) under Riboflavin.
Purity RancidityRiboflavin Powder is free from
any unpleasant or rancid odor or taste.
Uniformity of Dosage Units (divide)
requirement.
It meets the

using a light-resistant vessel. Weigh accurately Riboflavin Powder, equivalent to about 15 mg of riboflavin
(C17H20N4O6), add 800 mL of diluted glacial acetic acid
(1 in 400) and extract by warming for 30 minutes with
occasional shaking. Cool, dilute with water to make exactly 1000 mL and filter through a glass filter (G4). Use
this filtrate as the test solution and proceed as directed
in the Assay under Riboflavin.

A AT
AS AS
tight containers.
Riboflavin Tablets
Vitamin B2 Tablets
Riboflavin Tablets contain not less than 95.0% and not
more than 115.0% of the labeled amount of riboflavin
(C17H20N4O6: 367.36).
Tablets, with Riboflavin.
Identification Take a portion of powdered Riboflavin

Tablets, equivalent to 1 mg of Riboflavin according to
the labeled amount, add 100 mL of water, shake and filter. Proceed with the filtrate as directed in the Identification (1) and (2) under Riboflavin.
Uniformity of Dosage Units It meets the requirement, provided that M is regarded as X in this test.
using a light-resistant vessel. Weigh accurately and
powder not less than 20 Riboflavin Tablets, weigh accurately a portion of the powder, equivalent to about 15
mg of riboflavin (C17H20N4O6), add 800 mL of diluted
glacial acetic acid (1 in 400), frequently shake, mix and
warm for 30 minutes. Extract, cool and add water to
make exactly 1000 mL. Filter with a glass filter (G4)
and use the filtrate as the test solution. Proceed with the
test solution as directed in the Assay under Riboflavin.

A AT
AS AS

tight containers.
Riboflavin Butyrate
CH2
CH2OR
Description Riboflavin Butyrate is an orange-yellow

crystal, crystalline powder and has a slight, characteristic odor and a slightly bitter taste.
Riboflavin Butyrate is freely soluble in methanol, in
ethanol or in chloroform, slightly soluble in ether and
Riboflavin Butyrate is decomposed by light.
Identification (1) A solution of Riboflavin Butyrate
in ethanol (1 in 100000) shows a pale yellow-green
color with strong yellowish green fluorescence. To this
solution, add dilute hydrochloric acid or sodium hydroxide TS: the fluorescence disappears.
(2) Dissolve 10 mg of Riboflavin Butyrate in 5 mL
of ethanol, add 2 mL of a mixture of a solution of hydroxylamine hydrochloride (3 in 20) and a solution of
sodium hydroxide (3 in 20) (1 : 1) and shake well. To
this solution, add 0.8 mL of hydrochloric acid and 0.5
mL of ferric chloride TS and add 8 mL of ethanol: a
deep red-brown color is observed.
Riboflavin Butyrate and Riboflavin Butyrate RS in
Purity (1) ChlorideDissolve 2.0 g of Riboflavin
Butyrate in 10 mL of methanol and add 24 mL of dilute
nitric acid and water to make exactly 100 mL. After
shaking well, allow to stand for 10 minutes, filter, discard the first 10 mL of the filtrate and use the subsequent filtrate as the test solution. To 25 mL of the test
solution, add water to make exactly 50 mL, then add 1
mL of silver nitrate TS and allow to stand for 5 minutes: the turbidity of the solution is not thicker than
that of the following control solution.
Control solutionTake 25 mL of the test solution,
add 1 mL of silver nitrate TS, allow to stand for 10 minutes and filter. Wash the precipitate with four 5 mL
volumes of water and combine the washings with the
filtrate. To this solution, add 0.30 mL of 0.01 mol/L
hydrochloric acid VS and water to make exactly 50 mL,
add 1 mL of water and mix (not more than 0.021%).
OR OR OR
H3C
O
O
NH
H3C
CH2CH2CH3
C33H44N4O10: 656.72
Riboflavin Butyrate, when dried, contains not less than
98.5% and not more than 101.0% of riboflavin butyrate
(C33H44N4O10).
(2) Heavy metalsProceed with 2.0 g of Riboflavin Butyrate according to Method 2 and perform the
(3) Free acidTake 1.0 g of Riboflavin Butyrate,
add 50 mL of freshly boiled and cooled water, shake
and filter. To 25 mL of the filtrate, add 0.50 mL of 0.01
mol/L sodium hydroxide VS and 2 drops of phenolphthalein TS: the solutions shows a red color.
(4) Related substancesDissolve 0.10 g of Riboflavin Butyrate in 10 mL of chloroform and use this so-
KP 9 845
lution as the test solution. Pipet 1.0 mL of the test solution and add chloroform to make exactly 50 mL. Pipet
5 mL of this solution, add chloroform to make exactly
solution as directed under the Thin-layer Chromatography. Spot 10 L each of the test solution and the standard solution on a plate of silica gel with fluorescent
plate with a mixture of chloroform and isopropanol (9 :
nm): the spots other than the principal spot form the
standard solution.
mg of Riboflavin Butyrate, previously dried, and dissolve in ethanol to make exactly 500 mL. Pipet 10.0
mL of this solution, add ethanol to make exactly 50 mL
weigh accurately about 50 mg of Riboflavin RS, previously dried at 105 C for 2 hours, dissolve in 150 mL
of diluted glacial acetic acid (2 in 75) by warming and
after cooling, add water to make exactly 500 mL. Pipet
5.0 mL of this solution, add ethanol to make exactly 50
mL and use this solution as the standard solution. Determine the absorbances, AT and AS, of the test solution
Amount (mg) of riboflavin butyrate (C33H44N4O10)

1
A
= amount (mg) of Riboflavin RS T 1.7449
2
AS

tight containers.
Riboflavin Sodium Phosphate

H2C
OH
OH
OH
H3C
H3C
CH2OPO3HNa
NH
Riboflavin Phosphate
Vitamin B2 Phosphate Ester
C17H20N4NaO9P: 478.33
Riboflavin Sodium Phosphate contains not less than

92.0% and not more than 101.0% of riboflavin sodium
phosphate (C17H20N4 NaO9P), calculated on the anhydrous basis.
Description Riboflavin Sodium Phosphate is a yellow to orange-yellow, crystalline powder, is odorless
and has a slightly bitter taste.
Riboflavin Sodium phosphate is soluble in water and
practically insoluble in ethanol, chloroform or in ether,
Riboflavin Sodium Phosphate is decomposed by light.
Riboflavin Sodium Phosphate is very hygroscopic.
Identification (1) A solution of Riboflavin Sodium
Phosphate (1 in 100000) is pale yellow-green in color
and has an intense yellow-green fluorescence. The color and fluorescence of the solution disappear upon the
addition of 20mg of sodium hydrosulfite to 5 mL of the
solution and reappear on shaking the mixture in air.
This fluorescence disappears upon the addition of dilute hydrochloric acid or sodium hydroxide TS.
(2) Take 10 mL of a solution of Riboflavin Sodium
Phosphate (1 in 100000) placed in a glass-stoppered
test tube, add 1 mL of sodium hydroxide TS and after
illumination with a fluorescence lamp of 10 to 30 watts
at 20 cm distance for 30 minutes between 20 C and 40
C, acidify with 0.5 mL of acetic acid and shake with 5
mL of chloroform: the chloroform layer shows a yellow-green fluorescence.
Riboflavin Sodium Phosphate and Riboflavin Sodium
Phosphate RS in phosphate buffer solution, pH 7.0 (1
(4) Take 50mg of Riboflavin Sodium Phosphate,
add 10 mL of nitric acid, evaporate on a water-bath to
dryness and ignite. Boil the residue with 10 mL of diluted nitric acid (1 in 50) for 5 minutes, after cooling,
neutralize this solution with ammonia TS and filter, if
necessary: the solution responds to the Qualitative Tests
for sodium salt and phosphate.
D : Between +38 and
+43 (0.3 g, calculated on the anhydrous basis, 5 mol/L
hydrochloric acid TS, 20 mL, 100 mm).
pH Dissolve 0.20 g of Riboflavin Sodium Phosphate
in 20 mL of water: the pH of the solution is between
5.0 and 6.5.
0.20 g of Riboflavin Sodium Phosphate in 10 mL of
water: the solution is clear and yellow to orange-yellow
in color.
(2) LumiflavinTo 35 mg of Riboflavin Sodium
Phosphate, add 10 mL of ethanol-free chloroform and
shake for 5 minutes, then filter: the filtrate has no more
color than the control solution.

Control solutionTake 3.0 mL of 0.0167 mol/L
potassium bichromate VS, add water to make 1000 mL.
(3) Free phosphoric acidWeigh accurately about

0.4 g of Riboflavin Sodium Phosphate, dissolve in water to make exactly 100 mL and use this solution as the
test solution. Measure exactly 5 mL each of the test solution and phosphoric acid standard solution, respectively, transfer volumetric flasks, add 2.5 mL of ammonium molybdate-sulfuric acid TS and 1 mL of 1-amino2-naphthol-4-sulfonic acid TS to each of these flasks,
mix and add water to make exactly 25 mL. Allow to
stand for 30 minutes at 20 1 C and perform the test
with these solutions as directed under the Ultravioletvisible Spectrophotometry, using a solution prepared
with 5 mL of water in the same manner as a blank. Determine the absorbances, AT and AS, of the subsequent
solutions of the test solution and the phosphoric acid
standard solution at 740 nm: the free phosphoric acid
content is not more than 1.5%.
Amount (%) of free phosphoric acid (H3PO4)
A
1
257.8
= T
AS W
W: Amount (mg) of Riboflavin Sodium Phosphate
Water Place 25 mL of a mixture of methanol for Water Determination and ethylene glycol for Water Determination (1 : 1) in a dry flask for titration and titrate
with water determination TS to the end point. Weigh
accurately about 0.1 g of Riboflavin Sodium Phosphate,
place quickly into the flask, add a known excess volume of Karl Fischer TS, mix for 10 minutes and perform the test: the water content is not more than 10.0%.
using light-resistant vessels. Weigh accurately about
0.1 g of Riboflavin Sodium Phosphate, dissolve in diluted glacial acetic acid (1 in 500) to make exactly
1000 mL. Pipet 10 mL of this solution and add diluted
glacial acetic acid (1 in 500) to make exactly 50 mL,
accurately about 15 mg Riboflavin RS, previously dried
at 105 C for 2 hour, dissolve in 80 mL of diluted acetic
acid (1 in 400) by warming, cool add water to make exactly 1000 mL and use this solution as the standard solution. Perform the test with the test solution and the
standard solution as directed under the Ultravioletvisible Spectrophotometry, using water as the blank.
Determine the absorbances, AT and AS , at 445 nm.
Add 20 mg of sodium hydrosulfite to 5 mL of each solution, shake until decolorized and immediately measure the absorbances, AT and AS , of the solutions.
Amount (mg) of riboflavin sodium phosphate

(C17H20N4NaO9P)
= amount (mg) of Riboflavin RS

A AT
T
1.2709 5
AS AS
tight containers.
Riboflavin Sodium Phosphate

Injection
Riboflavin Phosphate Injection
Vitamin B2 Phosphate Ester Injection
Riboflavin Sodium Phosphate Injection is an aqueous
solution for injection. Riboflavin Sodium Phosphate Injection contains not less than 95.0% and not more than
120.0% of the labeled amount of riboflavin
(C17H20N4O6: 376.36). The concentration of Riboflavin
Sodium Phosphate Injection is stated as the amount of
riboflavin (C17H20N4O6).
Method of Preparation Prepare as directed under Injections, with Riboflavin Sodium Phosphate.
Description Riboflavin Sodium Phosphate Injection
is a clear, yellow to orange-yellow liquid.
Identification (1) Take a volume of Riboflavin Sodium Phosphate Injection, equivalent to 1 mg of Riboflavin according to the labeled amount, add water to
make 100 mL and proceed with this solution as directed
in the Identification (1) and (2) under Riboflavin Sodium Phosphate.
(2) Take a volume of Riboflavin Sodium Phosphate Injection, equivalent to 50 mg of Riboflavin according to
the labeled amount and evaporate on a water-bath to
dryness. Proceed with this residue as directed in the
Identification (2) under Riboflavin Sodium Phosphate.
using light-resistant vessels. To an accurately measured
volume of Riboflavin Sodium Phosphate Injection,
equivalent to about 15 mg of riboflavin (C17H20N4O6),
add diluted glacial acetic acid (1 in 500) to make exactly 1000 mL and use this solution as the test solution.
KP 9 847
Proceed as directed in the Assay under Riboflavin Sodium Phosphate.

A AT
AS AS
Packaging and Storage Preserve in hemetic, lightresistant containers.
Rifampicin
H
CH3

chromatography. Develop the plate with the developing
solvent which is a mixture of chloroform and ethanol
(2:1), and air-dry the plate. The red spots obtained from
the test solution and the standard solution are the same
in the Rf value.
(3) Make 4 % chloroform solution each of Rifampicin and Rifampicin RS, determine the infrared spectra
of this solutions, as directed in the solution method under the Infrared spectrophotometry: both spectra exhibit
0.1 g of Rifampicin in 10 mL of water is between 4.0
and 6.0.
CH3
HO
H
CH3
H3COOC
H3C
CH3
H
CH3
OH
OH
OH
NH
H
H3C
O
OH
O
H3C
CH3
C43H58N4O12: 822.94
Rifampicin is a derivative of a substance having antibacterial activity produced by the growth of Streptomyces mediterranei.
Rifampicin contains not less than 900 (potency)
per mg of rifampicin (C43H58N4O12), calculated on the
dried basis.
Description Rifampicin is orange-red to red-brown
crystal or crystalline powder, and is almost odorless
and tasteless.
Rifampicin is soluble in methanol, slightly soluble in
ether, and very slightly soluble in water or in ethanol.
Identification (1) Weigh about 0.1 g of Rifampicin,
dissolve in methanol and make to 500 mL. Pipet 5 mL
of the solution and add 0.05 mol/L phosphate buffer solution, pH 7.0 to make 100 mL. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectrophotometry, it exhibits maxima
between 234 nm and 238 nm, and between 252 nm and
256 nm, and between 331 nm and 335 nm, and between
472 nm and 476 nm.
(2) Weigh appropriate amount of Rifampicin, dissolve in methanol and make a solution contain 5 mg per
mL, and use this solution as the test solution. Separately, weigh appropriate amount of Rifampicin RS, dissolve in methanol and make a solution so that each mL
contains 5 mg, and use this solution as the standard solution. Perform the test with the test solution and the
standard solution as directed under Thin-layer Chromatography. Spot 10 L each of the test solution and the
Assay Weigh accurately about 0.1 g (potency) of Rifampicin and Rifampicin RS, dissolve each in methanol
and make exactly 100 mL, pipet exactly 5 mL of each
solution, add phosphate buffer pH 7.0 to make exactly
the standard solution. Perform the test with exactly 20
peak areas, AT and AS, of rifampicin.
Amount [g (potency)] of rifampicin (C43H58N4O12)

A
= Amount [g (potency)] of Rifampicin RS T
AS
chromatography (5 ~ 10 m in particle diameter).
Mobile phase: Adjust the pH of 0.05 mol/L potassium dihydrogenphosphate solution to 3.5 with phosphoric acid, and to 400 mL of this solution add 600 mL
of acetonitrile.
tight containers.
Rifampicin Capsules
Rifampicin Capsules contains not less than 90.0 % and
not more than 120 % of the labeled amount of rifampicin (C43H58N4O12: 822.94).
Mehtod of Preparation
Capsules, with Rifampicin.

Identification Powder the contents of the Rifampicin
Capsules, weigh about 0.1 g (potency) accurately of the
powder, according to the labeled potency, place it in
stopered-flask, add 10 mL of methanol, mix with vigorously shaking, filter and use the filtrate as the test solution. Proceed as directed in the Identification (2) under Rifampicin.
Dissolution Test
Uiformitty of Dosage Units

Assay Weigh accurately not less than 20 Rifampicin
Capsules, and powder. Weigh accurately about 0.1 g
(potency) of the powder, according to the labeled potency, dissolve in methanol and make exactly 100 mL.
Pipet exactly 5 mL of this solution, add phosphate buffer solution, pH 7.0 to make exactly 50 mL, and use
this solution as the test solution. Perform the test as directed in the Assay under Rifampicin.
Amount [g (potency)] of rifampicin (C43H58N4O12)

A
= Amount [g (potency)] of Rifampicin RS T
AS

tight containers.
Risperidone
N
CH3
N
F
N
O
C23H27FN4O2:
410.48
Risperidone contains not less than 99.0% and not more

than 101.0% of risperidone (C23H27FN4O2), calculated
on the dried basis.
Description Risperidone is a white powder.
Risperidone is freely soluble in dichloromethane, sparingly soluble in ethanol, and practically insoluble in
water.
Risperidone is soluble in dilute hydrochloric acid.
Risperidone shows crystalline polymorphism.
Identification Determine the infrared spectra of Risperidone and Risperidone RS as directed in the potassium bromide disk method under the Infrared Spectro-
photometry: both spectra exhibit similar intensities of

appears between the spectra, dissolve each with the
minimum possible volume of acetone, evaporate the
solvent to dryness, and repeat the test with the residue.
0.1 g of Risperidone in 0.75w/v% of tartaric acid solution to make 100 mL: the solution is clear and colorless.
(2) Related substancesWeigh accurately 0.1 g of
Risperidone, add methanol to make exactly 100 mL
of the test solution, add methanol to make exactly 25
mL and use this solution as the standard solution. Perform the test with 10 L each of ethanol (blank), the
operating conditions and determine the area of the
peaks from these solutions: the area of each peak other
than the principal peak obtained from the test solution
is not more than the area of the principal peak obtained
from the standard solution and total area of the peaks
other than the principal peak from the test solution is
not more than 1.5 times the area of the principal peak
from the standard solution. Disregard any peaks from
the blank and any peaks having the area not more than
0.25 times the area of the principal peak from the standard solution.
base-deactivated octadecylsilanized silica gel for liquid
Mobile phase A: 0.5w/v% ammonium acetate solution.
Mobile
Mobile
Elution conTime (min)
phase A
phase B
dition
(vol%)
(vol%)
Linear gra0-15
7030
3070
dient
15-20
30
70
Isocratic
Revert to the
20-21
3070
7030
initial composition
21-25
70
30
Equilibration
Linear gra25=0
70
30
dient

System suitability
Test for required detectability: Dissolve 5.0 mg
of Risperidone RS and 5.0 mg of Haloperidol RS in
250 mL of methanol, and use this solution as the solu-
KP 9 849
tion for the test for required detectability. Proceed with

10 L of this solution as directed under the Liquid
Chromatography according to the above operating conditions and adjust the sensitivity of the system so that
the heights of the two principal peaks obtained from the
solution are not less than 50 % of the full scale of the
recorder.
with 10 L of the solution for the test for required detectability under the above operating conditions, the retention time for risperidone and haloperidol is 10.5 minutes and 11 minutes, respectively, with the resolution
between the two peaks being not less than 3.0.
hours).
Assay Weigh accurately about 0.16 g of Risperidone,
add 70 mL of a mixture of methylethyl ketone and glacial acetic acid (7:1) and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, endpoint detection method in titrimetry). Perform a blank determination and make any necessary correction.

= 20.53 mg of C23H27FN4O2

Roxithromycin
O
N
H3C
CH3
OH
OH
OH
CH3
H3C
O
H3C
O
CH3
O
O
CH3
H
OH
O
CH3
OCH3
H
N
CH3
CH3
OH
H
CH3
C41H76N2O15: 837.05
Roxithromycin contains not less than 920 g (potency)
per mg of roxithromycin (C41H76N2O15), calculated on
Description
Roxithromycin is whtie crystalline
powder.
Roxithromycin is freely soluble in ethanol, in acetone,
in dichloromethane, in chloroform or in ethylactate, soluble in methanol, sparingly soluble in toluene, slightly

soluble in isopropylether, and very slightly soluble in
hexane.
Melting Point 120 ~ 130 C
Roxithromycin and Roxithromycin RS, as directed in
spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) Dissolve 0.1 g each of Roxithromycin and Roxithromycin RS in 100 mL of ethanol, and use these solutions as the test solution and the standard solution.
Thin-layer Chromatography. Spot 10 L of the test solution and the standard solution on a plate of silica gel
the mixture of toluene, chloroform and diethylamine
(50:40:7) as developing solvent mixture, dry the plate
at 100 ~ 105 C for 5 minutes. Spray evenly the color
developing solution on the plate and heat the plate at
100 ~ 105 C. The spots obtained from the test solution
and the standard solution are the same in color tone and
the Rf value. The color developing solution mixture
contains 2.5 g of phosphomolybdic acid, 2.5 mL of sulfuric acid and 50 mL of glacial acetic acid.
Purity (1) Heavy metalsProceed with 1 g of Roxithromycin according to Method 2 and perform the test.
(2) Erythromycin and erythromycin oxime
Weigh accurately 0.2 g (potency) of Roxithromycin,
dissolve in methanol, make to exactly 10 mL and use
this solution as the test solution. Separately, weigh accurately 40 mg (potency) of Erythromycin RS, dissolve
in methanol, make to exactly 100 mL and use this solution as the erythromycin standard solution. Weigh accurately 40 mg of Erythromycin oxime RS, dissolve in
methanol, make to exactly 100 mL and use this solution
as the erythromycin oxime standard solution. Perform
the test with these solutions as directed under Thinlayer Chromatography. Spot 10 L of each solution on
a plate of silica gel for thin-layer chromatography, develop the plate with the mixture of toluene, chloroform
and diethylamine (50:40:7) as the developing solvent
mixture, and dry the plate at 100 ~ 105 C for 5 minutes. Spray evenly the color developing solution on
the plate and heat the plate at 100 ~ 105 C. The color
developing solution mixture contains 2.5 g of phosphomolybdic acid, 2.5 mL of sulfuric acid and 50mL of
glacial acetic acid. The spots obtained from the test solution are not larger or more intense than the spot from
the erythromycin standard solution ( Rf about 0.35)
and the spot from the erythromycin oxime standard solution ( Rf about 0.28) (Each is not more than 2.0 %).
Water Not more than 3.0 % (0.2 g, volumetric titra-
has a characteristic odor and a slightly sweet taste.

Saccharated Pepsin is soluble in water with slight turbidity and insoluble in ethanol or in ether.
Saccharated Pepsin is slightly hygroscopic.
tion, direct titration).

Assay Weigh accurately an amount of Roxithromycin
and Roxithromycin RS, equivalent to about 50 mg (potency), dissolve each in the mobile phase and make exactly 25 mL, and use these solutions as the test solution
and the standard solution. Perform the test with exactly
20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions, and determine the
peak areas, AT and AS, of Roxithromycin.
Amount [g (potency)] of Roxithromycin

= Amount [g (potency)] of Roxithromycin RS
AT
AS
Column temperature: A room temperature
Mobile phase: Adjust pH of the mixture of water,
17 % ammonium dihydrogenphosphate and 2 mol/L
sodium hydroxide TS (1020:400:23) to 5.3 with 2mol/L
sodium hydroxide TS. To this solution add 630 mL of
acetonitrile
Flow rate: 1.8 mL per minute.
System suitability
System performance: Dissolve 5 mg (potency) of
Roxithromycin RS in the mobile phase to make exactly
solution under the above operating conditions, the theoretical plate number of roxithromycin is more than
2000 and symmetry factor is 1.3.
times with 20 L of the standard solution under the operating conditions, the relative standard deviation of the
peak area of is not more than 3.0 %.
Time span of measurement: 16 minutes.
Purity (1) DeteriorationSaccharated Pepsin doses

not have a unpleasant or deteriorated odor.
(2) AcidDissolve 0.5 g of Saccharated Pepsin in
50 mL of water and add 0.50 mL of 0.1 mol/L sodium
hydroxide VS and 2 drops of phenolphthalein TS: a red
color develops.
Loss of Drying Not more than 1.0% (1 g, 80 C, 4
hours).
Assay
(1) Test solution
Weigh accurately an
amount of Saccharated Pepsin equivalent to about 1250
units, dissolve in ice-cold 0.01 mol/L hydrochloric acid
TS to make exactly 50 mL.
(2) Standard solution Weigh accurately a suitable
amount of Saccharated Pepsin RS and dissolve in 0.01
mol/L hydrochloric acid TS to make a solution containing about 25 units per mL
(3) Substrate solution Use the substrate solution 1
described in (2) Assay for protein digestive activity under the Digestion Test. After adjusting pH to 2.0.
(4) Procedure Proceed with the test solution as directed in (2) Assay for protein digestive activity under
the Digestion Test and determine the absorbances, AT ,
and ATB . useing trichloroacetic acid TS A as the precipitation reagent. Separately, determine the absorbances,
AS and ASB . of the standard solution in the same
manner as the test solution. Calculate the unit in 1 g of
Saccharated Pepsin as the following equation.
Units in 1 g of Saccharated Pepsin

( A ATB ) 1
= US T
( AS ASB ) W
U S : Units per 1 mL of the standard solution,
W : Amount (g) of Saccharated Pepsin per 1 mL of
the test solution.

Packaging and Storage Preserve in well-closed containers, not exceeding 30 C.
Saccharated Pepsin
Saccharated Pepsin is an enzyme with protein digestibility and is prepared by mixing lactose hydrate into
pepsin obtained from stomach mucosa of swine or bovis.
1 g of Saccharated Pepsin contains not less than 3800
units and not more than 6000 units.
Description Saccharated Pepsin is a white powder,
Salbutamol Sulfate
HOH2C
H
HO
CH3
CCH2NHC
OH
H2SO4
CH3
CH3
KP 9 851
(C13H21NO3)2H2SO4: 576.70
Salbutamol Sulfate, when dried, contains not less than
98.0% and not more than 101.0% of salbutamol sulfate
[(C13H21NO3)2H2SO4].
Description Salbutamol Sulfate is a white powder.
Salbutamol Sulfate is freely soluble in water, slightly
soluble in ethanol or in glacial acetic acid and practically insoluble in ether.
A solution of Salbutamol Sulfate (1 in 20) does not
show any optical rotation.
of the solutions of Salbutamol Sulfate and Salbutamol
Sulfate RS in 0.1 mol/L hydrochloric acid TS (1 in
(2) Determine the infrared spectra of Salbutamol
Sulfate and Salbutamol Sulfate RS, previously dried, as
(3) A solution of Salbutamol Sulfate (1 in 20) responds to the Qualitative Tests for sulfate.
1.0 g of Salbutamol Sulfate in 20 mL of water: the solution is clear and colorless.
(2) Heavy metalsProceed with 1.0 g of Salbutamol Sulfate according to Method 1 and perform the test.
(3) Related substancesDissolve 20 mg of Salbutamol Sulfate in 10 mL of water and use this solution as
gel for thin-layer chromatography. Develop the plate
with a mixture of ethyl acetate, isopropanol, water and
strong ammonia water (25: 15 : 8 : 2) to a distance of
about 15 cm and air-dry the plate. Leave the plate in a
well-closed vessel saturated with diethylamine vapor
for 5 minutes and spray evenly p-nitrobenzenediazonium chloride TS for spray: the spots other than
the principal spot from the test solution are not more intense than the spot from the standard solution in color.
(4) BoronTake 50 mg of Salbutamol Sulfate and
5.0 mL of the boron standard solution and transfer to a
platinum crucible, respectively. Add 5 mL of potassium
carbonate-sodium carbonate TS, evaporate on a waterbath to dryness, dry at 120 C for 1 hour and ignite the
residue immediately. After cooling, add 0.5 mL of water and 3 mL of curcumin TS to the residue and warm
gently in a water-bath for 5 minutes. After cooling, add
3 mL of glacial acetic acid-sulfuric acid TS, mix and allow to stand for 30 minutes. Add ethanol to make exactly 100 mL and filter. Discard the first 10 mL of the
filtrate and use the subsequent filtrate as the test solution and the standard solution, respectively. Perform the
directed under the Ultraviolet-visible Spectrophotometry, using ethanol as the blank: the absorbance of the
test solution at 555 nm is not larger than that of the
standard solution.
Loss on Drying Not more than 0.5% (1 g, not more
than 0.67 kPa, 100 C, 3 hours).
Assay Weigh accurately about 0.9 g of Salbutamol
Sulfate, previously dried and dissolve in 50 mL of glacial acetic acid by warming. After cooling, titrate with
0.1 mol/L perchloric acid VS until the color of the solution changes from purple through blue to blue-green
correction.

= 57.67 mg of (C13H21NO3)2H2SO4
Salicylic Acid
CO2H
OH
C7H6O3: 138.12
Salicylic Acid, when dried, contains not less than
99.5% and not more than 101.0% of salicylic acid
(C7H6O3).
Description Salicylic Acid is a white crystal or crystalline powder, is odorless and has a slightly acidic, followed by an acrid taste.
Salicylic Acid is freely soluble in ethanol, in acetone or
in ether, soluble in hot water and slightly soluble in water.
Identification A solution of Salicylic Acid (1 in 500)
responds to the Qualitative Tests (1) and (3) for salicylate.
Purity (1) ChlorideDissolve 5.0 g of Salicylic Acid in 90 mL of water by heating, cool, dilute with water
to make 100 mL and filter. Discard the first 20 mL of

the filtrate, take subsequent 30 mL of the filtrate, add 6
0.008%).
50 mL and Perform the test. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not
more than 0.011%).
(3) Heavy metalsDissolve 2.0 g of Salicylic Acid
in 25 mL of acetone, add 4 mL of sodium hydroxide, 2
mL of dilute acetic acid and water to make 50 mL and
Perform the test. Prepare the control solution as follows: to 2.0 mL of standard lead solution, add 25 mL of
acetone, 2 mL of dilute acetic acid and water to make
50 mL (not more than 10 ppm).
test with 0.5 g of Salicylic Acid: the solution has no
more color than Color Matching Fluid C.
3 hours).
Assay Weigh accurately about 0.5 g of Salicylic Acid,
previously dried, dissolve in 25 mL of neutralized ethanol and titrate with 0.1 mol/L sodium hydroxide VS
(indicator: 3 drops of phenolphthalein TS).

= 13.812 mg of C7H6O3
Scopolamine Butylbromide
H
H
O
H
H
C
Br
CH3(CH2)3NCH3
CH2OH
2
C21H30BrNO4: 440.37
Scopolamine Butylbromide, when dried, contains not
less than 98.5% and not more than 101.0% of scopolamine butylbromide (C21H30BrNO4).
Description Scopolamine Butylbromide is a white
Scopolamine Butylbromide is very soluble in water,
freely soluble in glacial acetic acid, soluble in ethanol,
sparingly soluble in methanol, slightly soluble in acetic
anhydride and practically insoluble in ether.

Identification (1) To 1 mg of Scopolamine Butylbromide, add 3 to 4 drops of fuming nitric acid and
evaporate on a water-bath to dryness. After cooling,
dissolve the residue in 1 mL of dimethylformamide and
add 6 drops of tetra-ethylammonium hydroxide TS: a
red-purple color develops.
(2) Determine the absorption spectra of the solutions of Scopolamine Butylbromide and Scopolamine
Butylbromide RS (1 in 1000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(3) Determine the infrared spectra of Scopolamine
Butylbromide and Scopolamine Butylbromide RS, previously dried, as directed in the potassium bromide disk
same wavenumbers.
(4) A solution of Scopolamine Butylbromide (1 in
20) responds to the Qualitative Tests for bromide.
pH Dissolve 1.0 g of Scopolamine Butylbromide in
and 6.5.
D : Between -18.0
and -20.0 (after drying, 1 g, water, 10 mL, 100 mm).
1.0 g of Scopolamine Butylbromide in 10 mL of water:
the solution is clear and has no more color than the following control solution.
Control solutionTo 0.5 mL of Color Matching
Fluid F, add diluted hydrochloric acid (1 in 40) to make
20 mL.
(2) Heavy metalsProceed with 2.0 g of Scopolamine Butylbromide according to Method 1 and perform
(3) Related substancesDissolve 0.10 g of Scopolamine Butylbromide in the mobile phase to make exactly 10 mL and use this solution as the test solution.
Separately, dissolve 10 mg of Scopolamine Hydrobromide RS in the mobile phase to make exactly 100 mL.
Pipet 10.0 mL of this solution. add the mobile phase to
make exactly 50 mL and use this solution as the standard solution (1). Pipet 5.0 mL of the standard solution
(1), add the mobile phase to make exactly 10 mL and
standard solutions (1) and (2) as directed under the
conditions. Determine each peak area of these solutions
by the automatic integration method: the peak area of
KP 9 853
scopolamine from the test solution is not larger than

that from the standard solution (2) and each area of the
peaks other than the peak appearing in the first and the
peak of scopolamine and butylscopolamine from the
test solution are not larger than the peak area from the
about 30 C.
Mobile phase: Dissolve 2 g of sodium lauryl sulfate
in 370 mL of water and 680 mL of methanol and adjust
with diluted phosphoric acid (1 in 10) to a pH of 3.6.
time of butylscopolamine is about 7 minutes.
System suitability
Scopolamine Butylbromide and Scopolamine Hydrobromide in 50 mL of mobile phase. When the procedure is run with with 20 L of this solution under the
above operating conditions, Scopolamine and Scopolamine Butylbromide are eluted in this order with a
Detection sensitivity: Adjust the detection sensitivity so that the peak height of scopolamine from 20
L of the standard solution (2) is between 5 mm and 10
mm.
the retention time of butylscopolamine.
hours).
Assay Weigh accurately 0.8 g of Scopolamine Butylbromide, previously dried, dissolve in 40 mL of glacial
correction.

Scopolamine Hydrobromide
Hydrate
H
H
HBr
OC
NCH3
H
H
3H2O
CH2OH
C17H21NO4HBr3H2O: 438.31
Scopolamine Hydrobromide Hydrate, when dried, contains not less than 98.5% and not more than 101.0% of
scopolamine hydrobromide (C17H21NO4HBr: 384.27).
Description Scopolamine Hydrobromide Hydrate is a
colorless or white crystals, or white granules or powder
and is odorless.
Scopolamine Hydrobromide Hydrate is freely soluble
in water, sparingly soluble in ethanol or in glacial acetic acid and practically insoluble in ether.
Identification (1) To 1 mg of Scopolamine Hydrobromide Hydrate, add 3 to 4 drops of fuming nitric acid,
evaporate on a water-bath to dryness and cool. Dissolve
the residue in 1 mL of dimethylformamide and add 6
drops of tetraethylammonium hydroxide TS: a redpurple color is produced.
(2) A solution of Scopolamine Hydrobromide Hydrate (1 in 20) responds to the Qualitative Tests for
bromide.
Melting Point Between 195 C and 199 C (after
drying, previously heat the bath to 180 C).
20
Specific Optical Rotation [] D : Between -24.0

0.5 g of Scopolamine Hydrobromide Hydrate in 10 mL
(2) AcidDissolve 0.50 g of Scopolamine Hydrobromide Hydrate in 15 mL of water and add 0.50 mL of
0.02 mol/L sodium hydroxide VS and 1 drop of methyl
red-methylene blue TS: a green color develops.
(3) ApoatropineDissolve 0.20 g of Scopolamine
Hydrobromide Hydrate in 20 mL of water, add 0.60 mL
of 0.002 mol/L potassium permanganate VS and allow
to stand for 5 minutes: the red color in the solution does
not disappear.
(4) Related substancesDissolve 0.15 g of Scopolamine Hydrobromide Hydrate in 3 mL of water and
use this solution as the test solution. (i) To 1 mL of the
test solution, add 2 to 3 drops of ammonia TS: no turbidity is produced. (ii) To 1 mL of the test solution, add
2 to 3 drops of potassium hydroxide TS: a transient

white turbidity might be produced and disappears clearly in a little while.
Loss on Drying Not more than 13.0% [1.5 g: first
dry in a desiccator (silica gel) for 24 hours, then dry at
105 C for 3 hours].
Assay Weigh accurately about 0.5 g of Scopolamine
Hydrobromide Hydrate, previously dried and dissolve
in 10 mL of glacial acetic acid by warming. After cooling, add 40 mL of acetic anhydride and titrate with 0.1

= 38.426 mg of C17H21NO4HBr
tight containers.
solution (1 in 100), add 300 5 mg of a solution of

bromo-p-nitrobenzyl in 10 mL of ethanol, reflux for 30
minutes, cool, collect the precipitation on a small filter,
wash with water and recrystallize the precipitate from
25 mL of ethanol and dried at 105 C for 30 minutes;
the precipitate melts between 156 C and 161 C.
18 hours)
Residue on Ignition Not more than 0.1% (1 g)
Assay Weigh accurately about 0.45 g of Secobarbital
and dissolve in 60 mL of dimethylformamide. Titrate
with 0.1 mol/L sodium methoxide VS, taking precautions against the absorption of atmospheric carbon dioxide (Indicator: 4 drops of thymol blue TS). Perform a
Each mL of 0.1 mol/L sodium methoxide VS

= 23.828 mg of C12H18N2O3
Secobarbital
O
CH2
H
N
CHCH2
Secobarbital Sodium
O
CH2
NH
CH3CH2CH2CH
CH3
CHCH2
ONa
NH
CH3CH2CH2CH
CH3
C12H18N2O3: 238.28
Secobarbital contains not less than 97.5% and not more
than 100.5% of scobarbital (C12H18N2O3), calculated on
the dried basis.
Description Secobarbital is a white amorphous or
crystalline powder, is odorless and has a slightly bitter
taste.
Secobarbital is very slightly soluble in water, freely soluble in ethanol or in ether and soluble in chloroform.
Secobarbital dissolves in sodium hydroxide TS or sodium carbonate TS.
pHThe pH of the saturated solution of Secobarbital is about 5.6.
C12H17N2NaO3: 260.27
Secobarbital Sodium contains not less than 98.5% and
not more than 100.5% of secobarbital sodium
Description Secobarbital Sodium is a white powder,
is ordorless and has a bitter taste.
Secobarbital Sodium is very soluble in water, soluble in
Secobarbital Sodium is hygroscopic.
The solution of Secobarbital Sodium degrades on
standing and its degradation is accelerated by heating.
Identification Determine the infrared spectra of Secobarbital and Secobarbital RS, as directed in the paste
method under Infrared Spectrophotometry: both spectra

chloroform solutions of the residue obtained from the
Assay and Secobarbital RS as directed in the solution
same wavenumbers.
(2) Ignite about 0.5 g: the residue effervesces with
acids and responds to the Qualitative Tests for sodium.
Purity Isomer content Weigh accurately about 0.3

g of Secobarbital, dissolve in 5 mL sodium hydroxide
pH
The pH of a solution of Secobarbital Sodium (1
KP 9 855

1.0 g of Secobarbital Sodium in 10 mL of a freshly
boiled and cooled water: the solution is clear and has
no undissolved material after 1 minute.
(2) Heavy metalsProceed with 1.0 g of Secobarbital Sodium according to Method 2 and perform the
(3) Isomer contentWeigh accurately about 0.3 g
of Secobarbital Sodium, dissolve in 5 mL of sodium
hydroxide solution (1 in 100), add 0.3 g of a solution of
bromo-p-nitrobenzyl in 10 mL of ethanol, reflux for 30
minutes, cool, collect the precipitation on a small filter
and wash with water, recrystallize the precipitate from
25 mL of alcohol and dry at 105 C for 30 minutes: the
precipitate melts between 156 C and 161 C.
hours).
Assay Dissolve about 0.5 g of Secobarbital Sodium,
accurately weighed, in 15 mL of water in a separatory
funnel. To this solution, add 2 mL of hydrochloric acid,
shake and extract the liberated Secobarbital with eight
times 25 mL volumes of chloroform. Test for completeness of extraction by extracting with an additional
10 mL of chloroform and evaporating the solvent: not
more than 0.5 mg of residue remains. Filter the extracts
into a tared beaker and finally rinse the separatory funnel and the filter with several small volumes of chloroform. Evaporate the combined filtrate and washings in
a steam-bath with the aid of a current of air just to dryness. Dissolve the residue in 2 mL of dehydrated ethanol and evaporate to dryness. Repeat the dissolution
and evaporation with 2 mL of dehydrated ethanol, dry
the residue at 100 C for 2 hours. and weigh its mass
after cooling.
Amount (mg) of secobarbital sodium (C12H17N2NaO3)

= amount (mg) of the residue 1.092
Selegiline Hydrochloride
Description Selegiline Hydrochloride occurs as a

white crystalline powder and is ordorless.
Selegiline Hydrochloride is freely soluble in water, in
chloroform, or in methanol.
of the solutions of Selegiline Hydrochloride and Selegiline Hydrochloride RS in water (1 in 2000) as directed
same wavelengths.
(2) Determine the infrared absorption spectra of Selegiline Hydrochloride and Selegiline Hydrochloride
under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) The retention time of the pricipal peak from the
test solution corresponds to that from the standard solution, as obtained in the Assay.
(4) The solution of Selegiline Hydrochloride in water (1 in 50) responds to the Qualitative Tests for chloride (the Flame Coloration Test 2).
D : Between 10 and
12 (2.0 g, water, 20 mL, 100 mm).
Purity (1) Heavy metalsProceed with 1.0 g of Selegiline Hydrochloride, according to Method 2 and perform the test. Prepare the control solution with 2.0 mL
of standard lead solution (20 ppm).
(2) Related substancesDissolve 50 mg of Selegiline Hydrochloride, in the mobile phase to make 50 mL,
and use this solution as the test solution. Separately, dilute the system suitability solution with the mobile
phase to make 100 mL. Add to 10 mL of the solution
the mobile phase to make 50 mL, and use this solution
each of the test solution and the standard solution as directed under the Liquid Chromatography, determine all
peak areas by the automatic integration method, and
calculate the percentage of each related substance in the
portion of Selegiline Hydrochloride. Not more than
0.2% of any individual related substance is found, and
the sum of all related substances is not more than 1.0%.
CH3
N
CH
HCl
CH3
C13H17NHCl : 223.74
Selegiline Hydrochloride contains not less than 98.0%
and not more than 101.0% of selegiline hydrochloride
(C13H17NHCl), calculated on the dried basis.
Amount (%) of each related substance

C A
= 5000 i
W AS
C is the concentration (mg/mL) of Selegiline Hydrochloride in the standard solution.
W is the amount (mg) of Selegiline Hydrochloride
taken to prepare the test solution.
Ai is the peak area for each related substance from
the test solution.

AS is the peak area of selegiline from the standard
solution.
Detector, column, mobile phase, flow rate, and system suitability solutionProceed as directed in the Assay.
System suitability
System performance: When the test is performed
above operating conditions, the resolution between the
peaks of methamphetamine and selegiline is not less
than 3.
above operating conditions, the relative standard deviation of the peak area of selegiline is not more than 5.0%.
long as the retention time of selegiline.
Loss on Drying Not more than 1.0% (1 g, 60 o C , vacuum, 3 hours).
Assay Dissolve about 50 mg each of Selegiline Hydrochloride and Selegiline Hydrochloride RS, accurately weighed, in the mobile phase to make 50 mL. Add to
10 mL each of the solutions the mobile phase to make
under the Liquid Chromatography according to the following conditions, and determine the peak areas, AT
and AS , of selegiline hydrochloride.
Amount (mg) of selelgiline hydrochloride

(C13H17NHCl) = amount (mg) of Selelgiline Hydrochloride AT
AS
Column: A stainless steel column about 3.9 mm inside diameter and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (3
Mobile phase: a mixture of phosphate buffer solution and acetonitrile (80:20).
System suitability
System performance: Dissolve 10 mg of Methamphetamine Hydrochloride RS and 10 mg of Selegiline Hydrochloride RS in the mobile phase to obtain
100 mL, and use this solution as the system suitability
solution. When the procedure is run with 20 L of this
solution as directed in the Liquid chromatography un-
der the above operating conditions, the resolution between the peaks of methamphetamine and selegiline is
not less than 3.
times with 20 L of the system suitability solution under the above operating conditions, the relative standard deviation of the peak area of selegiline is not more
than 2.0%.
Phosphate buffer solutionPrepare a solution of
0.1 mol/L monobasic ammonium phosphate, and adjust
with phosphoric acid to a pH of 3.1.
resistant containers.
Preserve in tight, light-
Selenium Sulfide
SeS2: 143.09
Selenium Sulfide contains not less than 52.0% and not
more than 55.5% of selenium (Se: 78.96).
Description Selenium Sulfide is a reddish brown to
orange powder and has an odor slightly.
Selenium Sulfide is practically insoluble in water or organic solvents.
Identification (1) Filter 20 mL of the solution of Selenium Sulfide prepared as directed in the Assay and to
10 mL of the filtrate, add 5 mL of water and 5 g of urea.
Heat to boiling, cool and add 2 mL of potassium iodide
solution (1 in 10): a yellowish orange to orange color is
observed and it darkens rapidly.
(2) Allow the solution obtained in Identification (1)
to stand for 10 minutes, filter and to the filtrate, add 10
mL of barium chloride TS: the solution becomes turbid.
Purity Soluble selenium compoundsMix 10.0 g of
Selenium Sulfide with 100 mL of water in a 250 mL
flask, allow to stand for 1 hour, with frequent shaking
and filter. Pipet 10.0 mL of the filtrate, add 2 mL of 2.5
mol/L formic acid, add 50 mL of water, mix and adjust,
if necessary, to a pH of 2.5 0.5. Add 2 mL of freshly
prepared 3,3'-diamino-benzidine hydrochloride solution
(1 in 200), mix, allow to stand for 45 minutes and adjust with ammonium hydroxide to a pH of 6.5 0.5.
Transfer to a separatory funnel, add 10.0 mL of toluene,
shake vigorously for 1 minute, allow the layer to separate, discard the aqueous phase and use the toluene
layer as the test solution. Pipet exactly 50 mL of the
standard selenium stock solution, add water to make
exactly 100 mL. Pipet exactly 10 mL of this solution,
add 2 mL of 2.5 mol/L of formic acid and prepare a solution as directed in the same manner as the test solution and use this solution as the standard solution. Perform the test with the test solution and the standard solution as directed under the Ultraviolet-visible Spectrophotometry. Determine the absorbances of the test solu-
KP 9 857
tion and the standard solution at 420 nm using a blank

consisting of the same quantities of the same reagents
treated in the same manner as the test solution: the absorbance of the test solution is not greater than that of
the standard solution (not more than 5 ppm).
Assay Weigh accurately about 0.1 g of Selenium Sulfide, add 25 mL of fuming nitric acid and digest over
gently heat until no further dissolution occurs. Cool,
transfer the solution to a volumetric flask containing
100 mL of water, cool again and add water to make exactly 250 mL and mix. Pipet exactly 50 mL of the solution into a flask, add 25 mL of water and 10 g of urea
and heat to boiling. Cool, add 3 mL of starch TS, then
add 10 mL of potassium iodide solution (1 in 10) and
immediately titrate with 0.05 mol/L sodium thiosulfate
VS. Perform a blank determination and make any necessary correction.

= 0.987 mg Se
add 2 mL of nitric acid and titrate with 0.1 mol/L ammonium thiocyanate VS (indicator: 2 mL of ferric ammonium sulfate TS).
= 16.987 mg of AgNO3
tight containers.
Silver Protein
Silver Protein is a compound of silver and proteins.
Silver Protein contains not less than 7.5% and not more
than 8.5% of silver (Ag: 107.87).
Description Silver Protein is a pale yellow-brown to
brown powder and is odorless.
One g of Silver Protein dissolves slowly in 2 mL of water and Silver Protein is practically insoluble in ethanol,
in ether or in chloroform.
pHA solution of 1.0 g of Silver Protein in 10 mL
of water is between 7.0 and 8.5.
Silver Protein is slightly hygroscopic.
Silver Protein is affected by light.
Description Silver Nitrate is lustrous, colorless or

white crystals.
Silver Nitrate is very soluble in water, soluble in ethanol and practically insoluble in ether.
Silver Nitrate gradually turns grayish black by light.
Identification (1) To 10 mL of a solution of Silver

Protein (1 in 100), add 2 mL of dilute hydrochloric acid,
shake frequently for 5 minutes and filter. To the filtrate,
add 5 mL of a solution of sodium hydroxide (1 in 10)
and add 2 mL of diluted cupric sulfate TS (2 in 25): a
(2) To 5 mL of a solution of Silver Protein (1 in
100), add drop-wise ferric chloride TS: the color of the
solution fades and a precipitate is gradually formed.
(3) Incinerate 0.2 g of Silver Protein by ignition,
dissolve the residue in 1 mL of nitric acid by warming
and add 10 mL of water: this solution responds to the
Qualitative Tests (1) for silver salt.
Identification A solution of Silver Nitrate (1 in 50)

responds to the Qualitative Tests for silver salt and for
nitrate.
Purity Silver saltDissolve 0.10 g of Silver Protein

in 10 mL of water and filter. To the filtrate, add 1 mL of
potassium chromate TS: no turbidity is produced.
Purity (1) Clarity and color of solution and acidity
Assay Transfer about 1 g of Silver Protein, accurately

weighed, to a decomposition flask, add 10 mL of sulfuric acid, cover the flask with a funnel and boil for 5
minutes. Cool, add drop-wise 3 mL of nitric acid with
caution and heat for 30 minutes without boiling. Cool,
add 1 mL of nitric acid, boil and, if necessary, repeat
this operation until the solution becomes colorless at
cooling. After cooling, transfer the solution to a 250 mL
of Erlenmeyer flask, wash the decomposition flask with
100 mL of water, combine the washings to the Erlenmeyer flask and titrate with 0.1 mol/L ammonium thiocyanate VS (indicator: 3 mL of ferric ammonium sulfate TS).
Silver Nitrate
AgNO3: 169.87
Silver Nitrate, when dried, contains not less than 99.8%
and not more than 101.0% of silver nitrate (AgNO3).
or alkalinityDissolve 1.0 g of Silver Nitrate in 10

mL of a freshly boiled and cooled water: the solution is
clear, colorless and neutral.
(2) Bismuth, copper and leadTo 5 mL of a solution of Silver Nitrate (1 in 10), add 3 mL of ammonia
light resistant, 4 hours).
Assay Weigh accurately 0.7 g of Silver Nitrate, previously powdered and dried, dissolve in 50 mL of water,

= 10.787 mg of Ag
tight containers.
Silver Sulfadiazine
H2N
Ag
with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform,
methanol and strong ammonia water (10 : 5 : 2) to a
spots other than the principal spot and spot of the starting point from the test solution are not more intense
P2O5, 80 C, 4 hours).
C10H9AgN4O2S: 357.14
Silver Sulfadiazine, when dried, contains not less than
99.0% and not more than 102.0% of silver sulfadiazine
(C10H9AgN4O2S).
Description Silver Sulfadiazine is a white to pale
yellow, crystalline powder and is odorless.
Silver Sulfadiazine is practically insoluble in water, in
Silver Sulfadiazine dissolves in ammonia TS.
Silver Sulfadiazine is gradually colored by light.
Identification Determine the infrared spectra of Silver Sulfadiazine and Silver Sulfadiazine RS, previously
wavenumbers.
Purity (1) NitrateTo 250 mL of water, add 1.0 g of
Silver Sulfadiazine, shake well for 50 minutes, filter
and use this filtrate as the test solution. Separately,
weigh accurately 0.25 g of potassium nitrate and dissolve in water to make exactly 2000 mL. Pipet 5.0 mL
of this solution and add water to make exactly 200 mL
and use this solution as the standard solution. Pipet 2.0
mL each of the test solution and the standard solution
and add 5 mL of a solution of chromotropic acid in sulfuric acid (1 in 10000) and sulfuric acid to make exactly 10 mL. Determine the absorbances, AT and AS, of the
408 nm as directed under the Ultraviolet-visible Spectrophotometry, using a solution prepared with exactly
2.0 mL of water in the same manner as the blank: AT is
not larger than AS (not more than 0.05%).
(2) Related substancesDissolve 50 mg of Silver
Sulfadiazine in 5 mL of a mixture of ethanol and strong
ammonia water (3 : 2) and use this solution as the test
solution. Pipet 2.0 mL of the test solution and add a
mixture of ethanol and strong ammonia water (3 : 2) to
make exactly 20 mL. Pipet 2.0 mL of this solution, add
a mixture of ethanol and strong ammonia water (3 : 2)
Residue on Ignition Between 41.0% and 45.0% (1 g).

Silver Content Weigh accurately 50 mg of Silver
Sulfadiazine, previously dried, dissolve in 2 mL of nitric acid and add water to make exactly 100 mL. Pipet
exactly 1 mL of this solution, add water to make exactly 100 mL and use this solution as the test solution.
Separately, measure accurately a suitable portion of
standard silver solution for Atomic Absorption Spectrophotometry, dilute with water to make a solution
containing 1.0 to 2.0 g of silver (Ag: 107.87) per mL
as directed under the Atomic Absorption Spectrophotometry according to the following conditions and calculate the silver content of the test solution from the calibration curve obtained from the absorbance of the
standard solution; content of silver is not less than
28.7% and not more than 30.8%.
Gas: Combustible gasAcetylene.
Supporting gasAir.
Lamp: A silver hollow cathode lamp.
Assay Weigh accurately about 0.1 g each of Silver
Sulfadiazine and Silver Sulfadiazine RS, each previously dried and add ammonia TS to make exactly 100
mL. Pipet exactly 1 mL each of these solutions, add
water to make exactly 100 mL and use these solutions
as the test solution and the standard solution, respectively. Determine the absorbances, AT and AS , of
at 255 nm, using a solution, prepared with exact 1 mL
of ammonia TS and a sufficient water to make exactly
100 mL, as the blank.
Amount (mg) of silver sulfadiazine (C10H9AgN4O2S)

A
= amount (mg) of Silver Sulfadiazine RS T
AS
tight containers.
KP 9 859
Simethicone
H3C
CH3
CH3
Si
OSi
CH3 + SiO2
CH3
CH3
Simethicone is a mixture of fullyl methylated linear siloxane polymers containing repeating units of the formula [-(CH3)2SiO-]n, stabilized with trimethylsiloxy
endblocking units of the formular [(CH3)2SiO-] and silicon dioxide. Simethicone contains not less than 90.5%
and not more than 99.0% of polydimethylsiloxane
([(CH3)2SiO-]n) and not less than 4.0% and not more
than 7.0% of silicone dioxide.
Description Simethicone is a translucent, gray, viscous liquid.
Simethicone is insoluble in water or ethanol. The liquid
phase of Simethicone is soluble in chloroform, in ether
or in benzene, but silicon dioxide remains as residue in
these solvents.
the test solution and the standard solution prepared as
directed in the Assay in the solution method under the
Infrared Spectrophotometry using 0.5 mm cell: both
same wavenumbers.
Purity Heavy metalsWeigh 1.0 g of Simethicone,
dissolve in 10 mL of chloroform, mix and add chloroform more to make 20 mL. Add 1.0 mL of a freshly
prepared 0.002% solution of dithizone chloroform, 0.5
mL of water and 9.5 mL of a mixture of ammonia TS
and 0.2% solution of hydroxylamine hydrochloride(1 :
9) and use this solution as the test solution. Separately,
to 20 mL of chloroform, add 1.0 mL of a freshly prepared 0.002% solution of dithizone in chloroform, 0.5
mL of standard lead solution and 0.5 mL of a mixture
of ammonia TS and 0.2% solution of hydroxylamine
hydrochloride(1 : 9) and use this solution as the standard solution. Immediately shake both solutions vigorously for 1 minute: Any red color in the test solution is
not more intense than that in the Standard solution (Not
more than 5 ppm).
Defoaming Activity Dissolve 1.0 g of octoxynol in
100 mL of water and use this solution as the foaming
solution. Weigh accurately 0.2 g of Simethicone and
transfer to a 60 mL bottle. Add 50 mL of tertiary butyl
alcohol, cap the bottle, shake and use this solution as
the test solution. Warm this solution slightly, if necessary. Add, dropwise, 0.5 mL of the test solution to a
clean, cylindrical 250 mL glass jar, fitted with a 50 mm
cap, containing 100 mL of the foaming solution. Cap
the jar and clamp it in an upright position on a wristaction shaker. Employing a radius of 13.3 0.4 cm
measured from center of shaft to center of bottle, shake

for 10 seconds through an arc of 10 at a frequency of
300 3 stroke per minute. Record the time required
for the foam to collapse. The time for foam collapse is
determined at the instant the first portion of foam-free
liquid surface appears, measured from the end of the
shaking period. The defoaming activity time does not
exceed 15 seconds.
Content of Silicon Dioxide Transfer 3.00 g each of
Simethicone, Simethicone RS and dimethicone (500
mm2/s) to a screw-capped bottle, add 10.0 mL of nhexane, cap, mix by shaking and use these solutions as
the test solution, the standard solution and dimethicone
solution respectively. Perform the test as directed in the
solution method under the Infrared Spectrophotometry
with these solutions. Using 0.1 mm fixed cells, determine the absorbance spectra of these solutions between
7 and 9 m, using n-hexane as the blank. Determine the
absorbance of the test solution, the standard solution
and the dimethicone solution at the wavelength of minimum absorbance at about 8.2 m observed in the spectrum obtained from the dimethicone solution.
Amount (%) of silicon dioxide (SiO2) in Simethicone

= amount (%) of silicon dioxide in Simethicone RS
A AD
T
AS A D
AD : Absorbance of dimethicone solution
AT : Absorbance of the test solution
AS : Absorbance of the standard solution
Loss on Drying Not more than 18.0% (15.0 g, 200

C, 4 hours)
Assay Transfer about 50 mg each of Simethicone and
polydimethylsiloxane RS, accurately weighed, to a
round, narrow-mouth, screw-capped, 120-mL bottle,
add 25.0 mL of toluene and swirl to disperse. Add 50
mL of diluted hydrochloric acid (2 in 5), close the bottle securely with a cap having an inert liner and shake
for 5 minutes, accurately timed, on a reciprocating
shaker at a frequency of about 200 oscillations per
minute and a stroke of 38 2 mm. Transfer the mixture
to a 125-mL separatory funnel and remove about 5 mL
of the toluene layer to a 15-mL screw-capped test tube
containing 0.5 g of anhydrous sodium sulfate. Close the
tube with a screw-cap having an inert liner, agitate vigorously, centrifuge the mixture until a clear supernatant liquid is obtained and use these solutions as the test
solution and the standard solution, respectively. Perform the test as directed in the solution method under
the Infrared Spectrophotometry with these solutions,
using a solution, prepared with 25.0 mL of toluene in
the same manner to the test solution, as the blank. Determine the absorbances, AT and AS , of the test solution and the standard solution in 0.5-mm cells at the
wavelength of maximum absorbance at about 7.9 m,

with an Infrared Spectrophotometer, respectively.
Amount (mg) of polydimethylsiloxane ([-(CH3)2SiO-]n)
in Simethicone = concentration (mg/mL) of
A
Polydimethylsiloxane RS 25 T
AS
Simfibrate
CH3 O
Cl
C
CH3
O
O
CH2CH2CH2 O
CH3
C
Cl
CH3
C23H26Cl2O6: 469.36
Simfibrate, when dried, contains not less than 98.5%
and not more than 101.0% of simfibrate (C23H26Cl2O6).
Description Simfibrate is a white to pale yellow
crystal or crystalline powder, is odorless and tasteless.
Simfibrate is very soluble in acetonitrile or in ether, soluble in ethanol or in hexane, and practically insoluble
in water.
0.20 mL of 0.1 mol/L sodium hydroxide VS: a red color develops.

(3) Heavy metalsProceed with 1.0 g of Simfibrate according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
Simfibrate according to Method 3 and perform the test
(5) p-ChlorophenolTo 2.0 g of Simfibrate, add
1.0 mL of the internal standard solution, dissolve in
acetonitrile to make 10 mL and use this solution as the
test solution. Separately, dissolve 0.10 g of pchlorophenol in acetonitrile to make exactly 100 mL.
Pipet 2.0 mL of this solution and add acetonitrile to
add 1.0 mL of the internal standard solution and acetonitrile to make 10 mL and use this solution as the standard solution. Perform the test with 20 L each of the
conditions. Calculate the ratios, QT and QS , of the
peak height of p-chlorophenol to that of the internal
respectively. QT is not more than QS .
Internal standard solutionA solution of pethoxyphenol in acetonitrile (1 in 50000).
(1 : 1).
time of p-chlorophenol is about 7 minutes.
Selection of column: Proceed with 20 L of the
standard solution under the above operating conditions.
Use a column from which the internal standard and pchlorophenol are eluted in this order and showing a
complete separation between their peaks.
Identification (1) To 50 mg of Simfibrate, add 0.5

mL of ethanol and dissolve by warming in a water-bath.
After cooling, add 0.3 mL of a saturated solution of hydroxylamine hydrochloride in ethanol and 0.3 mL of
potassium hydroxide-ethanol TS, heat gently to boiling
and cool. To this solution, add 1 mL of 1 mol/L hydrochloric acid TS and 2 mL of ethanol and then add 1
drop of ferric chloride TS: a red-purple color develops.
of Simfibrate in n-hexane (3 in 50000) as directed under the Ultraviolet-visible Spectrophotometry: it exhibits maximum between 280 nm and 283 nm and between 288 nm and 291 nm and a minimum between
285 nm and 288 nm. Determine the absorption spectrum of a solution of Simfibrate in n-hexane (3 in
200000) as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 226 nm
and 229 nm.
(3) Perform the test with Simfibrate as directed under the Flame Coloration Test (2): a green color appears.

P2O5, 4 hours).

1.0 g of Simfibrate in 10 mL of ethanol by warming on
a water-bath: the solution is clear and colorless to pale
yellow.
(2) AcidTo 4.0 g of Simfibrate, add 40 mL of
neutralized ethanol, dissolved by warming in a waterbath, cool and add 2 drops of phenolphthalein TS and
Assay Weigh accurately about 0.8 g of Simfibrate,

previously dried, add exactly 50 mL of 0.1 mol/L potassium hydroxide-ethanol VS and boil gently under a
reflux condenser with a carbon dioxide absorption tube
(soda lime) in a water-bath for 60 minutes. After cooling, titrate the excess potassium hydroxide immediately
with 0.1 mol/L hydrochloric acid VS (indicator: 3 drops
KP 9 861
of phenolphthalein TS). Perform a blank determination

= 23.468 mg of C23H26Cl2O6
Simvastatin
HO
CH3
CH3
H3C
O
O
H
H
H
H
CH3
H3C
H
C25H38O5 : 418.57
Simvastatin contains not less than 98.0% and not more
than 101.0% of simvastatin (C25H38O5), calculated on
the dried basis. Simvastatin may contain a suitable antioxidant.
Description Simvastatin is a white powder.
Simvastatin is freely soluble in methanol, ethanol, or
chloroform, sparingly soluble in propylene glycol, very
slightly soluble in hexane, and practically insoluble in
water.
Identification (1) Weigh 10 mg each of Simvastatin
and Simvastatin RS, dissolve in acetonitrile to make
100 mL, pipet 5.0 mL each of these solutions, add separately acetonitrile to make 50 mL. Determine the absorption spectra of these solutions as directed under Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Simvastatin
and Simvastatin RS, previously dried, as directed in the
paste method under the Infrared Spectrophotometry:
D : Between +285
and 298 (after drying, 0.10 g, acetonitrile, 20 mL, 100
mm).
Simvastatin according to Method 2. and perform the
0.2 g of Simvastatin, dissolve in 0.05w/v% butylated

hydroxytoluene solution in acetonitrile to make exactly
10 mL, and use this solution as the test solution. Separately, weigh accurately about 20 mg of Simvastatin RS,
dissolve in and 0.05w/v% butylated hydroxytoluene solution in acetonitrile to make exactly 100 mL, and use
this solution as the standard solution (1). Pipet 4.0 mL,
2.0 mL and 1.0 mL of the standard solution (1), add
0.05w/v% butylated hydroxytoluene solution in acetonitrile to make exactly 10 mL each, and use these solutions as the standard solutions (2), (3), and (4), respectively. Perform the test with these solutions as directed
of the test solution and the standard solutions on a plate
chromatography and air-dry it. Develop the plate with
the mixture solution of cyclohexane, chloroform and 2propanol (5 : 2: 1) containing 0.5 mg of butylated toluene per mL to a distance of about 15 cm and air-dry the
plate. Spray evenly a mixture solution of methanol and
sulfuric acid (8 : 2) on the plate, heat at 110 C for 30
minutes: any spot other than the principal spot from the
test solution is not greater or more intense than the
principal spot from the standard solution (2) (not more
than 0.4%). Also the total area of all spots other than
the principal spot from the test solution is not more
than 1.0%.
(3) LovastatinCalculate the amount (%) of lovastatin from the chromatogram of the test solution and the
standard solution, AT and AS respectively, as directed under the Assay, the percentage of lovastatin is
not greater than 1.0%.
Amount (%) of lovastatin = 10000
C AT
W AS
C : Concentration of Lovastatin RS in the standard

solution (mg/mL)
W : Amount of Simvastatin (mg)
Assay Weigh accurately about 30 mg of Simvastatin,
dissolve in diluent to make exactly 100 mL, and use
this solution as the test solution. Separately, weigh accurately about 30 mg of Simvastatin RS, dissolve in diluent to make exactly 10 mL, and use this solution as
the stock solution (1). Also weigh accurately about 30
mg of Simvastatin RS, dissolve in diluent to make exactly 100 mL, and use this solution as the stock solution (2). Pipet 10.0 mL of the stock solution (1) and 1.0
mL of the stock solution (2), dilute with diluent to
make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 5 L each
under Liquid Chromatography according to the follow-
ing conditions, and determine each peak area of simvastatin, AT and AS , respectively.
Amount (mg) of Simvastatin (C25H38O5) =
A
100 C T
AS
C : Concentration of Simvastatin RS in the standard
solution (mg/mL)
with octadecylsilanized silica gel for Liquid Chromatography (between 3 and 10 m in particle diameter).
Mobile phase: the mixture of diluted phosphoric acid (1 in 1000) and acetonitrile (50 : 50).
System suitability
with 5 L of the standard solution under the above operating condition, the relative retention times of lovastatin and simvastatin are 0.65 and 1.0, respectively with
resolution being not less than 3.0. The number of theoretical plates and the symmetry factor of the peak are
not less than 2000 and not more than 2.0, respectively.
DiluentMix acetonitrile and 0.01 mol/L potassium dihydrogen phosphate in a proportion to 60 : 40,
filter, and adjust with phosphoric acid to pH 4.0.
Packaging and Storage Preserve in well-closed containers under nitrogen.
Sodium Alendronate Hydrate

O

Sodium Alendronate Hydrate and Sodium Alendronate
Hydrate RS, previously dried, as directed in the paste
method Under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) Sodium Alendronate Hydrate responds to the
Qualitative Tests for (1) sodium.
pH Dissolve 0.5 g of Sodium Alendronate Hydrate in
and 5.0.
Purity (1) Heavy metalsProceed with 1.0 g of Sodium Alendronate Hydrate according to Method 2. and
30 mg of Sodium Alendronate Hydrate, dissolve in
2.94% solution of sodium citrate to make exactly 50
mL. Pipet 5.0 mL of this solution, transfer into the 50
mL polypropylene tube with cap for centrifuge containing 5.0 mL of 1.91% solution of sodium borate, add 5
mL of acetonitrile and 5 mL of 0.4% 9fluorenylmethylchloroformate in acetonitrile, prepared
before use, shake for 45 seconds, allow to stand for 30
minutes. Add 20 mL of the dichloromethane, shake for
1 minute vigorously, and centrifuge for 5 to 10 minutes.
Use the clear upper water layer as the test solution.
Separately, prepare for the blank solution by the same
procedure as for the test solution with 5.0 mL of 2.94%
solution of sodium citrate. Perform the test with exactly
20 L each of the test solution and the blank solution as
following conditions: Discard the peak being the same
retention time as the peak from blank solution. In the
determination of the each amount (%) of related substances each amount of related substances is not more
than 0.1% and total amount of related substances is not
more than 0.5%.
OH
P
HO
ONa
H2N
Amount (%) of each related substance = 100

3H2O
P
HO
Sodium Alendronate Hydrate is soluble in water, very

slightly soluble in methanol, and practically insoluble
in dichloromethane.
OH
C4H12NNaO7P23H2O : 325.12
Sodium Alendronate Hydrate contains not less than
98.0% and not more than 102.0% of sodium alendronate (C4H12NNaO7P2 : 257.07), calculated on the dried
basis.
Description Sodium Alendronate Hydrate is a white
crystalline powder.
Ai
AS
Ai : the peak area of the related substance

AS : the total area of all related substance
spherical styrene-divinylbenzene polymer for Liquid
Chromatography (between 5 to 10 m in particle diameter).
KP 9 863

about 45 C.
Mobile phase: Program with mobile phase A and
mobile phase B as follows in isocratic or linear gradient.
Mobile phase Athe mixture of buffer solution and
acetonitrile (17 : 3)
Mobile phase Bthe mixture of acetonitrile and
buffer solution (7 : 3)
Time
(minutes)
0
Mobile
phase A
(vol%)
100
Mobile
phase B
(vol%)
0
0~15
10050
050
15~25
500
50100
25~27
0100
1000
27~32
100
Elution
Isocratic
Linear
gradient
Linear
gradient
Linear
gradient
Reequilibration

System suitability
System performance: Separately, weigh 60.0 mg
of Sodium Alendronate Hydrate RS, dissolve in 2.94%
solution of sodium citrate to make 100 mL and use this
solution as the stock solution. Proceed with 5.0 mL of
the stock solution as directed above for the preparation
of the test solution and use this solution as the standard
solution. Separately, pipet 0.1 mL of the stock solution,
add 2.94% solution of sodium citrate to make exactly
100 mL, pipet 5.0 mL of this solution, proceed as directed above for the preparation of the test solution, and
use this solution as the dilute standard solution. When
the procedure is run with 20 L of the standard solution
and the dilute standard solution under the above operating condition, the symmetry factor of the principal peak
with the standard solution is not more than 2.0 and signal-to-noise ratio of the peak, detected in the same location as the dilute standard solution, is not less than 3.
Buffer solutionDissolve 5.88 g of sodium citrate and
2.84 g of anhydrous sodium monohydrogen phosphate
in water to make 2000 mL. Adjust with phosphoric acid
to pH 8.
Loss on Drying Between 16.1% and 17.1% (1 g, in
vacuum, 145 C, constant mass).
Assay Weigh accurately about 25 mg of Sodium
Alendronate Hydrate, dissolve in 2.94% solution of sodium citrate to make exactly 250 mL. Pipet 5.0 mL of
this solution, transfer into the 50 mL polypropylene
tube with cap for centrifuge containing 5 mL of the
1.91% solution of sodium borate, add 5 mL of 0.05%
9-fluorenylmethylchloroformate in acetonitrile, prepared before use, shake for 30 seconds, allow to stand
for 25 minutes at room temperature. Add 25 mL of the
dichloromethane, shake for 1 minute vigorously, and
centrifuge for 5 to 10 minutes. Use the clear upper wa-
ter layer as the test solution. Separately, weigh accurately about 10 mg of Sodium Alendronate Hydrate RS,
dissolve in 2.94% solution of sodium citrate to make
exactly 100 mL, and use this solution as the stock solution. Proceed with 5.0 mL of the stock solution as directed above for the preparation of the test solution, and
use this solution as the standard solution. Also proceed
with 5.0 mL of 2.94% solution of sodium citrate as directed above for the preparation of the test solution, and
use this solution as the blank solution. Perform the test
with exactly 10 L each of the blank solution, the test
solution and the standard solution as directed under
conditions, and determine principal peak area of the
test and the standard solution, AT and AS , respectively.
Amount (mg) of sodium alendronate(C4H12NNaO7P2)
A
= 250 C T
AS
C : the concentration of Sodium Alendronate RS in
the standard solution, calculated on the anhydrous basis
(mg/mL).
spherical styrene-divinylbenzene polymer for Liquid
Chromatography (between 5 and 10 m in particle diameter).
about 35 C.
Mobile phase: the mixture of buffer solution, acetonitrile and methanol (70 : 25 : 5)
System suitability
with 10 L of the standard solution under the above operating condition, the number of theoretical plates and
the symmetry factor of the principal peak are not less
than 1500 and not more than 1.5, respectively.
above operating conditions, the relative standard deviation of the peak area of sodium alendronate is not more
than 2.0%.
Buffer solutionDissolve 14.7 g of sodium citrate
and 7.05 g of anhydrous sodium monohydrogen phosphate in water to make 1000 mL. Adjust with phosphoric acid to pH 8.
Packaging and Storage Preserve in well-closed containers. Store at 15 C to 30 C.
Sodium Aurothiomalate
H
Au
C
-
O2CH2C
CO2-
+
xNa
( 2 - x )H+
and enantiomer
Mixture of C4H3AuNa2O4S: 390.08 and

C4H4AuNaO4S: 368.10
Sodium Aurothiomalate, when dried, contains not less
than 49.0% and not more than 52.5% of gold (Au:
196.97).
Description Sodium Aurothiomalate is a white to
pale yellow powder or granule and is odorless.
Sodium Aurothiomalate is very soluble in water,
slightly soluble in ethanol and very slightly soluble in
ether.
Sodium Aurothiomalate is hygroscopic.
Sodium Aurothiomalate changes in color by light to
greenish pale yellow
Identification (1) To 2 mL of a solution of Sodium
Aurothiomalate (1 in 10), add 1 mL of calcium nitrate
tetrahydrate solution (1 in 10): a white precipitate is
produced and it dissolves in dilute nitric acid and reappears on the addition of ammonium acetate TS.
(2) To 2 mL of a solution of Sodium Aurothiomalate (1 in 10), add 3 mL of silver nitrate TS: a yellow
precipitate is produced and it dissolves in an excess of
ammonia TS.
(3) Place 2 mL of a solution of Sodium Aurothiomalate (1 in 10) in a porcelain crucible, add 1 mL of
ammonia TS and 1 mL of strong hydrogen peroxide
water, evaporate to dryness and ignite. Add 20 mL of
water to the residue and filter: the residue on the filter
paper occurs as a yellow or dark yellow powder or yellow or dark yellow granule and the filtrate responds to
the Qualitative Tests for sodium salt and for sulfate.
(4) The filtrate obtained in (3) responds to the Qualitative Tests for sodium salt.
(5) The filtrate obtained in (3) responds to the Qualitative Tests for sulfate
pH Dissolve 1.0 g of Sodium Aurothiomalate in 10
6.5.
1.0 g of Sodium Aurothiomalate in 10 mL of water: the
solution is clear and pale yellow.
(2) Heavy metalsProceed with 1.0 g of Sodium
Aurothiomalate according to Method 2 and perform the
Sodium Aurothiomalate according to Method 3 and
(4) EthanolWeigh accurately about 0.2 g of So-
dium Aurothiomalate, add exactly 3 mL of the internal

standard solution and 2 mL of water to dissolve, and
use this solution as the test solution. Separately, pipet 3
mL of dehydrated ethanol, and add water to make exactly 1000 mL. Pipet 2 mL of this solution, add exactly
3 mL of the internal standard solution, and use this solution as the standard solution. Perform the test with 2
L each of the test solution and standard solution as directed under Gas Chromatography according to the following conditions, and determine the ratios of the peak
area of ethanol to that of the internal standard, QT and
QS : the amount of ethanol is not more than 3.0%
.
Amount (mg) of ethanol = QT / QS 60.793
0.793: Density (g/mL) of ethanol at 20
Internal standard solutionA solution of 2propanol (1 in 500).
Detector: Hydrogen flame-ionization detector.
Column: A column 3 mm in inside diameter and 3
m in length, packed with porous styrene
divinylbenzene copolymer for gas chromatography
(particle diameter: 150-180 m) (average pore size:
0.0085 m; 300-400 m2/g).
about 180 .
Carrier gas: Nitrogen
time of the internal standard is about 7 minutes.
Systemic suitability
with 2 L of the standard solution under the above operating conditions, ethanol and the internal standard are
System repeatability:When the test is repeated 6
above operating conditions, the relative standard deviation of the ratio of the peak area of ethanol to that of
Water Not more than 8.0% (0.1 g, coulometric titration). Use a water vaporizer (heating temperature:
105; heating time: 30 minutes).
Assay Weigh accurately 25 mg of Sodium Aurothiomalate, previously dried, dissolve in 2 mL of aqua regia by heating and add water to make exactly 100 mL.
Pipet 2.0 mL of the solution, add water to make exactly
25 mL and use this solution as the test solution. Pipet
5.0 mL, 10.0 mL and 15.0 mL of standard gold solution
for atomic absorption spectrophotometry, add water to
make exactly 25 mL and use these solutions as the
standard solutions. Perform the test with the test solution and the standard solutions as directed under the
KP 9 865
Atomic Absorption Spectrophotometry under the following conditions. Determine the amount of gold in the
test solution using the calibration curve obtained from
the absorbances of the standard solutions.
Gas: Combustible gasacetylene gas
Supporting gasair.
Lamp: A gold hollow cathode lamp.
tight containers.
Sodium Benzoate
CO 2Na
C7H5NaO2: 144.10
Sodium Benzoate, when dried, contains not less than
99.0% and not more than 101.0% of sodium benzoate
(C7H5NaO2).
Description Sodium Benzoate is a white granules,
crystals or crystalline powder, is odorless and has a
sweet and saline taste.
Sodium Benzoate is freely soluble in water, slightly soluble in ethanol and practically insoluble in ether.
Identification A solution of Sodium Benzoate (1 in
100) responds to the Qualitative Tests for benzoate and
Qualitative Tests for (1) and (2) for sodium salt.
1.0 g of Sodium Benzoate in 5 mL of water: the solution is clear and colorless.
(2) Acid or alkaliDissolve 2.0 g of Sodium Benzoate in 20 mL of freshly boiled and cooled water and
add 2 drops of phenolphthalein TS and 0.20 mL of 0.05
mol/L sulfuric acid VS: the solution remains colorless.
To this solution, add 0.40 mL of 0.1 mol/L sodium hydroxide VS: a red color develops.
(3) SulfateDissolve 0.40 g of Sodium Benzoate
in 40 mL of water, add slowly 3.5 mL of dilute hydrochloric acid with thorough stirring, allow to stand
for 5 minutes and filter. Discard the first 5 mL of the
filtrate, take the subsequent 20 mL of the filtrate, add
water to make 50 mL and perform the test. Prepare the
(4) Heavy metalsDissolve 2.0 g of Sodium Benzoate in 44 mL of water, add gradually 6 mL of dilute
hydrochloric acid with thorough stirring and filter. Discard the first 5 mL of the filtrate, take the subsequent
25 mL of the filtrate, neutralize with ammonia TS, add

2 mL of dilute acetic acid and water to make 50 mL and
perform the test. Prepare the control solution as follows: to 2.0 mL of standard lead solution, add 2 mL of
than 20 ppm).
(5) ArsenicMix well 1.0 g of Sodium Benzoate
with 0.40 g of calcium hydroxide, ignite, dissolve the
residue in 10 mL of dilute hydrochloric acid and perform the test (not more than 2 ppm).
(6) Chlorinated compoundsDissolve 1.0 g of
Sodium Benzoate in 10 mL of water, add 10 mL of dilute sulfuric acid and extract with two 20 mL volumes
of ether. Combine the ether extracts and evaporate the
ether on a water-bath. Place 0.5 g of the residue and 0.7
g of calcium carbonate in a crucible, mix with a small
amount of water and dry. Ignite it at about 600 C, dissolve in 20 mL of dilute nitric acid and filter. Wash the
residue with 15 mL of water, combine the filtrate and
the washing, add water to make 50 mL and add 0.5 mL
of silver nitrate TS: this solution has no more turbidity
Control solutionDissolve 0.7 g of calcium carbonate in 20 mL of dilute nitric acid and filter. Wash the
residue with 15 mL of water, combine the filtrate and
the washings, add 1.2 mL of 0.01 mol/L Hydrochloric
acid VS and water to make 50 mL and add 0.5 mL of
silver nitrate TS.
(7) Phthalic acidTo 0.10 g of Sodium Benzoate,

add 1 mL of water and 1 mL of resorcin-sulfuric acid
TS and heat the mixture in an oil-bath heated at a temperature between 120 C and 125 C to evaporate the
water, then heat the residue for further 90 minutes, cool
and dissolve in 5 mL of water. To 1 mL of the solution,
add 10 mL of a solution of sodium hydroxide (43 in
500), shake, then examine under light at a wavelength
between 470 nm and 490 nm: the green fluorescence of
the solution is not more intense than that of the following control solution.
Control solutionDissolve 61 mg of potassium
biphthalate in water to make exactly 1000 mL. Pipet
exactly 1 mL of the solution, add 1 mL of resorcinsulfuric acid TS and proceed as directed above.
hours).
Assay Weigh accurately 1.5 g of Sodium Benzoate,
previously dried, and transfer to a glass-stoppered flask.
Dissolve in 25 mL of water, add 75 mL of ether and 10
drops of bromophenol blue TS and titrate with 0.5
mol/L hydrochloric acid VS, while mixing the aqueous
and ether layers by vigorous shaking, until a persistent,
light green color is produced in the aqueous layer.

= 72.05 mg of C7H5NaO2

Sodium Bicarbonate
NaHCO3: 84.01
Sodium Bicarbonate contains not less than 99.0% and
not more than 101.0% of sodium bicarbonate (NaHCO3).
in 3 mL of water and 2 mL of hydrochloric acid and

Assay Weigh accurately about 2 g of Sodium Bicarbonate, dissolve in 100 mL of water and titrate with 1
mol/L hydrochloric acid VS. When the color of the solution changes from blue to reddish-purple, boil with
caution, cool and continue the titration until a reddishpurple color develops (indicator: 2 drops of methyl red
TS).
Each mL of 1 mol/L sulfuric acid VS

= 84.01 mg of NaHCO3
Description Sodium Bicarbonate is a white crystal or

crystalline powder, is odorless and has a characteristic,
saline taste.
Sodium Bicarbonate is soluble in water and practically
insoluble in ethanol or in ether.
Sodium Bicarbonate slowly decomposes in moist air.
Identification A solution of Sodium Bicarbonate (1

in 30) responds to the Qualitative Tests for sodium salt
and for bicarbonate.
Sodium Bicarbonate Injection is an aqueous solution

for injection. Sodium Bicarbonate Injection contains
labeled amount of sodium bicarbonate (NaHCO3:
84.01).
pH Dissolve 1.0 g of Sodium Bicarbonate in 20 mL

1.0 g of Sodium Bicarbonate in 20 mL of water: the solution is clear and colorless.
Sodium Bicarbonate Injection
Method of Preparation Prepare as directed under Injections, with Sodium Bicarbonate.

Description Sodium Bicarbonate Injection is a clear,
colorless liquid.
(2) ChlorideTo 0.40 g of Sodium Bicarbonate,

add 4 mL of dilute nitric acid, heat to boil, cool and add
6 mL of dilute nitric acid and water to make 50 mL.
0.040%).
Identification To a volume of Sodium Bicarbonate Injection, equivalent to 1 g of Sodium Bicarbonate according to the labeled amount, add water to make 30
mL: the solution responds to the Qualitative Tests for
sodium salt and for bicarbonate.
(3) CarbonateDissolve 1.0 g of Sodium Bicarbonate in 20 mL of freshly boiled and cooled water
with very gentle swirling at a temperature not exceeding 15 C. Add 2.0 mL of 0.1 mol/L hydrochloric acid
VS and 2 drops of phenolphthalein TS: no red color
develops immediately.
Purify CarbonateTo a volume of Sodium Bicarbonate Injection, equivalent to 0.10 g of Sodium Bicarbonate according to the labeled amount, add water, freshly boiled and cooled to 10 C, to make a 1.0 w/v% solution and determine the pH immediately: the pH of
this solution is between 7.9 and 8.6
(4) AmmoniumHeat 1.0 g of Sodium Bicarbonate: the gas evolved does not change moistened red
litmus paper to blue.
(5) Heavy metalsDissolve 4.0 g of Sodium Bicarbonate in 5 mL of water and 4.5 mL of hydrochloric
acid and evaporate on a water-bath to dryness. Dissolve
the residue in 2 mL of dilute acetic acid, 35 mL of water and 1 drop of ammonium TS, dilute with water to
make 50 mL and Perform the test. Prepare the control
solution as follows: evaporate 4.5 mL of hydrochloric
acid to dryness and add 2 mL of dilute acetic acid, 2.0
mL of standard lead solution and water to make 50 mL
(6) ArsenicDissolve 1.0 g of Sodium Bicarbonate
Bacterial Endotoxins Less than 5.0 EU per mEq of

Sodium Bicarbonate Injection.
Insoluble Particulte Matter Test
quirement.
It meets the re-
Insoluble Particulte Matter Test for Injections It

KP 9 867
Assay Measure exactly a volume of Sodium Bicarbonate Injection, equivalent to about 2 g of sodium bicarbonate (NaHCO3), titrate with 1 mol/L hydrochloric acid VS and proceed as directed in the Assay under Sodium Bicarbonate.
Each mL of 1 mol/L hydrochloric acid VS

Packaging and Storage Preserve in hermetic containers. Plastic containers for aqueous injections may
be used.
Sodium Bicarbonate Tablets

Sodium Bicarbonate Tablets contain not less than
of sodium bicarbonate (NaHCO3: 84.01)
Tablets, with Sodium Bicarbonate.
Identification A portion of the powered tablets responds to the Identification under Sodium Bicarbonate.
ment.

Sodium Bicarbonate Tablets. Weigh accurately a portion of powder, equivalent to about 2 g of sodium bicarbonate (NaHCO3), dissolve in 100 mL of water and
titrate with 1 mol/L hydrochloric acid VS When the
color of the solution changes from blue to reddishpurple, boil with caution, cool and continue the titration
until a reddish-purple color develops (indicator: 2 drops
of methy red TS).
has a slightly characteristic, saline taste.

Sodium Borate is freely soluble in glycerin, soluble in
water and practically insoluble in ethanol, in dehydrated ethanol or in ether.
When placed in dry air, Sodium Borate effloresces and
is coated with a white powder.
Identification A solution of Sodium Borate (1 in 20)
responds to the Qualitative Tests for sodium salt and for
borate.
pH Dissolve 1.0 g of Sodium Borate in 20 mL of water: the pH of this solution is between 9.1 and 9.6.
1.0 g of Sodium Borate in 20 mL of water by warming
slightly: the solution is clear and colorless.
(2) Carbonate or bicarbonateDissolve 1.0 g of

powdered Sodium Borate in 20 mL of freshly boiled
and cooled water and add 3 mL of dilute hydrochloric
acid: the solution does not effervesce.
(3) Heavy metalsDissolve 1.5 g of Sodium Borate in 25 mL of water and 7 mL of 1 mol/L hydrochloric acid TS, add 1 drop of phenolphthalein TS and
add ammonia TS until a pale red color develops. Then
add dilute acetic acid until the solution becomes colorless again, add 2 mL of dilute acetic acid and add water
to make 50 mL. Perform the test. Prepare the control
solution as follows: to 3.0 mL of standard lead solution,
add 2 mL of dilute acetic acid and water to make 50 mL
(4) Arsenic Prepare the test solution with 0.40 g
of Sodium Borate according to Method 1 and perform
the test. (not more than 5 ppm).
Assay Weigh accurately about 2 g of Sodium Borate,
dissolve in 50 mL of water and titrate with 0.5 mol/L
hydrochloric acid VS (indicator: 3 drops of methyl red
TS).
Each mL of 1 mol/L hydrochloric acid VS


= 95.34 mg of Na2B4O7.10H2O
Pakaging and Storage Preserve in well-closed containers
Sodium Borate
Sodium Bromide
NaBr: 102.89
Na2B4O710H2O: 381.37
Sodium Borate contains not less than 99.0% and not
more than 103.0% of sodium borate (Na2B4O710H2O).
Description Sodium Borate is a colorless or white
crystal or a white, crystalline powder, is odorless and
Sodium Bromide, when dried, contains not less than

99.0% and not more than 101.0% of sodium bromide
(NaBr).
Description Sodium Bromide is a colorless or white
crystals or crystalline powder and is odorless.
Sodium Bromide is freely soluble in water and soluble
in ethanol.
Sodium bromide is hygroscopic, but not deliquescent.
Identification A solution of Sodium Bromide (1 in
10) responds to the Qualitative Tests for sodium salt
and for bromide.
1.0 g of Sodium Bromide in 3 mL of water: the solution
(2) AlkaliDissolve 1.0 g of Sodium Bromide in

10 mL of water, add 0.10 mL of 0.05 mol/L sulfuric acid VS and 1 drop of phenolphthalein TS, heat to boil
and cool: the solution is colorless.
(3) ChlorideMake a calculation from the result
obtained in the Assay. Not more than 97.9 mL of 0.1
mol/L silver nitrate VS is consumed for 1 g of Sodium
Bromide.
(4) SulfatePerform the test with 2.0 g of Sodium
Bromide. Prepare the control solution with 1.0 mL of
(5) IodideDissolve 0.5 g of Sodium Bromide in
10 mL of water, add 2 to 3 drops of ferric chloride TS
and 1 mL of chloroform and shake: no red-purple to
purple color develops in the chloroform layer.
(6) BromateDissolve 1.0 g of Sodium Bromide
in 10 mL of freshly boiled and cooled water and add 2
drops of potassium iodide TS, 1 mL of starch TS and 3
drops of dilute sulfuric acid. Shake the mixture gently
and allow to stand for 5 minutes: no blue color develops.
Bromide according to Method 1 and perform the test.
(8) BariumDissolve 0.5 g of Sodium Bromide in
10 mL of water, add 0.5 mL of dilute hydrochloric acid
and 1 mL of potassium sulfate TS and allow to stand
for 10 minutes: no turbidity is produced.
Sodium Bromide according to Method 1 and perform
hours).
Assay Weigh accurately 0.4 g of Sodium Bromide,
previously dried and dissolve in 50 mL of water. Add
10 mL of dilute nitric acid and 50 mL of 0.1 mol/L silver nitrate VS, exactly measured and titrate the excess
silver nitrate with 0.1 mol/L ammonium thiocyanate
VS (indicator: 2 mL of ferric ammonium sulfate TS).
correction.
Each mL of 0.1 mol/ L silver nitrate VS
= 10.289 mg of NaBr
Sodium Chloride
NaCl: 58.44
Sodium Chloride, when dried, contains not less than
99.5% and not more than 101.0% of sodium chloride
(NaCl).
Description Sodium Chloride is a colorless or white
Sodium Chloride is freely soluble in water, very
slightly soluble in dehydrated ethanol.
Identification (1) A solution of Sodium Chloride in
water (1 in 20) responds to the Qualitative Tests for sodium salt.
(2) A solution of Sodium Chloride in water (1 in
1.0 g of Sodium Chloride in 5 mL of water: the solution
(2) Acidity or alkalinity Dissolve 20.0 g of Sodium Chloride in 100.0 mL of freshly boiled and
cooled water, and use this solution as the test solution.
To 20 mL of the test solution, add 0.1 mL of bromthymol blue TS and 0.5 mL of 0.01 mol/L hydrochloric acid VS: the color of the solution is yellow. Separately, to
20 mL of the test solution add 0.1 mL of bromothymol
blue TS and 0.5 mL of 0.01 mol/L sodium hydroxide
VS: the color of the solution is blue.
(3) SulfatesTo 7.5 mL of the test solution obtained in (2) add water to make 30 mL, and use this solution as the test solution. Separately, dissolve 0.181 g
of the potassium sulfate in diluted dehydrated ethanol
(3 in 10) to make exactly 500 mL. Pipet exactly 5 mL
of this solution, and add diluted dehydrated ethanol (3
in 10) to make exactly 100 mL. To 4.5 mL of this solution add 3 mL of a solution of barium chloride dihydrate (1 in 4), shake, and allow to stand for 1 minute.
To 2.5 mL of this solution add 15 mL of the test solution and 0.5 mL of acetic acid, and allow to stand for 5
minutes: any turbidity produced is not more than that
produced in the following control solution.
Control solution: Dissolve 0.181 g of potassium sulfate
in water to make exactly 500 mL. Pipet 5 mL of this solution, add water to make exactly 100 mL, and proceed
in the same manner as directed above using this solution instead of the test solution
(4) PhosphatesTo 2.0 mL of the test solution obtained in (2) add 5 mL of 2 mol/L sulfuric acid TS and
KP 9 869
water to make 100.0 mL, then add 4 mL of ammonium

molybdate-sulfuric acid TS and 0.1 mL of tin (II) chloride-hydrochloric acid TS, and allow to stand for 10
minutes: the color of the solution is not darker than the
Control solution To 1.0 mL of Standard Phosphoric
acid Solution add 12.5 mL of 2 mol/L sulfuric acid TS
and water to make exactly 250 mL. To 100 mL of this
solution add 4 mL of ammonium molybdate-sulfuric
acid TS and 0.1 mL of tin (II) chloride-hydrochloric acid TS, and allow to stand for 10 minutes.
(5) BromidesTo 0.50 mL of the test solution obtained in (2) add 4.0 mL of water, 2.0 mL of dilute phenolred TS and 1.0 mL of a solution of sodium toluenesulfonchloramide trihydrate (1 in 10000), and mix immediately. After 2 minutes, add 0.15 mL of 0.1 mol/L
sodium thiosulfate VS, mix, add water to make exactly
10 mL, and use this solution as the test solution. Separately, to 5.0 mL of a solution of potassium bromide (3
in 1000000) add 2.0 mL of dilute phenol red TS and 1.0
mL of a solution of sodium toluenesulfonchloramide
trihydrate (1 in 10000), and mix immediately. Proceed
in the same manner as for the preparation of the test solution, and use the solution so obtained as the standard
standard solution, respectively, as directed under Ultraviolet-visible Spectrohotometry using water as the control: the absorbance at 590 nm of the test solution is not
more than that of the standard solution.
(6) IodidesWet 5 g of Sodium Chloride with
dropwise addition of 0.15 mL of a freshly prepared
mixture of starch TS, 0.5 mol/L sulfuric acid TS and
sodium nitrite TS (1000 : 40 : 3), allow to stand for 5
minutes, and examine under daylight: a blue color does
not appear.
(7) FerrocyanidesDissolve 2.0 g of Sodium
Chloride in 6 mL of water, and add 0.5 mL of a mixture
of a solution of iron (II) sulfate heptahydrate (1 in 100)
and a solution of ammonium iron (III) sulfate dodecahydrate in diluted sulfuric acid (1 in 400) (1 in 100)
(19 : 1): a blue color does not develop within 10 minutes.
Chloride according to Method 1 and perform the test.
(9) IronTo 10 mL of the test solution obtained in
(2) add 2 mL of a solution of citric acid monohydrate (1
in 5) and 0.1 mL of mercaptoacetic acid, alkalize with
ammonia TS, add water to make 20 mL, and allow to
stand for 5 minutes: the solution has not more color
Control solution: Pipet exactly 1 mL of Standard Iron
Solution, and add water to make exactly 25 mL. To 10
mL of this solution, add 2 mL of a solution of citric acid monohydrate (1 in 5) and 0.1 mL of mercaptoacetic
acid and proceed in the same manner as directed for the
test solution.
(10) BariumTo 5.0 mL of the test solution obtained in (2) add 5.0 mL of water and 2.0 mL of dilute
sulfuric acid, and allow to stand for 2 hours: the solution has not more turbidity than the following control
solution.
Control solutionTo 5.0 mL of the test solution obtained in (2) add 7.0 mL of water, and allow to stand
for 2 hours.
(11) Magnesium and alkaline-earth materialsTo

200 mL of water add 0.1 g of hydroxylammonium
chloride, 10 mL of ammonium chloride buffer solution,
pH 10, 1 mL of 0.1 mol/L zinc sulfate VS and 0.2 g of
eriochrome black T-sodium chloride indicator, and
warm to 40 C. Add 0.01 mol/L disodium dihdrogen
ethylenediamine tetraacetate VS dropwise until the redpurple color of the solution changes to blue-purple. To
this solution add a solution prepared by dissolving 10.0
g of Sodium Chloride in 100 mL of water, and add 2.5
mL of 0.01 mol/L disodium ethylenediamine tetraacetate VS: the color of the solution is a blue-purple.
of Sodium Chloride according to Method 1 and perform the test (not more than 2 ppm).
hours).
Assay Weigh accurately about 50 mg of Sodium
Chloride, previously dried, dissolve in 50 mL of water
and titrate with 0.1 mol/L silver nitrate VS (potentiometric titration, Endpoint Detection Method in Titrimetry).

= 5.844 mg of NaCl
10% Sodium Chloride Injection

10% Sodium Chloride Injection is an aqueous solution
for injection.
10% Sodium Chloride Injection contains not less than
9.5 w/v% and not more than 10.5 w/v% of sodium
chloride (NaCl: 58.44).
Sodium Chloride
100 g
Water for Injection
To make 1000 mL
Prepare as directed under Injections, with the above in-
gredients.
Description 10% Sodium Chloride Injection is a
clear, colorless liquid and has a saline taste.
10% Sodium Chloride Injection is neutral.
Identification 10% Sodium Chloride Injection responds to the Qualitative Tests for sodium salt and for
chloride.
Bacterial Endotoxins Less than 3.6 EU/mL.
Description Isotonic Sodium Chloride Injection is a

clear, colorless liquid and has a slightly saline taste.
Identification Isotonic Sodium Chloride Injection responds to the Qualitative Tests for sodium salt and for
chloride.
pH
Purity (1) Heavy metalsConcentrate 100 mL of

Isotonic Sodium Chloride Injection to about 40 mL in a
water-bath, and add 2 mL of dilute acetic acid and water to make 50 mL. Perform the test using this solution
as the test solution. Prepare the control solution with
3.0 mL of standard lead solution and 2 mL of dilute
acetic acid, and add water to make 50 mL (not more
than 0.3 ppm).
(2) ArsenicPrepare the test solution with 20 mL
of Isotonic Sodium Chloride Injection, and perform the
test (not more than 0.1 ppm).
Assay Pipet exactly 10 mL of 10% Sodium Chloride

Injection and add water to make exactly 100 mL. Pipet
exactly 20 mL of this solution, add 30 mL of water and
titrate with 0.1 mol/L silver nitrate VS while shaking
vigorously (indicator: 3 drops of fluorescein sodium
TS).

= 5.844 mg of NaCl

Packaging and Storage Preserve in hermetic containers. Plastic containers for aqueous injections may
be used.

Isotonic Sodium Chloride

Injection
0.9% Sodium Chloride Injection
Isotonic Salt Solution
Isotonic Sodium Chloride Injection is an aqueous solution for injection. Isotonic Sodium Chloride Injection
of sodium chloride (NaCl: 58.44).
Method of prepration
Sodium Chloride
9g
Water for Injection
To make 1000 mL

No preservative is added.
Bacterial Endotoxins Not more than 0.50 EU per

mL of Isotonic Sodium Chloride Injection.
Assay Measure exactly 20 mL of Isotonic Sodium

Chloride Injection, add 30 mL of water, and titrate with
0.1 mol/L silver nitrate VS with vigorous shaking (indicator: 3 drops of fluorescein sodium TS).

= 5.844 mg of NaCl
Packaging and Storage Preserve in hermetic containers, and plastic containers for aqueous injections
may be used.
Sodium Chromate (51Cr)

Injection
Sodium Chromate (51Cr) Injection is an aqueous solution for injection.
Sodium Chromate (51Cr) Injection contained 51Cr in the
form of Sodium Chromate.
Sodium Chromate (51Cr) Injection meets the requirement of Sodium Chromate (51Cr) Injection of the Ko-
KP 9 871
rean Pharmaceutical Codex (Third Edition).

The Test for Exractable Volume of Parenteral Preparations and the Insoluble Particulate Matter Test for Injections is not applied to this injection.
Description Sodium Chromate (51Cr) Injection is a
clear, colorless to pale yellow liquid and is odorless or
has an odor of the preservatives.
Sodium Citrate Hydrate

CH2CO2Na
HO
CO2Na
2H2O
CH2CO2Na
C6H5Na3O72H2O: 294.10
Sodium Citrate Hydrate, when dried, contains not less
than 99.0% and not more than 101.0% of sodium citrate (C6H5Na3O7: 258.07).
Description Sodium Citrate Hydrate is a colorless
crystal or a white crystalline powder, is odorless and
has a cooling saline taste.
Sodium Citrate Hydrate is freely soluble in water and
practically insoluble in ethanol or in ether.
Identification A solution of Sodium Citrate Hydrate
in water (1 in 20) responds to the Qualitative Tests for
citrate and for sodium salt.
pH Dissolve 1.0 g of Sodium Citrate Hydrate in 20
8.5.
of 1.0 g of Sodium Citrate Hydrate in 10 mL of water is
(2) ChlorideWeigh 0.6 g of Sodium Citrate Hydrate and perform the test. Prepare the control solution
more than 0.015%).
(3) SulfateTo 0.5 g of Sodium Citrate Hydrate,
add water to make 40 mL, then add 3.0 mL of dilute
hydrochloric acid and water to make 50 mL and perform the test. Prepare the control solution with 0.50 mL
0.048%).
Citrate Hydrate according to Method 2 and perform the
Sodium Citrate Hydrate according to Method 1 and
(6) TartrateTo 1.0 g of Sodium Citrate Hydrate,
add 2 mL of water, 1 mL of potassium acetate TS and 1
mL of acetic acid: no crystalline precipitate is formed

after the sides of the tube have been rubbed with a glass
rod.
(7) OxalateDissolve 1.0 g of Sodium Citrate Hydrate in a mixture of 1 mL of water and 3 mL of dilute
hydrochloric acid, add 4 mL of ethanol and 0.2 mL of
calcium chloride TS and allow to stand for 1 hour: the
solution is clear.
(8) Readily carbonizable substancesWeigh 0.5 g
of Sodium Citrate Hydrate and perform the test by
heating at 90 C for 1 hour: the solution has no more
color than Color Matching Fluid K.
C, 2 hours).
Assay Weigh accurately about 0.1 g of Sodium Citrate Hydrate, previously dried, dissolve in water, add
exactly 10 mL of internal standard solution, add water
solution. Separately, weigh accurately 0.1 g of Sodium
Citrate Hydrate RS, previously dried, dissolve in water,
add exactly 10 mL of internal standard solution and water to make exactly 100 mL and use this solution as the
under the Liquid Chromatography according to the following conditions and calculate the ratio, QT and
QS , of the peak area of Sodium Citrate to that of the
internal standard for the test solution and the standard
solution, respectively,
Amount (mg) of Sodium Citrate (C6H5Na3O7)

= amount (mg) of sodium citrate in Sodium Citrate HyQ
drate RS T
QS
Internal standard solutionAcetic acid solution (1
in 100).
inside diameter and about 15 cm to 30 cm in length,
chromatography.
Mobile phase: Dissolve 2.64 g of diammonium hydrogen phosphate and 2 mL of triethylamine in 1000
mL of water and adjust the pH to 2.5 with phosphoric
acid.
Flow rate: Adjust the flow rate to make the retention time of Sodium Citrate being about 5 minutes.
operating conditions, the internal standard and Sodium
Citrate are eluted in this order with the resolution be-
= 9.803 mg of C6H5Na3O7.2H2O
tween their peaks being not less than 2.0.

Sodium Citrate Injection for

Transfusion

tainers.
Sodium Cromoglicate
NaO2C
Sodium Citrate Injection for Transfusion is an aqueous

solution for injection. Sodium Citrate Injection for
Transfusion contains not less than 9.5 w/v% and not
more than 10.5 w/v% of sodium citrate hydrate
(C6H5Na3-O72H2O: 294.10).
Sodium Citrate Hydrate
100 g
Water for injection
To make
1000 mL

No preservative is added.
Description Sodium Citrate Injection for Transfusion
is a clear, colorless liquid.
Identification Sodium Citrate Injection for Transfusion responds to the Qualitative Tests for sodium salt
and for citrate.
pH

Bacterial Endotoxins Less than 5.6 EU per mL of
Sodium Citrate Injection for Transfusion.
Assay Pipet 5.0 mL of Sodium Citrate Injection for
Transfusion, add water to make exactly 25 mL, pipet
10.0 mL of this solution and evaporate on a water-bath
to dryness. Dry the residue at 180 C for 2 hours and
dissolve in 30 mL of glacial acetic acid by warming.
After cooling, titrate with 0.1 mol/L perchloric acid VS
correction.
OCH2CHCH2O
CO2Na
OH
C23H14Na2O11: 512.33
Sodium Cromoglicate contains not less than 98.0% and
not more than 101.0% of sodium cromoglicate
(C23H14Na2O11), calculated on the dried basis.
Description Sodium Cromoglicate is a white, crystalline powder, is odorless and tasteless at first and later
develops a slightly bitter taste.
Sodium Cromoglicate is freely soluble in water, sparingly soluble in propylene glycol, very slightly soluble
in ethanol and practically insoluble in isopropanol or in
ether.
Sodium Cromoglicate is hygroscopic.
Sodium Cromoglicate gradually acquire a yellow color
by light.
Identification (1) Dissolve 0.1 g of Sodium Cromoglicate in 2 mL of water, add 2 mL of sodium hydroxide
TS and boil for 1 minute: a yellow color is observed.
After cooling, add 0.5 mL of concentrated diazobenzene sulfonic acid TS: a dark red color is observed.
Sodium Cromoglicate and Sodium Cromoglicate RS in
phosphate buffer solution, pH 7.4, (1 in 100000), as directed under the Ultraviolet-visible Spectrophotometry:
(3) Sodium Cromoglicate responds to the Qualitative Tests for sodium salt.
0.50 g of Sodium Cromoglicate in 10 mL of water: the
(2) Acid or alkaliDissolve 2.0 g of Sodium Cromoglicate in 40 mL of freshly boiled and cooled water,
add 6 drops of bromothymol blue TS and use this solution as the test solution. To 20 mL of the test solution,
add 0.25 mL of 0.1 mol/L sodium hydroxide VS: a blue
color is observed. To another 20 mL of the test solution,
add 0.25 mL of 0.1 mol/L hydrochloric acid VS: a yellow color is observed.
Cromoglicate according to Method 2 and perform the
KP 9 873
(4) OxalateDissolve 0.25 g of Sodium Cromoglicate in water to make exactly 50 mL and use this solution as the test solution. Separately, dissolve 49 mg of
oxalic acid, exactly weighed, in water to make exactly
100 mL. Pipet 5.0 mL of this solution, add water to
make exactly 100 mL and use this solution as the standard solution. Pipet 20.0 mL each of the test solution
and the standard solution, add 5.0 mL of iron salicylate
TS to each solution and add water to make exactly 50
mL. Determine the absorbance of these solutions as directed under the Ultraviolet-visible Spectrophotometry
using water as a blank: the absorbance of the test solution at 480 nm is not smaller than that of the standard
solution.
(5) Related substancesDissolve 0.20 g of Sodium Cromoglicate in 10 mL of water and use this solution as the test solution. Pipet 1.0 mL of the test solution, add water to make exactly 10 mL, pipet 1.0 mL of
this solution, add water to make exactly 20 mL and use
thin-layer chromatography, Develop the plate with a
mixture of methanol, chloroform and glacial acetic acid
plate. Examine under ultraviolet light (main wavelength: 254 nm): spots other than the principal spot
Loss on Drying Not more than 10.0% (1 g, in vacuum, 105 C, 4 hours).
Assay Weigh accurately about 0.18 g of Sodium
Cromoglicate and dissolve in a mixture of 25 mL of
propylene glycol and 5 mL of isopropanol by warming.
After cooling, add 30 mL of dioxane and titrate with
0.1 mol/L perchloric acid-dioxane VS (potentiometric
titration, Endpoint Detection method in Titrimetry).
correction.
Each mL of 0.1 mol/L perchloric acid-dioxane VS

= 25.62 mg of C23H14Na2O11
tight containers.
Sodium Fluoride
NaF: 41.99
Sodium Fluoride contains not less than 98.0% and not
more than 102.0% of sodium fluoride (NaF), calculated
on the dried basis.

Description Sodium Fluoride is a white powder and
is odorless.
Sodium Fluoride is soluble in water and practically insoluble in ethanol.
Identification (1) Place 1 g of Sodium Fluoride in a
platinum crucible, add 15 mL of sulfuric acid and cover
the crucible with a glass plate. Heat the crucible in a
water-bath for 1 hour, remove the glass cover, rinse it
in water and wipe dry: the surface of the glass is etched.
(2) A solution of Sodium Fluoride (1 in 25) responds to the Qualitative Tests for sodium salt.
Purity (1) Acid or AlkaliDissolve 2.0 g of Sodium
Fluoride in 40 mL of water in a platinum dish, add 10
mL of a saturated solution of potassium nitrate, cool the
solution to 0 C and add 3 drops of phenolphthalein TS.
If no color appears, a pink color persisting for 15
seconds is produced by not more than 2.0 mL of 0.10
mol/L sodium hydroxide VS. If the solution is colored
pink by the addition of phenolphthalein TS, it is rendered colorless by not more than 0.50 mL of 0.05
mol/L sulfuric acid. Save the neutralized solution for
the test for Purity (2).
(2) FluosilicateAfter the solution obtained from

Purity (1) has been neutralized, heat to boiling and titrate while hot with 0.10 mol/L sodium hydroxide VS
until a permanent pink color is obtained: not more than
1.5 mL of 0.10 mol/L sodium hydroxide VS is required.
(3) ChlorideDissolve 0.3 g in 20 ml of water, add
0.2 g of boric acid, 1 mL of nitric acid and 1 mL of 0.1
mol/L silver nitrate VS: It has no more color than the
following control solution (not more than 0.012%).
Control solutionTo 1 mL of 0.0010 mol/L hydrochloric acid VS, add 0.2 g of boric acid, 1 mL of nitric acid and 1 mL of 0.1 mol/L silver nitrate VS.
(4) Heavy metalsTo 1.0 g of Sodium Fluoride, in

platinum crucible, add 1 mL of water and 3 mL of sulfuric acid and heat at as low a temperature as practicable until all of the sulfuric acid has been expelled. Dissolve the residue in 20 mL of water, neutralize the solution with strong ammonia water using phenolphthalein
TS as an indicator, add 1 mL of glacial acetic acid, dilute with water to make 45 mL, filter and perform the
test with 30 mL of the filtrate as a test solution. Prepare
hours).
Assay Weigh accurately about 80 mg of Sodium Fluoride, dissolve in 25 mL of mixture solution of acetic
anhydride and glacial acetic acid (1 : 4), and titrate with
0.1 mol/L perchloric acid VS (indicator : methylrosaniline chloride TS) until the color of the solution changes
into green. Perform a blank determination and make
= 4.199 mg Sodium Fluoride (NaF)
Sodium Hyaluronate
CO2Na
OH
O O
O
OH
OH
O
H
OH OH
H3C
NH
O
n
(C14H20NNaO11)n
Sodium Hyaluronate, extracted from cocks' combs or
obtained by fermentation from Streptococci Lancefield
Groups A and C, is produced by methods of minimizing or eliminating infectious agents. When Sodium
Hyaluronate is produced by fermentation of grampositive bacteria, the process that reduces or eliminates
pyrogenic or inflammatory components of the cell wall
must be specified.
Sodium Hyaluronate is the sodium salt of hyaluronic
acid, a glycosaminoglycan consisting of D-glucuronic
acid and N-acetyl-D-glucosamine disaccharide units.
Sodium Hyaluronate contains not less than 95.0% and
not more than 105.0% of sodium hyaluronate
(C14H20NNaO11)n, calculated on the dried basis. Sodium
Hyaluronate has an intrinsic viscosity of not less than
90% and not more than 120% of the value stated on the
label.
Description Sodium Hyaluronate is a white powder
or a fibrous aggregate.
Sodium Hyaluronate is sparingly soluble in water and
practically insoluble in acetone, in ethanol or in ether.
Sodium Hyaluronate is hygroscopic.
Sodium Hyaluronate and Sodium Hyaluronate RS as
(2) A solution of Sodium Hyaluronate (1 in 20) re-
sponds to the Qualitative Tests for sodium salt

pH Dissolve a portion of Sodium Hyaluronate,
equivalent to 50 mg on the dried basis, in 10 mL of water: the pH of this solution is between 5.0 and 8.5.
Intrinsic Viscosity Sodium Hyaluronate is highly
hygroscopic and must be protected from moisture during weighing. Weigh accurately 0.200 g (m0p) of Sodium Hyaluronate (this weight is an only indicative
value and should be adjusted after an initial measurement of the viscosity of the test solution (1)), add 50 g
(m0s) of buffer solution at 4 C and mix by shaking at
4 C for 24 hours. Weigh accurately 5.00 g (m1p) of this
solution, add 100.0 g of buffer solution (m1s) at 25 C,
mix by shaking for 20 minutes and filter this solution
with glass filter. Discard the first 10 mL of the filtrate
and use the remaining filtrate as the test solution (1)
(the concentration of Sodium Hyaluronate in the test
solution (1) as C1). Weigh accurately 30.0 g (m2p) of the
test solution (1), add 10.0 g (m2s) of buffer solution at
25 C, mix by shaking for 20 minutes and filter this solution with glass filter. Discard the first 10 mL and use
the remaining filtrate as the test solution (2) (the concentration of Sodium Hyaluronate in the test solution
(2) as C2). Weigh 20.0 g (m3p) of the test solution (1),
add 20.0 g (m3s) of buffer solution at 25 C, mix by
shaking for 20 minutes and filter this solution with
glass filter. Discard the first 10 mL and the remaining
filtrate as the test solution (3) (the concentration of Sodium Hyaluronate in the test solution (3) as C3). Weigh
10.0 g (m4p) of the test solution (1), add 30.0 g (m4s) of
buffer solution at 25 C, mix by shaking for 20 minutes
and filter this solution with glass filter. Discard the first
10 mL and the remaining filtrate as the test solution (4)
(the concentration of Sodium Hyaluronate in the test
solution (4) as C4). Determine the downflowing time
for the test solution (1), (2), (3), (4) and buffer solution,
t1, t2, t3, t4 and t0, respectively, at 25.00 0.03 C. Use
the same viscometer (viscometer constant 0.005 mm2/s2,
kinematic viscosity between 1 and 5 mm2/s2, internal
diameter of tube below the bulb C 0.53 mm, volume of
bulb B 5.6 mL, internal diameter of tube 2 between 2.8
mm and 3.2 mm) for all measurements. Measure the
downflowing time in triplicate from the upper marked
line to the lower marked line of the bulb B. The test is
not valid if the results differ by more than 0.35 % from
the mean and the downflowing time t1 is not less than
1.6 and not more than 1.8 times of t0. If the test is not
valid, adjust the value of m0p and retest.
Calculation of the relative viscositiesSince the
densities of the sodium hyaluronate solutions and of the
solvent are almost equal, calculate the relative viscosities ri (r1, r2, r3 and r4) from the ratio of the downflowing times for the respective solutions ti (t1, t2, t3 and
t4) to the downflowing time of the solvent t0 by the following equation.
KP 9 875
ti
ri =
ti2
t0
t02
B: Correction factor for kinetic energy for the capillary (30800 s3)
Calculation of C1The concentration (kg/m3) of
Sodium Hyaluronate in the test solution (1) (C1).
C1 = m0 p
m1 p
x 100 h
1
25
m0 p + m0s m1 p + m1s
100 100
x: Content (%) of sodium hyaluronate as determined in the Assay

h: Loss on Drying in %
25: 1005 kg/m3 (the density of the test solution at
25 C)
Calculation of the other concentrations
m2 p
C 2 = C1
m2 p + m2 s
C3 = C1
C 4 = C1
m3 p
m3 p + m3s
m4 p
m4 p + m4 s
Calculation of the intrinsic viscosityThe intrinsic

viscosity [] (m3/kg) is calculated by linear leastsquares regression analysis using the Martin equation
and by taking the decimal antilogarithm of the intercept.
log{( r 1) / C} = log[ ] + k [} C
Buffer solutionWeigh 0.78 g of sodium dihydrogen phosphate and 4.50 g of sodium chloride, add water to make 500 mL and use this solution as the solution
A. Weigh 1.79 g of disodium hydrogen phosphate and
4.50 g of sodium chloride, add water to make 500 mL
and use this solution as the solution B. Mix solutions A
and B, adjust pH to 7.0 and filter the solution with glass
filter.
Purity (1) Clarity and color of solutionDissolve a
portion of Sodium Hyaluronate, equivalent to 0.1 g of
sodium hyaluronate on the dried basis, in 30 mL of 0.9
w/v% sodium chloride solution by a gentle shaking for
12 hours: the solution is clear. Determine the absorbance of this solution at 600 nm as directed under the
Ultraviolet-visible Spectrophotometry: it is not more
than 0.01.
(2) ChlorideWeigh 67 mg of Sodium Hyaluronate, and add 100 mL of water. Pipet 15 mL of this solution, add 1 mL of dilute nitric acid and 1 mL of silver
nitrate TS. Perform the test using this solution as the
test solution. Prepare the control solution by mixing 10
mL of standard chloride solution, 5 mL of water, 1 mL

of dilute nitric acid and 1 mL of silver nitrate TS (not
more than 0.5%).
Standard chloride solutionWeigh accurately 1.32
g of sodium chloride, add water to make exactly 1000
mL. To 1 mL of this solution, add water to make exactly 100 mL immediately before use.
(3) IronWeigh accurately a portion of Sodium

Hyaluronate, equivalent to 0.25 g of sodium hyaluronate on the dried bases, add 1 mL of nitric acid, heat to
dissolve in a water-bath, cool, add water to make exactly 10 mL and use this solution as the test solution. Separately, pipet 1.0 mL and 2.0 mL of standard iron solution, prepare in the same manner as the test solution
and use so obtained solutions as the standard solutions
(1) and (2), respectively. Perform the test with the test
solution, the standard solutions (1) and (2) as directed
in the standard addition method under the Atomic Absorption Spectrophotometry (not more than 80 ppm).
Gas: Combustilbe gasAcetylene
Supporting gasAir
Lamp: An iron hollow cathode lamp
(4) Sulfated glycosaminoglycanWhen Sodium
Hyaluronate is extracted from cocks' combs, it meets
the requirement when the purity is tested according to
the following method. Weigh a portion of Sodium Hyaluronate, equivalent to 50.0 mg of sodium hyaluronate
on the dried basis, transfer to a test tube of 150 mm in
length and 16 mm in inside diameter, dissolve in 1 mL
of perchloric acid and use this solution as the test solution. Dissolve 0.149 g of sodium sulfate and add water
to make 100.0 mL. Pipet 10.0 mL of this solution and
add water to make 100.0 mL. Transfer 1.0 mL of this
solution to a fresh test tube of 150 mm in length and 16
mm in inside diameter, evaporate to dryness by heating
to 90~95 C, add 1.0 mL of perchloric acid to the residue to dissolve and use this solution as the standard solution. Plug each test tube with a piece of glass wool.
Heat the test solution and the standard solution at
180 C for 12 hours to obtain clear and colorless solution, and cool to room temperature. Add 3.0 mL each
of 3.33 w/v% barium chloride solution, cap, shake vigorously and allow to stand for 30 minutes. Determine
the absorption of these solutions at 660 nm, using water
as blank, as directed under the Ultraviolet-visible Spectrophotometry: the absorption from the test solution is
not greater that that from the standard solution.
(5) Nucleic acidsDissolve a portion of Sodium
Hyaluronate, equivalent to 0.1 g of sodium hyaluronate
on the dried basis, in 30 mL of 0.9 w/v% sodium chloride solution by a gentle shaking for 12 hours and determine the absorbance of this solution at 260 nm as directed under the Ultraviolet-visible Spectrophotometry:
not more than 0.5.
(6) ProteinWeigh accurately a portion of Sodium
Hyaluronate, equivalent to 0.1 g of sodium hyaluronate
on the dried bases, add water to make exactly 10 mL

and use this solution as the test solution (1). Mix the
test solution (1) with the equal volume of water and use
this solution as the test solution (2). Weigh accurately
50 mg of bovine serum albumin and add water to make
exactly 100 mL. Pipet 1.0, 3.0, 5.0, 7.0 and 10.0 mL of
this solution, add water to make 100 mL each and use
these solutions as the standard solutions. Pipet 2.5 mL
each of water (blank), the test solution (1), the test solution (2) and the standard solutions, add 2.5 mL each of
freshly prepared cupuric tartarate TS and mix for 10
minutes. Then, add 0.5 mL each of a mixture of water
and phophomolybdotungstic TS (1:1), prepared immediately before use, and allow the tubes to stand for 30
minutes. Perform the test with these solutions as directed under the Ultraviolet-visible Spectrophotometry
and determine the absorbances at 750 nm, using water
as the blank. Construct the calibration curve with the
absorbances from the standard solutions and calculate
the content of protein from the calibration curve: not
more than 0.3%, not more than 0.1% for parenteral dosage forms.
Microbial limit Not more than 100 viable microorganisms per g of Sodium Hyaluronate (1 g).
Sterility Test

Sodium Hyaluronate for parenteral dosage forms without a further procedure for the removal of bacterial endotoxins. Less than 0.05 EU per mg of Sodium Hyaluronate for intra-ocular preparations or intra-articular
preparations without a further procedure for the removal of bacterial endotoxins.
Loss on Drying Not more than 20.0% (0.50 g, P2O5,
105 C, 6 hours).
Assay Determine the content of glucuronic acid in
the test specimen by the reaction with carbazole. Weigh
accurately about 0.170 g of Sodium Hyaluronate, add
water to make exactly 100 g, pipet 10 g of the solution,
add water to make exactly 200 g and use this solution
as the test solution. Repeat this procedure to obtain the
test solution in three sets. Weigh accurately about 0.1 g
of D-glucuronic acid, previous dried under vacuum to a
constant mass, add water to make exactly 100 g. Pipet a
portion of this solution, add water to prepare 5 solutions having the concentration between 6.5 and 65 g
of D-glucuronic acid per g water and use these solutions as the standard solutions. Prepare 25 test tubes,
number the tubes 1 to 25, and place the tubes in iced
water. Transfer 1.0 ml each of the five standard solutions in triplicate to the test tubes 1 to 15 (standard
tubes), and 1.0 ml each of the three sets of the test solution in triplicate to the test-tubes 16 to 24 (test tubes).
Transfer 1.0 mL of water to the test tube 25 (blank).
Add 5.0 mL each of the freshly prepared 0.95 w/v%
disodium tetraborate in sulfuric acid solution to the test
tubes. Tightly close the test-tubes with plastic caps, mix

by shaking and place in a water-bath for exactly 15 min.
Cool in iced water, and add 0.20 mL each of 0.125
w/v% carbazole in ethanol to the test tubes. Recap the
tubes, mix by shaking, and put them again in a waterbath for exactly 15 min. Cool to room temperature and
measure the absorbances of the solutions at 530 nm
against the blank. From the calibration curve obtained
with the mean absorbances for each standard solution,
determine the mean concentration of D-glucuronic acid
in the test solutions.
Content (%) of sodium hyaluronate (C14H20NNaO11)n
Cg
100
401.3
=
Z
CS
100 h 194.1
Cg: Mean concentration (mg/g) of D-glucuronic acid in the test solutions
CS: Mean concentration (mg/g) of sodium hyaluronate to be examined in the test solutions
Z: Content (%) of D-glucuronic acid (C6H10O7)
h: Loss on Drying (%)
401.3: Relative molecular weight of the disaccharide fragment
194.1: Relative molecular weight of glucuronic acid
tight containers.
Sodium Iodide
NaI: 149.89
Sodium Iodide, when dried, contains not less than
99.0% and not more than 101.0% of sodium iodide
(NaI).
Description Sodium Iodide is a colorless crystal or a
Sodium Iodide is very soluble in water and freely soluble in glycerin or in ethanol.
Sodium Iodide deliquesces in moist air.
Identification A solution of Sodium Iodide (1 in 20)
responds to the Qualitative Tests for sodium salt and for
iodide.
1.0 g of Sodium Iodide in 2 mL of water: the solution is
(2) AlkaliDissolve 1.0 g of Sodium Iodide in 10
mL of freshly boiled and cooled water and add 1.0 mL
of 0.005 mol/L sulfuric acid VS and 1 drop of phenolphthalein TS: no color is observed.
(3) Chloride, bromide and thiosulfate Dissolve
0.20 g of Sodium Iodide in 5 mL of ammonia TS, add
15.0 mL of 0.1 mol/L silver nitrate VS, shake for a few
KP 9 877
minutes and filter. To 10 mL of the filtrate, add 15 mL

of dilute nitric acid: no brown color is observed. The
solution has no more turbidity than the following control solution.
purple color of the chloroform layer disappears. The

end point is attained only when the red-purple color
does not reappear in the chloroform layer within 5 minutes after the layer has been decolorized.
Control solutionTo 0.30 mL of 0.01 mol/L hydrochloric acid VS, add 2.5 mL of ammonia TS, 7.5
mL of 0.1 mol/L silver nitrate VS and 15 mL of dilute
nitric acid.

= 14.989 mg of NaI
(4) Nitrate, nitrite and ammoniumPlace 1.0 g of

Sodium Iodide in a test tube and add 5 mL of water, 5
mL of sodium hydroxide TS and 0.2 g of aluminum
wire. Insert a pledget of absorbent cotton in the mouth
of the test tube and place a piece of moistened red litmus paper on the cotton. Heat the test tube on a waterbath for 15 minutes: the evolved gas does not turn
(5) CyanideDissolve 0.5 g of Sodium Iodide in
10 mL of water. To 5 mL of this solution, add 1 drop of
ferrous sulfate TS and 2 mL of sodium hydroxide TS,
warm and add 4 mL of hydrochloric acid: no green color is observed.
(6) IodateDissolve 0.5 g of Sodium Iodide in 10
mL of freshly boiled and cooled water and add 2 drops
of dilute sulfuric acid and 1 drop of starch TS: no blue
color is observed immediately.
Iodide according to Method 1 and perform the test.
(8) BariumDissolve 0.5 g of Sodium Iodide in 10
mL of water, add 1 mL of dilute sulfuric acid and allow
to stand for 5 minutes: no turbidity is produced.
(9) PotassiumDissolve 1.0 g of Sodium Iodide in
water and add water to make 100 mL. To 4.0 mL of this
solution, add 1.0 mL of dilute acetic acid, shake, add
5.0 mL of a solution of sodium tetraphenylboron (1 in
30), immediately shake and allow to stand for 10 minutes: the solution has no more turbidity than the following control solution.
Control solutionDissolve 9.5 mg of potassium
chloride in water and add water to make 1000 mL. To
4.0 mL of this solution, add 1.0 mL of dilute acetic acid,
shake and then proceed as directed above.
(10) Arsenic Prepare the test solution with 0.40 g

of Sodium Iodide according to Method 1 and perform
hours).
Iodide, previously dried, in an iodine flask, dissolve in
10 mL of water, add 35 mL of hydrochloric acid and 5
mL of chloroform and titrate with 0.05 mol/L potassium iodate VS while shaking vigorously until the red-

tight containers.
Sodium Iodide (123I) Injection

Sodium Iodide (123I) Injection contains 123I as a form of
Sodium Iodide.
Sodium Iodide (123I) Injection contains not less than
90.0% and not more than 110.0% of the labeled of 123I
radioactivity at the date and hour stated on the label.
Preparation (1) Iodine-123 is obtained from proton
irradiation of tellurium-124. Separate and prepare it as
a form of Sodium Iodide (123I). Sodium Iodide (123I) Injection is produced following the preparation of Injections.
(2) Iodine-123 is obtained from by proton irradiation of xenon enriched in xenon-124 followed by the
decay of xenon-123 which is formed directly and by
the decay of caesium-123. Separate and prepare it as a
form of Sodium Iodide (123I). Sodium Iodide (123I) Injection is produced following the preparation of Injections.
Description Sodium Iodide (123I) Injection is a clear,
colorless liquid and is odorless.
Identification (1) The gamma ray spectrum of an
adequate amount of Sodium Iodide (123I) Injection is
identical to that of a specimen of 123I of known purity
that exhibits a major photoelectric peak having an
energy of 0.159 MeV.
(2) Perform the test (1) as directed under the Purity:
A maximum radioactivity is obtained from the principal
spot, corresponding to iodine-123, in the radiochromatogram.
pH
Between 7.0 and 9.0
Purity (1) Radiochemical impuritiesPerform the

test with a portion of Sodium Iodide (123I) Injection as
directed under the Thin-layer Chromatography. Develop the chromatogram with methanol to a distance of
about 10 cm, and determine the radioactivity distribution in the chromatographic plate: the radioactivity of
any impurities, apart from 123I, is not more than 5% of
the total radioactivity.
(2) Radionuclidic purityPerform the test (1) in
the Identification with a portion of Sodium Iodide (123I)
Injection, and determine the radioactivity of 123I (0.159

MeV) and 124I (0.603 MeV). The radioactivity of 123I is
not less than 95% of the total radioactivity at the date
and hour stated on the label.
Sodium Iopodate
CH2CH2COONa
Pyrogen Test
Assay Weigh accurately a portion of Sodium Iodide

(123I) Injection and determine the amount of iodine-123
as directed under the gamma-ray spectrometry.
Expiration Date Within 48 hours from the date and
hour stated on the label.
Sodium Iodide (131I) Capsules

Sodium Iodide (131I) Capsules contain iodine (131I) as a
form of Sodium Iodide.
Sodium Iodide (131I) Capsules conform to the requirements of Sodium Iodide (131I) Capsules in the Korean
Pharmaceutical Codes (Third Edition, 2007)
Sodium Iodide (131I) Solution

Sodium Iodide (131I) Solution contains iodine-131 (131I)
in the form of Sodium Iodide.
Sodium Iodide (131I) Solution conforms to the requirements of Sodium Iodide (131I) Solution in the Minimum
Requirements for the Specifications for the Pharmaceuticals.
Description Sodium Iodide (131I) Solution is a clear,
colorless liquid. Sodium Iodide (131I) Solution is odorless or has an odor of the preservative or stabilizer.
Sodium Iodohippurate (131I)

Injection
Sodium Iodohippurate (131I) Injection is an aqueous solution for injection containing iodine-131 (131I) in the
form of sodium o-iodohippurate.
Sodium Iodohippurate (131I) Injection conforms to the
requirements of Sodium Iodohippurate (131I) Injection
in the Korean Pharmaceuticals Codex (Third Edition).
The Insoluble Particulate Matter Test for Injections is
not applied to this injection.
Description Sodium Iodohippurate (131I) Injection is
a clear and colorless liquid and is odorless or has an
odor of the preservative or stabilizer.
I
CH3
N
CHN
CH3
C12H12I3N2NaO2: 619.94
Sodium Iopodate contains not less than 98.0% and not
more
than
101.0%
of
sodium
iopodate
(C12H12I3N2NaO2), calculated on the dried basis.
Description Sodium lopodate is a white to pale yellowish white powder, is odorless and has a slightly bitter taste.
Sodium lopodate is freely soluble in water, soluble in
ethanol, and practically insoluble in ether.
pHThe pH of the solution of 1.0 g of Sodium
Iopodate in 10 mL of water is between 8.9 and 9.9.
Sodium lopodate is gradually colored by light.
Identification (1) Heat 1.0 g of Sodium Iopodate
over a flame: a purple gas evolves.
(2) Determine the spectra of Sodium Iopodate and
Sodium Iopodate RS, previously dried, as directed in
Spectrophotometry, respectively: both spectra exhibit
(3) Sodium Iopodate responds to the Qualitative
Tests (1) for sodium salt.
1.0 g of Sodium Iopodate in 5 mL of water: the solution is clear and colorless or pale yellow.
(2) Primary aromatic aminesDissolve 0.20 g of
Sodiurn Iopodate in 6 mL of water, add 4 mL of a sodium nitrite solution (1 in 100) and 10 mL of 1 mol/L
hydrochloric acid TS, shake and allow to stand for 2
minutes. Then add 5 mL of ammonium sulfamate TS,
shake well, allow to stand for 1 minute and add 0.4 mL
of a solution of -naphthol in ethanol (1 in 10), 15 mL
of sodium hydroxide TS and water to make exactly 50
mL. Perform the test as directed under the Ultarvioletvisible Spectrophotometry and determine the absorbance of this solution at 485 nm using the blank prepared in the same manner as the control: the absorbance is not more than 0.16.
(3) Soluble halidesDissolve 2.5 g of Sodium lopodate in 20 mL of water and 2.5 mL of ammonia TS,
add 20 mL of dilute nitric acid and water to make 100
mL, allow to stand for 15 minutes with occasional
shaking and filter. Discard the first 10 mL of the filtrate,
take the subsequent 25 mL in a Nessler tube and add
ethanol to make 50 mL. Proceed as directed under the
KP 9 879
Chloride Limit Test, using this solution as the test solution. Prepare the control solution with 0.10 mL of 0.01
mol/L hydrochloric acid VS, add 6 mL of dilute nitric
acid and water to make 25 mL and add ethanol to make
50 mL.
(4) IodineDissolve 0.2 g of Sodium Iopodate in
2.0 mL of sodium hydroxide TS, add 2.5 mL of 0.5
mol/L sulfuric acid TS, allow to stand for 10 minutes
with occasional shaking, add 5 mL of chloroform,
shake and allow to stand: the chloroform layer is colorless.
Iopodate according to Method 2 and perform the test.
Sodium Iopodate according to Method 3 and perform
the test (not more than 3.3 ppm).
60 C, 3 hours).
Assay Transfer about 0.5 g of Sodium Iopodate, accurately weighed, to a flask, dissolve in 40 mL of sodium hydroxide TS, add 1 g of zinc powder, boil for 30
minutes under a reflux condenser and filter after cooling. Wash the flask and the filter paper with 50 mL of
water and combine the filtrate and the washings. To the
solution, add 5 mL of glacial acetic acid and titrate with
0.1 mol/L silver nitrate VS (indicator: 1 mL of Tetrabromophenolphthalein ethyl ester TS). The end point is
attained only when the precipitate turns from yellow to
green.

= 20.665 mg of C12H12I3N2NaO2
tight containers.
Sodium Iopodate Capsules

Sodium Iopodate Capsules contain not less than 93.0%
and not more than 107.0% of the labeled amount of sodium iopodate (C12H12I3N2NaO2: 619.94).
Method of Preparation Suspend Sodium Iopodate in
vegetable oil and prepare as directed under Capsules.
Identification Take out the contents of Sodium Iopodate Capsules. To an amount of the contents, equivalent
to 2 g of Sodium Iopodate according to the labeled
amount, add 20 mL of petroleum ether and stir well.
Filter by suction through a glass filter (G4), wash the
residue with three 10 mL volumes of petroleum ether
and dry at 60 C for 1 hour under reduced pressure.
Proceed as directed in the Identification under Sodium
Iopodate.

ment.
Assay Take a number of Sodium Iopodate Capsules,

equivalent to about 5 g of sodium iopodate
(C12H12I3N2NaO2), add 100 mL of water and warm on a
water-bath until the capsules are completely disintegrated. Transfer this solution to a separatory funnel after cooling, add 50 mL of hexane, shake and separate
the aqueous layer. And then, wash the hexane layer
with two 50 mL volumes of water, combine the washings and the aqueous layer and add water to make exactly 250 mL. Pipet exactly 10 mL of this solution, add
water to make exactly 500 mL. Pipet exactly 5 mL of
this solution, add water to make exactly 200 mL and
accurately about 0.1 g of Sodium Iopodate RS, (previously determine its loss on drying), dissolve in water
to make exactly 100 mL. Pipet exactly 4 mL of this solution, add water to make exactly 100 mL. Pipet exactly 5 mL of this solution, add water to make exactly 20
Chromatography according to the following conditions
and determine the peak areas, AT and AS , of iopodate for the test solution and the standard solution, respectively.
Amount (mg) of sodium iopodate (C12H12I3N2NaO2)

= amount (mg) of Sodium Iopodate RS,
A
AS
Operating condition
phenylated silica gel for liquid chromatography (5 m
about 25 C.
Mobile phase: Dissolve 1.7 g of tetrabutylammonium phosphate and 7.0 g of dibasic potassium phosphate in 350 mL of water, adjust the pH to 7.0 with diluted phosphoric acid (1 in 10) and add water to make
410 mL. To this solution, add 600 mL of methanol and
mix.
time of iopodate is about 6 minutes.
System suitability
System performance: Dissolve 20 mg of methyl parabene in 1 mL of ethanol and add water to make 100 mL.
Pipet 5 mL of this solution add water to make 100 mL,
To 5 mL of this solution and add 20 mL of the standard
solution. When the procedure is run with 20 L of this

solution under the above operating conditions, methyl
parabene and iopodate are eluted in this order with the
resolution between their peaks being not less than 4.
the peak area of iopodate is not more than 1.5%.
tight containers.
Sodium Iotalamate Injecton

Sodium Iotalamate Injection is an aqueous solution for
injection.
Sodium Iotalamate Injection contains not less than
iotalamic acid (C11H9I3N2O4: 613.92).
(1) Iotalamic Acid
645 g
Sodium hydroxide
42 g
Water for injection
To make 1000 mL
(2) Iotalamic Acid

772.5 g
Sodium hydroxide
50.5 g
Water for injection
To make 1000 mL
Prepare as directed under Injections, with the above ingredients (1) or (2).
Description Sodium Iotalamate Injection is a clear,
colorless or pale yellow and slightly viscous liquid.
Sodium Iotalamate Injection is gradually colored by
light.
Identification (1) To a volume of Sodium Iotalamate
Injection, equivalent to 1 g of Iotalamic Acid according
to the labeled amount, add 25 mL of water and add 2.5
mL of dilute hydrochloric acid with thorough stirring: a
white precipitate is produced. Filter the precipitate by
suction through a glass filter (G4), wash the precipitate
with two 10 mL volumes of water and dry at 105 C for
1 hour. Proceed with the precipitate as directed in the
Identification (2) under Iotalamic Acid.
(2) Sodium Iotalamate Injection responds to the
Qualitative Tests (1) for soidum salt.
pH
mL of water, shake, add 4 mL of a solution of sodium

nitrite (1 in 100) under ice-cooling and proceed as directed in the Purity (2) under Iotalamic Acid: the absorbance is not more than 0.17.
(2) Iodine and iodideTo a volume of Sodium
Iotalamate Injection, equivalent to 1.5 g of Iotalamic
Acid according to the labeled amount, add 20 mL of
water and 5 mL of dilute sulfuric acid, shake well and
filter the precipitate by suction through a glass filter
(G4). To the filtrate, add 5 mL of toluene and shake vigorously: the toluene layer is colorless. Then add 2 mL
of a solution of sodium nitrite (1 in 100) and shake vigorously: the toluene layer has no more color than the
iodide in water to make 1000 mL. To 2.0 mL of this solution, add 20 mL of water, 5 mL of dilute sulfuric acid,
5 mL of toluene and 2 mL of a solution of sodium nitrite (1 in 100) and shake vigorously.
Sterility Test It meets the requirement
Bacterial Endotoxin Less than 3.4 EU / mL
Assay Pipet accurately a volume of Sodium Iotalamate Injection, equivalent to about 4 g of iotalamic acid
(C11H9I3N2O4), dilute with water to make exactly 200
mL. Pipet 2.0 mL of this solution, add water to make
exactly 200 mL. To 5.0 mL of this solution, add 5.0 mL
of the internal standard solution, add the mobile phase
Iotalamic Acid RS, previously dried at 105 C for 4
hours, dissolve in 100 mL of water and 1 mL of sodium
hydroxide TS and add water to make exactly 200 mL.
Pipet 5.0 mL of this solution, add water to make exactly 50 mL. To 5.0 mL of this solution, add 5.0 mL of the
internal standard solution, add the mobile phase to
the peak area of Iotalamic Acid to that of the internal
standard.
Purity (1) Primary aromatic aminesTo a volume

of Sodium Iotalamate Injection, equivalent to 0.20 g of
Iotalamic Acid according to the labeled amount, add 15
Amount (mg) of iotalamic acid (C11H9I3N2O4)

Q
= amount (mg) of Iotalamic Acid RS T
QS
KP 9 881

Internal standard solutionA solution of Ltrypthophan in the mobile phase (3 in 2500).
about 20 C.
Mobile phase: To 3.9 g of phosphoric acid and 2.8
mL of triethylamine, add water to make 2000 mL. To
this solution, add 100 mL of acetonitile.
time of iotalamic acid is about 6 minutes.
System suitability
operating conditions iotalamic acid and the internal
six times with 10 L of standard solution under the
above operating conditions, the relative standard deviation of the ratios of the peak area of iotalamic acid is
not more than 1.0%.
Sodium Pertechnetate (99mTc)

Injection
Sodium Pertechnetate (99mTc) Injection is an aqueous
solution for injection containing technetium-99m
(99mTc) in the form of sodium pertechnetate.
Sodium Pertechnetate Injection conforms to the requirements of Sodium Pertechnetate (99mTc) Injection
in the Korean Pharmaceutical Codex (Third Edition,
2007) .
Description Sodium Pertechnetate (99mTc) Injection
is a clear, colorless liquid.
Sodium Phosphate (32P) solution

Sodium Phosphate (32P) Solution contains Phosphorous-32 in the form of sodium phosphate.
Sodium Phosphate (32P) Solution conforms to the requirements of Sodium Phosphate (32P) Solution in the
Korean Pharmaceutical Codex (Third Edition, 2007).
Description
Sodium Phosphate (32P) Solution is a
Sodium Picosulfate Hydrate

NaO3SO
CH
OSO3Na
H2O
C18H13NNa2O8S2H2O: 499.42
Sodium Picosulfate Hydrate contains not less than
98.5% and not more than 101.0% of sodium picosulfate
hydrate (C18H13NNa2O8S2H2O: 481.41), calculated on
Description Sodium Picosulfate Hydrate is a white
crystalline powder, is odorless and tasteless.
Sodium Picosulfate Hydrate is very soluble in water,
soluble in methanol, slightly soluble in dehydrated
Sodium Picosulfate Hydrate is gradually colored by
light.
pHDissolve 1.0 g of Sodium Picosulfate in 20
9.4.
Identification (1) To 5 mg of Sodium Picosulfate
Hydrate, add 10 mg of 2,4-dinitrochlorobenzene, mix
and fuse by gentle heating for 5 to 6 seconds. After
cooling, add 4 mL of potassium hydroxide and ethanol
TS: a reddish orange color is observed.
(2) To 0.2 g of Sodium Picosulfate Hydrate, add 5
mL of dilute hydrochloric acid, boil for 5 minutes, cool
and add 1 mL of barium chloride TS: a white precipitate is produced.
(3) Determine the absorbance spectra of the
aqueous solutions of Sodium Picosulfate Hydrate and
Sodium Picosulfate Hydrate RS (1 in 25000) as directed under the Ultraviolet-visible Spectrophotometry:
(4) Determine the infrared spectra of Sodium Picosulfate Hydrate and Sodium Picosulfate Hydrate RS,
previously dried at 105 C in vaccum for 4 hour, as directed in the potassium bromide disk method under the
Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wave numbers.
(5) A solution of Sodium Picosulfate Hydrate (1 in
10) responds to the Qualitative Tests for sodium salt.
Absorbance E
1%
1cm
(4 mg, calculated on the anhydrous basis, water, 100

mL).
1.0 g of Sodium Picosulfate Hydrate in 10 mL of water:
the solution is colorless to pale yellow.
(2) ChlorideWeigh 0.5 g of Sodium Picosulfate
Hydrate and perform the test. Prepare the control solution with 0.40 mL of 0.01 mol/L hydrochloric acid (not
more than 0.028%).
(3) SulfateWeigh 0.40 g of Sodium Picosulfate
Hydrate and test. Prepare the control solution with 0.35
mL of 0.005 mol/L sulfuric acid (not more than
0.042%).
Picosulfate Hydrate according to Method 2 and perform the test. Prepare the control solution with 2.0 mL
of Standard Lead Solution (not more than 10 ppm).
Sodium Picosulfate Hydrate according to Method 3 and
(6) Related substancesDissolve 0.25 g of Sodium Picosulfate Hydrate in 5 mL of methanol and use
the test solution, add methanol to make exactly 500 mL
thin-layer chromatography. Develop the chromatogram
with a mixture of n-butanol, water and glacial acetic acid (74 : 20 : 19) to a distance of about 10 cm and airdry the plate. Examine under ultraviolet light (principal
Assay Dissolve about 0.4 g of Sodium Picosulfate
Hydrate, accurately weighed, in 50 mL of methanol,

= 48.14 mg of C18H13NNa2O8S2
tight containers.
Sodium Polystyrene
Sulfonate
Sodium Polystyrene Sulfonate is a cation exchange resin prepared as the sodium form of the sulfonated styrene divinylbenzene copolymer.
Sodium Polystyrene Sulfonate contains not less than
9.4% and not more than 11.0% of sodium (Na: 22.99),
Each g of Sodium Polystyrene Sulfonate, calculated on
the anhydrous basis, exchanges with 0.110 to 0.135 g
of potassium (K: 39.10).
Description Sodium Polystyrene Sulfonate is a pale
yellowish brown powder, is odorless and tasteless.
Sodium Polystyrene Sulfonate is practically insoluble
in water, ethanol, acetone or ether.
Sodium Polystyrene Sulfonate and Sodium Polystyrene
Sulfonate RS as directed in the potassium bromide disk
same wavenumbers.
(2) To 1.0 g of Sodium Polystyrene Sulfonate, add
10 mL of dilute hydrochloric acid, mix with swirling,
filter and neutralize the filtrate with ammonia TS: the
solution responds to the Qualitative Tests for sodium
salt.
Purity (1) AmmoniaPlace 1.0 g of Sodium Polystyrene Sulfonate in a flask, add 5 mL of sodium hydroxide TS, cover the flask with a watch glass having a
moistened strip of red litmus paper on the underside
and boil for 15 minutes: the gas evolved does not
change the red litmus paper to blue.
Polystyrene Sulfonate according to Method 2 and perform the test. Prepare the control solution with 2.0 mL
Sodium Polystyrene Sulfonate according to Method 3
(4) StyreneTo 10.0 g of Sodium Polystyrene Sulfonate, add 10 mL of acetone, shake for 30 minutes,
centrifuge and use the supernatant liquid as the test solution. Separately, dissolve 10.0 mg of styrene in acetone to make exactly 100 mL. Pipet 1.0 mL of this solution, dilute with acetone to make exactly 100 mL and
test with 20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions. Determine the peak heights, AT and AS, of styrene for the test
solution and the standard solution, respectively: AT is
not larger than AS.
KP 9 883
(1 : 1).
time of styrene is about 7 to 8 minutes.
System suitability
styrene and butyl parahydroxybenzoate in 100 mL of
acetone. Pipet 5 mL of this solution and add acetone to
butyl parahydroxybenzoate and styrene are eluted in
this order with the resolution between these peaks being not less than 5.0.
above operating conditions, the relative standard deviation of the peak area of styrene is not more than 2.0%.
Assay (1) SodiumPipet 50 mL of 3 mol/L hydrochloric acid TS into a glass-stoppered flask containing
about 1.0 g of Sodium Polystyrene Sulfonate calculated
on the anhydrous basis, accurately weighed, stir for 60
minutes and filter. Discard the first 20 mL of the filtrate,
pipet 5.0 mL of the subsequent filtrate and add water to
make exactly 100 mL, pipet 20.0 mL of this solution,
add water to make exactly 1000 mL and use this solution as the test solution. Separately, measure exactly a
suitable volume of standard sodium chloride stock solution, dilute with water to make solutions containing 1
g to 3 g of sodium (Na: 22.99) per mL and use these solutions as the standard solutions. Perform the test with
under the Atomic Absorption Spectrophotometry according to the following conditions and determine the
amount of sodium in the test solution, using the calibration curve obtained from the standard solutions.
Gas used: Combustible gasAcetylene.

Supporting gasAir.
Lamp: A sodium hollow-cathode lamp.
(2) Potassium exchange capacityPipet 100.0 mL
of standard potassium stock solution into a glassstoppered flask containing about 1.5 g of Sodium Polystyrene Sulfonate calculated on the anhydrous basis,
accurately weighed, stir for 15 minutes and filter. Discard the first 20 mL of the filtrate, pipet 10.0 mL of the
subsequent filtrate and add water to make exactly 100
mL. Pipet 10.0 mL of this solution, add water to make

exactly 1000 mL and use this solution as the test solution. Separately, measure a suitable volume of standard
potassium stock solution, dilute with water to make solutions containing 1 g to 5 g of potassium (K: 39.10)
per mL and use these solutions as the standard solutions.
solutions as directed under the Atomic Absorption
Spectrophotometry according to the following conditions and determine the amount, Y (mg), of potassium
in 1000 mL of the test solution, using the calibration
curve obtained from the standard solutions. The exchange quantity for potassium per g of Sodium Polystyrene Sulfonate, calculated on the anhydrous basis, is
calculated by the following equation.
Exchange quantity (mg) for potassium (K)
Per g of Sodium Polystyrene Sulfonate,
X - 100Y
calculated on the anhydrous basis =
W
X: Amount (mg) of potassium in 100 mL of standard potassium stock solution before exchange,
W: Amount (g) of Calcium Polystyrene Sulfonate
taken, calculated on the anhydrous basis.
Gas used: Combustible gas-Acetylene.

Supporting gas-Air.
Lamp: A potassium hollow-cathode lamp.
.
Sodium Prasterone Sulfate

Hydrate
O
H 3C
H3C
2H2O
NaO3SO
C19H27NaO5S2H2O: 426.50
Sodium Prasterone Sulfate Hydrate contains not less
than 98.0% and not more than 101.0% of sodium prasterone sulfate (C19H27NaO5S: 390.47), calculated on the
dried basis.
Description Sodium Prasterone Sulfate Hydrate is a
Sodium Prasterone Sulfate Hydrate is soluble in methanol, sparingly soluble in water or in ethanol and
practically insoluble in acetone or in ether.
pHDissolve 1.0 g of Sodium Prasterone Sulfate
Hydrate in 200 mL of water: the pH of this solution is

after drying).
Identification (1) Dissolve 10 mg of Sodium Prasterone Sulfate Hydrate in 4 mL of ethanol, add 2 mL of
m-dinitrobenzene TS and 2 mL of a solution of sodium
hydroxide (1 in 8): a red-purple color is observed and
gradually changes to brown.
(2) To 10 mL of a solution of Sodium Prasterone
Sulfate Hydrate (1 in 200), add 0.5 mL of bromine TS:
the color of bromine TS immediately disappears.
(3) Determine the infrared spectra of Sodium Prasterone Sulfate Hydrate and Sodium Prasterone Sulfate
same wavenumbers.
(4) A solution of Sodium Prasterone Sulfate Hydrate (1 in 200) responds to the Qualitative Tests for
sodium salt.
Specific Optical Rtation [ ]20
+12.1 (0.73 g, calculated on the dried basis, methanol,
20 mL, 100 mm).
0.25 g of Sodium Prasterone Sulfate Hydrate in 50 mL
(2) ChlorideDissolve 1.0 g of Sodium Prasterone
Sulfate Hydrate in 20 mL of acetone and 20 mL of water and add 6 mL of dilute nitric acid and water to make
50 mL. Perform the test. Prepare the control solution as
follows: to 0.30 mL of 0.01 mol/L hydrochloric acid
VS, add 20 mL of acetone, 6 mL of dilute nitric acid
and water to make 50 mL (not more than 0.011%).
(3) Sulfate1.2 g of Sodium Prasterone Sulfate
Hydrate, add 20 mL of water, shake vigorously for 5
minutes and filter. To 10 mL of the filtrate, add 20 mL
of acetone, 1 mL of dilute hydrochloric acid and water
to make 50 mL. Perform the test using this solution ad
the test solution. Prepare the control solution as follows: to 0.40 mL of 0.005 mol/L sulfuric acid VS, add
20 mL of acetone, 1 mL of dilute hydrochloric acid and
Prasterone Sulfate Hydrate according to Method 2 and
(5) Related substancesDissolve 0.10 g of Sodium Prasterone Sulfate Hydrate in 10 mL of methanol
mL of the test solution, add methanol to make exactly
Perform the test with the rest solution and the standard
plate with a mixture of chloroform, methanol and water

plate. Spray evenly a mixture of sulfuric acid and ethanol (1 : 1) on the plate and heat at 80 C for 5 minutes:
Prasterone Sulfate Hydrate, dissolve in 30 mL of water.
Apply this solution to a chromatographic column, 10
mm in inside diameter, previously prepared by pouring
5 mL of strongly acidic ion-exchange resin (H type) for
column chromatography and elute at the rate of 4 mL
per minute. Wash the chromatographic column with
100 mL of water, combine the washings with above effluent solution and titrate with 0.05 mol/L sodium hydroxide VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.

= 19.523 mg of C19H27NaO5S
Sodium Pyrosulfite
Sodium Metabisulfite
Na2S2O5: 190.11
Sodium Pyrosulfite contains not less than 95.0% and

not more than 101.0% of sodium pyrosulfite (Na2S2O5).
Description Sodium Pyrosulfite is a white crystal or
crystalline powder and has the odor of sulfur dioxide.
Sodium Pyrosulfite is freely soluble in water, very
ether.
A solution of Sodium Pyrosulfite (1 in 20) is acidic.
Sodium Pyrosulfite is hygroscopic.
Sodium Pyrosulfite decomposes gradually on exposure
to air.
Identification A solution of Sodium Pyrosulfite (1 in
and for bisulfite.
1.0 g of Sodium Pyrosulfite in 10 mL of water: the solution is clear and colorless.
(2) ThiosulfateDissolve 1.0 g of Sodium Pyrosulfite in 15 mL of water, add slowly 5 mL of dilute

hydrochloric acid, shake and allow to stand for 5 mi-
KP 9 885
nutes: no turbidity is produced.

(3) Heavy metalsDissolve 1.0 g of Sodium Pyrosulfite in 10 mL of water and evaporate with 5 mL of
hydrochloric acid on a water-bath to dryness. Dissolve
the residue in 10 mL of water, add 1 drop of phenolphthalein TS and add ammonia TS until the solution becomes slightly red. Add 2 mL of dilute acetic acid and
water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as
follows: evaporate 5 mL of hydrochloric acid on a water-bath to dryness and to the residue, add 2 mL of dilute acetic acid, 2.0 mL of standard lead solution and
water to make 50 mL (not more than 20 ppm).
(4) IronPrepare the test solution with 1.0 g of
Sodium Pyrosulfite according to Method 1 and perform
the test according to Method A. Prepare the control solution with 2.0 mL of standard iron solution (not more
than 20 ppm).
(5) ArsenicDissolve 0.5 g of Sodium Pyrosulfite
in 10 mL of water, heat with 1 mL of sulfuric acid in a
sand-bath until white fumes are evolved and add water
to make 5 mL. Perform the test with this solution as the
test solution (not more than 4 ppm).
Assay Weigh accurately about 0.15 g of Sodium Pyrosulfite and transfer to an iodine flask containing an
exactly measured 50 mL of 0.05 mol/L iodine VS.
Stopper tightly, shake well and allow to stand for 5 minutes in a dark place. Add 1 mL of hydrochloric acid
VS and titrate the excess of iodine with 0.1mol/L sodium thiosulfate VS (indicator: 1 mL of starch TS).
correction.

= 4.753 mg of Na2S2O5
tight and preferably well-filled containers. Store at a
temperature not exceeding 30 C.
Sodium Salicylate
CO2Na
OH
C7H5NaO3: 160.10
Sodium Salicylate, when dried, contains not less than
98.0% and not more than 102.0% of sodium salicylate
(C7H5NaO3).
Description Sodium Salicylate is a white crystals or
crystalline powder.
Sodium Salicylate is very soluble in water, freely soluble in glacial acetic acid and soluble in ethanol.
Sodium Salicylate is gradually colored by light.
Sodium Salicylate and Sodium Salicylate RS as directed in the potassium bromide disk method under the
Infrared Spectrophotometry: both spectra exhibit similar intensities of absoption at the same wavenumbers.
(2) A solution of Sodium Salicylate (1 in 20) responds to the Qualitative Tests for sodium salt.
pH Dissolve 2.0 g of Sodium Salicylate in 20 mL of
Purify (1) Clarity and color of solutionDissolve
1.0 g of Sodium Salicylate in 10 mL of water: the solution is colorless. Perform the test as directed under the
Ultraviolet-visible Spectrophotometry and determine
the absorbance of this solution at 420 nm: the absorbance is not more than 0.02.
(2) ChlorideDissolve 0.5 g of Sodium Salicylate
in 15 mL of water, add 6 mL of dilute nitric acid and
ethanol to make 50 mL and perform the test. Prepare
the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS, 28 mL of ethanol, 6 mL of dilute
nitric acid and water to make 50 mL (not more than
0.021%).
(3) SulfateDissolve 0.25 g of Sodium Salicylate
in 5 mL of water and add 0.5 mL of barium chloride
TS: the solution shows no change.
(4) Sulfite and thiosulfateDissolve 1.0 g of Sodium Salicylate in 20 mL of water, add 1 mL of hydrochloric acid and filter. Add 0.15 mL of 0.05 mol/L
iodine VS to the filtrate: a yellow color develops.
Salicylate according to Method 2 and perform the test.
(6) ArsenicPlace 1.0 g of Sodium Salicylate in
decomposition flask, add 5 mL of nitric acid and 2 mL
of sulfuric acid and heat cautiously until white fumes
are evolved. After cooling, add 2 mL of nitric acid, heat
and cooling, add 2 mL of hydrogen peroxide and heat
again until the solution is colorless to pale yellow. Add,
if necessary, nitric acid and hydrogen peroxide, heat
and repeat this operation. After cooling, add 2 mL of a
saturated solution of ammonium oxalate and heat until
white fumes are evolved again. After cooling, add water to make 5 mL and perform the test with this solution
as the test solution (not more than 2 ppm).
hours).
Assay Weigh accurately each about 0.20 g of Sodium
Salicylate and Sodium Salicylate RS, previously dried,
dissolve in water to make exactly 100 mL. Pipet 10.0
mL each of these solutions, add 10.0 mL of the internal
standard and water to make exactly 100 mL and use

these solutions as the test solution and the standard solution, respectively. Perform the test with 20 L each of
under the Liquid Chromatography under the following
conditions and calculate the ratios, QT and QS , the
peak area of sodium salicylate to that of the internal
respectively.
Amount (mg) of sodium salicylate (C7H5NaO3)
Q
= amount (mg) of Sodium Salicylate RS T
QS
Anhydrous Caffeine RS and dissolve in water to make
100 mL.
chromatography. (5 m to 10 m in particle diameter)
Mobile phase: A mixture of water, methanol and
acetic acid (50 : 50 : 1).
time of sodium salicylate is about 8.5 minutes.
Selection of column: Proceed with 10 L of the
standard solution under the above operating conditions.
Use the column from which the internal standard and
sodium salicylate are eluted in this order with the resolution between their peaks being no less than 4.0.
tight containers.
melting point of the residue is between 158 C and 161

C.
Dissolution Test Perform the test with 1 tablet of Sodium Salicylate Tablets, at 100 revolution per minute
according to Method 1 under Dissolution Test using
900 mL of water. Filter after 45 minutes, if necessary
dilute with water and use this solution as the test solution. Separately, weigh exactly a portion of Sodium Salicylate RS, dissolve in the test solution, make the same
concentration with the test solution and use this solution as the standard solution. With the test solution and
the standard solution, determine the absorbances as directed under the Ultraviolet-visible Spetrophotometry,
at maximum absorption wavelength around 266 nm.
The dissolution rate of Sodium Salicylate Tablets for 45
ment.
Assay Transfer accurately not less than 20 tablets of

Sodium Salicylate Tablets into a volumetric flask. Add
100 mL of water and allow to stand with frequent agitation until complete dissolution and add water to make
200 mL. Filter this solution with dried filter paper. Discard the first 10 mL of the filtrate, weigh accurately a
volume of the filtrate, equivalent to about 0.5 g of sodium salicylate (C7H5NaO3), add water to make 25 mL
in a separatory funnel, if necessary. Add 75 mL of ether
and 10 drops of bromophenol blue TS, shake well, titrate with 0.1 mol/L hydrochloric acid VS until green
color appears in water layer. Transfer the water layer in
a small flask, wash ether layer once with 5 mL of water,
collect washings and water layer. Add 20 mL of ether in
water layer and titrate with shaking until the water
layer becomes green.

= 16.010 mg of C7H5NaO3
Sodium Salicylate Tablets
Sodium Salicylate Tablets contain not less than 95.0%

and not more than 105.0% of the labeled amount of sodium salicylate (C7H5NaO3: 160.10).
Sodium Thiosulfate Hydrate

Tablets, with Sodium Salicylate.
Identification (1) To a portion of powdered Sodium
Salicylate Tablets, equivalent to about 1 g of Sodium
Salicylate according to the labeled amount, reconstitute
in 20 mL of water and filter. The filtrate responds to the
Qualitative Test for sodium salt and salicylate.
(2) Add a little more volume of 3 mol/L hydrochloric acid TS in 10 mL of the filtrate (1), then produced
precipitate, filter, wash with a little cold water until no
respond of chloride and dry at 105 C for 1 hour: the
Na2S2O35H2O: 248.18
Sodium Thiosulfate Hydrate, when dried, contains not
less than 99.0% and not more than 101.0% of sodium
thiosulfate (Na2S2O3: 158.11).
Description Sodium thiosulfate occurs as a colorless
Sodium Thiosulfate is very soluble in water and very
ether.
Sodium Thiosulfate effervesces in dry air and is deli-
KP 9 887
quescent in moist air.

Identification A solution of Sodium Thiosulfate (1 in
and for thiosulfate.
pH Dissolve 1.0 g of Sodium Thiosulfate in 10 mL of
water: the pH of the solution is between 6.0 and 8.0.
1.0 g of Sodium Thiosulfate in 10 mL of water: the solution is clear and colorless.
(2) Heavy metalsDissolve 1.0 g of Sodium Thiosulfate in 10 mL of water, add slowly 5 mL of dilute
hydrochloric acid and evaporate in a water-bath to dryness. Add 15 mL of water to the residue, boil gently for
2 minutes and filter. Heat the filtrate to boil and add
bromine TS to the hot filtrate to produce a clear solution and provide a slight excess of bromine. Boil the
solution to expel the bromine. After cooling, add 1 drop
of phenolphthalein TS and add drop-wise sodium hydroxide TS until a slight red color is produced. Add 2
mL of dilute acetic acid and water to make 50 mL. Perform the test. Prepare the control solution as follows: to
2.0 mL of standard lead solution, add 2 mL of dilute
acetic acid and water to make 50 mL (not more than 20
ppm).
(3) CalciumDissolve 1.0 g of Sodium Thiosulfate in 10 mL of water, add 2 mL of ammonium oxalate
TS and allow to stand for 4 minutes: no turbidity is
produced.
(4) ArsenicTo 0.40 g of Sodium Thiosulfate, add
3 mL of nitric acid and 5 mL of water, evaporate in a
water-bath to dryness and perform the test with the residue. Prepare the test solution according to Method 2
Loss on Drying Between 32.0% and 37.0% (1 g, dry
first over silica gel for 2 hours in vacuum and then dry
at 105 C for 3 hours).
Assay Weigh accurately 0.4 g of Sodium Thiosulfate,
with 0.05 mol/L iodine VS (indicator: 1 mL of starch
TS).

= 15.811 mg of Na2S2O3.
Sodium Thiosulfate Injection

Sodium Thiosulfate Injection is an aqueous solution for
injection. Sodium Thiosulfate Injection contains not
less that 95.0% and not more than 105.0% of the labeled amount of sodium thiosulfate (Na2S2O35H2O:
248.18).
Method of Preparation Prepare as directed under Injections, with Sodium Thiosulfate.

Description Sodium Thiosulfate Injection is a clear,
colorless liquid.
Identification Sodium Thiosulfate Injection responds
to the Qualitative Tests for sodium salt and for thiosulfate.
Pyrogen Test Perform the test with Sodium Thiosulfate Injection stored in a container in a volume exceeding 10 mL: it meets the requirement.
Assay Measure exactly a volume of Sodium Thiosulfate Injection, equivalent to about 0.5 g of sodium thiosulfate (Na2S2O35H2O), add water to make 30 mL
and titrate with 0.05 mol/L iodine VS (indicator: 1 mL
of starch TS).

= 24.818 mg of Na2S2O35H2O
tainers.
Sodium Valproate
H3CH2CH2C
CHCO2Na
H3CH2CH2C
C8Hl5NaO2: 166.19
Sodium Valproate, when dried, contains not less than
98.5% and not more than 101.0% of Sodium valproate
(C8Hl5NaO2).
Description Sodium Valproate is a white, crystalline
powder, has a characteristic odor and a slightly bitter
taste.
Sodium Valproate is very soluble in water, freely soluble in formic acid, in ethanol, in dehydrated ethanol
or in glacial acetic acid and practically insoluble in
chloroform or in ether.
Sodium Valproate is hygroscopic.

Identification (1) To 1 mL of a solution of Sodium
Valproate in dehydrated ethanol (1 in 200), add 4 mL of
hydroxylamine perchlorate-dehydrated ethanol TS and
1 mL of N,N'-dicyclohexyl-carbodiimide-dehydrated
ethanol TS, shake well and allow to stand in lukewarm
water for 20 minutes. After cooling, add 1 mL of ferric
perchlorate-dehydrated ethanol TS and shake: a purple
color is observed.
(2) To 5 mL of a solution of Sodium Valproate (1 in
20), add 1 mL of a solution of cobaltous nitrate (1 in
20) and warm in a water-bath: a purple precipitate is
formed.
(3) Dissolve 0.5 g of Sodium Valproate in 5 mL of
water, add 5 mL of chloroform and 1 mL of 2 mol/L
hydrochloric acid TS and shake vigorously for 1 minute.
Proceed the same procedure with Sodium Valproate RS.
After allowing to stand, separate the chloroform layers,
dehydrate the chloroform layers with anhydrous sodium sulfate and filter. Evaporate the solvent of the filtrates and determine the infrared spectra of the residues
as directed in the liquid film method under the Infrared
(4) A solution of Sodium Valproate (1 in 10) responds to the Qualitative Tests for sodium salt.
pH Dissolve 1.0 g of Sodium Valproate in 20 mL of
1.0 g of Sodium Valproate in 10 mL of water: the solution is clear and colorless.
(2) ChlorideDissolve 0.5 g of Sodium Valproate
in 25 mL of ethanol and add 6 mL of dilute nitric acid
control solution as follows: to 0.70 mL of 0.01 mol/ L
hydrochloric acid VS, add 25 mL of ethanol, 6 mL of
dilute nitric acid and water to make 50 mL (not more
than 0.050%).
(3) SulfateDissolve 0.5 g of Sodium Valproate in
25 mL of ethanol and add 1 mL of dilute hydrochloric
acid and water to make 50 mL. Perform the test. Prepare the control solution as follows: to 0.50 mL of
0.005 mol/L sulfuric acid VS, add 25 mL of ethanol, 1
mL (not more than 0.048%).
(4) Heavy metalsDissolve 2.0 g of Sodium Valproate in 44 mL of water, shake with 6 mL of dilute
hydrochloric acid, allow to stand for 5 minutes and filter. Discard the first 5 mL of the filtrate, neutralize the
subsequent 25 mL with ammonia TS and add 2 mL of
dilute acetic acid and water to make 50 mL. Perform
the test. Prepare the control solution as follows: to 2.0
mL of standard lead solution, add 2 mL of dilute acetic
acid and water to make 50 mL (not more than 20 ppm).
(5) ArsenicDissolve 2.0 g of Sodium Valproate in
10 mL of water, shake with 10 mL of dilute hydrochloric acid, allow to stand for 5 minutes and filter. Discard
the first 5 mL of the filtrate and perform the test with
the subsequent 10 mL as the test solution (not more

than 2 ppm).
(6) Related substancesDissolve 0.10 g of Sodium Valproate in 10 mL of a mixture of formic acid
and chloroform (1 : 1) and use this solution as the test
solution. Pipet 1.0 mL of the test solution, add a mixture of formic acid and chloroform (1:1) to make exactly 200 mL and use this solution as the standard solution.
Perform the test with 2 L each of the test solution and
the standard solution as directed under the Gas Chromatography according to the following conditions. Determine each peak area of both solutions by the automatic integration method: the total area of all peaks
other than the area of the valproic acid from the test solution is not larger than the peak area of the valproic
acid from the standard solution.
and about 2 m in length, packed with siliceous earth for
gas chromatography (150 m to 180 m in particle diameter) coated with diethylene glycol adipate ester for
gas chromatography and phosphoric acid at the ratios
of 5% and 1%, respectively.
about 145 C.
time of valproic acid is between 6 minutes and 10 minutes.
System suitability
System performance: Mix 1 mL of the test solution and 4 mL of a solution of n-valerianic acid in a
mixture of formic acid and chloroform (1 : 1) (1 in
1000). When the procedure is run with 2 L of this solution under the above operating conditions, nvalerianic acid and valproic acid are eluted in this order
with a resolution between their peaks being not less
than 3.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of valproic acid obtained
and 10 mm.
as the retention time of valproic acid after the solvent
peak.
hours).
Assay Weigh accurately about 0.2 g of Sodium Valproate, previously dried, dissolve in 80 mL of glacial
KP 9 889
= 16.619 mg of C8H15NaO2
D-Sorbitol
OH
HOH2C
OH
OH
OH
CH2OH
C6H14O6: 182.17
D-Sorbitol, when dried, contains not less than 97.0%
and not more than 101.0% of D-sorbitol (C6H14O6).
Description D-Sorbitol is a white granule, powder, or

crystalline mass, is odorless and has a sweet taste with
a cold sensation.
D-Sorbitol is very soluble in water, sparingly soluble in
D-Sorbitol is hygroscopic.
Identification (1) To 1 mL of a solution of D-Sorbitol
(7 in 10), add 2 mL of ferrous sulfate TS and 1 mL of a
solution of sodium hydroxide (1 in 5): a blue-green
color is observed, but no turbidity is produced.
(2) Shake thoroughly 1 mL of a solution of DSorbitol (1 in 20) with 1 mL of a freshly prepared solution of catechol (1 in 10), add rapidly 2 mL of sulfuric
acid and shake: a reddish purple to red-purple color
immediately is observed.
(3) Boil 0.5 g of D-Sorbitol with 10 mL of acetic
anhydride and 1 mL of pyridine under a reflux condenser for 10 minutes, cool, shake with 25 mL of water
and allow to stand in a cold place. Transfer the solution
to a separatory funnel, extract with 30 mL of chloroform and evaporate the extract on a water-bath. Add 80
mL of water to the oily residue, heat for 10 minutes in a
water-bath, then filter the hot mixture. After cooling,
collect the produced precipitate through a glass filter
(G3), wash with water, recrystallize once from ethanol
and dry in a desiccator (in vacuum, silica gel) for 4
hours: the precipitate melts between 97 C and 101 C.
Purity (1) Clarity and color of solution and acidity
or alkalinityDissolve 5 g of D-Sorbitol in 20 mL of
water by warming with shaking: the solution is clear,
colorless and neutral.
(2) ChloridePerform the test with 2.0 g of DSorbitol. Prepare the control solution with 0.30 mL of
0.005%).
(3) SulfatePerform the test with 4.0 g of DSorbitol. Prepare the control solution with 0.50 mL of
(4) Heavy metalsProceed with 5.0 g of DSorbitol according to Method 1 and perform the test.

(5) NickelDissolve 0.5 g of D-Sorbitol in 5 mL of
water, add 3 drops of dimethylglyoxime TS and 3 drops
of ammonia TS and allow to stand for 5 minutes: no
red color develops.
D-Sorbitol according to Method 1 and perform the test
(not more than 1.3 ppm).
(7) GlucoseDissolve 20.0 g of D-Sorbitol in 25
mL of water and boil gently with 40 mL of Fehling's
TS for 3 minutes, After cooling, filter the supernatant
liquid cautiously through a glass filter (G4), leaving the
precipitate in the flask as much as possible, wash the
precipitate with hot water until the last washings no
longer show an alkali reaction and filter the washings
through the glass filter. Dissolve the precipitate in 20
mL of ferric sulfate TS in a flask, filter through the
glass filter and wash with water. Combine the filtrate
and the washings, heat at 80 C and titrate with 0.02
mol/L potassium permanganate VS: not more than 6.3
mL is consumed.
(8) SugarsDissolve 20.0 g of D-Sorbitol in 25
mL of water and heat with 8 mL of dilute hydrochloric
acid under a reflux condenser in a water-bath for 3
hours. After cooling, add 2 drops of methyl orange TS,
followed by sodium hydroxide TS until an orange color
develops and add water to make 100 mL. Boil gently
10 mL of this solution with 10 mL of water and 40 mL
of Fehling's TS for 3 minutes and proceed as directed in
(7).
Residue on Ignition Not more than 0.02% (5 g),
Assay Weigh accurately about 0.2 g of D-Sorbitol,
previously dried, dissolve in water and add water to
make exactly 100 mL. Pipet 10.0 mL of the solution into an iodine flask, add exactly 50 mL of potassium periodate TS and heat for 15 minutes in a water-bath. After cooling, add 2.5 g of potassium iodide, immediately
stopper tightly and shake well. Allow to stand for 5 minutes in a dark place and titrate with 0.1 mol/L sodium
thiosulfate VS (indicator: 3 mL of starch TS). Perform

= 1.8217 mg of C6H14O6
D-Sorbitol
Solution
D-Sorbitol Solution Contains not less than 97.0% and

not more than 103.0% of the labeled amount of Dsorbitol (C6H14O6: 182.17).

Description D-Sorbitol Solution is a clear, colorless
liquid, is odorless and has a sweet taste.
D-Sorbitol is miscible with water, ethanol, glycerin or
propylene glycol.
D-Sorbitol Solution sometimes separates crystalline
masses.
Identification (1) Take a volume of D-Sorbitol Solution, equivalent to 0.7 g of D-Sorbitol according to the
labeled amount, proceed as directed in the Identification (1) under D-Sorbitol.
(2) Take a volume of D-Sorbitol Solution, equivalent to 1 g of D-Sorbitol according to the labeled
amount, add water to make 20 mL. Pipet 1 mL of this
solution, proceed as directed in the identification (2)
under D-Sorbitol.
Purity (1) Acidity or alkalinityD-Sorbitol Solution
is neutral.
(2) ChlorideProceed with a volume of D-Sorbitol
Solution, equivalent to 2.0 g of D-Sorbitol according to
the labeled amount, proceed as directed in the Purity
(2) under D-Sorbitol (not more than 0.005%).
(3) SulfateTake a volume of D-Sorbitol Solution,
equivalent to 4.0 g of D-Sorbitol according to the labeled amount, proceed as directed in the Purity (3) under D-Sorbitol (not more than 0.006%).
(4) Heavy metalsProceed with a volume of DSorbitol Solution, equivalent to 5.0 g of D-Sorbitol according to the labeled amount, proceed as directed in
the Purity (4) under D-Sorbitol (not more than 5 ppm).
(5) NickelTake a volume of D-Sorbitol Solution,
equivalent to 0.5 g of D-Sorbitol according to the labeled amount, proceed as directed in the Purity (5) under D-Sorbitol.
(6) ArsenicTake a volume of D-Sorbitol Solution,
equivalent to 1.5 g of D-Sorbitol according to the labeled amount, dilute with water or concentrate to 5 mL
on a water-bath, if necessary, cool and perform the test
using this solution as the test solution (not more than
1.3 ppm).
(7) GlucoseTake a volume of D-Sorbitol Solution,
equivalent to 20.0 g of D-Sorbitol according to the labeled amount, dilute with water or concentrate to 40
mL on a water-bath, if necessary, add 40 mL of Fehlings TS and proceed as directed in the Purity (7) under
D-Sorbitol.
(8) SugarsTake a volume of D-Sorbitol Solution,
equivalent to 20.0 g of D-Sorbitol according to the labeled amount, proceed as directed in the Purity (8) under D-Sorbitol.
Residue on Ignition Take exactly a volume of DSorbitol Solution, equivalent to 5 g of D-Sorbitol according to the labeled amount, add 3 to 4 drops of sulfuric acid and heat gently to evaporate. Ignite to burn,
cool and perform the test with the residue: not more
than 1.0 mg.
Assay Take exactly a volume of D-Sorbitol Solution,

equivalent to about 5 g of D-sorbitol (C6H14O6) according to the labeled amount and add water to make exactly 250 mL. Pipet 10.0 mL of this solution, add water to
make exactly 100 mL. Pipet 10.0 mL of the solution into an iodine flask and proceed as directed in the Assay
under D-Sorbitol.

= 1.8217 mg of C6H14O6
Spectinomycin Hydrochloride
Hydrate
OH
H
H
N
H
O
CH3
H3C
OH
O
H
OH
HN
CH3
2HCl
5H2O
C14H24N2O72HCl5H2O: 495.35
Spectinomycin Hydrochloride Hydrate is the hydrochloride of a substance having antibacterial activity produced by the growth of Streptomyces spectabilis.
Spectinomycin Hydrochloride Hydrate contains not
less than 603 g (potency) of spectinomycin
(C14H24N2O7: 332.35) per mg, calculated on the anhydrous basis
Description Spectinomycin Hydrochloride Hydrate
is a white crystalline powder.
Spectinomycin Hydrochloride Hydrate is freely soluble
in water, and sparingly soluble in ethanol, in acetone, in
chloroform or in benzene.
of Spectinomycin Hydrochloride Hydrate and Spectinomycin Hydrochloride RS as directed in the paste method under Infrared Spectrophotometry, both spectra
exhibit similar intensities of absorption at the same
wave numbers.
(2) The aqueous solution of Spectinomycin Hydrochloride Hydrate responds to the Qualitative Tests
for chloride.
(3) Determine the retention times according to the
procedure of Assay: the retention time of the principal
peak in the chromatogram obtained with test solution is
the same as that of the principal peak in the chromatogram obtained with the standard solution.
of Streptomycin Hydrochloride Hydrate in 10 mL of
KP 9 891
Spironolactone
Sterility Test It meets the requirement, when Spectinomycin Hydrochloride Hydrate is used in a sterile
preparation.
O
H3C
Bacterial Endotoxins Less than 0.09 EU per mg (potency) of spectinomycin, when Spectinomycin Hydrochloride Hydrate is used in a sterile preparation.
H3C
Histamine It meets the requirement, when Spectinomycin Hydrochloride Hydrate is used in a sterile preparation. Weigh appropriate an amount of Spectinomycin
Hydrochloride Hydrate, dissolve in Isotonic Sodium
Chloride Injection, make the solution so that each mL
contains 15 mg, and use the solution as the test solution.
Water Not less than 16.0 % and not more than
20.0 % (0.1 g, volumetric titration, direct titration).
of Spectinomycin Hydrochloride Hydrate and Spectinomycin Hydrochloride RS, dissolve each in the 1.0
mL of internal standard solution and 1.0 mL of hexamethyldisilazane with shaking for 1 hour, and use
these solutions as the test solution and the standard solution, respectively. Perform the test with 0.5 L each
under the Gas Chromatography according to the following operating conditions, and determine the ratios,
QT and QS, of the peak area of spectinomycin to that of
Amount [g (potency)] of spectinomycin (C14H24N2O7)

= Amount [g (potency)] of Spectinomycin HydrochloQ
ride RS T
QS
Internal standard solutionWeigh 50 mg of triphenylantimony, dissolve in dimethylformamide to make 25
mL.
Detector: A hydrogen flame-ionization detector
Column: A glass column, about 3 mm in inside diameter and about 600 mm in length, packed with Column Gas-chrom Q (80/100 mesh) for gas chromatography impregnated with 5 % SE-52.
about 90 C
Carrier gas: Helium
CH3
C24H32O4S: 416.57
Spironolactone, when dried, contains not less than
97.0% and not more than 103.0% of spironolactone
(C24H32O4S).
Description Spironolactone is a white to pale yellowbrown, fine powder.
Spironolactone is freely soluble in chloroform, soluble
in ethanol, slightly soluble in methanol and practically
insoluble in water.
Melting pointBetween 198 C and 207 C. In a
bath at about 125 C, continue the heating so that the
temperature rises at a rate of about 10 C per minute in
the range between 140 C and 185 C and when the
temperature is near the expected melting range, reduce
the heating so that the temperature rises at a rate of
about 3 C per minute.
of solutions of Spironolactone and Spironolactone RS,
in methanol (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibits
(2) Determine the infrared spectra of Spironolactone and Spironolactone RS, previously dried, as directed in the potassium bromide disk method under the
If any difference appears between the spectra, dissolve
Spironolactone and Spironolactone RS in methanol, respectively, then evaporate methanol to dryness and repeat the test on the residues.
D : Between -33 and 37 (after drying, 0.25 g, chloroform, 25 mL, 200 mm).
Purity (1) Mercapto compoundsShake 2.0 g of
Spironolactone with 20 mL of water and filter. To 10
mL of the filtrate, add 1 mL of starch TS and 0.05 mL
of 0.01 mol/L iodine VS and mix: a blue color is observed.
(2) Related substancesDissolve 0.20 g of Spironolactone in 10 mL of ethanol and use this solution as
the test solution. Pipet exactly 1 mL of this solution,
add ethanol to make exactly 100 mL and use this solution as the standard solution. Perform the test with
these solutions as directed under the Thin-layer Chromatography. Spot 5 L each of the test solution and the
chromatography. Develop the plate with n-butyl acetate
to a distance of about 15 cm and air-dry the plate.
Spray evenly a solution of sulfuric acid in methanol (1
in 10) on the plate and heat the plate at 105 C for 10
minutes: any spot other than the principal spot from the
test solution is not more intense than the spot from the
standard solution.
hours).
Assay Weigh accurately about 50 mg each of Spironolactone and Spironolactone RS, previously dried at
105 C for 2 hours and dissolve separately in methanol
to make exactly 250 mL. Pipet exactly 5 mL each of
these solutions, add methanol to make exact1y 100 mL
and use theses solutions as the test solution and the
under the Ultraviolet-visible Spectrophotometry and
determine the absorbances, AT and AS , of these solutions at 238 nm.
Amount (mg) of spironolactone (C24H32O4S)

A
= amount (mg) of Spironolactone RS T
AS
tight containers.
Stannous Fluoride
SnF2: 156.71
Stannous Fluoride contains not less than 71.2% of
stannous tin (Sn2+: 118.71), and not less than 22.3%
and not more than 25.5% of fluoride (F: 19.00), calculated on the dried basis.
(3) Add 1 drop of a solution of Stannous Fluoride (1 in

100) to 2 drops of mercuric chloride TS: a white, silky
precipitate is formed. On further addition of the solution (1 in 100), a brown-black precipitate is produced.
pH Dissolve about 0.1 g of Stannous Fluoride in 25
mL of fresh boiled water: the pH of this solution is between 2.8 and 3.5.
Purity
(1) Water-insoluble substancesTransfer
about 10 g of Stannous Fluoride, accurately weighed, to
a plastic beaker, add 200 mL of water and stir with a
plastic rod for 3 minutes, or until no more solid dissolves. Filter through a tared filtering crucible and
wash thoroughly, first with ammonium fluoride solution (1 in 100), then with water. Dry the residue at 105
C for 4 hours, cool and weigh: not more than 0.2%.
(2) AntimonyRhodamine B solutionDissolve
20 mg of rhodamine B in 200 mL of 0.5 mol/L hydrochloric acid.
Standard solutionWeigh accurately about 55.0

mg of antimony potassium tartrate, dissolve in water to
make exactly 200 mL. Pipet exactly 5 mL of this solution, add 6 mol/L hydrochloric acid to make exactly
Test solution Weigh accurately about 1.0 g of
Stannous Fuloride, add 6 mol/L hydrochloric acid to
ProcedurePipet exactly 5 mL each of the test solution and the standard solution into separatory funnels,
add 15 mL of hydrochloric acid and 1 g of ceric sulfite
and allow to stand for 5 minutes, with occasional shaking. Add 0.5 g of hydroxylamine hydrochloride and
shake for 1 minute. Pipet 15 mL of isopropyl ether into
the mixture, shake for 30 seconds, add 7 mL of water
and mix. Cool in a water-bath at room temperature for
10 minutes, shake for 30 seconds, allow the layers to
separate and discard the aqueous layer. Add 20 mL of
Rodamin B solution, shake for 30 seconds and discard
the aqueous layer again. Decant the ether layer from the
top of separatory funnel and centrifuge, if necessary, to
obtain a clear solution. Perform the test with the ether
layer obtained from the test solution and the standard
solution at the wavelength of a maximum absorbance at
about 550 nm, as directed under the Ultraviolet-visible
spectrophotometer, using water as the blank: the absorbance of the test solution does not exceed that of the
standard solution (no more than 0.005%).
Description Stannous Fluoride is a white crystalline

powder, has a bitter and salty taste.
Stannous Fluoride is freely soluble in water and practically insoluble in ethanol, ether or chloroform.

hours).
Identification (1) To 5 mL of a solution of Stannous

Fluoride in water (1 in 100) in a test tube, add 2 mL of
calcium chloride TS: a fine, white precipitate of calcium fluoride is produced.
(2) Mix on a spot plate, 2 drops of a solution of Stannous Fluoride (1 in 100) with 2 drops of silver nitrate
TS: a brown-black precipitate is produced.
Assay (1) Stannous ionTransfer about 0.25 g of

Stannous Fluoride, accurately weighed, to an Erlenmeyer flask and add 300 mL of hot, freshly boiled 3
mol/L hydrochloric acid. While passing a stream of an
oxygen-free inert gas over the surface of the liquid,
swirl the flask of dissolve the Stannous Fluoride and
cool to room temperature, Add 5 mL of potassium
KP 9 893
iodide TS and titrate in an inert atmosphere with 0.05

mol/L potassium iodide-iodate VS, adding 3 mL of
starch TS as the endpoint is approached.
NH
NH
OH
Solution ADissolve 3.16 g of trisodium 4,5dihydroxy-3-(p-sulfophenylazo)-2,7-naphthalen disulfonate in 550 mL of water.

Solution BDissolve 0.113 g of oxychlorozirconium in 50 mL of water, add 350 mL of hydrochloric acid to make exactly 500 mL.
Solution CDilute 50 mL of Solution A with 500
mL of water and 35 mL of hydrochloric acid.
Solution DMix equal volume of Solution A with
Solution B and preserve in brown bottle.
Solution ETo 10.0 mL of Solution D, add water
to make exactly 100 mL.
Streptomycin Sulfate
OH
OH
Each mL of 0.05 mol/L potassium iodide-iodate VS

= 5.935 mg of Sn2+
(2) FluorideDissolve about 0.1 g of Stannous
Fluoride, accurately weighed, in 50 mL of water, shake
vigorously for 5 minutes and add water to make exactly
250 mL. Pipet exactly 5 mL of this solution, add water
solution. Separately, weigh accurately a certain amount
of Stannous Fluoride RS, dissolve in water and use this
solution as the standard solution, containing about 10
g of fluorine per mL. Pipet 1.0, 2.0, 3.0 and 4.0 mL
volumes of the standard solution in volumetric flasks,
add respectively 10.0 mL of Solution D and water to
make 100 mL each and mix. Determine the absorbances of each of these solutions and Solution E at 590
nm as directed under the Ultraviolet-visible Spectrophotometry, using Solution C as the blank. Subtract the
absorbance of Solution E from those of the fluoridecontained solutions and make a standard curve of content of fluoride (g) with these absorbances. Separately,
pipet 5.0 mL of the test solution, handle as the same
method above, obtain the fluoride content (g) of 5 mL
of the test solution from the standard curve.
NH2
HN
NH
H2N
CHO
3H2SO4
CH3
HO
CH3
HN
OH
HO
OH
(C21H39N7O12)23H2SO4: 1457.38
Streptomycin Sulfate is the sulfate of an aminoglycoside substance having antibacterial activity produced by
the growth of Streptomyces griseus.
Streptomycin Sulfate contains not less than 650 g (potency) of streptomycin (C21H39N7O12: 581.57) per mg,
calculated on the dried basis
Description Streptomycin Sulfate is a white to light
yellowish white powder, and is odorless.
Streptomycin Sulfate is freely soluble in water, very
ether.
Identification (1) To 5 mL of aqueous solution of
Streptomycin Sulfate (1 in 100) add 1 mL of ninhydrin
TS and 0.5 mL of pyridine, heat for 10 minutes: a purple color is developed.
(2) To 4 mg of 5 mL of Streptomycin Sulfate add 2
mL of sodium hydroxide solution (1 in 200), heat in
water bath for 10 minutes, neutralize the solution with
diluted hydrochloric acid (1 in 100), add 2 to 3 drops of
ferric(III) chloride solution (1 in 100): a purple color is
developed.
(3) To 5 mL of aqueous solution of Streptomycin
Sulfate (1 in 100) add 0.5 mL of 1 mol/L sodium hydroxide TS. To this solution add 1 mL of 0.1 % naphthol70 % ethanol solution and 2 to 3 drops of sodium hypochlorate: a red color is developed.
(4) To an aqueous solution of Streptomycin Sulfate
(1 in 5) add 1 drop of barium chloride TS: a white precipitate is developed.
of Streptomycin Sulfate in 10 mL of water is between
4.5 and 7.0.
Sterility Test It meets the requirement, when Streptomycin Sulfate is used in a sterile preparation.
streptomycin, when Streptomycin Sulfate is used in a
sterile preparation.
Histamine It meets the requirement, when Streptomycin Sulfate is used in a sterile preparation. Weigh
appropriate amount of Streptomycin Sulfate, dissolve

in Isotonic Sodium Chloride Injection, make the solution contain 3.0 mg per mL, and use the solution as the
test solution.

(3) Weigh accurately about 20 mg (potency) of
Streptomycin Sulfate, and dissolve in sterile distilled
water to make the solution so that each mL contains
400 g (potency), and use the solution as the test stock
solution. Take exactly a suitable amount of the test
stock solution, add 0.1 mol/L phosphate buffer solution,
pH 8.0 to make solutions so that each mL contains 8.0
g (potency) and 2.0 g (potency), and use these solutions as the high concentration test solution and the low
concentration test solution, respectively. Separately,
weigh accurately about 20 mg (potency) of Streptomycin Sulfate RS, previously dried, dissolve in sterile distilled water to make the solution so that each mL contains 400 g (potency), and use the solution as the
standard stock solution. Keep the standard stock solution between 5 C and 15 C, and use within 30 days.
Take exactly a suitable amount of the standard stock
solution, add 0.1 mol/L phosphate buffer solution, pH
8.0 to make solutions so that each mL contains 8.0 g
(potency) and 2.0 g (potency), and use these solutions
as the high concentration standard solution and the low
concentration standard solution, respectively. Perform
the test with these solutions according to the Cylinderplate method (I 8) as directed under Microbial Assay
for Antibiotics.
Sucralfate Hydrate
CH2OR
CH2OR
O
H
H
OR
RO
Al(OH)3
YH2O
CH2OR
H
O
RO
H
OR
H
R=SO3Al(OH)2
OR
C12H30Al8O51S8xAl(OH)3yH2O
Sucralfate Hydrate contains not less than 17.0% and
not more than 21.0% of aluminum (Al: 26.98) and not
less than 34.0% and not more than 43.0% of sucrose
octasulfate ester (C12H22O35S8: 982.80), calculated on
the dried basis.
Description Sucralfate Hydrate is a white powder.

Sucralfate Hydrate is odorless and tasteless.
Sucralfate Hydrate is practically insoluble in water, hot
water, ethanol or ether.
Sucralfate Hydrate dissolves in dilute hydrochloric acid
or Sulfuric acid-sodium hydroxide TS.
Identification (1) To 50 mg of Sucralfate Hydrate in
a small test tube, add 50 mg of fresh pieces of metallic
sodium and melt by careful heating. Immerse the test
tube immediately in 100 mL of water, break the test
tube, shake well and filter. To 5 mL of the filtrate, add 1
drop of Sodium nitroprusside TS: a red-purple color is
observed.
(2) Dissolve 40 mg of Sucralfate Hydrate in 2 mL
of dilute sulfuric acid and add gently 2 mL of Anthrone
TS to make 2 layers: a blue color develops at the zone
of contact and gradually changes to blue-green.
(3) Dissolve 0.5 g of Sucralfate Hydrate in 10 mL
of dilute hydrochloric acid: the solution responds to the
Qualitative Tests for aluminum.
1.0 g of Sucralfate Hydrate in 10 mL of dilute sulfuric
acid: the solution is clear and colorless.
(2) ChlorideDissolve 0.5 g of Sucralfate Hydrate
in 30 mL of dilute nitric acid and heat gently to boiling.
After cooling, add water to make 100 mL and to 10 mL
of this solution, add 3 mL of dilute nitric acid and water
to make 50 mL. Perform the test with this solution as
the test solution . Prepare the control solution with 0.70
0.50%).
(3) Heavy metalsDissolve 1.0 g of Sucralfate
Hydrate in 20 mL of a solution of sodium chloride (1 in
5) and 1 mL of dilute hydrochloric acid and to this solution, add 2 mL of dilute acetic acid and water to make
50 mL. Perform the test with this solution as the test
solution. Prepare the control solution as follows: evaporate 1 mL of dilute hydrochloric acid on a water-bath to
dryness and add 20 mL of a solution of sodium chloride
(1 in 5), 2 mL of dilute acetic acid, 2.0 mL of standard
lead solution and water to make 50 mL (not more than
20 ppm).
(4) Free aluminumTo 3.0 g of Sucralfate Hydrate, add 50 mL of water, heat in a water-bath for 5
minutes, cool and filter. Wash the residue with four 5
mL volumes of water, combine the filtrate with the
washings, add 2 mL of dilute hydrochloric acid and
heat in a water-bath for 30 minutes. After cooling, neutralize the solution with Sodium hydroxide TS, add water to make exactly 100 mL and use this solution as the
test solution. Pipet 50.0 mL of the test solution, add exactly 25 mL of 0.05 mol/L disodium ethylenediaminetetraacetate VS and 20 mL of acetic acid-ammomum
acetate buffer solution, pH 4.5 and boil for 5 minutes.
After cooling, add 50 mL of ethanol and titrate the
excess disodium ethylenediaminetetraacetate with 0.05
mol/L zinc acetate VS until the color of the solution
changes from green-purple through purple to red (indi-
KP 9 895
cator: 3 mL of Dithizone TS). Perform a blank determination and make any necessary correction (not more
than 0.2%).
Each mL of 0.05 mol/ L disodium ethylenediaminetetraacetate VS = 1.3491 mg of Al
(5) ArsenicDissolve 1.0 g of Sucralfate Hydrate
in 5 mL of dilute hydrochloric acid, use this solution as
the test solution and perform the test (not more than 2
ppm).
(6) Related substancesProceed with 50 L of the
test solution obtained in the Assay (2) under Sucrose
octasulfate ester as directed in the Assay (2) under Sucrose octasulfate ester and perform the test as directed
under the Liquid Chromatography. Determine the peak
area of sucrose octasulfate ester from the test solution
and that of a related substance with the relative retention time about 0.7 to the peak of sucrose octasulfate
ester by the automatic integration method and calculate
the ratio of the peak area of the related substance to that
of sucrose octasulfate ester: it is not more than 0.1.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of sucrose octasulfate ester
from 50 L of the standard solution obtained in the Assay (2): Sucrose octasulfate ester composes 60% to
100% of the full scale.
hours).
Acid-Consuming Capacity Weigh accurately about
0.25 g of Sucralfate Hydrate, previously dried and perform the test: the amount of 0.1 mol/L hydrochloric acid VS consumed per g of Sucralfate Hydrate is not less
than 130 mL.
Assay (1) AluminumWeigh accurately about 1 g of
Sucralfate Hydrate, dissolve in 10 mL of dilute hydrochloric acid by warming on a water-bath, cool and
add water to make exactly 250 mL. Pipet exactly 25
mL of this solution, add exactly 25 mL of 0.05 mol/L
disodium ethylenediaminetetraacetate VS and 20 mL of
acetic acid-ammonium acetate buffer solution, pH 4.5
and boil for 5 minutes. After cooling, add 50 mL of
ethanol and titrate the excess disodium ethylenediaminetetraacetate with 0.05 mol/L zinc acetate VS until the
color of the solution changes from green-purple
through purple to red (indicator: 3 mL of Dithizone TS).
correction.
Each mL of 0.05 mol/L disodium ethylenediaminetetraacetate VS = 1.3491 mg of Al

(2) Sucrose octasulfate esterWeigh accurately
about 0.55 g of Sucralfate Hydrate, add exactly 10 mL
of Sulfuric acid-sodium hydroxide TS, shake vigorously and dissolve with ultrasonic wave at below 30 C for
5 minutes. To this solution, add 0.1 mol/L sodium hydroxide VS to make exactly 25 mL and use this solution as the test solution. Separately, weigh accurately
about 0.25 g of Potassium Sucrose Octasulfate RS, add
the mobile phase to make exactly 25 mL and use this
solution as the standard solution. Prepare rapidly the
test solution and the standard solution and perform the
test immediately. Proceed with 50 L each of the test
conditions. Determine the peak areas, AT and AS , of
sucrose octasulfate ester for the test solution and the
Amount (mg) of sucrose octasulfate ester (C12H22O35S8)
= amount (mg) of Potassium Sucrose Octasulfate RS,
A
calculated on the dried basis T 0.7633
AS
aminopropylsilanized silica gel for liquid chromatography (about 8 m in particle diameter).
Mobile phase: Dissolve a suitable amount (26 g to
132 g) of ammonium sulfate in 1000 mL of water and
adjust with phosphoric acid to a pH of 3.5. Allow a solution of Potassium Sucrose Octasulfate RS in dilute
hydrochloric acid (1 in 100) to stand at 60 C for 10
minutes, cool and perform the test immediately. Adjust
the amount of ammonium sulfate in the mobile phase
so that the peak of a related substance with the relative
retention time being about 0.7 to that of sucrose octasulfate ester almost becomes close to the base line and
the peak of sucrose octasulfate ester elutes most rapidly.
time of sucrose octasulfate ester is between 6 and 11
minutes.
System suitablilty
System performance: Allow a solution of Potassium Sucrose Octasulfate RS in dilute hydrochloric acid (1 in 100) to stand at 60 C for 10 minutes and cool.
When the procedure is run immediately with 50 L of
resolution between sucrose octasulfate ester and a related substance with the relative retention time being
about 0.7 to sucrose octasulfate ester is not less than 1.5.
System repeatibility: When the test is repeated 6
times with the standard solution under the above operating conditions: the relative standard deviation of the
peak area of sucrose octasulfate ester is not more than
2.0%.
Sulbactam Sodium
O
NaO
H
O
N
CH3
Pyrogen Test It meets the requirement, when Sulbactam Sodium is used in a sterile preparation. Weigh appropriate amount of Sulbactam Sodium, dissolve in water, make the solution so that each mL contains 20 mg
(potency), and use the solution as the test solution. The
of body weight.
CH3
H
S
O
C8H10NNaO5S: 255.22
Sulbactam Sodium contains not less than 823 g (potency) per mg of sulbactam (C8H11NO5S: 233.24), calculated on the anhydrous basis
Description Sulbactam Sodium is a white to yellowish white crystalline powder.
Sulbactam Sodium is freely soluble in water, sparingly
soluble in methanol, slightly soluble in ethanol, and
Identification (1) Weigh 10 mg of Sulbactam Sodium in 1 mL of a mixture of water and methanol (1:1),
spot one drop of this solution, dry, spray hydroiodic acid TS, dry in vacuum at room temperature for 15 minutes, while protected from light; the brown spot develops. To this spot spray 5 % starch TS, the spot turns
to purple color.
(2) Weigh 10 mg of Sulbactam Sodium in 2 mL of
water, add 3 mL of hydroxylamine hydrochlorideethanol TS, allow to stand for 5 minutes, add 1 mL
of acidic ferric ammonium sulfate TS and shake: the
blown clolor deveops.
(3) Determine the absorption spectrum of Sulbactam Sodium as directed in the paste method under
Infrared Spectrophotometry, it exhibits absorption at
the wavenumbers about 1780 cm 1 , 1600 cm 1 , 1410
cm 1 , 1400 cm 1 , 1320 cm 1 , 1300 cm 1 , 1200
cm 1 , and 1130 cm 1 .
4) Sulbactam Sodium responds to the Qualitative Tests
1) for sodium salt.
D : +219 ~ +233(1.0
g, water, 100 mL, 100 mm).
of Sulbactam Sodium in 10 mL of water is between 5.2
and 7.2.
Assay Weigh accurately about 0.1 g of Sulbactam
Sodium and Sulbactam Sodium RS, dissolve each in a
suitable amount of the mobile phase, add exactly 10
mL of the internal standard solution, then add the mobile phase to make 100 mL, and use these solutions as
Perform the test with 10 L of each of the test solution
conditions, and determine the ratios, QT and QS, of the
peak area of sulbactam to that of the internal standard.
Amount [g (potency)] of sulbactam (C8H11NO5S)

Q
= Amount [g (potency)] of Sulbactam RS T
QS
Internal standard solutionA solution of ethyl parahydroxybenzoate in the mobile phase (7 in 1000)
Mobile phase: To 250 mL of acetonitrile add 0.005
mol/L tetrabutylammonium hydroxide TS to make exactly 1000 mL.
time of sulbactam is about 6 minutes.
System suitability
operating conditions, sulbactam and the internal standard are eluted in this order with the resolution between
these peaks being not less than 1.5.
Purity Heavy metals Proceed with 1 g of Sulbactam Sodium according to Method 2 and perform the
Sterility Test It meets the requirement, when Sulbactam Sodium is used in a sterile preparation.
Sulfamethizole
O
H2N
S
O
CH3
NH
N
C9H10N4O2S2: 270.33
KP 9 897
Sulfamethizole, when dried, contains not less than

99.0% and not more than 101.0% of sulfamethizole
(C9H10N4O2S2).
Description Sulfamethizole is a white to yellowish
Sulfamethizole is slightly soluble in ethanol or in glacial acetic acid and practically insoluble in water or in
ether.
Sulfamethizole dissolves in dilute hydrochloric acid or
Sulfamethizole is gradually colored by light.
Identification Determine the infrared spectra of Sulfamethizole and Sulfamethizole RS, previously dried,
Assay Weigh accurately about 0.4 g of Sulfamethizole, previously dried, dissolve in 5 mL of hydrochloric
acid and 50 mL of water, add 10 mL of a solution of
potassium bromide (3 in 10), cool below 15 C and titrate with 0.1 mol/L sodium nitrite VS (potentiometric
titration or amperometric titration, Endpoint Detection
Methods in Titrimetry).

= 27.033 mg of C9H10N4O2S2
Sulfamethoxazole
O
CH3
H2N

0.5 g of Sulfamethizole in 3 mL of sodium hydroxide
TS and 20 mL of water: the solution is clear and colorless.
(2) AcidTo 1.0 g of Sulfamethizole, add 50 mL of
water, warm at 70 C for 5 minutes, allow to stand for 1
hour in an ice-bath and filter. To 25 mL of the filtrate,
add 2 drops of methyl red TS and 0.60 mL of 0.1 mol/L
sodium hydroxide VS: a yellow color is observed.
(3) Heavy metalsProceed with 1.0 g of Sulfamethizole according to Method 2 and perform the test.
Sulfamethizole according to Method 3 and perform the
(5) Related substancesDissolve 0.10 g of Sulfamethizole in acetone to make 10 mL and use this solution as the test solution. Pipet 1.0 mL of the test solution, add acetone to make exactly 50 mL, then pipet 5.0
mL of this solution, add acetone to make exactly 20 mL
mixture of ethyl acetate and glacial acetic acid (20 : 1)
test solution are not more intense than that from the
standard solution.
hours).
S
O
Sulfisomezole
NH
N
C20H11N3O3S: 253.28
Sulfamethoxazole, when dried, contains not less than

99.0% and not more than 101.0% of sulfamethoxazole
(C20H11N3O3S).
Description Sulfamethoxazole is a white crystal or
ctystalline powder, is odorless and has a slightly bitter
taste.
Sulfamethoxazole is very soluble in dimethylformamide, sparingly soluble in ethanol, slightly soluble in
ether and very slightly soluble in water.
Sulfamethoxazole dissolves in sodium hydroxide TS.
Sulfamethoxazole is gradually colored by light.
Identification Determine the infrared spectra of dried
Sulfamethoxazole and Sulfamethoxazole RS as directed in the potassium bromide disk method under the
1.0 g of Sulfamethoxazole in 5 mL of sodium hydroxide TS and 20 mL of water: the solution is clear and colorless.
(2) AcidsTo 1.0 g of Sulfamethoxazole, add 50
mL of water, warm at 70 C for 5 minutes, allow to
stand in an ice-bath for 1 hour and filter. To 25 mL of
the filtrate, add 2 drops of methyl red TS and 0.60 mL
of 0.1 mol/L sodium hydroxide TS: a yellow color is
observed.
(3) Heavy metalsProceed with 1.0 g of Sulfamethoxazole according to Method 2 and perform the test.

Sulfamethoxazole according to Method 3 and perform
(5) Related substancesDissolve 0.2 g of Sulfamethoxazole in strong ammonia water methanol solution (1 in 50) to make 10 mL and use this solution as
strong ammonia water methanol solution (1 in 50) to
make exactly 10 mL. Pipet 1.0 mL of this solution, add
strong ammonia water methanol solution (1 in 50) to
and the standard solution as directed under the Thinlater Chromatography. Spot 5 L each of the test solution and the standard solution on a plate of silica gel
with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate,
acetonitrile and diluted ammonia water (7 in 100) (10 :
8 : 1) to a distance of about 10 cm and air-dry the plate.
standard solution.
hours).
Assay Weigh accurately 0.4 g of Sulfamethoxazole,
previously dried, dissolve in 30 mL of dimethylformamide and 10 mL of water. Titrate with 0.1 mol/L of sodium hydroxide VS (indicator: 0.5 mL of thymolphthalein TS) until the color of the solution is pale blue.
Separately, perform a blank determination using a mixture of 30 mL dimethylformamide and 26 mL of water

= 25.328 mg C20H11N3O3S
Packagin and Storage
Sulfamonomethoxine Hydrate
N
H2N
SO 2NH
Identification Determine the infrared spectra of Sulfamonomethoxine Hydrate and Sulfamonomethoxine

Hydrate RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
1.0 g of Sulfamonomethoxine Hydrate in 5 mL of sodium hydroxide TS and 20 mL of water: the solution is
clear and colorless to pale yellow. Dissolve 0.5 g of
Sulfamonomethoxine Hydrate in 5 mL of sodium hydroxide TS and heat: no turbidity is produced. After
cooling, add 5 mL of acetone: the solution is clear.
(2) Heavy metalsProceed with 1.0 g of Sulfamonomethoxine Hydrate according to Method 2 and perform the test. Prepare the control solution with 2.0 mL
Sulfamonomethoxine Hydrate according to Method 3
(4) Related substancesDissolve 2 mg of Sulfamonoruethoxine Hydrate in ethanol to make exactly 10
mL and use this solution as the test solution. Pipet 1.0
mL of the test solution, add ethanol to make exactly
plate with a mixture of n-butanol and strong ammonia
water (4 : 1) to a distance of about 10 cm and air-dry
the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot
H2O
OCH 3
Sulfamonomethoxine
Description Sulfamonomethoxine Hydrate is a white

to pale yellow crystal, granules or crystalline powder
and is odorless.
Sulfamonomethoxine Hydrate is soluble in acetone,
slightly soluble in ethanol, very slightly soluble in ether
Sulfamonomethoxine Hydrate dissolves in dilute hydrochloric acid or sodium hydroxide TS.
Sulfamonomethoxine Hydrate is gradually colored by
light.
C11H12N4O3S.H2O: 298.32
Sulfamonomethoxine Hydrate, when dried, contains

not less then 99.0% and not more than 101.0% of sulfamonomethoxine (C11H12N4O3S).
Loss on Drying
C, 4 hours).
Between 4.5% and 6.5% (1 g, 105

Assay Weigh accurately 0.5 g of Sulfamonomethoxine Hydrate, previously dried, dissolve in 5 mL of hydrochloric acid and 50 mL of water, add 10 mL of po-
KP 9 899
tassium bromide (3 in 10) and cool under 15 C. Titrate

with 0.1 mol/L of sodium nitrite VS (potentiometric titration or amperometric titration, Endpoint Detection
Methods in Titrimetry).
sodium hydroxide TS (1 in 100000) as directed under


= 28.030 mg of C11H12N4O3SH2O
Purity (1) ChlorideDissolve 2.0 g of Sulfasalazine

in 12 mL of sodium hydroxide TS and 36 mL of water,
add 2 mL of nitric acid, shake and filter. To 25 mL of
the filtrate, add 6 mL of dilute nitric acid and water to
(2) SulfateDissolve 2.0 g of Sulfasalazine in 12
mL of sodium hydroxide TS and 36 mL of water, add 2
mL of hydrochloric acid, shake and filter. To 25 mL of
the filtrate, add 1 mL of dilute hydrochloric acid and
water to make 50 mL and Perform the test. Prepare the
(3) Heavy metalsProceed with 1.0 g of Sulfasalazine according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
(4) ArsenicTake 1.0 g of Sulfasalazine in a decomposition flask, add 20 mL of nitric acid and heat
gently until becomes fluid. After cooling, add 5 mL of
sulfuric acid and heat until white fumes are evolved.
Add, if necessary, 5 mL of nitric acid after cooling and
heat again. Repeat this operation until the solution becomes colorless to slightly yellow. After cooling, add
15 mL of a saturated solution of ammonium oxalate
and heat until white fumes are evolved again. After
cooling, add water to make 25 mL. Perform the test
with 5 mL of this solution as the test solution: the color
of the test solution is not deeper than that of the following standard solution (not more than 10 ppm).

Sulfasalazine
COOH
HO
N
N
Salazosulfapyridine
SO2NH
C18H14N4O5S: 398.39
Sulfasalazine, when dried, contains not less than 96.0%

and not more than 101.0% of sulfasalazine
(C18H14N4O5S).
Description Sulfasalazine is a yellow to yellowbrown, fine powder, is odorless and tasteless.
Sulfasalazine is sparingly soluble in pyridine, slightly
soluble in ethanol, practically insoluble in water, in
chloroform or in ether.
Sulfasalazine dissolves in sodium hydroxide TS.
decomposition).
Identification (1) Dissolve 0.1 g of Sulfasalazine in
20 mL of dilute sodium hydroxide TS: a red-brown
color is observed. This color gradually fades upon gradual addition of 0.5 g of sodium hydrosulfite with
shaking. Use this solution in the following Identification (2) to Identification (4).
(2) To 1 mL of the solution obtained in Identification (1), add 40 mL of water, neutralize with 0.1 mol/L
hydrochloric acid TS and add water to make 50 mL. To
5 mL of this solution, add 2 to 3 drops of dilute ferric
chloride TS: a red color develops and changes to purple,
then fades when dilute hydrochloric acid is added
dropwise.
(3) The solution obtained in Identification (1) responds to the Qualitative Tests for primary aromatic
amines.
(4) To 1 mL of the solution obtained in Identification (1), add 1 mL of pyridine and 2 drops of cupric
sulfate TS and shake. Add 3 mL of water and 5 mL of
chloroform, shake and allow to stand: a green color is
observed in the chloroform layer.
(5) Determine the absorption spectra of the solutions of Sulfasalazine and Sulfasalazine RS in dilute
Standard solutionProceed in the same manner

without Sulfasalazine, transfer 5 mL of the obtained solution to a generator bottle, add exactly 2 mL of standard arsenic solution and proceed in the same manner
as the test solution.
(5) Related substancesDissolve 0.20 g of Sulfasalazine in 20 mL of pyridine and use this solution as
the test solution. Pipet 1.0 mL of this solution, add pyridine to make exactly 100 mL and use this solution as
test solution and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with diluted methanol (9 in
Examine the plate under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot
from the test solution are not more intense than the
spots from the standard solution.
(6) Salicylic acidTo 0.10 g of Sulfasalazine, add
15 mL of ether and shake vigorously. Add 5 mL of di-
lute hydrochloric acid, shake vigorously for 3 minutes,

collect the ether layer and filter. To the water layer, add
15 mL of ether, shake vigorously for 3 minutes, collect
the ether layer, filter and combine the filtrates. Wash
the residue on the filter paper with a small quantity of
ether and combine the washings and the filtrate. Evaporate the ether with the aid of air-stream at room temperature. To the residue, add dilute ferric ammonium sulfate TS, shake and filter, if necessary. Wash the residue
on the filter paper with a small quantity of dilute ferric
ammonium sulfate TS, combine the washings and the
filtrate, add dilute ferric ammonium sulfate TS to make
Separately, weigh accurately 10 mg of Salicylic Acid
hours, dissolve in dilute ferric ammonium sulfate TS to
make exactly 400 mL and use this solution as the standard solution. Determine the absorbances, AT and
AS , of the test solution and the standard solution, respectively, at 535 nm as directed under the Ultravioletvisible Spectrophotometry: Salicylic Acid content is
not more than 0.5%.
Content (%) of salicylic acid (C7H6O3)
A
= amount (mg) of Salicylic Acid RS T 0.05
AS
hours).
Assay Weigh accurately 20 mg of Sulfasalazine, previously dried and perform the test as directed in the
procedure of determination for sulfur under the Oxygen
Flask Combustion Method, using 10 mL of diluted
strong hydrogen peroxide water (1 in 40) as an absorbing liquid.
Each mL of 0.005 mol/L barium perchlorate VS

= 1.9920 mg of C18H14N4O5S
tight containers.
Sulfinpyrazone
N
N
O
S
CH2CH2
C23H20N2O3S: 404.48
Sulfinpyrazone, when dried, contains not less than
98.5% and not more than 101.0% of sulfinpyrazone
(C23H20N2O3S).
Description Sulfinpyrazone is a white to pale yellowish white powder, is odorless and has a bitter taste.
Sulfinpyrazone is freely soluble in glacial acetic acid or
in acetone, soluble in ethanol, slightly soluble in ether
Sulfinpyrazone dissolves in sodium hydroxide TS.
Identification (1) Dissolve 2 mg of Sulfinpyrazone
in 1 mL of glacial acetic acid, add 1 mL of palladium
chloride TS and 2 mL of chloroform and shake: a yellow color is observed in the chloroform layer.
(2) Determine the absorption spectra of the solutions of Sulfinpyrazone and Sulfinpyrazone RS in 0.01
mol/L sodium hydroxide TS (1 in 100000) as directed
same wavelengths.
(3) Determine the infrared spectra of Sulfinpyrazone and Sulfinpyrazone RS, previously dried, as directed in the potassium bromide disk method under the
0.5 g of Sulfinpyrazone in 10 mL of acetone: the solution is clear and colorless. Dissolve 0.5 g of Sulfinpyrazone in 10 mL of sodium hydroxide TS: the solution
(2) Heavy metalsProceed with 2.0 g of Sulfipyrazone according to Method 4 and perform the test.
Sulfinpyrazone according to Method 3 and perform the
(4) Related substancesDissovle 0.10 g of Sulfinpyrazone in 5 mL of acetone and use this solution as
acetone to make exactly 100 mL and use this solution
as the standard solution (1). Pipet 1.0 mL of the test solution, add acetone to make exactly 200 mL and use
this solution as the standard solution (2). Perform the
test with the test solution and the standard solutions (1)
and (2) as directed under the Thin-layer Chromatography. Spot rapidly 5 L each of the test solution and the
standard solutions (1) and (2) on a plate of silica gel
with fluorescent indicator for thin-layer chromatography under a stream of nitrogen. Develop the plate with
a mixture of chloroform and glacial acetic acid (4 : 1)
nm): the most intense spot other than the principal spot
KP 9 901
from the standard solution (1) and the spots other than
the principal and above spots from the test solution are
not more intense than the spot from the standard solution (2).
hours).
second fluid to make exactly 100 mL. Pipet 10.0 mL of

this solution, add the second fluid to make exactly 100
mL and use this solution as the standard solution. Determine the absorbances, AT and AS , of the test solution and the standard solution, respectively, at 259 nm
The dissolution rate of Sulfinpyrazone Tablets in 45
amount of Sulfinpyrazone (C23H20N2O3S)
A
1
= W S T 900
AS C
Assay Weigh accurately about 0.5 g of Sulfinpyrazone, previously dried, dissolve in 40 mL of acetone,
add 40 mL of water and titrate with 0.1 mol/L sodium
hydroxide VS (potentiometric titration, Endpoint Detection Methods in Titrimetry). Perform a blank determination and make any necessary correction.

= 40.45 mg of C23H20N2O3S
Packging and Storage Preserve in well-closed containers.
Sulfinpyrazone Tablets
Sulfinpyrazone Tablets contain not less than 93.0% and
not more than 107.0% of the labeled amount of sulfinpyazone (C23H20N2O3S: 404.48).
Tablets, with Sulfinpyrazone.
Identification (1) Weigh a portion of powdered Sulfinpyrazone Tablets, equivalent to 2 mg of Sulfinpyrazone according to the labeled amount, add 1 mL of glacial acetic acid and shake. To this solution, add 1 mL of
palladium chloride TS and 2 mL of chloroform and
shake: a yellow color is observed in the chloroform
layer.
(2) Determine the absorption spectrum of the test
solution obtained in the Assay as directed under the Ultraviolet-visible Spectrophotometry: it exhibits a maximum between 257 nm and 261 nm.
Dissolution Test Perform the test with 1 tablet of Sulfinpyrazone Tablets at 50 revolutions per minute according to Method 2 under the Dissolution Test, using
900 mL of the second fluid under the Disintegration
Test. Take 20 mL or more of the dissolved solution 45
minutes after starting the test and filter through a membrane filter with pore size of not more 0.8 m. Discard
the first 10 mL of the filtrate, pipet 2.0 mL of the subsequent, add the second fluid to make exactly 20 mL
weigh accurately about 10 mg of Sulfinpyrazone RS,
previously dried at 105 C for 2 hours, dissolve in the
WS : Amount (mg) of Sulfinpyrazone RS,

C: Labeled amount (mg) of Sulfinpyrazone in 1 tablet.

ment.

Sulfinpyrazone Tablets. Weigh accurately a portion of
the powder, equivalent to about 50 mg of sulfinpyrazone (C23H20N2O3S), add 25 mL of methanol and shake
for 15 minutes. To this solution, add 50 mL of sodium
hydroxide TS, shake, cool and add water to make exactly 200 mL. After centrifuging, pipet 4.0 mL of the
supernatant liquid, add water to make exactly 100 mL
weigh accurately about 50 mg of Sulfinpyrazone RS,
previously dried at 105 C for 2 hours, dissolve in 25
mL of methanol, add 50 mL of sodium hydroxide TS
and cool. To this solution, add water to make exactly
200 mL, pipet 4.0 mL of this solution, add water to
make exactly 100 mL and use this solution as the standard solution. Determine the absorbances, AT and
AS , of the test solution and the standard solution, respectively, at 260 nm as directed under the Ultravioletvisible Spectrophotometry.
Amount (mg) of sulfinpyrazone (C23H20N2O3S)
A
= amount (mg) of Sulfinpyrazone RS T
AS
Sulfisoxazole
O
H2N
SO2NH
H3C
CH3
Sulfafurazole
C11H13N3O3S: 267.30
Sulfisoxazole, when dried, contains not less than 99.0%

and not more than 101.0% of sulfisoxazole
(C11H13N3O3S).
Description Sulfisoxazole is a white crystal or crystalline powder, is odorless and has a slightly bitter taste.
Sulfisoxazole is freely soluble in pyridine or in nbutylamine, soluble in methanol, sparingly soluble in
ethanol, slightly soluble in glacial acetic acid and very
Sulifisoxazole dissolves in dilute hydrochloric acid, sodium hydroxide TS or ammonia TS.
Sulifisoxazole is gradually colored by light.
Identification Determine the infrared spectra of Sulfisoxazole and Sulfisoxazole RS, previously dried, as
1.0 g of Sulfisoxazole in 5 mL of sodium hydroxide TS
and 20 mL of water: the solution is clear and colorless
to pale yellow.
(2) AcidTo 1.0 g of Sulfisoxazole, add 50 mL of
water, warm at 70 C for 5 minutes, allow to stand in
an ice-bath for 1 hour and filter. To 25 mL of the filtrate,
add 2 drops of methyl red VS and 0.20 mL of 0.1 mol/L
sodium hydroxide VS: a yellow color is observed.
(3) Heavy metalsProceed with 1.0 g of Sulfisoxazole according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
hours).
Assay Weigh accurately about 1 g of Sulfisoxazole,
previously dried, dissolve in 50 mL of methanol by
warming, cool and titrate with 0.2 mol/L sodium hydroxide VS (indicalor: 3 drops of phenolphthalein TS).
Perform a blank determination using a mixture of 50
mL of methanol and 18 mL of water and make any necessary correction.

= 53.46 mg of C11H13N3O3S
Sulfisoxazole Tablets
Sulfisoxazole Tablets contain not less than 95.0% and
more than 105.0% of labeled amount of sulfisoxazole
(C11H13N3O3S: 267.30).
Tablets, with Sulfisoxazole.
Identification Extract a portion of powdered Tablets,
equivalent to about 1 g of Sulfisoxazole, with 50 mL of
ethanol by boiling in a water-bath for 3 minutes, then
immediately filter into a beaker. Allow to stand until a
quantity of fine, needle-like cystals form. Cool, filter
off the crystals, recrystallize from a small volume of
ethanol and dry at 105 C. Determine the infrared spectra of this crystal and the Sulfinpyrazone RS, as directed in the potassium bromide disk method under the
Dissolution Test Perform the test with 1 tablet of Sulfisoxazole Tablets at 100 revolution per minute according to Method 1 under the Dissolution Test, using 900
mL of the diluted hydrochloric acid (1 in 12.5). Take 20
mL or more of the dissolved solution after 30 minutes
from starting the test and filter through a membrane filter. Discard the first 10 mL of the filtrate, pipet 2.0 mL
of the filtrate, add water to make exactly 100 mL and
use this solution as the test solution. Separately weigh
accurately about 50 mg of Sulfisoxazole RS, dissolve
this in dilute hydrochloric acid (1 in 12.5) and make
exactly 100 mL. Then, pipet 2.0 mL of this solution,
as the standard solution. Determine the absorbances,
AT and AS , of the test solution and the standard solution, respectively, at 267 nm as directed under the Ultraviolet-visible Spectrophotometry.
The dissolution rate of Sulfisoxazole Tablets in 30 minutes is not less than 70%.
The dissolution rate (%) of sulfisoxazole

A
1
(C11H13N3O3S) = W S T 900
AS C
WS : Amount (mg) of Sulfisoxazole RS,
C: Labeled amount (mg) of 1 tablet of Sulfisoxazole Tablets.

ment.

Sulfisoxazole Tablets. Weigh accurately a portion of the
powder, equivalent to about 20 mg of sulfisoxazole
(C11H13N3O3S), add methanol and shake for 15 minutes,
KP 9 903
extract, to make exactly 50 mL and filter. Discard the

first 10 mL of the filtrate, pipet 5.0 mL of filtrate and
8.0 mL of internal standard solution, add methanol to
Sulfisoxazole RS, previously dried at 105 C for 4
hours, dissolve in methanol to make exactly 50 mL, pipet 5.0 mL of this solution and 8.0 mL of internal standard solution, add methanol to make exactly 50 mL and
test with 20 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following conditions and calculated the ratios, QT and QS , of the peak area of
Sulfisoxazole to that of the internal standard for the test
Amount (mg) of sulfisoxazole (C11H13N3O3S)
Q
= amount (mg) of Sulfisoxazole RS T
QS
Internal standard solutionDissolve 20 mg of Anhydrous Caffeine RS in 50 mL of methanol.
inside diameter and about 15 to 30 cm in length,
Mobile phase: The mixture of water, methanol and
acetic acid (70 : 30 : 1).
time of Sulfisoxazole is about 8 minutes.
operating conditions, the internal standard and Sulisoxazole are eluted in this order with a resolution between
their peaks being not less then 2.0.
Identification (1) Ignite Sulfur: it burns with a blue

flame and gives a pungent odor of sulfur dioxide.
(2) Dissolve 5 mg of Sulfur in 5 mL of sodium hydroxide TS by heating in a water-bath, cool and add 1
drop of sodium nitroprusside TS: a blue-purple color is
observed.
(3) Boil 1 mg of Sulfur with 2 mL of pyridine and
0.2 mL of sodium bicarbonate TS: a blue color is observed.
1.0 g of Sulfur in a mixture of 20 mL of a solution of
sodium hydroxide (1 in 6) and 2 mL of ethanol by boiling: the solution is clear. Dissolve 2.0 g of Sulfur in 10
mL of carbon disulfide: the solution is almost clear or
slightly opalescent.
(2) Acid or alkaliShake 2.0 g of Sulfur with 50
mL of freshly boiled and cooled water and add 2 drops
of phenolphthalein TS: no red color is observed. Further add 1.0 mL of 0.1 mol/L sodium hydroxide VS: a
of Sulfur according to Method 3 and perform the test
not more than 0.67 kPa, silica gel, 4 hours).
Assay Weigh accurately about 0.4 g of Sulfur, previously dried, dissolve in 20 mL of potassium hydroxide-ethanol TS and 10 mL of water by boiling, cool and
add water to make exactly 100 mL. Transfer exactly 25
mL of the solution to a 400-mL beaker, add 50 mL of
hydrogen peroxide TS and heat in a water-bath for 1
hour. Acidify the solution with dilute hydrochloric acid,
add 200 mL of water, heat to boil, add hot barium chloride TS drop-wise until no more precipitate is produced
and heat in a water-bath for 1 hour. Collect the precipitate and wash with water until the last washing shows
no opalescence with silver nitrate TS. Dry the precipitate, heat strongly to constant mass and weigh as barium sulfate (BaSO4: 233.39). Perform a blank determination and make any necessary correction.
Amount (mg) of sulfur (S)

= amount (mg) of barium sulfate (BaSO4) 0.13739
Sulfur
S: 32.07
Sulfur, when dried, contains not less than 99.5% and

not more than 101.0% of sulfur (S: 32.07).
Description Sulfur is a pale yellow to yellow powder.
Sulfur is odorless and tasteless.
Sulfur is freely soluble in carbon disulfide and practically insoluble in water, in ethanol or in ether.
Sulpiride
C15H23N3O4S: 341.43
about 10 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): spots other
than the principal spot from the test solution have no
more color than the spot from the standard solution.
When the plate is exposed to iodine vapor for 30 minutes, the spots other than the principal spot from the
test solution have no more color than the spot from the
standard solution.
Sulpiride, when dried, contains not less than 98.5% and

not more than 101.0% of sulpiride (C15H23N3O4S).

hours).
Description Sulpiride is a white, crystalline powder

and is odorless.
Sulpiride is freely soluble in glacial acetic acid or in dilute acetic acid, sparingly soluble in methanol, slightly
soluble in ethanol or in acetone and practically insoluble in water, in ether or in chloroform.
Sulpiride dissolves in dilute hydrochloric acid or 0.05
mol/L sulfuric acid TS.
decomposition).
CONHCH 2
N
OCH 3
C2H5
H2NO 2S
Identification (1) Dissolve 0.1 g each of Sulpiride

and Sulpiride RS in 0.05 mol/L sulfuric acid TS to
make 100 mL. Determine the absorption spectra of
both solutions, prepared by diluting 5 mL each of the
above solutions with water to make 100 mL, as directed
water as the blank: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Sulpiride and
Sulpiride RS as directed in the potassium bromide disk
same wavenumbers.
Assay Weigh accurately about 0.4 g of Sulpiride,

previously dried, dissolve in 80 mL of glacial acetic acid and titrate with 0.1 mol/L perchloric acid VS (indicator: 2 drops of methylrosaniline chloride TS). The end
point of titration is only when the color of the solution
changes from violet through blue to bluish green. Perform a blank determination and make any necessary
correction.

= 34.143 mg of C15H23N3O4S
Sultiame
O
H2N
O
S
N

2.0 g of Sulpiride in 7 mL of dilute acetic acid and add
water to make 20 mL: the solution is clear. Perform the
test as directed under the Ultraviolet-visible Spectrophotometry, using water as the blank: the absorbance at
a wavelength of 450 nm does not exceed 0.020.
(2) Heavy metalsProceed with 2.0 g of Sulpiride
as directed under Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
(3) Related substancesDissolve 50 mg of Sulpiride in 10 mL of methanol and use this solution as the
test solution. Dilute 1 mL of the test solution, accurately measured, with methanol to make exactly 100 mL.
Dilute 5 mL of this solution, accurately measured, with
methanol to make exactly 10 mL and use this solution
test solution and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of n-butanol,
C10H14N2O4S2: 290.36
Sultiame, when dried, contains not less than 98.5% and
not more than 101.0% of sultiame (C10H14N2O4S2).
Description Sultiame is a white crystal or crystalline
powder, is odorless and has a slightly bitter taste.
Sultiame is very soluble in dimethylformamide, freely
soluble in n-butylamine, slightly soluble in methanol or
in ethanol, very slightly soluble in water and practically
insoluble in ether.
Sultiame dissolves in sodium hydroxide TS.
Identification (1) Dissolve 20 mg of Sultiame in 5
mL of water and 1 mL of n-butylamine, add 2 to 3
drops of cupric sulfate TS and shake well. To this solution, add 5 mL of chloroform, shake and allow to stand:
a green color is observed in the chloroform layer.
(2) Mix 0.1 g of Sultiame with 0.5 g of sodium carbonate and melt carefully: the gas evolved changes
moistened red litmus paper to blue. After cooling, crush
KP 9 905
the fused substance with a glass rod, stir with 10 mL of

water and filter. To 4 mL of the filtrate, add 2 drops of
strong hydrogen peroxide water, 5 mL of diluted hydrochloric acid (1 in 5) and 2 to 3 drops of barium chloride TS: a white precipitate is produced.
(3) Determine the absorption spectra of the solutions of Sultiame and Sultiame RS in methanol (1 in
Purity (1) ChlorideDissolve 1.0 g of Sultiame in
20 mL of sodium hydroxide TS by warming, cool and
add 2 mL of glacial acetic acid and water to make 100
mL. After shaking, filter and discard the first 10 mL of
the filtrate. To the subsequent 40 mL, add 6 mL of dilute nitric acid and water to make 50 mL and perform
the test. Prepare the control solution as follows: to 0.25
mL of 0.01 mol/L hydrochloric acid VS, add 8 mL of
sodium hydroxide, 0.8 mL of glacial acetic acid, 6 mL
of dilute nitric acid and water to make 50 mL (not more
than 0.022%).
(2) SulfateDissolve 1.0 g of Sultiame in 20 mL
of sodium hydroxide TS by warming, cool and add 8
mL. After shaking, discard the first 10 mL of the filtrate.
To the subsequent 40 mL, add 1 mL of dilute hydrochloric acid and water to make 50 mL and perform the
test. Prepare the control solution as follows: to 0.40 mL
of 0.005 mol/L sulfuric acid VS, add 8 mL of sodium
hydroxide, 4.2 mL of dilute hydrochloric acid and water to make 50 mL (not more than 0.048%).
(3) Heavy metalsProceed with 2.0 g of Sultiame
Sultiame according to Method 3 and perform the test
(5) Related substancesDisslove 0.10 g of Sultiame in methanol to make exactly 20 mL and use this
of Sulfanilamide in methanol to make exactly 100 mL.
Pipet 10.0 mL of this solution, add methanol to make
Develop the plate with a mixture of chloroform, methanol and strong ammonia water (30 : 8 : 1) to a distance of about 12 cm and air-dry the plate. Examine

hours).
Assay Weigh accurately about 0.8 g of Sultiame, previously dried, dissolve in 70 mL of dimethylformamide
and titrate with 0.2 mol/L tetramethylammonium hydroxide VS (potentiometric titration, Endpoint Detection Methods in Titrimetry). Perform a blank determination and make any necessary correction.

hydroxide VS = 58.07 mg of C10H14N2O4S2
Suxamethonium Chloride
Hydrate
COOCH 2CH 2N(CH 3)3
2Cl
(CH 2)2
2H 2O
COOCH 2CH 2N(CH 3)3
C14H30Cl2N2O42H2O: 397.34
Suxamethonium Chloride Hydrate contains not less
than 98.0% and not more than 101.0% of suxamethonium chloride (C14H30Cl2N2O4: 361.31), calculated on
Description Suxamethonium Chloride Hydrate is a
white and crystalline powder.
Suxamethonium Chloride Hydrate is freely soluble in
water, in methanol or in glacial acetic acid, slightly soluble in ethanol, very slightly soluble in acetic anhydride, and practically insoluble in ether.
Suxamethonium Chloride Hydrate and Suxamethonium
Chloride Hydrate RS, as directed in the potassium
(2) A solution of Suxamethonium Chloride Hydrate
Melting Point Between 159 C and 164 C (hydrate
form).
pH Dissolve 1.0 g of Suxamethonium Chloride Hydrate in 10 mL of water: the pH of this solution is between 4.0 and 5.0.
1.0 g of Suxamethonium Chloride Hydrate in 10 mL of

(2) Related substancesDissolve 0.25 g of Suxamethonium Chloride Hydrate in 5 mL of water and
of the test solution, add water to make exactly 200 mL
on a plate of cellulose for thin-layer chromatography.
Develop the plate with the mixture of a solution of
ammonium acetate (1 in 100), acetone, n-butanol and
formic acid (20 : 20 : 20 : 1) to a distance of about 10
cm and dry the plate at 105 C for 15 minutes. Spray
evenly platinic chloride-potassium iodide TS on the
plate and allow to stand for 15 minutes: any spot other
than the principal spot from the test solution is not
Assay Weigh accurately about 0.4 g of Suxamethonium Chloride Hydrate, dissolve in 80 mL of the mixture of acetic anhydride and glacial acetic acid (7 : 3)

= 18.065 mg of C14H30Cl2N2O4
Chloride for Injection, equivalent to 50 mg of Suxamethonium Chloride Hydrate according to the labeled
amount, dissolve in water to make 10 mL and use this
of Suxamethonium Chloride Hydrate RS in 10 mL of
water and use this solution as the standard solution.
solution as directed under the Thin-layer Chromatography. Spot 1 L each of the test solution and the standard solution on a plate of cellulose for thin-layer
chromatography. Develop the plate with the mixture of
a solution of ammonium acetate (1 in 100), acetone, nbutanol and formic acid (20 : 20 : 20 : 1) to a distance
of about 10 cm and dry the plate at 105 C for 15 minutes. Spray evenly platinic chloridepotassium iodide
TS on the plate: the spots from the test solution and the
standard solution are blue-purple in color and have similar Rf .
pH Dissolve 0.1 g of Suxamethonium Chloride for
Injection in 10 mL of water: the pH of this solution is
Purity Related substancesWeigh an amount of
Suxamethonium Chloride for Injection, equivalent to
0.25 g of Suxamethonium Chloride Hydrate according
to the labeled amount and proceed as directed in the
Purity (2) under Suxamethonium Chloride Hydrate.
ment.
Suxamethonium Chloride for

Injection
Suxamethonium Chloride for Injection is a preparation
for injection which is reconstituted before use. Suxamethonium Chloride for Injection contains not less than
suxamethonium chloride (C14H30Cl2N2O4: 361.31).
The concentration of Suxamethonium Chloride for Injection is stated as the amount of suxamethonium chloride (C14H30Cl2N2O4).
Method for Preparation Prepare as directed under
Injections, with Suxamethonium Chloride Hydrate.
Description Suxamethonium Chloride for Injection
is a white, crystalline powder or mass.
Identification Weigh an amount of Suxamethonium

10 preparations of Suxamethonium Chloride for Injection. Weigh accurately about 0.5 g of the contents and
proceed as directed in the Assay under Suxamethonium
Chloride Hydrate.

= 18.065 mg of C14H30Cl2N2O4
tainers.
Suxamethonium Chloride
Injection
Suxamethonium Chloride Injection is an aqueous solution for injection. Suxamethonium Chloride Injection
KP 9 907
of the labeled amount of suxamethonium chloride
(C14H30Cl2N2O4: 361.31).
The concentration of Suxamethonium Chloride Injection is stated as the amount of suxamethonium chloride
(C14H30Cl2N2O4).
Method of Preparation Prepare as directed under Injections, with Suxamethonium Chloride Hydrate.
Description Suxamethonium Chloride Injection is a
clear and colorless liquid.
Identification Take a volume of Suxamethonium
Chloride Injection, equivalent to 50 mg of Suxamethonium Chloride Hydrate according to the labeled amount,
add water to make 10 mL and use this solution as the
test solution. Separately, dissolve 50 mg of Suxamethonium Chloride Hydrate RS in 10 mL of water and
on a plate of cellulose for thin-layer chromatography.
Develop the plate with a mixture of a solution of ammonium acetate (1 in 100), acetone, n-butanol and formic acid (20 : 20 : 20 : 1) to a distance of about 10 cm
and dry the plate at 105 C for 15 minutes. Spray platinic chloride-potassium iodide TS on the plate: the
solution are blue-purple in color and have similar Rf.
bine the first solution and the water extracts, add 2

drops of bromthymol blue TS and neutralize with 0.1
mol/L sodium hydroxide VS. Add accurately measured
25 mL of 0.1 mol/L sodium hydroxide VS and boil for
40 minutes under a reflux condenser and cool. Titrate
the excess sodium hydroxide with 0.1 mol/L hydrochloric acid VS. Transfer 50 mL of the freshly boiled and
cooled water to a flask, add 2 drops of bromthymol
blue TS, neutralize the solution with 0.1 mol/L sodium
hydroxide VS, perform a blank determination using this
solution as the blank and make any necessary correction.
= 18.065 mg of C14H30Cl2N2O4
Packaging and Storage Preserve in hermetic containers. Store at 5 C or less and avoid freezing.
Expiration Date 12 months after preparation.
Tamoxifen Citrate
HO
CH3
H3C
O
HO
CH3
O
H
OH
O

Purity Hydrolysis productsPerform the preliminary neutralization with 0.1 mol/L sodium hydroxide
VS in the Assay: not more than 0.7 mL of 0.1 mol/L
sodium hydroxide VS is required for each 0.2 g of suxamethonium chloride (C14H30Cl2N2O4) taken.
Assay Transfer an accurately measured volume of
Suxamethonium Chloride Injection, equivalent to about
0.2 g of suxamethonium chloride (C14H30Cl2N2O4) to a
separatory funnel, add 30 mL of freshly boiled and
cooled water and wash the solution with five 20 mL volumes of ether. Combine the ether washings and extract
the combined ether layer with two 10 mL volumes of
freshly boiled and cooled water. Wash the combined
water extracts with two 10 mL volumes of ether. Com-
C26H29NOC6H8O7 : 563.64
Tamoxifen Citrate contains not less than 99.0% and not
more than 101.0% of tamoxifen citrate (C26H29NO
C6H8O7), calculated on the dried basis.
Description Tamoxifen Citrate is a white, fine, crystalline powder.
Tamoxifen Citrate is soluble in methanol, and very
slightly soluble in water, in acetone, in chloroform or in
ethanol.
of solutions of Tamoxifen Citrate and Tamoxifen Citrate RS in methanol (1 in 50000) as directed under the
Ultraviolet-visible Spectrophotometry: both spectra
exhibit similar intensities of absorption at the same wavelength.
(2) Determine the infrared spectra of Tamoxifen Citrate and Tamoxifen Citrate RS, previously dried, as directed in the potassium bromide disk method under the
Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumber.
Purity (1) Heavy metalsProceed with 1.0 g of Ta-
moxifen Citrate according to Method 2 and perform the

(2) IronProceed with 1.0 g of Tamoxifen Citrate
according to Method 3, and use this solution as the test
solution. Separately, proceed with 5.0 mL of standard
Iron solution according to the procedure of the test solution, and use this solution as the control solution. Perform the test with the test solution and the control solution according to method A: the test solution is not
more intense than the control solution (not more than
50 ppm).
(3) E-isomersWeigh accurately about 30 mg of
Tamoxifen, dissolve in the mobile phase to make exactly 50 mL and use this solution as the test solution. Separately, weigh accurately about 30 mg of Tamoxifen
Citrate RS, dissolve in the mobile phase to make exactly 50 mL, and use this solution as the standard solution.
conditions and determine peak areas, AT and AS , of
E-isomers as citrate for the test solution and the standard solution, respectively (not more than 0.3%).
Amount (mg) of E-isomers (C26H29NOC6H8O7)
A
= 0.05 T
AS
C : Concentration (g/mL) of E-isomer as citrate
(C26H29NOC6H8O7) based on its delared content in
Tamoxifen Citrate RS in the standard solution.
Column : A stainless steel column, about 4.0 mm in
to 10 m in particle diameter).
Mobile phase : Dissolve 2 mL of glacial acetic acid
and 1.08 g of sodium 1-octanesulfonic acid in 320 mL
of water, and add methanol to make 1000 mL.
Flow rate : 0.7 mL/minute
System suitability
System performance : When the procedure is run
above operating conditions, the relative retention time
of E-isomer peak to the retention time of Z-isomer is
not more than 0.93.
System repeatability : When the test is repeated 5
deviation of the peak area of Tamoxifen Citrate is not
more than 3.0%.
(4) Related substancesTransfer 3 g of Tamoxifen

Citrate in a separatory funnel, add 100 mL of water,
and mix with stirring. Over 10-minutes period add 50
mL of 0.5 mol/L sodium hydroxide. Extract with two

50-mL portion of ether, and combine the extracts.
Wash with 20 mL of water, discard the water layer, and
evaporate the ether layer in a stream of nitrogen, and
dry in vacuum at room temperature for 2 hours. Weigh
exactly 1.5 g of the residue, add 5.0 mL of a mixture of
pyridine and acetic anhydride (95 : 5), and heat at 60
for 10 to 15 minutes. Cool, dilute exactly with a mixture of pyridine and acetic anhydride (95 : 5) to make
exactly 10 mL, and use this solution as the test solution.
Take exactly 0.5 mL of the test solution, add a mixture
of pyridine and acetic anhydride (95 : 5) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with each 2 L of the test solution and the standard solution, respectively, as directed
under the Gas Chromatography. Measure the each peak
areas of solutions according to automatic integration
method: each peak areas other than solvent peak and
the principal peak is not larger than total area of Tamoxifen peak obtained from the standard solution
(0.5%), and sum area of these peaks is not larger than
twice the total area of the Tamoxifen peak obtained
from the standard solution (1.0%).
Detector: A hydrogen Flame ionized detector
and about 4 m in length, packed with supports for gas
chromatography (125 to 149 m in particle diameter at
300, 24 hours) coated with 75% phenyl and 25% methyl polysiloxane for gas chromatography at the ratio of
5%.
Carrier gas: Helium
about 260 C.
Injection port temperature: A constant temperature
of about 260 C.
Detector temperature: A constant temperature of
about 300 C.
hours).
Assay Weigh exactly about 1.0 g of Tamoxifen Citrate,
and dissolve in 150 mL of glacial acetic acid, and titrate the solution with 0.1 mol/L perchloric acid VS
Each mL of 0.1mol/L perchloric acid VS

= 56.36 mg of C26H29NOC6H8O
tight containers.
KP 9 909
Tannic Acid
Tannic Acid is the tannin usually obtained from nutgalls or rhusgalls.
Description Tannic Acid is a yellowish white to pale
brown, amorphous powder, glistening leaflets, or spongy masses, is odorless or has a faint, characteristic odor
and has a strongly astringent taste.
Tannic Acid is very soluble in water or in ethanol and
Identification (1) To 5 mL of a solution of Tannic
Acid (1 in 400), add 2 drops of ferric chloride TS: a
blue-black color is observed. Allow the solution to
stand: a blue-black precipitate is produced.
(2) To 5 mL of a solution of Tannic Acid (1 in 20),
add 1 drop each of albumin TS, gelatin TS, or 1 mL of
starch TS: a precipitate is produced in each solution.
Purity (1) Gum, dextrin and sucroseDissolve 3.0
g of Tannic Acid in 15 mL of boiling water: the solution is clear or slightly turbid. Cool and fiter the solution. To 5 mL of the filtrate, add 5 mL of ethanol: no
turbidity is produced, add further 3 mL of ether to this
solution: no turbidity is produced.
(2) Resinous substancesTo 5 mL of the filtrate
obtained in (1), add 10 mL of water: no turbidity is
produced.
hours).
tight containers.
Tegafur
O
NH
F
O
and enantiomer
C8H9FN2O3: 200.17
Tegafur, when dried, contains not less than 98.0% and

not more than 101.0% of tegafur (C8H9FN2O3).
Description Tegafur is a white, crystalline powder.
Tegafur is soluble in methanol, sparingly soluble in water or in ethanol and slightly soluble in ether.
Tegafur dissolves in dilute sodium hydroxide TS.
Identification (1) Prepare the test solution with 10

mg of Tegafur as directed under the Oxygen Flask
Combustion Method, using a mixture of 0.5 mL of 0.01
mol/L sodium hydroxide TS and 20 mL of water as an
absorbing liquid: the test solution responds to the Qualitative Tests (2) for fluoride.
Tegafur and tegafur RS in 0.01 mol/L sodium hydroxide TS (1 in 100000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(3) Determine the infrared spectra of Tegafur and
Tegafur RS as directed in the potassium bromide disk
same wavelengths.
pH Dissolve 0.5 g of Tegafur in 50 mL of water: the
0.2 g of Tegafur in 10 mL of dilute sodium hydroxide
(2) ChlorideDissolve 0.8 g of Tegafur in 40 mL
of water by warming, cool, filter, if necessary and add 6
mL of dilute nitric acid and water to make 50 mL. Perform the test. Prepare the control solution with 0.25 mL
0.011%).
(3) Heavy metalsDissolve 1.0 g of Tegafur in 40
mL of water by warming, cool, filter, if necessary and
add 2 mL of dilute acetic acid and water to make 50
ppm).
(4) ArsenicTo 1.0 g of Tegafur in a crucible, add
10 mL of a solution of magnesium nitrate in ethanol (1
in 10), fire the ethanol to burn and incinerate by ignition between 750 C and 850 C. If a carbonized substance remains, moisten with a small quantity of nitric
acid and ignite again to incinerate. After cooling, dissolve the residue in 10 mL of dilute hydrochloric acid
by warming in a water-bath and perform the test with
this solution as the test solution (not more than 2 ppm).
(5) Related substancesDissolve 0.1 g of Tegafur
in 10 mL of methanol and use this solution as the test
solution. Pipet 1.0 mL of the test solution, add methanol to make exactly 200 mL and use this solution as the
and the standard solution as directed under the Thinlayer Chromatography. Spot 5L each of the test solution and the standard solution on a plate of silica gel
with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform
and ethanol (5 : 1) to a distance of about 10 cm and airdry the plate. Examine under ultraviolet light (main
hours).
Assay Weigh accurately about 0.15 g of Tegafur, previously dried, place in an iodine bottle, dissolve in 75
mL of water and add exactly 25 mL of 1/60 mol/L potassium bromate VS. Add rapidly 1.0 g of potassium
bromide and 12 mL of hydrochloric acid, stopper the
bottle tightly at once and allow to stand for 30 minutes
with occasional shaking. To this solution, add 1.6 g of
potassium iodide, shake gently, allow to stand for exactly 5 minutes and titrate the liberated iodine with 0.1
Each mL of 1/60 mol/L potassium bromate VS

= 10.008 mg of C8H9FN2O3
Temazepam
H3C
O
N
OH
Cl
C16H13O2N2Cl : 300.74
Temazepam containes not less than 98.0% not more
than 102.0% of temazepam (C16H13O2N2Cl), calculated
on the dried basis.
Description
Temazepam is a white, crystalline
powder.
Temazepam is slightly soluble in ethanol and practically insoluble in water.
Melting point Between 157 C and 163 C.
Identification (1) Determine the absorption spectra of
solutions of Temazepam and Temazepam RS in methanol (1 in 80000) as directed under the Ultravioletvisible Spectrophotometry: both specra exhibit similar
(2) Determine the infrared spectra of Temazepam
and Temazepam RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibits similar intensities of absorption at the same wavenumbers.
(3) The retention time of the principal peak obtained from the test solution in the Assay corresponds
to the retention time of the principal peak obtained
Purity (1) Heavy metalsProceed with 1.0 g of Temazepam according to Method 2 and perform the test.
Prepare the control solution with 2 mL of standard lead
(2) Related substancesWeigh exactly about 0.1 g
of Temazepam, dissolve in chloroform to make exactly
10 mL, and use this solution as the test solution. Weigh
exactly 0.1 g of Temazepam RS, dissolve in chloroform
to make exactly 10 mL. Pipet 1.0 mL of this solution,
add chloroform to make each 100 mL and 200 mL, and
use these solutions as the standard solution (1) and the
standard solution (2). Perform the test with these solutions as directed under Thin-layer Chromatography.
Spot each 10 L of the test solution, the standard solution (1) and the standard solution (2) on a plate of silica
gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of cyclohexane, chloroform, methanol and strong ammonia water
(50:40:12:1) to a distance of about 10 cm and air-dry
the plate. Examine the plate under UV light (main wavelength: 254 nm), and compare the intensities of any
secondary spots observed in the chromatograms of the
test solution with those of the principal spots in the
chromatograms of the standard solutions: the spots other than the principal spot obtained from the test solution are not dark than the principal spot obtained from
the standard solution (1) (1.0%), and the sum of the intensities of the spots other than the principal spot obtained from the test solution is not greater than 4 times
of intensity of the spot obtained from the standard solution (2) (2.0%).
Loss on Drying not more than 0.5% (1 g, 105 C.
2hours).
Residue on Ignition not more than 0.1% (1 g).
Assay Weigh acculately about 40 mg each Temazepam and Temazepam RS, dissolve in the internal
standard solution, to make exactly 200 mL and use
Liquid Chromatography according to the following operating conditions. Calculate the ratios of peak areas of
Temazepam, QT and QS , to peak area of the internal
standard substance.
Amount (mg) of temazepam (C16H13O2N2Cl)
KP 9 911
= amount (mg) of Temazepam RS
QT
QS
Internal standard solutionDissolve an acculately

weighed 20 mg of benzophenone in a mixture of methanol and water (9:1), and make to exactly 100 mL.
Column : A stainless steel column, about 4 mm in
dimethylsilanized silica gel for the liquid chromatography (5 to 10 m in particle diameter).
Mobile phase : A mixture of phosphate buffer solution and acetonitril (53:47).
Flow rate : 2.0 mL/minute.
System suitability
operating conditions, the numbers of theoretical plates
are not less than 800, the symmetry factor is not more
than 2, and the resolution between the Temazepam
peak and any other peak is not less than 1.0.
System repeatability : When the test is repeated
operating conditions, the relative deviation of peak area
obtained from Temazepam is not more than 2.0%.
phosphate buffer solutionDissolve 5.444 g of potassium dihydrogen phosphate in 2000 mL of water.
Adjust with phosphoric acid to pH of 3.0.
light-resistant containers.
Preserve in well-closed,
Tenoxicam
O
O
S
CH3
N
H
N
S
OH
C13H11N3O4S2: 337.37
Tenoxicam contains not less than 99.0% and not more
than 101.0% of tenoxicam (C13H11N3O4S2), calculated
Description
Tenoxicam is a yellow, crystalline
powder.
Tenoxicam is sparingly soluble in dichloromethane,
very slightly soluble in ethanol, and practically insoluble in water.
Tenoxicam dissoves in a solution of acids or alkalis.

Tenoxicam shows polymorphism.
Identification Determine the infrared spectra with
Tenoxicam and Tenoxicam RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
appears, dissolve Tenoxicam and Tenoxicam RS respectively in the minimum quantity of dichloromethane,
evaporate to dryness on a water bath and repeat the test
with the residues.
0.10 g of Tenoxicam in 20 mL of dichloromethane.
This solution is clear.
(2) Heavy metalsProceed with 1.0 g of Tenoxicam according to the Method 2, and perform the test.
Prepare the control solution with 2 mL of standard lead
(3) Related substancesweigh exactly 0.4 g of
Tenoxicam, dissolve in a mixture of methanol and concentrated ammonia (96 : 4) to make exactly 5 mL, and
use this solution as the test solution. Add a mixture of
methanol and concentrated ammonia (96 : 4) to 1.0 mL
of this solution to make exactly 20 mL, and use this solution as the standard solution (1). Separately, weigh
exactly 20 mg of salicylic acid RS and 20 mg of Tenoxicam RS, dissolve in a mixture of methanol and
concentrated ammonia (96 : 4) to make 5 mL, and use
this solution as the standard solution (2). Weigh exactly
20 mg of pyridine-2-amine, dissolve it in a mixture of
methanol and concentrated ammonia (96 : 4) to make
exactly 5 mL, add a mixture of methanol and concentrated ammonia (96 : 4) to 2 mL of this solution to
make exactly 50 mL, and use this solution as the standard solution (3). Perform the test with these solutions
each 10 L each of the test solution and the standard
solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate
with a mixture of dichloromethane, acetone, methanol
and formic acid (70 : 20 : 5 : 5) to a distance of about
15 cm. Air-dry the plate. Examine under ultraviolet
light (main wavelength: 254 nm). The spot corresponding to pyridine-2-amine in the chromatogram obtained
with the test solution is not more intense than the spot
in the chromatogram obtained with standard solution
(3), and any spot in the chromatogram obtained with
the test solution other than the principal spot and the
spot corresponding to pyridine-2-amine, is not more intense than the spot in the chromatogram obtained with
direct titration).

Assay Dissolve 0.25 g of Tenoxicam in 5 mL of formic acid, add 70 mL of glacial acetic acid, and titrate
with 0.1 mol/L perchloric acid (potentiometric titration,
blank determination and any necessary correction.
1 mL of 0.1 mol/L perchloric acid

= 33.74 mg of C13H11N3O4S2

Terbutaline Sulfate
HO
CH3
CCH2NHCCH3
OH
HO
H2SO4
CH3
2
and enantiomer
(C12H19NO3)2H2SO4: 548.65
Terbutaline Sulfate contains not less than 98.5% and
not more than 101.0% of terbutaline sulfate
[(C12H19NO3)2H2SO4], calculated on the anhydrous basis.
Description Terbutaline Sulfate is a white to brownish white crystal or crystalline powder, is odorless or
has a faint odor of acetic acid.
Terbutaline Sulfate is freely soluble in water and practically insoluble in acetonitrile, in ethanol, in glacial
acetic acid, in chloroform or in ether.
Terbutaline Sulfate is gradually colored by light and by
air.
Identification (1) Dissolve 1 mg of Terbutaline Sulfate in 1 mL of water and add 5 mL of Tris buffer solution, pH 9.5, 0.5 mL of 4-aminoantipyrine solution (1
in 50) and 2 drops of potassium ferricyanide solution (2
in 25): a reddish purple color is observed.
Terbutaline Sulfate and Terbutaline Sulfate RS in 0.01
mol/L hydrochloric acid TS (1 in 10000) as directed
same wavelengths. The maximum may be biphasic.
(3) A solution of Terbutaline Sulfate (1 in 50) responds to the Qualitative Tests for sulfate.
pH Dissolve 0.10 g of Terbutaline Sulfate in 10 mL
0.10 g of Terbutaline Sulfate in 10 mL of water: the so-
lution is clear and colorless or pale yellow.

(2) ChloridePerform the test with 2.0 g of Terbutaline Sulfate. Prepare the control solution with 0.25
0.004%).
(3) Acetic acidDissolve about 0.50 g of Terbutaline Sulfate in a solution of phosphoric acid (59 in
1000) to make exactly 10 mL and use this solution as
the test solution. Separately, dissolve 1.50 g of glacial
acetic acid in a solution of phosphoric acid (59 in 1000)
to make exactly 100 mL. Dilute 2 mL of this solution,
accurately measured, with a solution of phosphoric acid
(59 in 1000) to make exactly 200 mL and use this solution as the standard solution. Perform the test with 2 L
each of the test solution and the standard solution as directed under the Gas Chromatography according to the
following operating conditions. Measure the peak areas,
AT and AS, of acetic acid for the test solution and the
standard solution, respectively: AT is not larger than AS.
and about 1 m in length, packed with 10% of macrogol
6000 on 180 m to 250 m terephthalic acid for gas
chromatography.
about 120 C.
time of acetic acid is about 5 minutes.
System suitability
glacial acetic acid and propionic acid in 100 mL of a
solution of phosphoric acid (59 in 1000). When the
above operating conditions, acetic acid and propionic
acid are eluted in this order with the resolution between
the peak area of acetic acid is not more than 3.0%.
(4) 3,5-Dihydroxy--tert-butylaminoacetophenone
sulfateDissolve 0.50 g of Terbutaline Sulfate in 0.01
mol/L hydrochloric acid TS to make exactly 25 mL and
perform the test as directed under the Ultravioletvisible Spectrophotometry: the absorbance at a wavelength of 330 nm does not exceed 0.47.
(5) Heavy metalsProceed with 2.0 g of Terbutaline Sulfate as directed under Method 2 and perform
Terbutaline Sulfate according to method 3 and perform
direct titration).
KP 9 913
Assay Weigh accurately about 0.5 g of Terbutaline
Sulfate, dissolve in 50 mL of a mixture of acetonitrile
and glacial acetic acid (1 : 1) by stirring and warming.
After cooling, titrate with 0.1 mol/L perchloric acid VS
Titrimetry, substituting a saturated solution of potassium chloride in methanol for the internal solution).

= 54.87 mg of (C12H19NO3)2H2SO4
tight containers.

+0.10(1 g, dichloromethane, 10 mL, 100 mm)
Terconazole
Cl
Cl
H3C
O
N
solution and the standard solutions on the plate of octadecylsilanized silica gel for thin-layer chromatography.
Develop the plate with a mixture of methanol, dioxane
and ammonium acetic acid (40 : 40 : 20) to distance of
about 10 cm, dry the plate in a current of warm air for
15 minutes and expose the plate to iodine vapor: the
principal spot obtained from test solution and the principal spot obtained from standard solution (1) show
same color and same Rf value. This test is effective
when two spots obtained from standard solution (2) in
the chromatogram are separated apparently.
(3) Add 30 mg of Terconazole in a porcelain crucible,
add 0.3 g of anhydrous sodium carbonate. Heat over an
open flame for 10 minutes, cool. Add 5 mL of dilute nitric acid to the residue, mix under the stirring and filter.
The solution added 1 mL of water to 1 mL of the filtrate shows the qualitative reaction (2) of chlorides.
N
N
H3C
N
and enantiomer
C26H31Cl2N5O3: 532.46
Terconazole containes not less than 99.0% and not
more than 101.0% of terconazole (C26H31Cl2N5O3), calculated on the dried basis.
Description Terconazole is a white powder.
Terconazole is very soluble in dichloromethane, soluble in acetone, and sparingly insoluble in water.
Identification (1) Determine the infrared specta of
Terconazole and Terconazole RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
of absorption at the same wave numbers. If any difference appears, dissolve Terconazole and Terconazole
RS in the minimum volume of acetone, evaporate to
dryness in a current of air and repeat the test with the
residues.
(2) Weigh 30 mg of Terconazole, dissolve in methanol to make 5 mL, use this solution as the test solution.
Separately, weigh 30 mg of Terconazole RS, dissolve
in methanol to make 5 mL, use this solution as the
standard solution (1). Separately, dissolve 30 mg of
Terconazole and 30 mg of Ketoconazole RS in methanol to make 5 mL, use this solution as the standard solution (2). Perform the test with these solutions as directed under the Thin-layer Chromatography according
to the operating conditions. Spots 5 L each of the test
Purity (1) Related substances - Weigh exactly 0.1 g

of Terconazole, dissolve in methanol to make exactly
10 mL, use this solution as the test solution. Dissolve
2.5 mg of Terconazole RS and 2.0 mg of Ketoconazole RS in methanol to make exactly 100 mL, use this
solution as the standard solution (1). Add methanol in
1.0 mL of the test solution to make exactly 100 mL,
add methanol in 5.0 mL of this solution to make exactly 20 mL, use this solution as the standard solution (2).
Perform the test with 10 L each of methanol (blank
solution), the test solution and the standard solution (2)
as directed under the Liquid Chromatography, determine the peak areas of each solutions according to the
automatic integration method: the area of any peak other than the principal peak from the test solution is not
greater than area of the principal peak from standard
solution (2) (0.25%), the sum of areas of the peaks other than the principal peak from the test solution is not
greater than 2 times the area of the principal peak obtained from standard solution (1) (0.5%). Disregard any
peak obtained with the blank test and any peak with an
area less than 0.2 times the area of the principal peak in
the chromatogram from standard solution (2).
Detector: Ultraviolet-visible photometer (wavelength: 220 nm)
base-deactivated octadecylsilanized silica gel for liquid
gradient by mixing mobile phase A and mobile phase B.
Mobile phase A: Dissolve 3.4 g of tetrabutylammonium hydrogen sulfate in water to make 1000 mL.
Mobile phase B: acetonitrile
Time
Mobile phase Mobile phase
Elution

(minute)
0 ~ 10
10 ~ 15
A(vol%)
95 50
50
B (vol%)
5 50
50
15 ~ 20
95
20 ~ 0
95
condition
linear gradient
isocratic elution
switch to initial
eluent composition
restart gradient

System suitability
System performance: Elute the column for at
least 30 minutes with acetonitrile at a flow rate of 2
mL/minute and then equilibrate at the initial elution
composition for at least 5 minutes. Adjust the sensitivity of the system so that the height of the principal peak
in the chromatogram obtained with 10 L of standard
solution (2) is at least 50% of the full scale of the recorder. When the procedure is run with 10 L of the
standard solution, the retention times of Ketoconazole
and Terconazole are about 6 minutes and about 7.5 minutes, respectively, with the resolution between the
peaks corresponding to Ketoconazole and Terconazole
being not less than 13.
Loss on Drying Not more than 0.5% (1 g, 105 ,
constant mass).
Assay Weigh accurately about 0.15 g of Terconazole,
dissolve in 70 mL of a mixture of methyl ethyl ketone
perchloric acid until the second point of inflexion (potentiometric titration, Endpoint Detection Method in
Titrimetry).
1 mL of 0.1 mol/L perchloric acid

= 17.75 mg of C26H31Cl2N5O3
Preserve in the lightresistant, well-closed containers.
Testosterone Enanthate
O
H3C
H3C
C
H
(CH2)5CH3
Description Testosterone Enanthate is a white to pale

yellow crystal, crystalline powder or a pale yellowbrown, viscous liquid and is odorless or has a slight
Testosterone Enanthate is very soluble in ethanol, in
dioxane or in ether and practically insoluble in water.
Identification Heat 25 mg of Testosterone Enanthate
with 2 mL of a solution of potassium hydroxide in methanol (1 in 100) under a reflux condenser in a waterbath for 1 hour. After cooling, add 10 mL of water, collect the precipitate by filtering with suction, wash with
water until the last washing is neutral and dry the precipitate in a desiccator (in vacuum, P2O5) for 4 hours:
this precipitate melts between 151 C and 157 C.
D : Between +77 and
Purity AcidDissolve 0.5 g of Testosterone Enanthate in 10 mL of ethanol which has previously been
rendered neutral to bromothymol blue TS and add 2
drops of bromothymol blue TS and 0.50 mL of 0.01
mol/L sodium hydroxide VS: the color of the solution
is pale blue.
Assay Weigh accurately about 0.1 g of Testosterone
Enanthate, previously dried and dissolve in ethanol to
make exactly 100 mL. Pipet 10.0 mL of this solution
and dilute with ethanol to make exactly 100 mL. Pipet
10.0 mL of this solution and dilute with ethanol to
make exactly 100 mL. Perform the test as directed under the Ultraviolet-visible Spectrophotometry with this
solution. Read the absorbance, A, of this solution at the
wavelength of a maximum absorption at about 241 nm.
Amount (mg) of testosterone enanthate (C26H40O3)

A
= 426 100000
tight containers not exceeding 30 C.
C26H40O3: 400.59
Testosterone Enanthate, when dried, contains not less
than 95.0% and not more than 105.0% of testosterone
enanthate (C26H40O3).
Testosterone Enanthate
Injection
Testosterone Enanthate Injection is an oily solution for
injection. Testosterone Enanthate Injection contains not
less than 90.0% and not more than 110.0% of the labeled amount of testosterone enanthate (C26H40O3:
KP 9 915
400.59).
Method of Preparation Prepare as directed under Injections, with Testosterone Enanthate.
Descriptlon Testosterone Enanthate Injection is a
clear, colorless or pale yellow oily liquid.
Identification Measure a volume of Testosterone
Enanthate Injection, equivalent to 50 mg of Testosterone Enanthate according to the labeled amount, add 8
mL of petroleum ether and extract with three 10 mL volumes of diluted acetic acid (7 in 10). Combine the extracts, wash with 10 mL of petroleum ether, add 0.5 mL
of diluted sulfuric acid (7 in 10) to 0.1 mL of the extract and heat in a water-bath for 5 minutes. After cooling, add 0.5 mL of ferric chloride-acetic acid TS: the
color of the solution is blue.

Mobile phase: A mixture of water and acetonirile
(15 : 85)
time of Testosterone Enanthate is about 10 minutes.
System suitablilty
operating conditions: internal standard and testosterone
enanthate are eluted in this order with the resolution between these peaks being not less than 2.5.
the peak area of testosterone enanthate is not more than
2.0%.
Testosterone Propionate

Assay Measure accurately a volume of Testosterone
Enanthate Injection, equivalent to about 50 mg of testosterone enanthate (C26H40O3) and dissolve in chloroform to make exactly 100 mL. Pipet 15.0 mL of this solution, add 1.0 mL of internal standard solution and
chloroform to make exactly 50 mL and use this solution
50 mg of Testosterone Enanthate RS, previously dried
in a desiccator (in vacuum, P2O5) for 4 hours, proceed
in the same manner as for the test solution and use this
20 L each of the test solution and the standard solution as directed under the Liquid chromatography according to the following conditions and calculate the
ratios, QT and QS , of the peak area of testosterone
enanthate to that of internal standard, for the test solution and the standard solution, respectively.
Amount (mg) of testosterone enanthate (C26H40O3)

Q
= amount (mg) of Testosterone Enanthate RS T
QS
Internal standard solutionA solution of phenanthrene in methanol (1 in 2000).
O
H3C
H3C
C
H
CH2CH3
C22H32O3: 344.49
Testosterone Propionate, when dried, contains not less
than 97.0% and not more than 103.0% of testosterone
propionate (C22H32O3).
Description Testosterone Propionate is a white to
pale yellow crystal or crystalline powder and is odorless.
Testosterone Propionate is freely soluble in methanol or
of solutions of Testosterone Propionate and Testosterone Propionate RS in ethanol (1 in 100000), as directed under the Ultraviolet-visible Spectrophotometry:
(2) Determine the infrared spectra of Testosterone
Propionate and Testosterone Propionate RS, previously
dried, as directed under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
[ ]20
D :

between +83 and
+90 (after drying, 0.1 g, dioxane, 10 mL, 100 mm)
Purity Related substancesDissolve 40.0 mg of
Testosterone Propionate in 2 mL of ethanol and use this
solution as the test solution. Pipet 1.0 mL of this solution, add ethanol to make exactly 100 mL and use this
the test solution and standard solution as directed under
test solution and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform and diethylamine (19 : 1) to a distance of about 15
cm and air-dry the plate. Examine under ultraviolet
Loss on Drying Not more than 0.5% (0.5 g, in vacuum, P2O5. 4 hours).
Assay Weigh accurately each about 10 mg of Testosterone Propionate and Testosterone Propionate RS, previously dried, and dissolve in methanol to make exactly
100 mL, respectively. To exactly 5.0 mL of these solutions, add exactly 5 mL of the internal standard solution
and methanol to make exactly 20 mL, and use these solutions as the test solution and the standard solution.
Perform the test with 5 L each of the test solution and
the standard solution as directed under Liquid Chromatography according to the following conditions, determine the ratios QT and QS , of the peak area of Tetosterone Propionate to that of the internal standard.
Amount (mg) of testosterone propionate (C22H32O3)

Q
= amount (mg) of Testosterone Propionate RS T
QS
Internal standard solutionA solution of progesterone in methanol (9 in 100000).
5 m in particle diameter octadecylsilanized silica gel
for liquid chromatography.
about 35.
(7 : 3).
time of Testosterone Propionate is about 10 minutes.

System suitability
with 5 L of the standard solution under the above operating conditions, the internal standard and Testosterone Propionate are eluted in this order, with the resolution between their peaks being not less than 9.
above operating conditions, the relative standard deviation of the ratio of peak area of Testosterone Propionate
tight containers.
Testosterone Propionate
Injection
Testosterone Propionate Injection is an oily solution for
injection. Testosterone Propionate Injection contains
labeled amount of testosterone propionate (C22H32O3:
344.49).
Method of Preparation Prepare as directed under Injections, with Testosterone Propionate.
Description Testosterone Propionate Injection is a
clear, colorless or pale yellow oily liquid.
Identification Dissolve the residue obtained as directed in the procedure in the Assay in exact 20mL of
methanol, and use this solution as the test solution. Seperately, dissolve 1 mg in 10 mL of methanol, and use
with these solutions as directed under the Thinlayer
Develop the plate with a mixture of chloroform and diethylamine (19 : 1)to a distance of about 15 cm and airdry the plate. Examine under ultraviolet light (main
wavelength: 254 nm): the Rf values of the principal
spot with the test solution and of the spot with the standard solution are not different each other.
KP 9 917
Assay (1) Chromatograph tubeA glass tube about 1
cm in inside diameter and about 18 cm in length, with a
glass filter (G3) at the lower end.
(2) Chromatographic columnTo about 2 g of silica gel for liquid chromatography add 5 mL of dichloromethane, and mix gently. Transfer and wash into the
chromatographic tube with the aid of dichloromethane,
allow to elute the dichloromethane through the column,
and put a filter paper on the upper end of the silica gel.
(3) Standard solutionWeigh accurately about 10
mg of Testosterone Propionate RS, previously dried at
105 for 4 hours, and dissolve in methanol to make
exactly 100 mL. Pipet 5 mL of this solution, add exactly 5 mL of the internal standard and methanol to make
exactly 20mL.
(4) Standard stock solutionTo exactly a volume of
Testosterone Propionate Injection, equivalent to about
20 mg of testosterone propionate (C22H32O3), and add
dichloromethane to make exactly 20 mL.
(5) ProcedureTransfer exactly 2 mL of the sample
stock solution into the chromatographic column, and
elute to the upper surface of the silica gel. Wash the inner surface of the chromatographic tube with 15 mL of
dichloromethane, elute to the upper surface of the silica
gel, and discard the effluent. Elute 15 mL of a mixture
of dichloromethane and methanol (39 : 1), discard the
first 5 mL of the effluent, and collect the subsequent effluent. Wash the lower part of the column with a few
amount of dichloromethane, combine the washings and
the effluent, and evaporate the solvent under reduced
pressure. Dissolve the residue so obtained with methanol to make exactly 20 mL. Pipet 5 mL of this solution,
add exactly 5 mL of the internal standard solution and
methanol to make exactly 20 mL and use this solution
as the test solution. Perform the test with 5 L each of
the test solution and standard solution as directed in the
Assay under Testosterone Propionate.

= amount (mg) of Testosterone Propionate RS
Q
T 2
QS
Internal standard solutionA solution of progesterone in methanol (9 in 100000).
tainers.
Testosterone Propionate Injection (Aqueous Suspension)

Testosterone Propionate Injection (Aqueous Suspension) is an aqueous suspension for injection. Testosterone Propionate Injection contains not less than 90.0%
and not more than 110.0% of the labeled amount of testosterone propionate (C22H32O3: 344.49).
Method of Preparation Prepare as directed under Injections, with Testosterone Propionate.
Description
Testosterone Propionate Injection
(Aqueous Suspension) produces a white turbidity on
shaking.
Identification (1) Shake thoroughly and transfer a
volume of Testosterone Propionate Injection (Aqueous
Suspension), equivalent to about 30 mg of testosterone
propionate (C22H32O3), to a flask. Add 2 to 3 drops of
bromophenol blue TS and dilute hydrochloric acid until
the color of the solution changes to yellow. Shake thoroughly, cool in ice for 15 minutes and filter by suction
through a tared glass filter (G4) to collect the precipitate. Wash the precipitate with five 5 mL volumes of
cold water. Dry the precipitate in a desiccator (in vacuum, P2O5) for 4 hours: it melts between 118 C and
123 C.
(2) Proceed with 20 mg of the precipitate in the
Identification (1) as directed in the Identification (2)
under Testosterone Propionate.
Assay Shake thoroughly and pipet an exactly measured volume of Testosterone Propionate Injection
(Aqueous Suspension), equivalent to about 50 mg of
testosterone propionate (C22H32O3) and add methanol to
make exactly 100 mL. Pipet exactly 5 mL of this solution, add 4.0 mL of internal standard solution, add methanol to make exactly 50 mL and use this solution as
mg of Testosterone Propionate RS, previously dried in
a desiccator for 4 hours (in vacuum, P2O5) and prepare
the standard solution in the same manner as directed for
the preparation of the test solution. Perform the test
ratios, QT and QS, of the peak area of testosterone propionate to that of the internal standard, for the test solution and the standard solution, respectively.

QT
= amount (mg) of Testosterone Propionate RS Q
S
Internal standard solutionA solution of methyltestosteron in ethanol (1 in 2000).

(15 : 85).
time of testosterone propionate is about 8 minutes.
System suitability
above operating conditions, internal standard and testosterone propionate are eluted in this order with the
deviation of the ratio of the peak area of testosterone
propionate is not more than 2.0%.
tainers.
Tetracaine Hydrochloride
for 2 hours: it melts between 130 C and 132 C.

Tetracaine Hydrochloride and Tetracaine Hydrochloride RS in dehydrated ethanol (1 in 200000) as directed
same wavelengths.
(4) A solution of Tetracaine Hydrochloride (1 in 10)
respond to the Qualitative Tests for chloride.
Purity Heavy metalsProceed with 1.0 g of Tetracaine Hydrochloride according to Method 1 and perform the test. Prepare the control solution with 2.0 mL
hours).
Assay Weigh accurately about 0.5 g of Tetracaine
formic acid, add 80 mL of acetic anhydride, allow to
stand at 30 C in a water-bath for 15 minutes, cool and
correction.
CH3
CH3CH2CH2CH2NH
HCl
COOCH2CH2N
CH3
C15H24N2O2HCl: 300.82
Tetracaine Hydrochloride, when dried, contains not less
than 98.5 and not more than 101.0% of tetracaine hydrochloride (C15H24N2O2HCl).
Description Tetracaine Hydrochloride is a white
crystal or crystalline powder, is odorless and has a
slightly bitter taste followed by a sense of numbness on
the tongue.
Tetracaine Hydrochloride is very soluble in formic acid,
freely soluble in water, soluble in ethanol, sparingly soluble in dehydrated ethanol, slightly soluble in acetic
anhydride and practically insoluble in ether.
A solution of Tetracaine Hydrochloride (1 in 10) is neutral.
Identification (1) Dissolve 0.5 g of Tetracaine Hydrochloride in 50 mL of water, add 5 mL of ammonia
TS, shake, allow to stand in a cold place and collect the
precipitate. Wash with water until the washings is neutral and dry in a desiccator (silica gel) for 24 hours: it
(2) Dissolve 0.1 g of Tetracaine Hydrochloride in 8
mL of water and add 3 mL of ammonium thiocyanate
TS: a crystalline precipitate is produced. Collect the
precipitate, recrystallize from water and dry at 80 C

= 30.082 mg of C15H24N2O2.HCl
Tetracycline Hydrochloride
OH
OH
OH
NH2
OH
H
H3C
OH
N
H3C
HCl
CH3
C22H24N2O8HCl: 480.90
Tetracycline Hydrochloride is the hydrochloride of a tetracycline substance having antibacterial activity produced by the growth of Streptomyces aureofaciens
Tetracycline Hydrochloride contains not less than 900
g (potency) and not more than 980 g (potency) per
mg of tetracycline hydrochloride (C22H24N2O8HCl),
Description Tetracycline Hydrochloride is a yellow
crystalline powder, and is odorless.
Tetracycline Hydrochloride is freely soluble in water,
sparingly soluble in ethanol, and practically insoluble
KP 9 919
in ether.
Identification (1) Weigh 2 ~ 3 mg of Tetracycline
Hydrochloride, and add 2 mL of sulfuric acid: the redpurple color develops.
(2) Weigh 2mg of Tetracycline Hydrochloride, and
dissolve in 3 mL of water, add silver nitrate TS: the solution turns to be turbid.
(3) Determine the absorption spectra of the solutions of Tetracycline Hydrochloride and Tetracycline
Hydrochloride RS in water (1 in 62500), as directed
under Ultraviolet-visible Spectrophotometry, both spectra exhibit similar intensities of absorption at the same
wavelengths.
4.0, 5.0, and 6.0 mL of this solution, add exactly each 5

mL of diluted hydrochloric acid (1 in 5), heat for 5 minutes in water bath and cool down, add water to make
exactly 50 mL, and use these solutions as the standard
solutions. Separately, pipet each 2.0, 3.0, 4.0, 5.0, and
6.0 mL of the standard solution and 4.0 mL of the test
solution, add 5 mL of water, heat for 5 minutes in water
bath and cool down, add exactly each 5 mL of diluted
hydrochloric acid (1 in 5) before use, add water to
control solutions. Determine the transmission or the absorbances at 440 nm, of these solutions as directed under Ultraviolet-visible Spectrophotometry.

of Tetracycline Hydrochloride in 10 mL of water is between 1.8 and 2.8.
Sterility Test It meets the requirement, when Tetracycline Hydrochloride is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Tetracycline Hydrochloride is used in a sterile preparation.
Weigh an appropriate amount of Tetracycline Hydrochloride, dissolve in water to make a solution so that each
mL contains 5.0 mg, and use the solution as the test solution. The amount of injection is 1.0 mL of the test solution per kg of body weight of rabbit.
Histamine It meets the requirement, when Tetracycline Hydrochloride is used in a sterile preparation.
Weigh an appropriate amount of Tetracycline Hydrochloride, dissolve in Isotonic Sodium Chloride Injection
to make a solution so that each mL contains 5.0 mg,
and use the solution as the test solution. Use 0.5 mL of
this solution for the test.
Tetracycline Hydrochloride, dissolve in diluted hydrochloric acid (1 in 1000) to make a solution so that
each mL contains 1 mg (potency), take exactly an appropriate amount of this solution, add 0.1mol/L phosphate buffer, pH 4.5 to make a solution so that each mL
contains 250 g (potency), and use this solution as the
test stock solution. Pipet exactly 4 mL of this stock solution, add exactly 5 mL of diluted hydrochloric acid (1
in 5), heat for 5 minutes in water bath and cool down,
add water to make exactly 50 mL, and use this solution
25 mg (potency) of Tetracycline Hydrochloride RS,
dissolve in water to make a solution so that each mL
contains 500 g (potency), and use this solution as the
standard stock solution. Pipet exactly an appropriate
amount of this solution, add water to make a solution
so that each mL contains 250 g (potency), and use this
solution as the standard solution. Pipet each 2.0, 3.0,
Tetrahydrozoline Hydrochloride
H
N
HCl
and enantiomer
C13H16N2HCl: 236.74
Tetrahydrozoline Hydrochloride contains not less than
98.0% and not more than 100.5% of tetrahydrozoline
hydrochloride (C13H16N2HCl), calculated on the dried
basis.
Description Tetrahydrozoline Hydrochloride is a
white solid and is odorless.
Tetrahydrozoline Hydrochloride is freely soluble in water or in ethanol, very slightly soluble in chloroform
Melting pointAbout 256 C(with decomposition).
of solutions of Tetrahydrozoline Hydrochloride and Tetrahydrozoline Hydrochloride RS (1 in 4000) as directed under the Ultraviolet-visible Spectrophotometry:
both spectra exhibit similar intensities at the same wavelengths and the respective absorbances, calculated on
the dried basis, at the wavelengths of a maximum absorbance near 264 nm and near 271 nm do not differ by
more than 4.0%.
(2) Determine the infrared spectra of Tetrahydrozoline Hydrochloride and Tetrahydrozoline Hydrochloride RS, previously dried at 105 C for 2 hours, as directed in the potassium bromide disk method under the
Infrared spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) A solution of Tetrahydrozoline Hydrochloride (1
Purity (1) Heavy metalsWeigh 0.40 g of Tetrahy-
drozoline Hydrochloride, dissolve in 23 mL of water,

add 2 mL of 1 mol/L acetic acid TS and perform the
test according to the Method 1. Prepare the control solution with 2.0 mL of standard lead solution (not more
than 50 ppm).
(2) Related substancesWeigh 0.1 g of Tetrahydrozoline Hydrochloride in 10 mL of methanol and use
this solution as the test solution. Separately, weigh 10
mg of Tetrahydrozoline Hydrochloride RS, previously
dried at 105 C for 2 hours and dissolve in methanol to
make exactly 10 mL. Pipet exactly 0.1 mL, 0.5 mL, 1
mL and 2 mL of this solution, add methanol to each solution to make exactly 10 mL and use these solutions as
the standard solutions (1), (2), (3) and (4), respectively.
Spot 20 L each of the test solution and standard solutions (1), (2), (3) and (4) on a plate of silica gel. Develop the plate with a mixture of methanol, anhydrous
acetic acid and water (8 : 1 : 1) to a distance of about
15 cm and air-dry the plate. Spray evenly platinic chloride-potassium iodide solution on the plate and examine under ultraviolet light (254 nm and 366 nm): intensity of the spots other than the principal spot from
the test solution is not more than 2.0% of the spot from
hours)
Residues on Ignition Not more than 0.1% (1 g)
Assay Weigh accurately about 0.4 g of Tetrahydrozoline Hydrochloride, transfer to a beaker and add 60 mL
of anhydrous acetic acid. Dissolve the solution by
warming, if necessary. Add 5 mL of acetic anhydride
and 5 mL of mercuric acetate and titrate with 0.1 mol/L
of perchloric acid VS (indicator: 3 drops of quinaldine
red reagent). Perform a blank determination and make

= 23.674 mg of C13H16N2HCl
Thallium (201Tl) Chloride

Injection
Thallium (201Tl) Chloride Injection is an aqueous solution for injection containing Thallium-201 in the form
of thallous chloride.
Thallium (201Tl) Chloride Injection conforms to the requirements of Thallium (201Tl) Chloride Injection in the
Korean Pharmaceutical Codex (Third Edition, 2007).
The Insoluble Particulate Matter Test for Injections is
not applied to this injection.
Description Thallium (201Tl) Chloride Injection is a
Theophylline
O
H
N
H 3C
N
N
O
N
CH3
C7H8N4O2: 180.16
Theophylline, when dried, contains not less than 99.0
and not more than 101.0% of theophylline (C7H8N4O2).
Description Theophylline is a white crystal or crystalline powder and is odorless.
Theophylline is soluble in dimethylformamide, slightly
soluble in water, in ethanol or in chloroform and practically insoluble in ether.
Theophylline dissolves in potassium hydroxide TS or
in ammonia TS.
of solutions of Theophylline and Theophylline RS in
0.1moL/L hydrochloric acid TS (1 in 200000) as directed under the Ultraviolet-visible Spectrophotometry:
(2) Determine the infrared spectra of Theophylline
and Theophylline RS, previously dried, as directed in
Purity (1) AcidTo 0.5 g of Theophylline, add 75
mL of water, 2.0 mL of 0.01 mol/L sodium hydroxide
VS and 1 drop of methyl red TS: a yellow color is observed.
(2) Heavy metalsProceed with 1.0 g of Theophylline according to Method 4 and perform the test.
Theophylline according to Method 3 and perform the
(4) Related substancesDissolve 0.10 g of Theophylline in 3 mL of dimethylformamide, add 10 mL of
methanol and use this solution as the test solution. Pipet 1.0 mL of the test solution, add methanol to make
Chromatography, Spot 10 L each of the test solution
KP 9 921
Develop the plate with a mixture of acetone, chloroform, methanol, n-butanol and strong ammonia water
(3 : 3 : 2 : 2 : 1) to a distance of about 10 cm and airdry the plate. Examine under ultraviolet light (main
test with 0.20 g of Theophylline. The solution has no
more color than diluted Color Matching Fluid A (1 in
5).
hours).
Assay Weigh accurately about 0.25 g of Theophylline,
previously dried, dissolve in 100 mL of water, add exactly 20 mL of 0.1 mol/L silver nitrate VS, shake the
mixture and titrate with 0.1 mol/L sodium hydroxide
VS (potentiometric titration, Endpoint Detection Method in Titrimetry), Perform a blank determination and
= 18.016 mg of C7H8N4O2
Theophylline Tablets
Theophyllin Tablets contains not less than 94.0% and
not more than 106.0% of the labeled amount of theophyllin (C7H8N4O2: 180.16).
Tablets, with Theophylline.
Identification (1) Weigh a quantity of powdered Tablets, equivalent to about 0.5 g of theophylline, triturate
with 10 mL and 5 mL volumes of hexane and discard
the hexane. Triturate the residue with two 10 mL volumes of a mixture of ammonium hydroxide TS and
water (1 : 1) and filter each time. Evaporate the combined filtrates to about 15 mL, neutralize, if necessary,
with 6 mol/L acetic acid TS, using litmus and then cool
to about 15 C, with stirring. Collect the precipitate on
a filter, wash it with cold water and dry at 105 C for 2
hours: the residue so obtained melts between 270 C
and 274 C.
(2) Determine the infrared spectra of the residue obtained in Identification (1) and Theophylline RS, previously dried, as directed in the potassium bromide disk
same wavenumbers.
(3) The retention time of the main peak obtained as
directed in the Assay from the test solution corresponds

to that exhibited by the standard solution.
Theophylline Tablets at 50 revolutions per minute according to Method 2 under the dissolution test, using
900 mL of water. Take a portion of dissolved solution
45 minutes after start of the test, filter, dilute with a
portion of test solution, if necessary and use this solution as the test solution. Separately, weigh accurately a
portion of Theophylline RS, previously dried at 105 C
for 4 hours, prepare the solution according to the same
method as the test solution and use this solution as the
standard solution. Determine the absorbances of the test
solution and the standard solution at 272 nm as directed
the dissolution solution as blank.
The dissolution rate of Theophylline Tablets in 45 minutes is not less than 80%.
ment.
Assay To 10 tablets of Theophylline Tablets, add 50

mL of water and 50 mL of ammonium hydroxide TS,
disintegrated the tablets completely by shaking well,
add water to make exactly 500 mL and filter through a
dry filter. Discard the first 20 mL of the filtrate, pipet
exactly a portion of the filtrate (V mL), equivalent to
about 10 mg of theophylline (C7H8N4O2) according to
the labeled amount, add 20 mL of internal standard solution, dilute with the mobile phase to make exactly
100 mL and use this solution as the test solution. Separately, weigh accurately a portion of theophylline RS,
previously dried at 105 C for 4 hours and dissolve in
mobile phase so that each mL contains 1 mg of theophylline. Pipet exactly 10 mL of this solution, add 20.0
mL of the internal standard solution, dilute with the
ratios of peak area, QT and QS of theophylline for the
test solution and the standard solution to that of the internal standard.
Amount (mg) of theophyllin (C7H8N4O2)

C
QT
= 5000 V Q
S
C: Concentration (mg/mL) of theophylline in the
standard solution,
Internal standard solutionWeigh accurately about
50 mg of theobromine, dissolve in 10 mL of ammonium hydroxide TS and add mobile phase to make exactly 100 mL.

octadecylsilanized silica gel for liquid chromatography.
Mobile phase: 70 mL of acetonitrile in buffer to
make 1000 mL.
System suitablilty
operating conditions, the resolution between internal
standard and theophylline is not less than 1.5.
System repeatability: When the test repeated 6
the peak area of theophylline is not more than 1.5%.
Buffer solutionDissolve 2.72 g of sodium acetate
in 200 mL of water, add 20 mL of anhydrous acetic acid and add water to make exactly 2000 mL.
Packaging and Storage Preserve in well-closed containers
Thiamazole
CH3
N
SH
C4H6N2S: 114.17
Thiamazole, when dried, contains not less than 98.0%
and not more than 101.0% of thiamazole (C4H6N2S).
Description Thiamazole is a white to pale yellowish
white crystal or crystalline powder, has a faint, characteristic odor and has a bitter taste.
Thiamazole is freely soluble in water or in ethanol and
pHDissolve 1.0 g of Thiamazole in 50 mL of water: the pH of this solution is between 5.0 and 7.0.
Identification (1) Dissolve 5 mg of Thiamazole in 1
mL of water, shake with 1 mL of sodium hydroxide TS
and add 3 drops of sodium nitroprusside TS: a yellow
color is observed and it gradually changes to yellowgreen to green. To this solution, add 1 mL of acetic acid: it changes to blue.
(2) To 2 mL of a solution of Thiamazole (1 in 200),
add 1 mL of sodium carbonate TS and 1 mL of diluted
Folin's TS (1 in 5): a deep blue color is observed.
Melting Point
Purity (1) SeleniumProceed with 0.10 g of Thiamazole as directed under the Oxygen Flask Combustion Method, using 25 mL of diluted nitric acid (1 in
30) as the absorbing liquid and prepare the test solution.
Apply a small volume of water to the upper part of apparatus A, pull out C carefully and transfer the test solution to a beaker. Wash C, B and the inner side of A
with 25 mL of water and combine the washings with
the test solution. Boil gently for 10 minutes, cool to
room temperature, add water to make exactly 50 mL
weigh exactly 40 mg of selenium, dissolve in 100 mL
of diluted nitric acid (1 in 2), heat to dissolve on a water-bath, if necessary and add water to make exactly
1000 mL. Pipet exactly 1 mL of this solution and add
water to make exactly 200 mL. To 2 mL of this solution,
exactly measured, add diluted nitric acid (1 in 60) to
make exactly 50 mL and use this solution as the standard solution. Pipet exactly 40 mL each of the test solution and the standard solution into separate beakers and
adjust each solution with strong ammonia water to a pH
of 1.8 to 2.2. To each solution, add 0.2 g of hydroxylamine hydrochloride, shake gently to dissolve, then add
5 mL of 2,3-diaminonaphthalene TS, shake and allow
to stand for 100 minutes. Transfer these solutions to
corresponding separatory funnels, rinse the beakers
with 10 mL of water, combine the rinsings in the respective separatory funnels, shake well with 5.0 mL of
cyclohexane for 2 minutes and extract. Centrifuge the
cyclohexane extracts to remove any water remaining in
these solutions. Perform the test with the test solution
and the standard solution as directed under the Ultraviolet-visible Spectrophotometry, using a solution prepared with 40 mL of diluted nitric acid (1 in 60) in the
same manner as the blank. The absorbance of the test
solution at the wavelength of maximum absorbance
near 378 nm does not exceed the absorbance of the
standard solution.
(2) Heavy metalsProceed with 1.0 g of Thiamazole according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead
Thiamazole according to Method 1 and perform the test
hours).
Assay Weigh accurately about 0.25 g of Thiamazole,
previously dried, dissolve in 75 mL of water, add 15.0
mL of 0.1 mol/L sodium hydroxide VS from a burette
and add 30 mL of 0.1 mol/L silver nitrate VS with stirring. Add 1 mL of bromothymol blue TS and titrate
with 0.1 mol/L sodium hydroxide VS, until a persistent
blue-green color is observed. Determine the total volume of 0.1 mol/L sodium hydroxide VS consumed.
KP 9 923

= 11.417 mg of C4H6N2S
well-closed container.
Thiamine Hydrochloride
N
H3C
NH2
Thiamazole Tablets contain not less than 94.0% and not

more than 106.0% of the labeled amount of thiamazole
(C4H6N2S: 114.17).
Tablets, with Thiamazole.
Identification (1) To a quantity of powdered Thiamazole Tablets, equivalent to 50 mg of thiamazole according to the labeled amount, add 20 mL of hot ethanol, shake for 15 minutes, filter and evaporate the filtrate on a water-bath to dryness. Dissolve the residue in
10 mL of water, filter, if necessary and use this solution
as the test solution. To 1 mL of the test solution, add 1
mL of sodium hydroxide TS, shake and add 3 drops of
sodium nitroprusside TS: a yellow color develops and it
gradually changes to yellow-green to green. To this solution, add 1 mL of acetic acid: it changes to blue.
(2) With 2 mL of the test solution obtained in (1),
proceed as directed in the Identification (2) under
Thiamazole.
ment.

Thiamazole Tablets. Weigh accurately a quantity of the
powder, equivalent to about 0.15 g of thiamazole
(C4H6N2S), add 80 mL of water, shake for 15 minutes,
add water to make exactly 100 mL and centrifuge. Filter, discard the first 20 mL of the filtrate, take exactly
50 mL of the subsequent filtrate, add 1 mL of bromothymol blue TS and if a blue color develops, neutralize
with 0.1 mol/L hydrochloric acid VS until the color of
the solution changes to green. To this solution, add 4.5
mL of 0.1 mol/L sodium hydroxide VS from a burette,
add 15 mL of 0.1 mol/L silver nitrate VS while stirring
and titrate with 0.1 mol/L sodium hydroxide VS. Continue the titration until a persistent blue-green color is
produced and determine the total volume of 0.1 mol/L
sodium hydroxide VS consumed.

= 11.417 mg of C4H6N2S
well-closed container.
CH2CH2OH
Cl-
Thiamazole Tablets
CH2
HCl
N
CH3
Vitamin B1 Hydrochloride C12H17ClN4OSHCl: 337.27

Thiamine Hydrochloride contains not less than 98.5%
and not more than 101.0% of thiamine hydrochloride
(C12H17ClN4OSHCl), calculated on the anhydrous basis.
Description Thiamine Hyrochloride is a white crystal
or crystalline powder and is odorless or has a slight
Thiamine Hydrochloride is freely soluble in water, sparingly soluble in methanol, slightly soluble in ethanol
Identification (1) To 5 mL of a solution of Thiamine
Hydrochloride (1 in 500), add 2.5 mL of sodium hydroxide TS and 0.5 mL of potassium ferricyanide TS.
Then add 5 mL of isobutanol, shake the mixture vigorously for 2 minutes, allow to stand and examine under
ultraviolet light (main wavelength: 365 nm): the isobutanol layer shows a blue-purple fluorescence. This fluorescence disappears when the mixture is acidified, but
reappears when made alkaline again.
(2) Determine the absorption spectra of Thiamine
Hydrochloride and Thiamine Hydrochloride RS (1 in
100000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar absorption
at same wavelengths.
(3) Determine the infrared spectra of Thiamine Hydrochloride and Thiamine Hydrochloride RS, previously dried at 105 C for 2 hours, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
appears between the spectra, dissolve each in water,
evaporate water to dryness, dry at 105 C for 2 hours
and repeat the test on the residues.
(4) A solution of Thiamine Hydrochloride (1 in
pH Dissolve 1.0 g of Thiamine Hydrochloride in 100
3.4.
1.0 g of Thiamine Hydrochloride in 10 mL of water:
the solution is clear and has no more color than the following control solution.

Control solutionTo 1.5 mL of 1/60 mol/L potassium bichromate VS, add water to make 1000 mL.
thiamine to that of the internal standard for the test solution and the standard solution, respectively.
(2) SulfateWeigh 1.5 g of Thiamine Hydrochloride and perform the test. Prepare the control solution
more than 0.011%).
(3) NitrateDissolve 0.5 g of Thiamine Hydrochloride in 25 mL of water. Add 2 mL of sulfuric acid to 2
mL of this solution, shake, cool and superimpose ferrous sulfate TS: no dark brown ring is observed at the
junction of the two layers.
(4) Heavy metalsProceed with 1.0 g of Thiamine
test. Prepare the control solution: with 2.0 mL of standard lead solution (not more than 20 ppm).
(5) Related substancesDissolve 0.10 g of Thiamine Hydrochloride in 100 mL of the mobile phase and
conditions and determine the area of each peak from
these solutions by the automatic integration method: total area of the peaks other than the principal peak is not
larger than the peak area of the principal peak from the
standard solution.
Amount (mg) of thiamine hydrochloride

(C12H17ClN4OSHCl)
= amount (mg) of Thiamine Hydrochloride RS, calcuQT
lated on the anhydrous basis Q
S
phase, flow rate and selection of column: Proceed as directed in the operating conditions under Assay.
Test for required detectability: To exactly 5 mL of
the standard solution add water to make exactly 50 mL.
Confirm that the peak area of thiamine obtained from
l0 L of this solution is equivalent to 7 to 13% of that
of thiamine obtained from l0 L of the standard solution.
Time span of measurement: About 3 times of the retention time of thiamine.
Water Not more than 5.0% (0.5 g, coulometric titration).
Assay Weigh accurately about 0.1 g each of Thiamine
Hydrochloride and Thiamine Hydrochloride RS (water
content is determined previously) and dissolve the mobile phase to make exactly 50 mL. Pipet exactly 10 mL
each of the solutions, add exactly 5 mL of the internal
standard solution, then add the mobile phase to make
exactly 50 mL and use these solutions as the test solution and the standard solution, respectively. Perform the
test with 10 L each of the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions
and calculate the ratios, QT and QS, of the peak area of

benzoate in methanol (1 in 50).
with octadecylsilanized silica gel for liquid chromatography (5m to 10 m in particle diameter).
about 25 C.
Mobile phase: Dissolve 1.1 g of sodium 1octanesulfonate in 1000 mL of diluted anhydrous acetic
acid (1 in 100). To 600 mL of this solution, add 400 mL
of a mixture of methanol and acetonitrile (3 : 2).
time of thiamine is about 12 minutes.
System suitability
above operating conditions, thiamine and the internal
System repeatability: When the test repeated 6
the ratio of peak area of thiamine to that of the internal
standard is not more than 1.0%.
tight containers.
Injection
Vitamin B1 Hydrochloride Injection
Thiamine Hydrochloride Injection is an aqueous solution for injection. Thiamine Hydrochloride Injection
of the labeled amount of thiamine hydrochloride
(C12H17ClN4OSHCl: 337.27).
Method of Preparation Prepare as directed under Injections, with Thiamine Hydrochloride.
Description
Thiamine Hydrochloride Injection is a
KP 9 925

Identification To a volume of Thiamine Hydrochloride Injection, equivalent to 50 mg of thiamine hydrochloride according to the labeled amount, add water
to make 25 mL. Proceed with 5 mL of this solution as
directed in the Identification (1) under Thiamine Hydrochloride.
Assay Dilute with 0.001 mol/L hydrochloric acid TS,
if necessary, then measure exactly a volume of Thiamine Hydrochloride Injection, equivalent to about 20
mg of thiamine hydrochloride (C12H17ClN4OSHCl)
and add 20 mL of methanol and 0.001 mol/L hydrochloric acid TS to make 100 mL. To exactly 25 mL of this
solution, add exactly 5 mL of the internal standard solution and 0.001 mol/L hydrochloric acid TS to make
Separately, weigh accurately about 0.1 g of Tiamine
Hydrochloride RS (water content is determined previously) and dissolve in 0.001 mol/L hydrochloric acid
TS to make exactly 50 mL. To exactly 10 mL of this
solution, add 20 mL of methanol and 0.001 mol/L hydrochloric acid TS to make exactly 100 mL. To exactly
25 mL of this solution, add exactly 5 mL of the internal
standard solution and 0.001 mol/L hydrochloric acid
TS to make exactly 50 mL and use this solution as the
standard solution. Proceed as directed in the Assay under Thiamine Hydrochloride.
Amount (mg) of C12H17ClN4OSHCl

= amount (mg) of Thiamine Hydrochloride RS,
1
QT
calculated on the anhydrous basis Q 5
S
tight containers.
Powder
Vitamin B1 Hydrochloride Powder
Thiamine Hydrochloride Powder contains not less than

of thiamine hydrochloride (C12H17ClN4OSHCl:
337.27).
Powders, with Thiamine Hydrochloride.
Identification To a portion of Thiamine Hydrochloride Powder, equivalent to 20 mg of Thiamine Hydrochloride according to the labeled amount, add 50
mL of water and 10 mL of dilute acetic acid, shake and
filter. Proceed with 5 mL of the filtrate as directed in
the Identification (1) under Thiamine Hydrochloride.
Purity RancidityThiamine Hydrochloride Powder
has no unpleasant or rancid odor. Thiamine Hydrochloride Powder is tasteless.
Particle Size Determination
ment.

requirement.
Assay Weigh accurately a portion of Thiamine Hydrochloride Powder, equivalent to about 20 mg of
thiamine hydrochloride (C12H17ClN4OSHCl), add 60
mL of methanol and 0.01 mol/L hydrochloric acid TS
and heat in a water-bath for 30 minutes. Shake vigorously for 10 minutes, cool, add methanol to make exactly 100 mL and centrifuge. Pipet exactly 25 mL of
the supernatant, add exactly 5 mL of the internal standard solution and water to make exactly 50 mL and use
this solution as the test solution. Separately, weigh accurately about 0.1 g of Thiamine Hydrochloride RS
(water content is determined previously) and dissolve
in 0.01 mol/L hydrochloric acid TS to make exactly 50
mL. Pipet exactly 10 mL of this solution, add 50 mL of
0.01 mol/L hydrochloric acid TS and add methanol to
make exactly 100 mL. Pipet exactly 25 mL of this solution, add exactly 5 mL of the internal standard solution
and add water to make exactly 50 mL and use this solution as the standard solution. Proceed as directed in the
Assay under Thiamine Hydrochloride.

(C12H17ClN4OSHCl) = amount (mg) of Thiamine Hydrochloride RS, calculated on the anhydrous basis
1
QT
Q 5
S
tight containers.
Tablets
Thiamine Hydrochloride Tablets contain not less than
of thiamine hydrochloride (C12H17ClN4OSHCl:
337.27).

tight containers.
Thiamine Nitrate
H3C
NH2
CH2CH2OH
-
NO3

the Tablets, with Thiamine Hydrochloride.
Identification (1) To a quantity of powdered Thiamine Hydrochloride Tablets, equivalent to 10 mg of
thiamine hydrochloride according to the labeled
amount, add 10 mL of 0.5 mol/L of sodium hydroxide
TS, shake well and filter. Perform the test with 5 mL of
the filtrate according to the Identification (2) of Thiamine Hydrochloride.
(2) To a quantity of powdered Thiamine Hydrochloride Tablets, equivalent to 10 mg of thiamine hydrochloride according to the labeled amount, add 10 mL of
water and filter. To 2 mL of the filtrate, add each of
iodine TS and mercuric chloride TS: a reddish brown
and white precipitate is produced respectively.
(3) To the filtrate of (2), add 1 mL of lead acetate
TS and 1 mL of 2.5 mol/L sodium hydroxide TS: a yellow color appears. Heat on the steam-bath for a few
minutes: a color is changed to brown and the lead sulfate precipitate is separated.
(4) The filtrate of (2) responds to the Qualitative
Tests for chloride.
Thiamine Hydrochloride Tablets at 50 revolution per
Test, using 900 mL of water as the dissolution solution.
Take a portion of dissolved solution 45 minutes after
start of the test and use this solution as the test solution.
Perform the test, as directed in the Assay. If necessary,
perform the test using the standard solution, prepared
from a certain amount, weighed accurately, by the same
manner with the test solution.
The dissolution rate of Thiamine Hydrochloride Tablets
in 45 minutes is not less than 75.0%.
ment.

Thiamine Hydrochloride Tablet and proceed as directed
in the Assay under Thiamine Hydrochloride.

(C12H17ClN4OSHCl) = amount (mg) of Thiamine Hydrochloride RS, calculated on the anhydrous
1
QT
basis Q 5
S
N
CH2
Vitamin B1 Nitrate
CH3
C12H17N5O4S: 327.36
Thiamine Nitrate, when dried, contains not less than

98.0% and not more than 102.0% of thiamine nitrate
(C12H17N5O4S).
Description Thiamine Nitrate is a white crystal or
crystalline powder and is odorless or has a slight, characteristic odor.
Thiamine Nitrate is sparingly soluble in water and very
ether.
Identification (1) Take 2 mL of a solution of Thiamine Nitrate (1 in 500) and add 2 to 3 drops of iodine
TS: a red-brown precipitate or turbidity is produced.
Upon further addition of 1 mL of picric acid TS; a yellow precipitate or turbidity is produced.
(2) To 1 mL of a solution of Thiamine Nitrate (1 in
500), add 1 mL of lead acetate TS and 1 mL of a solution of sodium hydroxide (1 in 10) and warm: the color
of the solution changes through yellow to brown and on
standing, a black-brown precipitate is produced.
(3) To 5 mL of a solution of Thiamine Nitrate (1 in
500), add 2.5 mL of sodium hydroxide TS and 0.5 mL
of potassiurn ferricyanide TS. Then add 5 mL of isobutanol, shake the mixture vigorously for 2 minutes, allow to stand and examine under ultraviolet light (main
wavelength: 365 nm): the isobutanol layer shows a
blue-purple fluorescence. This fluorescence disappears
when the mixture is acidified, but reappears when it is
made alkaline again.
(4) A solution of Thiamine Nitrate (1 in 50) responds to the Qualitative Tests (1) and (2) for nitrate.
pH Dissolve 1.0 g of Thiamine Nitrate in 100 mL of
Purity (1) ChloridePerform the test with 0.20 g of
Thiamine Nitrate. Prepare the control solution with
than 0.053%).
(2) SulfateDissolve 1.5 g of Thiamine Nitrate in
and add water to make 50 mL. Perform the test using
this solution as the test solution. Prepare the control so-
KP 9 927
lution with 0.35 mL of 0.005 mol/L sulfuric acid VS

and 2 mL of dilute hydrochloric acid and add water to
make 50 mL (not more than 0.011%).
(3) Heavy metalsDissolve 1.0 g of Thiamine Nitrate in 30 mL of water by warming, cool and add 12
mL of 6 mol/L acetic acid TS and water to make 50 mL.
Perform the test with this solution as the test solution.

above operating conditions, the relative standard deviation of the ratios of the peak area of thiamine to that of
the internal standard is not more than l.0%.

tight containers.

2 hours).
Assay Weigh accurately about 0.1 g each of Thiamine Nitrate, previously dried, and Thiamine Hydrochloride RS (water content is determined previously) and
dissolve each of them in the mobile phase to make exactly 50 mL. Pipet exactly 10 mL each of the solutions,
add exactly 5 mL each of the internal standard solution,
add the mobile phase to make exactly 50 mL, and use
these solutions as the test solution and the standard solution, respectively. Perform the test with 10 L each of
under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS,
of the peak area of thiamine to that of the internal standard.
Amount (mg) of thiamine nitrate (C12H17N5O4S)

= amount (mg) of Thiamine Hydrochloride RS, calcuQT
lated on the anhydrous basis Q 0.9706
S
Column: A stainless steel column 4.6 mm in inside diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 m
in particle diameter)
about 30 C.
Mobile phase: Dissolve 1.1 g of sodium 1octanesulfonate in 1000 mL of diluted glacial acetic acid (1 in 100). To 600 mL of this solution add 400 mL
of a mixture of methanol and acetonitrile (3:2).
Flow rate: Adjust the flow rate so that the retention time of thiamine is about 12 minutes.
System suitability
operating conditions, thiamine and the internal standard
Thiamylal Sodium
H
N
O
CH2
SNa
CHCH2
N
CH3CH2CH2C
CH3
and enantiomer
Cl2H17N2NaO2S: 276.33
Thiamylal Sodium contains not less than 97.5% and not

more than 101.0% of Thiamylal Sodium
(Cl2H17N2NaO2S), calculated on the dried basis.
Description Thiamylal Sodium is a pale yellow crystal or powder.
Thiamylal Sodium is very soluble in water, and freely
soluble in ethanol.
Thiamylal Sodium is hygroscopic.
Thiamylal Sodium is affected gradually by light.
A solution of Thiamylal Sodium in ethanol (1 in 10)
pHDissolve 1.0 g of Thiamylal Sodium in 10 mL
of water: the pH of this solution is between 10.0 and
11.0.
of solutions of Thiamylal Sodium and Thiamylal Sodium RS in ethanol (7 in 1000000) as directed under
Thiamylal Sodium and Thiamylal Sodium RS, previously dried, as directed in the potassium bromide disk
mcthod under Infrared Spectrophotomctry: both spectra
(3) A solution of Thiamylal Sodium (1 in 10) responds to the Qualitative Tests (1) and (2) for sodium
salt.
Purity (1) Clarity and color of solutionTo 1.0 g of
Thiamylal Sodium in a 11 to 13 mL glass-stoppered
test tube, add 10 mL of freshly boiled and cooled water,
stopper tightly, allow to stand and dissolve by occasional gentle shaking: the solution is clear and pale yellow.
(2) Heavy metalsProceed with 1.0 g of Thiamylal
Sodium according to Method 2 and perform the test.
(3) Related substancesDissolve about 0.10 g of
Thiamylal Sodium in 10 mL of ethanol, and use this solution as the test solution. Pipet exactly 1 mL and 3 mL.
of the test solution, add ethanol to make exactly 200
mL, and use these solutions as the standard solution (1)
and the standard solution (2). Perform the test with
these solutions as directed under Thin-layer Chromatography. Spot 10 L each of the test solution and the
standard solutions (1) and (2) on a plate of silica gel for
thin-layer chromatography, develop with a mixture of
toluene, methanol and ethyl acetate (40 : 7 : 3) to a distance of about 12 cm, and air-dry the plate. Allow the
plate to stand in iodine vapor overnight: the spot appeared with Rf of about 0.1 obtained with the test solution is not more intense than the spot with the standard
solution (2), and the spot other than the principal spot,
the spot at origin and the spot mentioned above obtained with the test solution is not more intense than the
spot with the standard solution (1).
hour).
Assay Weigh accurately about 0.25 g of Thiamylal
Sodium, dissolve in 50 mL of methanol and 5 mL of dilute hydrochloric acid, and add methanol to make exactly 100 mL. Pipet exactly 10 mL of this solution, and
add methanol to make exactly 100 mL. Pipet exactly 5
mL of this solution, add exactly 10 mL of the internal
standard solution and the mobile phase to make exactly
200 mL, and use this solution as the test solution. Separately, weigh accurately about 23 mg of Thiamylal RS,
previously dried at 105 C for 1 hour, dissolve in 50
mL of methanol and 0.5 mL of dilute hydrochloric acid,
and add methanol to make exactly 100 mL. Pipet exactly 5 mL of this solution, add exactly 10 mL of the internal standard solution and the mobile phase to make
exactly 200 mL and use this solution as the standard solution. Perform the test with 20 L each of the test solution and the standard solution as directed under Liquid Chromatography according to the following conditions, and determine the ratios, QT and QS, of the peak
area of thiamylal to that of the internal standard.
Amount (mg) of thiamylal sodium (Cl2H17N2NaO2S)

QT
= amount (mg) of Thiamylal RS Q 10 1.0864
S
Internal standard solutionA solution of phenyl

Column: A stainless steel column about 4 mm in inside diameter and about 15 cm in length, packed with
octadecylsilanised silica gel for liquid chromatography
about 25 C.
Mobile phase: A mixture of methanol and 0.05
mol/L acetic acid-sodium acetate buffer solution, pH
4.6 (13:7).
time of thiamylal is about 6 minutes.
System suitability
operating conditions, thiamylal and the internal standard are eluted in this order with the resolution between
above operating conditions, the relative standard deviation of the ratio of the peak area of thiamylal to that of
tight containers.
Thiamylal Sodium for Injection

Thiamylal Sodium for Injection is a preparation for injection which is reconstituted before use. Thyamylal
Sodium for Injection contains not less than 93.0% and
not more than 107.0% of the labeled amount of thiamylal sodium (C12H17N2NaO2S).
Method of Preparation Prepare as directed under Injections, with 100 parts of Thiamylal Sodium and 7
parts by mass of Dried Sodium Carbonate.
Description Thiamylal Sodium for Injection is as
pale yellow crystal, powder or mass.
Thiamylal Sodium for Injection is hygroscopic.
Thiamylal Sodium for Injection is affected gradually by
light.
Identification (1) Dissolve 0.1 g of Thiamylal Sodium for Injection in 10 mL of water and add 0.5 mL of
barium chloride TS: a white precipitate is produced.
Collect the precipitate and add dilute hydrochloric acid
dropwise: the precipitate dissolves with effervescence.
(2) To 50 mg of Thiamylal Sodium for Injection
add 100 mL of ethanol, shake vigorously, and filter. To
3 mL of the filtrate add ethanol to make 200 mL. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectrophotometry: it
exhibits absorption maxima between 236 nm and 240
nm, and between 287 nm and 291 nm.
KP 9 929
pH Dissolve 1.0 g of Thiamylal Sodium for Injection
in 40 mL of water: the pH of this solution is between
10.5 and 11.5.
Thianthol, when cold, may separate crystal, which melt

on warming.
20
: Between 1.19 and 1.23.
Purity Related substancesTo 0.10 g of Thiamylal

Sodium for Injection add 10 mL of ethanol, shake vigorously, filter, and use the filtrate as the sample solution.
Proceed as directed in the Purity (3) under Thiamylal
Sodium
Identification To 0.1 g of Thianthol, add cautiously 5

mL of sulfuric acid: a blue-purple color is observed.
Add 5 to 6 drops of nitric acid to this solution: the color
of the solution changes to yellow-red with evolution of
gas.

Bacterial Endotoxin Less than 1.0 EU per 1 mg of
Thiamylal Sodium for Injection.
ment.
Assay Open carefully 10 containers of Thiamylal Sodium for Injection, dissolve the contents with water,
wash out the inside of each container with water, combine them, and add water to make exactly V mL so that
each mL contains about 5 mg of thiamylal sodium
(Cl2H17N2NaO2S). Pipet exactly 5 mL of this solution,
and add 0.5 mL of dilute hydrochloric acid and methanol to make exactly 100 mL. Pipet exactly 5 mL of this
solution, add exactly 10 mL of the internal standard solution and the mobile phase to make exactly 200 mL,
and use this solution as the test solution. Proceed the
test with the sample solution as directed in the Assay
under Thiamylal Sodium.
Amount (mg) of thiamylal sodium (Cl2H17N2NaO2S)

QT
V
= amount (mg) of Thiamylal RS Q 50 1.0864
S
Internal standard solutionA solution of phenyl
Packing and Storage
Thianthol
Thianthol consists of dimethylthianthrene and ditoluene
disulfide. Thianthol contains not less than 23.5% and
not more than 26.5% of sulfur (S: 32.07).
Description Thianthol is a yellowish, viscous liquid
and has a faint, agreeable odor.
Thianthol is freely soluble in ether, slightly soluble in
ethanol and practically insoluble in water.
Purity (1) Acidity or alkalinityTo 10 g of Thianthol, add 20 mL of water, mix with shaking, allow to
stand and separate the water layer: the solution is neutral.
(2) SulfateTo 10 mL of the water layer obtained
in (1), add 2 to 3 drops of barium chloride TS: no opalescence is produced.
Assay Weigh accurately about 10 mg of Thianthol
and proceed as directed in the sulfur determination of
the Oxygen Flask Combustion Method, using a mixture
of 5 mL of diluted sodium hydroxide TS (1 in 10) and
1.0 mL of hydrogen peroxide TS as an absorbing liquid.
Thiopental Sodium
H
N
SNa
C2H5
N
CH3CH2CH2C
CH3
C11H17N2NaO2S: 264.32
Thiopental Sodium, when dried, contains not less than
97.0% and not more than 101.0% of thiopental sodium
(C11H17N2NaO2S).
Description Thiopental Sodium is a pale yellow
powder and has a faint, characteristic odor.
Thiopental Sodium is very soluble in water, freely soluble in ethanol and practically insoluble in ether.
A solution of Thiopental Sodium (1 in 10) is alkaline.
Thiopental Sodium is hygroscopic.
A solution of Thiopental Sodium gradually decomposes
on standing.
Identification (1) Dissolve 0.2 g of Thiopental Sodium in 5 mL of sodium hydroxide TS and add 2 mL of
lead acetate TS: a white precipitate, which dissolves
upon heating, is produced. Boil the solution thus obtained: a black precipitate forms gradually and the precipitate responds to the Qualitative Tests for sulfide.
(2) Dissolve 0.5 g of Thiopental Sodium in 15 mL
of water, add 10 mL of dilute hydrochloric acid to produce white precipitate and extract with four 25 mL volumes of chloroform. Combine the chloroform extracts,
evaporate on a water-bath and dry at 105 C for 2
hours: the residue melts between 157 C and 162 C.
(3) A solution of Thiopental Sodium (1 in 10) responds to the Qualitative Tests (1) and (2) for sodium
salt.
1.0 g of Thiopental Sodium in 10 mL of freshly boiled
and cooled water: the solution is clear and pale yellow.
(2) Heavy metalsDissolve 2.0 g of Thipental Sodium in 76 mL of water, add 4 mL of dilute hydrochloric acid, shake and filter through a glass filter (G4). To
40 mL of the filtrate, add 2 mL of ammonium acetate
TS, dilute with water to make 50 mL and perform the
test using this solution as the test solution. Prepare a
control solution as follows: to 2.0 mL of standard lead
solution, add 2 mL of dilute acetic acid, 2 mL of ammonium acetate TS and water to make 50 mL (not more
than 20 ppm).
(3) Neutral and basic substancesWeigh accurately about 1.0 g of Thiopental Sodium, dissolve in 10
mL of water and 5 mL of sodium hydroxide TS and
shake vigorously with 40 mL of chloroform. Separate
the chloroform layer, wash with two 5 mL volumes of
water, filter and evaporate the filtrate on a water-bath to
dryness. Dry the residue at 105C for 1 hour: the
amount of the residue is not more than 0.50%.
(4) Related substancesDissolve 50 mg of Thiopental Sodium in 50 mL of the mobile phase and use
the test solution, add the mobile phase to make exactly
Measure each peak area of each solution by the automatic integration method: the total area of peaks other
than those of thiopental in the test solution is not larger
than the peak area of thiopental in the standard solution.
with octadecylsilanized silica gel (5 m in particle diameter).
about 40 C.
Mobile phase: Dissolve 1 g of potassium dihydrogen phosphate in 1000 mL of water and adjust with
phosphoric acid to a pH of 3.0. To 700 mL of this solution, add 300 mL of acetonitrile.
time of thiopental is about 15 minutes.
System suitablilty
of the standard solution add the mobile phase to make

exactly 10 mL. Confirm that the peak area of thiopental
obtained from 20 L of this solution is equivalent to 15
to 25% of that of thiopental obtained from 20 L of the
standard solution.
System performance: Dissolve 5 mg each of isopropyl parahydroxybenzoate and propyl parahydroxybenzoate in 50 mL of acetonitrile and add water to
isopropyl parahydroxybenzoate and propyl parahydroxybenzoate are eluted in this order with the resolution being not less than 1.9.
as the retention time of thiopental.
80 C, 4 hours).
Assay Weigh accurately about 0.5 g of Thiopental
Sodium, previously dried, transfer to a separatory funnel, dissolve in 20 mL of water, add 5 mL of ethanol
and 10 mL of dilute hydrochloric acid and extract with
50 mL of chloroform, then with three 25 mL volumes
of chloroform. Combine the chloroform extracts, wash
with two 5 mL volumes of water and extract the washings with two 10 mL volumes of chloroform. Filter the
combined chloroform extracts into an Erlenmeyer flask
and wash the filter paper with three 5 mL volumes of
chloroform. Combine the filtrate and the washings and
add 10 mL of ethanol. Titrate with 0.1 mol/L potassium
hydroxide-ethanol VS until the color of the solution
changes from yellow through pale blue to purple (indicator: 2 mL of alizarin yellow GG-thymolphthalein TS).
Perform a blank determination with a mixture of 160
mL of chloroform and 30 mL of ethanol and make any

= 26.43 mg of C11H17N2NaO2S
tight containers.
Thiopental Sodium for Injection

Thiopental Sodium for Injection is a preparation for injection which is reconstituted before use. Thiopental
Sodium for Injection contains not less than 93.0% and
not more than 107.0% of the labeled amount of thiopental sodium (C11H17N2NaO2S: 264.32).
Method of Preparation Prepare as directed under Injections, with 100 parts of Thiopental Sodium and 6
parts of Dried Sodium Carbonate by mass.
Description Thiopental Sodium for Injection is a pale
yellow powder or mass and has a slight, characteristic
KP 9 931
odor.
Thiopental Sodium for Injection is very soluble in water and practically insoluble in dehydrated ether.
Thiopental Sodium for Injection is hygroscopic.
Identification (1) Dissolve 0.1 g of Thiopental Sodium for Injection in 10 mL of water and add 0.5 mL of
barium chloride TS: a white precipitate is produced.
Collect the precipitate and add dilute hydrochloric acid
dropwise: the precipitate dissolves with effervescence.
(2) Proceed as directed in the Identification under
Thiopental Sodium.
pH Dissolve 1 g of Thiopental Sodium for Injection
10.2 and 11.2.
Purity Proceed as directed in the Purity under Thiopental Sodium.
80 C, 4 hours).
Bacterial Endotoxin Less than 1.0 EU per 1 mg of
Thiopental Sodium for Injection.
ment.
Assay Take 10 samples of Thiopental Sodium for Injection and open each container carefully. Dissolve
each content with water, wash each container with water, combine the washings with the former solution and
add water to make exactly 1000 mL. Pipet exactly 10
mL of this solution and add water to make exactly 100
mL. Measure exactly a volume (V mL) of this solution,
equivalent to about 15 mg of thiopental sodium
(C11H17N2NaO2S) and add water to make exactly 1000
mL. Pipet exactly 10 mL of this solution, add 15 mL of
diluted dilute sodium hydroxide TS (1 in 100), add water to make exactly 30 mL and use this solution as the
test solution. Separately, weigh accurately about 46 mg
of Thiopental RS, previously dried at 105 C for 3
hours, dissolve in 50 mL of dilute sodium hydroxide
TS and add water to make exactly 200 mL. Pipet 2.0
mL of this solution, add water to make exactly 100 mL
as directed under the Ultraviolet-visible Spectrophotometry and determine the absorbances, AT and AS, at 304
nm, for the test solution and the standard solution, respectively.
Amount (mg) of thiopental sodium (C11H17N2NaO2S)

in each sample of Thiopental Sodium for Injection
= amount (mg) of Thiopental RS
300
AT
A V 1.0907
S
Thioridazine Hydrochloride
CH3
N
H
CH2
HCl
CH2
N
SCH3
C21H26N2S2HCl: 407.04
Thioridazine Hydrochloride, when dried, contains not
less than 99.0% and not more than 101.0% of thioridazine hydrochloride (C21H26N2S2HCl).
Description Thioridazine Hydrochloride is a white to
pale yellowish, crystalline powder, is odorless and has
a bitter taste.
Thioridazine Hydrochloride is freely soluble in water,
in methanol, in glacial acetic acid or in ethanol, sparingly soluble in acetic anhydride and practically insoluble in ether.
Thioridazine Hydrochloride is gradually colored by
light.
pHDissolve 1.0 g of Thioridazine Hydrochloride
4.2 and 5.2.
Identification (1) Dissolve 10 mg of Thioridazine
Hydrochloride in 2 mL of sulfuric acid: a deep blue
color is observed.
(2) Dissolve 10 mg of Thioridazine Hydrochloride
in 2 mL of water and add 1 drop of ceric ammonium
sulfate TS: a blue color is observed and the color disappears on the addition of excess of the reagent.
(3) Determine the infrared spectra of Thioridazine
Hydrochloride and Thioridazine Hydrochloride RS,
(4) To 5 mL of a solution of Thioridazine Hydrochloride (1 in 100), add 2 mL of ammonia TS and heat in
a water-bath for 5 minutes. After cooling, filter and
acidify the filtrate with dilute nitric acid: the solution

Melting Point
Purity (1) Heavy metalsProceed with 1.0 g of Thioridazine Hydrochloride according to Method 2 and
Thioridazine Hydrochloride according to Method 3 and
(3) Related substancesDissolve 0.10 g of Thioridazine Hydrochloride in 10 mL of methanol and use
the test solution, add methanol to make exactly 20 mL,
pipet exactly 2 mL of this solution, add methanol to
with fluorescent indicator for thin-layer chromatography. After air-drying, immediately develop the plate
with a mixture of chloroform, isopropanol and ammonia water (74 : 25 : 1) to a distance of about 10 cm and
air-dry the plate. After cooling, examine under ultraviolet light (main wavelength: 254 nm): the spots other
than the principal spot and the spots of the starting
point from the test solution are not more intense than
hours).
Assay Weigh accurately about 0.35 g of Thioridazine
1) and titrate with 0.1 mol/L perchloric acid (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any

= 40.70 mg C21H26N2S2HCl
tight containers.
Thiotepa
P
S
Thiotepa, when dried, contains not less than 98.0% and

not more than 101.0% of thiotepa (C6Hl2N3PS).
Description Thiotepa is a colorless or white crystal
Thiotepa is freely soluble in water, in ethanol or in ether.
Dissolve 1.0 g of Thiotepa in 10 mL of water: the solution is neutral.
Identification (1) To 5 mL of a solution of Thiotepa
(1 in 100), add 1 mL of ammonium molybdate TS and
allow to stand: a dark blue color develops slowly when
the solution is cold, or quickly when warm.
(2) To 5 mL of a solution of Thiotepa (1 in 100),
add 1 mL of nitric acid: this solution responds to the
Qualitative Tests (2) for phosphate.
(3) Dissolve 0.1 g of Thiotepa in a mixture of 1 mL
of lead acetate TS and 10 mL of sodium hydroxide TS
and boil: the gas evolved changes moistened red litmus
paper to blue and the solution shows a grayish red color.
1.0 g of Thiotepa in 20 mL of water: the solution is
(2) Heavy metalsProceed with 1.0 g of Thiotepa
in a platinum crucible according to Method 2 and perform the test. Prepare the control solution with 2.0 mL
(3) ArsenicDissolve 0.20g of Thiotepa in 5 mL
of water and add 1 mL of nitric acid and 1 mL of sulfuric acid. Proceed with this solution according to Method 2 and perform the test (not more than 10 ppm).
Loss on Drying Not more than 0.20% (1 g, in vacuum, silica gel, 4 hours).
Assay Weigh accurately about 0.1 g of Thiotepa, previously dried, dissolve in 50 mL of a solution of potassium thiocyanate (3 in 20), add 25 mL of 0.05 mol/L
sulfuric acid VS, exactly measured and allow to stand
for 20 minutes with occasional shaking. Titrate the
VS. The end point titration is only when the color of
the solution changes from red to pale yellow (indicator:
3 drops of methyl red TS). Perform a blank determination and make any necessary correction.

= 6.307 mg of C6Hl2N3PS
N
N
C6Hl2N3PS: 189.22

tight containers. Store in a cold place.
KP 9 933
L-Threonine
H 3C
OH
NH 2
COOH
C4H9NO3: 119.12
L-Threonine,

and not more than 101.0% of L-threonine (C4H9NO3).
Description L-Threonine is a white crystal or crystalline powder, is odorless or has a slight, characteristic
odor and has a slightly sweet taste.
L-Threonine is freely soluble in formic acid, soluble in
water, and practically insoluble in ethanol or in ether.
Identificatlon Determine the infrared spectra of LThreonine and L-Threonine RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
D : Between -26.0
pH Dissolve 0.20 g of L-Threonine in 20 mL of waters: the pH of this solution is between 5.2 and 6.2.
1.0 g of L-Threonine in 20 mL of water: the solution is
(2) ChloridePerform the test with 0.5 g of LThreonine. Prepare the control solution with 0.30 mL
0.021%).
(3) SulfatePerform the test with 0.6 g of LThreonine. Prepare the control solution with 0.35 mL
0.028%).
(4) AmmoniumPerform the test with 0.25g of LThreonine. Prepare the control solution with 5.0 mL of
standard ammonium solution (not more than 0.02%).
(5) Heavy metalsProceed with 1.0 g of LThreonine according to Method 1 and perform the test.
(6) ArsenicDissolve 1.0 g of L-Threonine in 5
mL of dilute hydrochloric acid and perform the test
ppm).
(7) Related substancesDissolve 0.30 g of LThreonine in water to make exactly 50 mL and use this
solution as the test solution. Pipet exactly 1 mL of this
solution, add water to make exactly 50 mL. Pipet exactly 5 mL of this solution, add water to make exactly 20
mL and use this solution as the standard solution. Per-
form the test with the test solution and the standard solution as directed under the Thin-layer Chromatography.
Spot each 5 L of the test solution and the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of 1-butanol,
water, glacial acetic acid (3 : 1 : 1) to a distance of
about 10 cm and air-dry the plate at 80 C for 30 minutes, Spray evenly a solution of ninhydrin in acetone
(1 in 50) upon the plate and dry at 80 C for 5 minutes:
the spots other than the principal spot are not more intense than the spot from the standard solution.
hours).
Assay Weigh accurately about 0.12 g of L-Threonine,
previously dried, dissolve in 3 mL of formic acid, add

= 11.912 mg of C4H9NO3
Thrombin
Thrombin is prepared from prothrombin obtained from
blood of man or bull, through interaction with added
thromboplastin in the presence of calcium ions, sterilized and lyophilized.
Thrombin contains not less than 80.0% and not more
than 150.0% of the labeled units of thrombin.
Each mg of Thrombine contains not less than 10 units
of thrombin.
Description Thrombin is a white to pale yellow,
amorphous substance.
Thrombin equivalent to 500 units is dissolved in 1.0
mL of Isotonic Sodium Chloride Injection: this solution
is clear or slight turbid within 1 minute.
Loss on Drying Not more than 3.0% (50 mg, in vacuum, P2O5, 4 hours).
Assay (1) Fibrinogen solutionWeigh accurately
about 30 mg of fibrinogen and dissolve in 3 mL of Isotonic Sodium Chloride Injection. Allow the solution to
clot sufficiently with frequent shaking after the addition
of about 3 units of Thrombin. Wash the precipitated
clot thoroughly until the washings yield no turbidity on
addition of silver nitrate TS, weigh the clot after drying
at 105 C for 3 hours and calculate the content of the

clot in the fibrinogen. Dissolve the fibrinogen in Isotonic Sodium Chloride Injection so that the clot should
be 0.20%, adjust the pH of the solution between 7.0
and 7.4 by addition of 0.05 mol/L sodium hydrogen
phosphate TS (or if necessary, use 0.5 mol/L of sodium
hydrogen phosphate TS) and dilute with Isotonic Sodium Chloride Injection to make a 0.10% solution.
(2) ProcedureDissolve Thrombin RS in Isotonic
Sodium Chloride Injection and prepare four standard
solutions which contain 4.0, 5.0, 6.2 and 7.5 units in 1
mL, respectively. Transfer accurately 0.10 mL each of
the standard solutions maintained at a given temperature l C between 20 C and 30 C to a small test tube,
10 mm in inside diameter, 100 mm in length, blow out
0.90 mL of the fibrinogen solution at the same temperature into the test tube from a pipet, start a stop-watch
simultaneously, shake the tube constantly and determine the time for the first appearance of clot. Calculate
the average values of five determinations for the four
standard solutions, respectively. If the deviation between the maximum and the minimum values of five
determinations is more than 10% of the average value,
reject the whole run and try the experiment again. The
concentration of the standard solution may be changed
appropriately within the range between 14 and 60
seconds of the clotting time. The determination
proceeds at the same temperature described above.
Next, weigh accurately the whole contents of a single
container of Thrombin, dissolve it in Isotonic Sodium
Chloride Injection to provide a solution which is presumed to contain about 5 units in each mL, treat 0.10
mL of the solution with the same reagents in the same
manner 5 times, determine the clotting times and calculate the average value. Plot the average values of the
clotting times of the four standard solutions on a logarithmic graph, using units as the abscissa and clotting
times as the ordinate and draw a calibration line which
best fits the four plotted points. Using this line, read the
units (U) from the average value of the clotting times of
the test solution.
Units of a single container of Thrombin = U 10 V
V: Number of mL of the volume in which the contents of a single container of Thrombin has been dissolved.
Calculate the units per 1 mg of the contents.

Packaging and Storage Preserve in hermetic containers not exceeding 10 C.
Expiration Date Use within 36 months after the date
of manufacture.
Thymol
OH
CH3
H3C
CH
CH3
C10H14O: 150.22
Thymol contains not less than 98.0% and not more than
101.0% of thymol (C10H14O).
Description Thymol is a colorless crystal or white,
crystalline masses, has an aromatic odor and has a
burning taste.
Thymol is very soluble in glacial acetic acid, freely soluble in ethanol or in ether, and slightly soluble in water.
Thymol sinks in water, but when warmed, it melts and
rises to the surface of water.
Identification (1) To 1 mL of a solution of Thymol in
glacial acetic acid (1 in 300), add 6 drops of sulfuric acid and 1 drop of nitric acid: a blue-green color is observed by reflected light and a red-purple color is observed by transmitted light.
(2) Dissolve 1 g of Thymol in 5 mL of solution of
sodium hydroxide (1 in 10) by heating in a water-bath
and continue heating for several minutes: a pale yellow-red color is slowly observed. Allow this solution to
stand at room temperature: the color changes to dark
yellow-brown. Shake this solution with 2 to 3 drops of
chloroform: a purple color is gradually observed.
(3) Triturate Thymol with an equal mass of camphor or menthol: the mixture liquefies.
Purity (1) Non-volatile residueVolatilize 2.0 g of
Thymol by heating on a water-bath and dry the residue
at 105 C for 2 hours: the mass is not more than 1.0 mg.
(2) Other phenolsShake vigorously 1.0 g of
Thymol with 20 mL of warm water for 1 minute and
filter. To 5 mL of the filtrate, add 1 drop of ferric chloride TS: a green color may be observed, but no blue to
Assay Weigh accurately about 0.5 g of Thymol, dissolve in 10 mL of sodium hydroxide TS and add water
to make exactly 100 mL. Measure exactly 10 mL of the
solution into an iodine flask, add 50 mL of water and
20 mL of dilute sulfuric acid and cool in ice water for
30 minutes. Add exactly 20 mL of 0.05 mol/L bromine
VS, stopper tightly immediately, allow to stand for 30
minutes in ice-water with occasional shaking in a dark
place, add 14 mL of potassium iodide TS and 5 mL of
chloroform, stopper tightly, shake vigorously and titrate
the liberated iodine with 0.1 mol/L sodium thiosulfate
VS (indicator: 3 mL of starch TS). Stopper tightly,
shake vigorously near the end point and continue the titration until the blue color in the chloroform layer disappears. Perform a blank determination and make any
necessary correcting.
KP 9 935

= 3.7554 mg of C10H14O
tight containers.
Dried Thyroid
Dried Thyroid is the fresh thyroid gland, previously
deprived of connective tissue and fat, minced, dried rapidly at a temperature not above 50 C, and powdered
or diluted with suitable diluents. Dried Thyroid is obtained from domesticated animals that are used for food
by human.
Dried Thyroid contains not less than 0.30% and not
more than 0.35% of iodine (I: 126.90) in the form of
organic compounds peculiar to the thyroid gland.
Description Dried Thyroid is a pale yellow to
grayish brown powder and has a slight, characteristic,
meat-like odor.
Identification Mount Dried Thyroid in diluted formalin (1 in 10), stain in hematoxylin TS for 10 to 30
minutes, wash with water, soak in a mixture of 1 mL of
hydrochloric acid and 99 mL of diluted ethanol (7 in
10) for 5 to 10 seconds, and wash again with water for
about 1 hour. Stain in a solution of eosin (1 in 100) for
1 to 5 minutes, wash with water, and soak successively
in diluted ethanol (7 in 10) for 5 to 10 seconds, in diluted ethanol (4 in 5) for 5 to 10 seconds, in diluted
ethanol (9 in 10) for 1 to 2 minutes, in ethanol for 1 to
5 minutes, then in dehydrated ethanol for 1 to 5 minutes. Interpenetrate in xylene, seal with balsam, and
examine under a microscope: epithelial nuclei forming
follicles peculiar to the thyroid gland are observed.
Purity (1) Inorganic iodidesMix 1.0 g of Dried
Thyroid with 10 mL of a saturated solution of zinc sulfate, shake for 5 minutes, and filter. To 5 mL of the filtrate, add 0.5 mL of starch TS, 4 drops of sodium nitrite
TS and 4 drops of dilute sulfuric acid with thorough
shaking: no blue color is observed.
(2) FatExtract 1.0 g of Dried Thyroid with ether
for 2 hours using a Soxhlet extractor. Evaporate the
ether extract, and dry the residue at 105 C to constant
mass: the weight of the residue is not more than 30 mg.
constant mass).
Ash Not more than 5.0% (0.5 g, proceed as directed
in Ash under the Crude Drugs Test).
Assay Transfer about 1 g of Dried Thyroid, accurately weighed, to a crucible, add 7 g of anhydrous potassium carbonate, mix carefully, and gently tap the crucible on the table to compact the mixture. Overlay with
10 g of anhydrous potassium carbonate, and compact
again thoroughly by tapping. Place the crucible in a
muffle furnace preheated to a temperature between 600
C and 700 C, and ignite the mixture for 25 minutes.
Cool, add 20 mL of water, heat gently to boiling, and
filter into a flask. To the residue, add 20 mL of water,
boil, and filter into the same flask. Rinse the crucible
and the char on the funnel with boiling water until the
filtrate measures 200 mL. Add slowly 7 mL of freshly
prepared bromine TS, 40 mL of diluted phosphoric acid
(1 in 2), and boil until starch iodide paper is no longer
colored blue by the evolved gas. Wash down inside of
the flask with water, and continue boiling for 5 minutes.
During the boiling add water from time to time to
maintain at not less than 200 mL. Cool, add 5 mL of a
solution of phenol (1 in 20), again rinse inside the flask
with water, and allow to stand for 5 minutes. Add 2 mL
of diluted phosphoric acid (1 in 2) and 5 mL of potassium iodide TS, and titrate immediately the liberated
iodine with 0.01 mol/L sodium thiosulfate VS (indicator: 3 mL of starch TS). Perform a blank determination,
= 0.21151 mg of I
Tiapride Hydrochloride
O
CH2CH3
N
S
H3C
N
H
OCH3
CH2CH3
HCl
C15H24N2O4SHCl : 364.89
Tiapride Hydrochloride contains not less than 98.5%
and not more than 101.0% of tiapride hydrochloride
(C15H24N2O4SHCl), calculated on the dried basis.
Description Tiapride Hydrochloride is a white, crystalline powder.
Tiapride Hydrochloride is very soluble in water, soluble in methanol, and slightly insoluble in ethanol.
spectra of Tiapride Hydrochloride and Tiapride Hydrochloride RS, as directed in the potassium bromide
disk method under lnfrared Spectrophotornetry : both
same wavenumbers.
(2) A solution of Tiapride Hydrochloride (2.5 in 50)
of Tiapride Hydrochloride in 50 mL of water is between 4.0 and 6.0.
of 2.5 g of Tiapride Hydrochloride in 50 mL of water is
clear. When the test is performed with this solution as
directed under the Ultraviolet-visible Spectrophotome-
KP 9 937
try, the absorbance at the wavelength of 450 nm is not

more than 0.030.
(2) Heavy metalsProceed with 1.0 g of Tiapride
Hydrochloride according to Method 1, and perform the
test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm).
(3) Related substance IDissolve 0.40 g of Tiapride
Hydrochloride, accurately weighed, in methanol to
make exactly 10 mL and use this solution as the test solution. Seperately, dissolve 20.0 mg of tiapride related
substance I RS {N,N-diethylethane-1,2-diamine} in
methanol to make exactly 50 mL. To 2.0 mL of this solution, add methanol to make exactly 20 mL and use
with these solutions, as directed under Thin Layer
and the standard solution on silica gel plate for thinlayer chromatography. Develop the plate with a mixture
of dichloromethane, methanol, dioxane and strong ammonia water (90 : 14 : 10 : 2) to a distance of about 12
cm, and air-dry the plate. Spray with 0.2 w/v% ninhydrin 1-butanol solution and heat at 100 C for 15 minutes: the spot of the related substance I from the test
standard solution (not more than 0.1%).
(4) Related substancesDissolve 0.1 g of Tiapride
Hydrochloride, accurately weighed, in the mobile phase
solution. To 1.0 mL of the test solution, add the mobile
phase to make exactly 10 mL. To 1.0 mL of this solution, add the mobile phase to make exactly 100 mL and
test with 10 L each of the test solution and the standard solution, as directed under the Liquid Chromatography, according to the following operating conditions
and measure the areas of peaks: the area of any peak,
except the principal peak, from the test solution is not
more than the area of the principal peak from the standard solution (0.1%), and the sum of the areas of any
such peaks is not more than 3 times the area of the
principal peak from the standard solution (0.3%). Disregard any peak with an area not more than 0.5 times
the area of the principal peak from the standard solution (not more than 0.05%)
octylsilanized silica gel for liquid chromatography (5
about 40 C.
Mobile phase: Dissolve 5.44 g of potassium dihydrogen phosphate and 80 mg of sodium ocatanesulphonate in 780 mL of water, adjust the pH to 2.7 with
phosphoric acid and add water to make 800 mL. Add
150 mL of methanol and 50 mL of acetonitrile to this
solution.

System suitability
System performance: Dissolve 5.0 mg of Tiapride Hydrochloride RS and 5.0 mg of tiapride N-oxide
RS in the mobile phase to make 100 mL. When the
procedure is run with 10 L each of this solution under
the above operating conditions, the resolution between
the peaks of tiapride (the retention time is about 9 minutes) and tiapride N-oxide (the retention time is about
13 minutes) is not less than 4.0.
constant mass).
Assay Weigh accurately about 0.3 g of Tiapride Hydrochloride, dissolve in 20 mL of glacial acetic acid
and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in the Titrimetry). Perform a blank determination and make any

= 36.489 mg of C15H24N2O4SHCl
Tiaprofenic Acid
CH3
H
O
CO2H
and enantiomer
C14H12O3S : 260.31
Tiaprofenic Acid contains not less than 99.0% and not
more than 101.0% of tiaprofenic acid (C14H12O3S), calculated on the dried basis.
Description Tiaprofenic Acid is a white, crystalline
powder.
Tiaprofenic Acid is very soluble in acetone, in ethanol
or in dichloromethane, and practically insoluble in water.
Identification (1) Dissolve each 25.0 mg of Tiaprofenic Acid and Tiaprofenic Acid RS in 0.01 mol/L
ethanolic hydrochloric acid TS to 50.0 mL. Add 0.01
mol/L ethanolic hydrochloric acid TS to 1.0 mL of this
solution to make 50 mL. Determine the absorption

spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit
(2) Determine the infrared spectra of Tiaprofenic
Acid and Tiaprofenic Acid RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
(3) Dissolve 10 mg of Tiaprofenic Acid in dichloromethane to make 10 mL, and use this solution as the
test solution. Separately, dissolve 10 mg of Tiaprofenic
Acid RS in dichloromethane to make 10 mL, and use
this solution as the standard solution (1). Dissolve 10
mg of Ketoprofene RS in dichloromethane to make 10
mL, add the standard solution (1) to 1 mL of this solution, and use this solution as the standard solution (2).
the Thin-layer Chromatography. Spot 10 L of each solution on a plate of silica gel with fluoroscent indicator
mixture of acetone, dichloromethane and acetic acid
(80 : 20 : 1) to a distance of about 15 cm, and air-dry
the plate examine under ultraviolet light (main wavelanght : 254 nm). The principal spot obtained from the
test solution and the principal spot obtained from the
standard solution (1) show same Rf -value. This test is
effective when clearly separated principal spots of two
kinds in the chromatogram of the standard solution (2).
Melting Point Between 95 and 99
+0.10 (0.5 g, ethylacetate,
10 mL, 100 mm)
[ ]20

about 2.0 g of Tiaprofenic Acid in ethanol to make 20
mL. This solution is clear and not more than intensely
colored than a mixture of 5 mL of control solution and
95 mL of 1 w/v hydrochloric acid.
(2) Heavy metalsProceed with 2.0 g of Tiaprofenic Acid according to method 2 and perform the test.
(3) Related substancesDissolve 20.0 mg of Tiaprofenic Acid in the mobile phase to make 20 mL, and
use this solution as the test solution. Add the mobile
phase to 1.0 mL of test solution to make exactly 50 mL,
add the mobile phase to 1.0 mL of this solution to make
exactly 10 mL, and use this solution as the standard solution (1). Add the mobile phase to 5.0 mL of the standard solution (1) to make exactly 10 mL, and use this
solution as the standard solution (2). Dissolve 10.0 mg
of Tiaprofenic Acid related substance I RS [(2RS)-2(5-benzoylthiopene-3-yl)propanosan] in the mobile
phase to make 100 mL. Add the mobile phase to 1.0
mL of this solution to make exactly 50 mL, and use this
solution as the standard solution (3). Add the standard

solution (3) to 1.0 mL of the standard solution (1) to
make exactly 2 mL, and use this solution as the standard solution (4). Perform the test with each 20 L of
under the Liquid Chromatography according to the following operating conditions. The peak area of the related substance I from the test solution is not greater
than the peak area of that from the standard solution (3)
(not more than 0.2%). The peak area, other than the
principal peak and the peak area of the related substance I are not greater than the area of the principal
peak obtained from the standard solution (2) (0.1%),
the sum of the areas of all the peaks, other than the
principal peak and the peak of the related substance I,
is not greater than 1.5 times the area of the principal
peak obtained from the standard solution (1) (0.3%).
Disregard any peak with an area less than 0.5 times the
area of the principal peak obtained from the standard
solution (2).
diameter).
Mobile phase : A mixture of dichloromethane, hexane, glacial acetic acid and water (500 : 500 : 20 : 1).
Add the water to glacial acetic acid, then hexane and
dichloromethane. Sonicate the mixture for 2 minutes.
Do not degas with helium during analysis.
System suitability
System performance : when the procedure is run
solution (4), as directed under the above operating conditions, the relative retention time of related substance
II, III and I are 0.19, 0.48 and 0.86 to the retention time
of tiaprofenic acid, respectively, with the resolution of
the peak between tiaprofenic acid and the peak of related substance I being not less than 3.0. Adjust the
sensitivity of the system so that the heights of the main
peak obtained from the standard solution (4) is not less
than 50% of the full scale of the recorder.
Loss on Drying Not more than 0.5% (1.0 g, 60,
not more than 0.9 kPa, 3 hours).
Assay Weigh accurately about 0.25 g of Tiaprofenic
Acid, dissolve in 25 mL of ethanol, add 25 mL of water,
and titrate with 0.1 mol/L sodium hydroxide (Indicator:
0.5 mL of phenolphthalein TS). Perform a blank determination and make any necessary correction.
1 mL of 0.1 mol/L sodium hydroxide

= 26.03 mg of C14H12O3S
KP 9 939

Tiaramide Hydrochloride
S
N
Cl
CH2CO
CH2CH2OH
HCl
C15H18ClN3O3SHCl: 392.30
Tiaramide Hydrochloride, when dried, contains not less
than 98.5% and not more than 101.0% of tiaramide hydrochloride (C15H18ClN3O3SHCl).
Description Tiaramide Hydrochloride is a white
Tiaramide Hydrochloride is freely soluble in water,
slightly soluble in ethanol or in glacial acetic acid and
practically insoluble in acetic anhydride or in ether.
pHDissolve 1.0 g of Tiaramide Hydrochloride in
and 4.5.
Identification (1) Dissolve 5 mg of Tiaramide Hydrochloride in 5 mL of 0.1 mol/L hydrochloric acid TS
and add 3 drops of Dragendorffs TS: an orange precipitate is produced.
(2) Determine the infrared spectra of Tiaramide
Hydrochloride and Tiaramide Hydrochloride RS, previously dried, as directed in the paste method under the
(3) A solution of Tiaramide Hydrochloride (1 in 50)
0.5 g of Tiaramide Hydrochloride in 10 mL of water:
(2) Heavy metalsProceed with 2.0 g of Tiaramide
Tiaramide Hydrochloride according to Method 1 and
perform the test. In the procedure, use 20 mL of dilute
hydrochloric acid (1 in 2) (not more than 2 ppm).
(4) Related substancesDissolve 0.20 g of Tiaramide Hydrochloride in 10 mL of diluted ethanol (7 in
10) and use this solution as the test solution. Pipet 1.0
mL of the test solution and add diluted ethanol (7 in 10)
to make exactly 100 mL. Pipet exactly 2 mL of this solution, add diluted ethanol (7 in 10) to make exactly 10
mL and use this solution as the standard solution. Perform the test with the test solution and the standard so-
lution as directed under the Thin-layer Chromatography.

Spot 5 L each of the test solution and the standard solution on a plate of silica gel with fluorescent indicator
for thin-layer chromatography. After air-drying, immediately develop the plate with a mixture of n-butanol,
about 10 cm, air-dry the plate and then dry at 100 C
for 30 minutes. After cooling, examine under ultraviolet light (main wavelength: 254 nm): the spots other
than the principal spot and the spots of the starting
point from the test solution are not more intense than
the spot from the standard solution. Allow the plate to
stand in iodine vapor for 30 minutes: the spots other
than the principal spot and the spot of the starting point
hours).
Assay Weigh accurately about 0.5 g of Tiaramide
3) by warming, cool and titrate with 0.1 mol/L perchloric acid VS until the color of the solution changes
from red through purple to blue-purple (indicator: 3
drops of neutral red TS). Perform a blank determination

= 39.230 mg C15H18ClN3O3SHCl
Ticarcillin Sodium
O
NaO
H
S
O
CH3
N
H
NaO
CH3
S
H
C15H14N2Na2O6S2: 428.39
Ticarcillin Sodium contains not less than 800 g (potency) per mg of ticarcillin (C15H16N2O6S2: 384.43) 800,
Description Ticarcillin Sodium is a white to pale yellowish white powder, and has not a characteristic odor.
Ticarcillin Sodium is very soluble in water, freely soluble in methanol, sparingly soluble in ethanol, and

Identification Weigh accurately about 40 mg each of
Ticarcillin Sodium and Ticarcillin Sodium RS, dissolve
in water to make exactly 100 mL, pipet 5 mL each of
these solutions and add 0.1 mol/L hydrochloric acidmethanol TS to make exactly 100 mL, and use these
solutions as the test solution and the standard solution.
Determine the absorption spectra of these solutions between 200 nm and 300 nm, using 0.1 mol/L hydrochloric acidmethanol TS as the blank, as directed under
Ultraviolet-visible Spectrophotometry, they exhibit
maximum about 230 nm and similar intensities of absorption at the same wavelengths.
of Ticarcillin Sodium in 10 mL of water is between 6.0
and 8.0.
Sterility Test It meets the requirement, when Ticarcillin Sodium is used in a sterile preparation.
Pyrogen Test It meets the requirement, when Ticarcillin Sodium is used in a sterile preparation,. Weigh an
appropriate amount of Ticarcillin Sodium, dissolve in
water, make a solution so that each mL contains 0.1 g,
and use the solution as the test solution. The amount of
injection is 1.0 mL of the test solution per kg of body
weight.
(2) Test organism- Pseudomonas aeruginosa ATCC

10490.
(3) Weigh accurately about 25 mg (potency) of Ticarcillin Sodium, and dissolve in 1 % phosphate buffer
solution, pH 6.0 to make a solution so that each mL
contains 1 mg (potency). Pipet exactly appropriate
amount of this solution, add 0.1 mol/L phosphate buffer
these solutions as the high concentration test solution
and low concentration test solution, respectively. Separately, weigh accurately about 25 mg (potency) of Ticarcillin Sodium RS, and dissolve in 1 % phosphate
buffer solution, pH 6.0 to make a solution so that each
mL contains 1 mg (potency). Pipet exactly appropriate
amount of this solution, add 0.1 mol/L phosphate buffer
these solutions as the high concentration standard solution and the low concentration standard solution, respectively. Perform the test with these solutions according to the Cylinder-plate method (I 8) as directed under

( 2 ~ 8 o C ).
Ticlopidine Hydrochloride
S
HCl
CH2
Cl
C14H14ClNSHCl: 300.25
Ticlopidine Hydrochloride contains not less than 99.0%
and not more than 101.0% of ticlopidine hydrochloride
(C14H14ClNSHCl), calculated on the anhydrous basis.
Description Ticlopidine Hydrochloride is a white to
pale yellowish white crystalline powder.
Ticlopidine Hydrochloride is freely soluble in glacial
acetic acid, soluble in water or in methanol, sparingly
Ticlopidine Hydrochloride and Ticlopidine Hydrochloride RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same
wavenumbers.
(2) A solution of Ticlopidine Hydrochloride (1 in
Purity (1) Heavy metalsProceed with 2.0 g of Ticlopidine Hydrochloride according to Method 3 and perform the test. Prepare the control solution with 2.0 mL
Ticlopidine Hydrochloride according to Method 4 and
(3) Related substancesDissolve 0.5 g of Ticlopidine Hydrochloride in 20 mL of solution of hydrochloric acid in methanol (1 in 20000) and use this solution as
add a solution of hydrochloric acid in methanol (1 in
20000) to make exactly 200 mL and use this solution as
the standard solution (1). Separately, pipet exactly 1
mL of the test solution, add a solution of hydrochloric
acid in methanol (1 in 20000) to make exactly 50 mL
and use this solution as the standard solution (2). Perform the test with the test solution and standard solutions (1) and (2) as directed under the Thin-layer
and the standard solution (1) on a plate of silica gel for
thin-layer chromatography (plate 1) and spot 10 L
each of the test solution and the standard solution (2)
on another plate of silica gel with a fluorescence indicator for thin-layer chromatography (plate 2). Develop
the plates with an upper layer of a mixture of water, n-
KP 9 941
butanol and glacial acetic acid (5 : 4 : 1) to a distance

of about 15 cm and air-dry the plates. Spray evenly a
solution of ninhydrin in acetone (1 in 50) on plate 1 and
heat at 100 C for 20 minutes: the spots other than
principal spot from the test solution are not more intense than the spot from the standard solution (1). Allow plate 2 to stand in iodine vapor for 30 minutes: the
are not more intense than the spot from the standard solution (2).
(4) FormaldehydeDissolve 0.80 g of Ticlopidine
Hydrochloride in 19.0 mL of water, add 1.0 mL of 4
mol/L sodium hydroxide TS, shake well. Centrifuge
and filter the supernatant liquid. Pipet 5.0 mL of the filtrate, add 5.0 mL of acetylacetone TS, mix and warm at
40 C for 40 minutes: the solution has no more color
Control solutionWeigh accurately 0.54 g of formalin and add water to make exactly 1000 mL. Pipet
10.0 mL of this solution, add water to make exactly
1000 mL. Prepare before use. To 8.0 mL of this solution, add water to make 20.0 mL and filter. To 5.0 mL
of the filtrate, add 5.0 mL of acetylacetone TS and proceed in the same manner.
Assay Weigh accurately about 0.4 g of Ticlopidine
Hydrochloride, dissolve in 20 mL of anhydrous acetic

= 30.025 mg of C14H14ClNSHCl
Timolol Maleate
CH3
O
N
CH3
OH
N
H
CH3
HO
OH
C13H24N4O3SC4H4O4 : 432.49
Timolol Maleate, when dried, contains not less than
98.0% and not more than 101.0% of timolol maleate
(C13H24N4O3SC4H4O4).
Description Timolol Maleate is a white to pale yellowish white crystalline power.
Timolol Maleate is freely soluble in glacial acetic acid,
and soluble in water or in ethanol.
Timolol Maleate dissolves in 0.1 mol/L hydrochloric
acid TS.
of a solution of Timolol Maleate and Timolol Maleate
RS in 0.1 mol/L hydrochloric acid TS (3 in 100,000) as
directed under Ultraviolet-visible Spectrophotometry:
(2) Determine the infrared absorption spectra of Timolol Maleate and Timolol Maleate RS as directed in
the potassium bromide disk method under Infrared
Spectrophotornetry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) To 5 mL of a solution of Timolol Maleate (1 in
500) add 1 drop of potassium permanganate TS: the red
color of the TS disappears immediately.
-6.2 (after drying, 1.25 g, 1 mol/L hydrochloric acid
TS, 25 mL, 100 mm).
pH The pH of a solution prepared by dissolving 1.0 g
of Timnolol Maleate in 20 mL of water is between 3.8
and 4.3.
1.0 g of Timolol Maleate in 20 mL of water: the solution is clear, and its absorbance at 440 nm, determined
as directed under Ultraviolet-visible Spectrophotometry
(2) Heavy metalsProceed with 2.0 g of Timolol
Maleate according to Method 4, arid perform the test.
(3) Related substancesDissolve 30 mg of Timolol
Maleate in 20 mL of the mobile phase and use this solution as the test solution. Pipet exactly 1 mL of the test
solution, add the mobile phase to make exactly 100 mL,
the test with exactly 25 L each of the test solution and
standard solution as directed under Liquid Chromatography according to the following conditions, and determine each peak area by the automatic integration
method: the area of the peak other than timolol and
maleic acid is not larger than 0.2 times the peak area of
timolol from the standard solution, and the total area of
the peaks other than the peak of timolol and maleic acid
is not larger than 0.5 times the peak area of timolol

diameter and 25 cm in length, packed with phenylsilanized silica gel for liquid chromatography (5 m in particle diameter).
about 40 C.
Mobile phase: Dissolve 1.9 g of sodium 1hexanesulfonate in 1800 mL of water, add 6.0 mL of
triethylamine and 8.0 mL of formic acid, adiust to pH
3.0 with formic acid, and add water to make 2000 mL.
To 1400 mL of this solution add 500 mL of methanol
and 100 mL of acetonitrile.
time of timolol is about 18 minutes.
System suitability
10 mL. Confirm that the peak area of timolol obtained
from 25 L of this solution is equivalent to 7% to 13%
of that from 25 L of the standard solution.
with 25 L of the test solution under the above operating condition, the number of theoretical plates and the
symmetry factor of the peak of timolol are not less than
1500 and not more than 2.5, respectively.
above operating conditions, the relative standard deviation of the peak area of timolol is not more than 2.0%.
long as the retention time of timolol beginning after the
solvent peak.
100 C, 3 hours).
Assay Weigh accurately about 0.8 g of Timolol Maleate, previously dried, dissolve in 90 mL of glacial
acetic acid, and titrate with 0.1 mol/L perchioric acid
VS (potentiometric titration, Endpoint Detection method in Titrimetry). Perform a blank determination in
the same manner, and make any necessary correction.

= 43.25 mg of C13H24N4O3SC4H4O4
Tinidazole
CH2CH2SO2CH2CH3
O2N
CH3
C8Hl3N3O4S: 247.27
Tinidazole, when dried, contains not less than 98.5%
and not more than 101.0% of tinidazole (C8Hl3N3O4S).
Description Tinidazole is a pale yellow, crystalline
powder.
Tinidazole is soluble in acetic anhydride or in acetone,
sparingly soluble in methanol or in ethanol, and very
of solutions of Tinidazole and Tinidazole RS in methanol (1 in 50000) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared spectra of Tinidazole
and Tinidazole RS as directed in the paste method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
Melting Point
Purity (1) SulfateTo 2.0 g of Tinidazole, add 100

mL of water, boil for 5 minutes, cool, add water to
make 100 mL and filter. Take 25 mL of the filtrate and
50 mL. Use this solution as the test solution and perform the test. Prepare the control solution with 0.45 mL
0.043%).
(2) Heavy metalsProceed with 1.0 g of Tinidazole according to Method 4 and perform the test. Prepare the control solution with 2.0 mL of standard lead
Tinidazole according to Method 3 and perform the test
(4) Related substancesDissolve 50 mg of Tinidazole in 20 mL of acetone and use this solution as the
add acetone to make exactly 200 mL and use this solution as the standard solution. Perform the test with the
test solution and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethyl
acetate and diethylamine (19 : 1) to a distance of about
10 cm, air-dry the plate, heat at 100 C for 5 minute
and cool. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot
hours).
KP 9 943
Assay Weigh accurately about 0.35 g of Tinidazole,

= 24.727 mg of C8Hl3N3O4S
tight containers.
Tipepidine Hibenzate
CH3
COOH
N
S
CO
OH
C
S
C15H17NS2C14H10O4: 517.66
Tipepidine Hibenzate, when dried, contains not less
than 98.5% and not more than 101.0% of tipepidine hibenzate (C15H17NS2C14H10O4).
Description Tipepidine Hibenzate is a white to pale
yellow, crystalline powder, is odorless and tasteless.
Tipepidine Hibenzate is freely soluble in glacial acetic
acid, slightly soluble in methanol or in ethanol, very
ether.
Identification (1) Dissolve 10 mg of Tipepidine Hibentate in 5 mL of sulfuric acid: an orange-red color is
observed.
(2) Dissolve 0.3 g of Tipepidine Hibenzate in 10
mL of sodium hydroxide TS and 5 mL of water and extract with two 20 mL volumes of chloroform. Wash the
chloroform extracts with 10 mL of water and filter the
chloroform layer. Evaporate the filtrate on a water-bath
to dryness and dissolve the residue in 0.5 mL of 1
mol/L hydrochloric acid TS and 5 mL of water. To 2
mL of this solution, add 5 mL of Reinecke salt TS: a
pale red precipitate is produced.
Tipepidine Hibenzate and Tipepidine Hibenzate RS in
dehydrated ethanol (1 in 100000) as directed under the
(4) Determine the infrared spectra of Tipepidine
Hibenzate and Tipepidine Hibenzate RS, previously
dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spec-
tra exhibit similar intensities of absorption at the same

wavenumbers.
Melting Point

1.0 g of Tipepidine Hibenzate in 10 mL of anhydrous
acetic acid: the solution is clear. Perform the test with
Spectrophotometry: its absorbance at 400 nm is not
more than 0.16.
(2) Heavy metalsProceed with 2.0 g of Tipepidine Hibenzate according to Method 2 and perform the
Tipepidine Hibenzate according to Method 3 and perform the test (not more than 2 ppm).
(4) Related substances (i) Dissolve 10 mg of Tipepidine Hibenzate in 20 mL of the mobile phase and
conditions. Determine each peak area of both solutions
any peaks other than the peaks of hibenzic acid and tipepidine from the test solution is not larger than the
peak area of the tipepidine from the standard solution.
about 50 C.
Mobile phase: A mixture of a solution of ammonium acetate (1 in 100) and tetrahydrofuran (32 : 13).
time of tipepidine is between 10 and 14 minutes.
System suitability
exactly 20 mL. Confirm that the peak area of tipepidine
obtained from 20 L of this solution is equivalent to
7% to 13% of that of tipepidine obtained from 20 L of
System performance: Dissolve 10 mg of Tipepidine Hibenzate and 3 mg of propyl parahydroxybenzoate in 100 mL of the mobile phase. When the procedure is run with 20 L of this solution under the above
operating conditions, hibenzic acid, tipepidine and
propyl parahydroxybenzoate are eluted in this order
with a resolution between the peaks of tipepidine and
propyl parahydroxybenzoate being not less than 3.0.

above operating conditions, the relative standard deviation of the peak area of tipepidine is not more than
1.5%.
Time span of measurement: A range of the retention
time of tipepidine after the solvent peak.
(ii) Dissolve 10 mg of Tipepidine Hibenzate in 20
mL of the mobile phase and use this solution as the test
solution. Pipet exactly 1 mL of the test solution, add the
the following conditions. Determine each peak area of
both solutions by the automatic integration method: the
total area of all peaks other than the area of the hibenzic acid and tipepidine from the test solution is not
larger than half of the peak area of the tipepidine from
about 40 C.
Mobile phase: A mixture of methanol and a solution
of ammonium acetate (1 in 500) (13 : 7).
time of tipepidine is between 8 and 12 minutes.
System suitability
exactly 20 mL. Confirm that the peak area of tipepidine
obtained from 20 L of this solution is equivalent to
7% to 13% of that of tipepidine obtained from 20 L of
System performance: Dissolve 10 mg of Tipepidine Hibenzate and 3 mg of propyl parahydroxybenzoate in 100 mL of the mobile phase. When the procedure is run with 20 L of this solution under the above
operating conditions, hibenzic acid, tipepidine and
propyl parahydroxybenzoate are eluted in this order
with a resolution between the peaks of tipepidine and
propyl parahydroxybenzoate being not less than 3.0.
above operating conditions, the relative standard deviation of the peak area of tipepidine is not more than
1.5%.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of tipepidine obtained from
20 L of the standard solution is between 3 mm and 6
mm.
the retention time of tipepidine after the solvent peak.

Loss on Drying Not more than 0.5% (1 g, 60 C, in
vacuum, P2O5, 3 hours).
Assay Weigh accurately about 1 g of Tipepidine Hibenzate, previously dried, dissolve in 40 mL of glacial
VS. The end point of titration is only when the color of
the solution changes from purple through blue to green
correction.

= 51.77 mg of C15H17NS2C14H10O4
Tipepidine Hibenzate Tablets

Tipepidine Hibenzate Tablets contain not less than
of tipepidine hibenzate (C15H17NS2C14 H10O4: 517.66).
Tablets, with Tipepidine Hibenzate.
Identification (1) To a portion of powdered Tipepidine Hibenzate Tablets, equivalent to 44 mg of tipepidine hibenzate according to the labeled amount, add 5
mL of water, shake for 1 minute, add 10 mL of sodium
hydroxide TS and extract with two 20 mL volumes of
chloroform. Combine the extracts, wash with 10 mL of
water and filter the chloroform layer. Evaporate the filtrate on a water-bath to dryness, dissolve the residue in
0.2 mL of 1 mol/L hydrochloric acid TS and 2 mL of
water and add 5 mL of Reinecke salt TS: a pale red
(2) To a portion of powdered Tipepidine Hibenzate
Tablets, equivalent to 11 mg of tipepidine hibenzate according to the labeled amount, add 30 mL of dehydrated ethanol and warm for 10 minutes with occasional shaking. After cooling, add dehydrated ethanol to
make 50 mL and filter. To 1 mL of the filtrate, add dehydrated ethanol to make 20 mL and determine the absorption spectrum of this solution as directed under the
Ultraviolet-visible Spectrophotometry: it exhibits a
maximum between 282 nm and 286 nm.
Dissolution Test Perform the test with 1 tablet of Tipepidine Hibenzate Tablets at 50 revolutions per minute
according to Method 2 under the Dissolution Test, using 900 mL of water. Use the dissolved solution after
30 minutes from starting of the test as the test solution.
KP 9 945
Separately, weigh accurately about 0.11 g of Tipepidine

Hibenzate RS, previously dried in a desiccator (in vacuum, P2O5, 60 C, 3 hours) and dissolve in diluted
ethanol (3 in 4) by warming occasionally. After cooling,
add diluted ethanol (3 in 4) to make exactly 300 mL.
Pipet exactly 20 mL of this solution, add water to make
exactly 900 mL and use this solution as the standard solution. Determine the absorbances, AT1 and AS1, at 286
nm and AT2 and AS2, at 360 nm of the test solution and
the standard solution, respectively, as directed under
the Ultraviolet-visible Spectrophotometry.
The dissolution rate of Tipepidine Hibenzate Tablets in
of tipepidine hibenzate (C15H17NS2C14H10O4)
20
AT1-AT2
= WS A -A C
S1 S2
WS: A mount (mg) of tipepidine hibenzate RS,
C: Labeled amount (mg) of tipepidine hibenzate
(C15H17NS2C14H10O4) in 1 tablet.
ment.

Tipepidine Hibenzate Tablets. Weigh accurately a portion of the powder, equivalent to about 22 mg of tipepidine hibenzate (C15H17NS2C14H10O4), add 10 mL of diluted glacial acetic acid (1 in 2) and 30 mL of methanol
and warm for 10 minutes with occasional shaking. After cooling, add diluted methanol (1 in 2) to make exactly 50 mL and filter. Discard the first 10 mL of the
filtrate, pipet exactly 5.0 mL of the subsequent filtrate,
add exactly 5 mL of the internal standard solution, then
add diluted methanol (1 in 2) to make exactly 25 mL
weigh accurately about 22 mg of Tipepidine Hibenzate
RS, previously dried in a desiccator (in vacuum, P2O5,
60 C, 3 hours), dissolve in 10 mL of diluted glacial
acetic acid (1 in 2) and 30 mL of methanol and add diluted methanol (1 in 2) to make exactly 50 mL. Pipet
5.0 mL of this solution, add 5.0 mL of the internal standard solution, then add diluted methanol (1 in 2) to
peak area of tipepidine to that of the internal standard,
Amount (mg) of tipepidine hibenzate

(C15H17NS2C14H10O4) = amount (mg) of
QT
Tipepidine Hibenzate RS Q
S
Internal standard solutionA solution of Dibu-
caine Hydrochloridc in methanol (1 in 2000).

about 40 C.
Mobile phase: A mixture of a solution of sodium
lauryl sulfate in diluted phosphoric acid (1 in 1000) (1
in 500), acetonitrile and isopropanol (3 : 2 : 1).
time of Tipepidine is about 7 minutes.
System suitablilty
operating conditions, tipepidine and the internal standard are eluted in this order with the resolution between
the peak area of tipepidine is not more than 3.0%.

tight containers.
Tobramycin
H2N
O
HO
OH
O
NH2
NH2
HO
NH2
O
OH
OH
NH2
C18H37N5O9: 467.51
Tobramycin is an aminoglycoside substance having antibacterial activity produced by the growth of Streptomyces tenebrarius.
Tobramycin contains not less than 900 g (potency) per
mg of tobramycin (C18H37N5O9), calculated on the anhydrous basis
Description Tobramycin is a white to pale yellowish
white powder, is odorless or has a little bit of a characteristic odor.
Tobramycin is freely soluble in water, slightly soluble
in methanol, very slightly soluble in ethanol, and practically insoluble in acetone, in ethylacetate, in chloro-
form, or in ether.
Identification Weigh 60 mg of Tobramycin, dissolve
in water to make a solution so that each mL contains 6
mg, and use this solution as the test solution. Separately,
weigh 60 mg of Tobramycin RS, dissolve in water to
make a solution so that each mL contains 6 mg, and use
with these solutions as directed under Thin-layer
Chromatography. Spot an appropriate amount each of
plate with a mixture of methanol, strong ammonia water and chloroform (60:30:25), and air-dry the plate.
Spray evenly the color developing solution on the plate,
and heat the plate at 110 C for 10 minutes. The color
developing solution mixture contains 100 mL of 1 %
ninhydrin solution in butanol and 1 mL of pyridine.
The spots obtained from the test solution are the same
with the corresponding spots from the standard solution
in the Rf value.
of Tobramycin in 10 mL of water is between 9.0 and
11.0.
Purity Heavy metalsProceed with 1.0 g of Tobramycin according to Method 2 and perform the test.
Tobramycin, transfer to a 250 mL flask, add 50 mL of
glacial acetic acid, dissolve with mixing and shaking,
Perform the potentiometric titration with 0.02 mol/L
perchloric acid VS that is standized with potassium hydrogen phthalate. Perform a blank determination and
make any necessary correction. In the potentiometric titration, use glass electrode and caromel electrode filled
with potassium chloride methanol solution as an eclectrolyte.
Amount [g (potency)] of tobramycin per mg

( A B) normality of perchloric acid 93.4 1000
=
amount [mg] of Tobramycin
A: amount[mL] of perchloric acid consumed in a titration of the test solution
B: amount[mL] of perchloric acid consumed in a
blank titration
93.4: the equivalent of tobramycin per mol of perchloric acid
Tocopherol
CH3
CH3
H3C
CH3
CH3
CH3
CH3
HO
CH3
Vitamin E
dl--Tocopherol
C29H50O2: 430.71
Tocopherol contains not less than 96.0% and not more

than 102.0% of tocopherol (C29H50O2).
Description Tocopherol is a clear, yellow to redbrown, viscous liquid and odorless.
Tocopherol is miscible with dehydrated ethanol, with
ether, with chloroform or with vegetable oils.
Tocopherol is freely soluble in ethanol and practically
insoluble in water.
Tocopherol shows no optical rotation.
Tocopherol is oxidized by air and light and acquires a
dark red color.
Identification (1) Dissolve 10 mg of Tocopherol in
10 mL of dehydrated ethanol, add 2 mL of nitric acid
and heat at 75 C for 15 minutes: a red to orange color
is observed.
(2) Determine the infrared spectra of Tocopherol
and Tocopherol RS as directed in the liquid film method under the Infrared Spectrophotometry: both spectra exhibit the similar intensities of absorption at the
same wavenumbers.
%
Absorbance E11cm
(292 nm): Between 71.0 and 76.0
(0.01 g, dehydrated ethanol, 200 mL).
Refractive index
nD20 : Between 1.503 and 1.507.
Specific gravity
20
: Between 0.947 and 0.955.
d 20

0.10 g of Tocopherol in 10 mL of dehydrated ethanol:
the solution is clear and has no more color than Color
Matching Fluid C.
(2) Heavy metalsProceed with 1.0 g of Tocopherol according to Method 4 and perform the test. Prepare
Assay Dissolve about 50 mg each of Tocopherol and
Tocopherol RS, accurately weighed, in dehydrated
ethanol to make exactly 50 mL and use these solutions
as the test solution and the standard solution, respectively. Perform the test with 20 L each of the test solution and the standard solution as directed under the
KP 9 947
conditions and determine the peak heights, H T and

H S , of Tocopherol in the test solution and the standard
Tocopherol Acetate is freely soluble in ethanol and

Tocopherol Acetate shows no optical rotation.
Tocopherol Acetate is affected by air and light.
Amount (mg) of tocopherol (C29H50O2)

H
= amount (mg) of Tocopherol RS T
HS
Identification (1) Dissolve 50 mg of Tocopherol

Acetate in 10 mL of dehydrated ethanol, add 2 mL of
nitric acid and heat at 75 C for 15 minutes: a red to
orange color is observed.
(2) Determine the infrared spectra of Tocopherol
Acetate and Tocopherol Acetate RS as directed in the
liquid film method under the Infrared Spectrophotometry: both spectra exhibit the similar intensity of absorption at the same wavenumbers.
with octadecylsilanized silica gel (5 to m 10 m in
particle diameter).
Mobile phase: A Mixture of methanol and water
(49 : 1).
time of Tocopherol is about 10 minutes.
System suitability
Tocopherol and Tocopherol Acetate in 50 mL of dehydrated ethanol. When the procedure is run with 20 L
tocopherol and tocopherol acetate are eluted in this order with the resolution between these peaks being not
less than 2.6.
times with standard solution under the above operating
conditions: the relative standard deviation of the peak
area of tocopherol is not more than 0.8%.
well-filled, tight containers under nitrogen atmosphere.
Tocopherol Acetate
CH3
CH3
H3C
CH3
CH3
H3C
C
O
CH3
CH3
O
CH3
Vitamin E Acetate
dl--Tocopherol Acetate
C3IH52O3: 472.74
Tocopherol Acetate contains not less than 96.0% and

not more than 102.0% of dl--tocopherol acetate
(C31H52O3).
Description Tocopherol Acetate is a clear, colorless or
yellow, viscous and odorless liquid.
Tocopherol Acetate is miscible with dehydrated ethanol,
with acetone, with chloroform, with ether, with hexane
or with fried oils.
%
Absorbance E11cm
(284 nm): Between 41.0 and 45.0
(10 mg, dehydrated ethanol, 100 mL).
Refractive Index
Specific gravity
nD20 : Between 1.494 and 1.499.

20
: Between 0.952 and 0.966.
d 20

0.10 g of Tocopherol Acetate in 10 mL of dehydrated
ethanol: the solution is clear and has no more color than
Control solutionTo 0.5 mL of ferric chloride colorimetric stock solution, add 0.5 mol/L hydrochloric
acid TS to make 100 mL.
(2) Heavy metalsCarbonize 1.0 g of Tocopherol

Acetate by gentle heating. After cooling, add 10 mL of
a solution of magnesium nitrate in ethanol (1 in 10) and
ignite the ethanol to burn. After cooling, add 1 mL of
sulfuric acid, proceed according to Method 4 and perform the test. Prepare the control solution with 2.0 mL
(3) -TocopherolDissolve 0.10 g of Tocopherol
Acetate in exactly 10 mL of hexane and use this solution as the test solution. Separately, dissolve 50 mg of
Tocopherol RS in hexane to make exactly 100 mL. Pipet 1.0 mL of this solution, add hexane to make exactly
Perform the test with the test solution at the standard
toluene and glacial acetic acid (19 : 1) to a distance of
about 10 cm and air-dry the plate. Spray evenly a solution of ferric chloride in dehydrated ethanol (1 in 500)
on the plate, then spray evenly a solution of ,dipyridyl in dehydrated ethanol (1 in 200) on the same
plate and allow to stand for 2 to 3 minutes: the spot
from the test solution corresponding to that from the
standard solution is not larger than and not more in-
tense than the spot from the standard solution.

Assay Dissolve 50 mg each of Tocopherol Acetate
and Tocopherol Acetate RS, accurately weighed, in dehydrated ethanol to make exactly 50 mL and use these
respectively. Perform the test with 20 L each of the
operating conditions and determine the peak heights,
H T and H S , of Tocopherol Acetate in the test solution and the standard solution, respectively.
Amount (mg) of tocopherol acetate (C31H52O3)

HT
= amount (mg) of Tocopherol Acetate RS
HS
octadecylsilanized silica gel (5 m to 10 m in particle
diameter).
about 35.
(49 : 1).
time of Tocopherol Acetate is about 12 minutes.
System suitability
Tocopherol Acetate and Tocopherol in 50 mL of dehydrated ethanol. When the procedure is run with 20 L
tocopherol and tocopherol acetate are eluted in this order with the resolution between these peaks being not
less than 2.6.
above operating conditions, the relative standard deviation of the peak area of tocopherol acetate is not more
than 0.8%.
tight containers.
Tocopherol Calcium Succinate

CH3
CH3
H3C
CH3
Ca2+
O2C
CH3
CH3
CH3
O
2
CH3
Vitamin E Calcium Succinate
C66H106CaO10: 1099.62
Tocopherol Calcium Succinate, when dried, contains

not less than 96.0% and not more than 102.0% of tocopherol calcium succinate (C66H106CaO10).
Description Tocopherol Calcium Succinate is a white
to yellowish white powder and is odorless.
Tocopherol Calcium Succinate is freely soluble in chloroform or in carbon tetrachloride and practically insoluble in water, in ethanol or in acetone.
Shake 1 g of Tocopherol Calcium Succinate with 7 mL
of glacial acetic acid: it dissolves and produces a turbidity after being allowed to stand for a while.
Tocopherol Calcium Succinate dissolves in glacial acetic acid.
Tocopherol Calcium Succinate shows no optical rotation.
Identification (1) Dissolve 50 mg of Tocopherol
Calcium Succinate in 1 mL of glacial acetic acid, add 9
mL of dehydrated ethanol and mix. To this solution,
add 2 mL of fuming nitric acid and heat at 75 C for 15
minutes: a red to orange color is observed.
(2) Dissolve 80 mg each of Tocopherol Calcium
Succinate and Tocopherol Calcium Succinate RS, previously dried, in 0.2 mL of carbon tetrachloride and determine the infrared spectra of these solutions as directed in the liquid film method under the Infrared
(3) Dissolve 5 g of Tocopherol Calcium Succinate
in 30 mL of chloroform, add 10 mL of hydrochloric acid, shake for 10 minutes, then draw off the water layer
and neutralize with ammonia TS: the solution responds
to the Qualitative Tests for calcium salt.
%
Absorbance E11cm
(286 nm): Between 36.0 and 40.0
(10 mg, chloroform, 100 mL).

0.10 g of Tocopherol Calcium Succinate in 10 mL of
chloroform: the solution is clear and has no more color
Control solutionTo 0.5 mL of ferric chloride colorimetric stock solution, add 0.5 mol/L hydrochloric
acid TS to make 100 mL.
(2) AlkaliTo 0.20 g of Tocopherol Caicium Succinate, add 10 mL of ether, 2 mL of water, 1 drop of
phenolphthalein TS and 0.10 mL of 0.1 mol/L hydrochloric acid VS and shake: no red color is observed in the
water layer.
(3) ChlorideDissolve 0.10 g of Tocopherol Calcium Succinate in 4 mL of glacial acetic acid, add 20
mL of water and 50 mL of ether, shake thoroughly and
collect the water layer. To the ether layer, add 10 mL of
water, shake and collect the water layer. Combine the
water layers, add 6 mL of dilute nitric acid and water to
make 50 mL and perform the test using this solution as
the test solution. Prepare the control solution in the
KP 9 949
same manner using 0.60 mL of 0.01 mol/L hydrochloric acid VS in place of Tocopherol Calcium Succinate
(4) Heavy metalsProceed with 1.0 g of Tocopherol Calcium Succinate according to Method 4 and perform the test. Prepare the control solution with 2.0 mL
Tocopherol Calcium Succinate according to Method 3
(6) -TocopherolDissolve 0.10 g of Tocopherol
Calcium Succinate in chloroform to make exactly 10
dissolve 50 mg of Tocopherol RS in chloroform to
add chloroform to make exactly 10 mL and use this solution as the standard solution. Perform the test with
plate with a mixture of toluene and glacial acetic acid
(19 : 1) to a distance of about 10 cm and air-dry the
plate. Spray evenly a solution of ferric chloride in dehydrated ethanol (1 in 500) on the plate, then spray
evenly a solution of ,-dipyridyl in dehydrated ethanol (1 in 200) on the same plate and allow to stand for
2 to 3 minutes: the spots from the test solution corresponding to the spots from the standard solution is not
larger than and not more intense than the spots from the
standard solution.
P2O5, 24 hours).
with octadecylsilanized silica gel (5 m to 10 m in

particle diameter).
Mobile phase: A mixture of methanol, water and
glacial acetic acid (97 : 2 : 1).
time of tocopherol succinate is about 8 minutes.
System suitability
System performance: Dissolve 50 mg each of tocopherol succinate and Tocopherol in 50 mL of a mixture (9 : 1) of dehydrated ethanol and diluted glacial
acetic acid (1 in 5). When the procedure is run with 20
L of this solution under the above operating conditions: tocopherol succinate and tocopherol are eluted in
this order with the resolution between these peaks being not less than 2.0.
the peak area of tocopherol succinate is not more than
0.8%.
tight containers.
Todralazine Hydrochloride
Hydrate
NHNHCOCH 2CH 3
O
N
HCl
H 2O
Assay Weigh accurately about 50 mg each of Tocopherol Calcium Succinate and tocopherol succinate RS,
previously dried, dissolve in a mixture of dehydrated
ethanol and diluted glacial acetic acid (1 in 5) (9 : 1) to
make exactly 50 mL and use these solutions as the test
solution and the standard solution, respectively. Perform the test with 20 L each of the test solution and
conditions. Determine the peak heights, H T and H S ,
of Tocopherol Succinate for the test solution and the
Amount (mg) of tocopherol calcium succinate

(C66H106CaO10) = amount (mg) of Tocopherol
HT
1.0358
Succinate RS
HS
Ecarazine Hydrochloride
Todralazine Hydrochloride
C11H12N4O2HClH2O: 286.72
Todralazine Hydrochloride contains not less than
98.5% and not more than 101.0% of todralazine hydrochloride (C11H12N4O2HCl), calculated on the anhydrous basis.
Description Todralazine Hydrochloride is a white
crystal or crystalline powder, has a slight, characteristic
odor and has a bitter taste.
Todralazine Hydrochloride is very soluble in formic acid, freely soluble in methanol, soluble in water, sparingly soluble in ethanol and practically insoluble in ether.
pHDissolve 1.0 g of Todralazine Hydrochloride
3.0 and 4.0.
Identification (1) To 2 mL of Todralazine Hydrochloride (1 in 200), add 5 mL of silver nitrate-ammonia
TS: the solution becomes turbid and a black precipitate
is produced.
Todralazine Hydrochloride and Todralazine Hydrochloride RS in 0.1 mol/L hydrochloric acid (3 in 100000) as
(3) Determine the infrared spectra of Todralazine
Hydrochloride and Todralazine Hydrochloride RS as
(4) A solution of Todralazine Hydrochloride (1 in
0.30 g of Todralazine Hydrochloride in 10 mL of water:
the solution is clear and colorless to pale yellow.
(2) SulfateProceed the test with 2.0 g of Todralazine Hydrochloride. Prepare the control solution with
than 0.012%).
(3) Heavy metalProceed with 1.0 g of Todralazine Hydrochloride according to Method 2 and perform
Todralazine Hydrochloride according to Method 1 and
(5) Related substancesDissolve 50 mg of Todralazine Hydrochloride in 100 mL of the mobile phase
conditions. Determine each peak area of both solutions
the peaks other than the peak of todralazine from the
test solution is not larger than the peak area of todralazine from the standard solution.
Detection: An ultraviolet absorption photometer
about 25 C.
Mobile phase: Dissolve 1.10 g of sodium 1-heptane
sulfonate in 1000 mL of diluted methanol (2 in 5). Adjust the pH of the solution to between 3.0 and 3.5 with
glacial acetic acid.
time of Todralazine is about 8 minutes.
System suitablilty
Test for required detection: To exactly 5 mL of
the standard solution add the mobile phase to make ex-
actly 25 mL. Confirm that the peak area of Todralazine

obtained from 10 L of this solutionis equivalent to 15
to 25% of that of Todralazine obtained from 10 L of
System performance: Dissolve 5 mg each of Todralazine Hydrochloride and potassium biphthalate in
100 mL of the mobile phase. When the procedure is run
conditions, potassium biphthalate and Todralazine are
the peak area of tipepidine is not more than 2.0%..
the retention time of Todralazine Hydrochloride after
the solvent peak.
Water Between 6.0 and 7.5% (0.5 g, volumetric titration, direct titration).
Assay Weigh accurately about 0.4 g of Todralazine
Hydrochloride, dissolve in 5 mL of formic acid, add 70
mL of acetic anhydride and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.

= 26.870 mg of C11 H12N4O2HCl
Tofisopam
CH3
O
O
H3C
H3C
N
H3C
O
CH3
H
CH3
and enantiomer
C22H26N2O4 : 382.45
Tofisopam, when dried, contains not less than 98.0%

and not more than 101.0% of tofisopam (C22H26N2O4).
Description Tofisopam is a pale yellowish white,
crystalline powder.
Tofisopam is freely soluble in glacial acetic acid, so-
KP 9 951
luble in acetone, sparingly soluble in ethanol, slightly

soluble in ether, and practically insoluble in water.
A solution of Tofisopam in ethanol (1 in 100) shows no
optical rotation.
of solutions of Tofisopam and Tofisopam RS in ethanol
Spcctrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared absorption spectra of Tofisopam and Tofisopam RS, previously dried, as directed in the potassium bromide disk method under the
Melting Point
Purity (1) Heavy metalsProcced with 1.0 g of Tofisopam according to Method 2, and perform the test.
Tofisopam according to Method 3, and perform the test
(3) Related substancesDissolve 50 mg of Tofisopam in 10 mL of acetone, and use this solution as the
add acetone to make exactly 25 mL. Pipet exactly 1 mL
of this solution, add acetone to make exactly 20 mL,
the test with these solutions as directed under the Thinlayer Chromatography. Spot 10 L each of the test solution and the standard solution on a plate of silica gel
with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate,
acetone, methanol and formic acid (24 : 12 : 2 : 1) to a
spots other than the principal spot from the sample solution are not more intense than the spot from the standard solution.
Assay Weigh accurately about 0.2 g of Tofisopam,
previously dried, dissolve in 50 mnL of acetic acid
(100), and titrate with 0.1 mnol/L perchloric acid VS
(poterntiometric titration, Endpoint Detection Method
in Titrimetry). Perform a blank determination, and

= 38.25 mg of C22H26N2O4
tight containers.
Tolazamide
H3C
SO2NHCONH N
C14H21N3O3S: 311.40
Tolazamide, when dried, contains not less than 97.5%
and not more than 102.0% of tolazamide
(C14H21N3O3S).
Description Tolazamide is a white to pale yellow,
Tolazamide is freely soluble in chloroform, soluble in
acetone, slightly soluble in ethanol or in n-butylamine
and practically insoluble in water or in ether.
Identification (1) Dissolve 20 mg of Tolazamide in 5
mL of water and 1 mL of n-butylamine and 2 to 3 drops
of cupric sulfate TS. Shake well this solution with 5 mL
of chloroform and allow to stand: a green color is observed in the chloroform layer.
Tolazamide and Tolazamide RS in ethanol (1 in
(3) Determine the infrared spectra of Tolazamide
and Tolazamide RS, previously dried, as directed in the
Spectrophotometry: both specta exhibit similar intensities of absorption at the same wavenumbers.
Purity (1) Heavy metalsProceed with 1.0 g of Tolazamide according to Method 2 and perform the test.
Tolazamide according to Method 3 and perform the test
(3) Related substancesDissolve 0.20 g of Tolazamide in acetone to make exactly 10 mL and use this
solution as the test solution. Pipet 1.0 mL of the test solution, add acetone to make exactly 200 mL and use
dissolve 20 mg of p-toluenesulfonamide in acetone to
make exactly 200 mL and use this solution as the standard solution (2). Perform the test with the test solution
and the standard solutions (1) and (2) as directed under
test solution and the standard solutions (1) and (2) on a
plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chloroform, methanol,
cyclohexane and diluted strong ammonia water (10 in
11) (200 : 100 : 60 : 23) to a distance of about 12 cm
and air-dry the plate. Heat the plate at 110 C for 10
minutes and immediately expose to chlorine for 2 minutes. Expose the plate to cold wind until a very pale
blue color develops when 1 drop of potassium iodidestarch TS is placed on a site below the starting line on
the plate. Spray evenly potassium iodide-starch TS on
the plate: the spot from the test solution corresponding
to the spot from the standard solution (2) is not more
intense than the spot from the standard solution (2) and
the spots other than the principal and above spots from
the standard solution (1).
(4) N-AminohexamethyleneimineTo 0.50 g of
Tolazamide, add 20 mL of acetone, stopper the flask
tightly, shake vigorously for 15 minutes, add 8.0 mL of
dibasic sodium phosphate-citric acid buffer solution,
pH 5.4, shake, allow to stand for 15 minutes and filter,
To the filtrate, add 1.0 mL of trisodium ferrous pentacyanoamine TS and shake: the color developing within
30 minutes is not deeper than that of the following control solution.
Control solutionDissolve 0.125 g of Naminohexamethyleneimine in acetone to make exactly
100 mL. Pipet 1.0 mL of this solution and add acetone
to make exactly 100 mL. To 2.0 mL of this solution,
add 8.0 mL of dibasic sodium phosphate-citric acid
buffer solution, pH 5.4, shake and proceed in the same
manner.
60 C, 3 hours).
Assay Weigh accurately about 30 mg each of Tolazamide and Tolazamide RS, previously dried, dissolve
each in 10.0 mL of the internal standard solution and
under the Liquid Chromatography according to the following conditions and calculate the ratios, QT and QS ,
of the peak area of Tolazamide to that of the internal
standard, respectively.
Amount (mg) of tolazamide (C14H21N3O3S)

Q
= amount (mg) of Tolazamide RS T
QS
Internal standard solutionA solution of Tolbutamide in ethanol-free chloroform (3 in 2000).
diameter).

about 25 C.
Mobile phase: A mixture of hexane, water-saturated
hexane, tetrahydrofuran, ethanol and glacial acetic acid
(475 : 475 : 20 : 15 : 9).
time of Tolazamide is about 12 minutes.
System suitability
System performance: When the prodecure is run with
10 L of the standard solution under the above operating conditions, the internal standard and Tolazamide
with 10 L of standard solution under the above operating conditions, the relative standard deviation of ratios
of peak area of Tolazamide to that of the internal standard is not more than 1.0%.
Packaging and Storage Preserve in well-closed containers
Tolazoline Hydrochloride
H
N
CH2
HCl
C10H12N2HCl: 196.68
Tolazoline Hydrochloride contains not less than 98.0%
and not more than 101.0% of tolazoline hydrochloride
(C10H12N2HCl), calculated on the dried basis.
Description Tolazoline Hydrochloride is a white to
grayish white crystalline powder.
Tolazoline Hydrochloride is freely soluble in water or
in ethanol.
An aqueous solution of Tolazoline Hydrochloride is a
weak acid, as tested with litmus paper.
Tolazoline Hydrochloride and Tolazoline Hydrochloride RS as directed in the paste method under the Infrared Spectrophotometry: both spectra exhibit the similar
intensities of absorption at the same wavenumbers.
(2) Perform the test with the identification solution
used in the Related substances: The Rf value of the
principal spot from the identification solution corresponds to the Rf value of the spot from the standard solution A.
Melting Point Between 172.0 C and 176.0 C.
Purity (1) Heavy metalsProceed with 1.0 g of Tolazoline Hydrochloride according to Method 2 and perform the test. Prepare the control solution with 1.0 mL
KP 9 953

(2) Related substancesWeigh accurately a portion of Tolazoline Hydrochloride, dissolve in methanol
to obtain a solution containing 20 mg per mL and use
this solution as the test solution. Dilute a volume of the
test solution quantitatively with methanol to obtain a
solution containing 100 g per mL and use this solution
as the identification solution. Separately, weigh accurately a portion of tolazoline hydrochloride RS, previously dried (silica gel, in vacuum, 4 hours), dissolve
in methanol to obtain a solution containing 100 g per
mL and use this solution as the standard solution (1).
Pipet 4.0 mL, 3.0 mL, 2.0 mL and 1.0 mL of this solution, add methanol to make 5 mL and use these solutions as the standard solution (2), the standard solution
(3), the standard solution (4) and the standard solution
(5), respectively. Perform the test with these solutions
separately 5 L each of the test solution, the identification solution and the standard solutions (1) to (5) on a
plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of methanol and ammonia water (95 : 5) to a distance of about 15 cm and airdry the plate for at least 30 min. Expose the plate to
chlorine gas for not more than 5 minutes and air-dry
until the chlorine has dissipated. Spray the detection
reagent on the plate and compare the intensities of any
secondary spots observed in the chromatogram of the
test solution with those of the principal spots in the
chromatograms of the standard solution: the sum of the
intensities of all secondary spots obtained from the test
solution is not more than 1.0%, as compared with the
intensity of the principal spot from the standard solution.
Tolbutamide
H3C
SO2NHCONHCH 2CH2CH2CH3
C12H18N2O3S: 270.35
Tolbutamide, when dried, contains not less than 99.0%
and not more than 101.0% of tolbutamide
(C12H18N2O3S).
Description Tolbutamide is a white crystal or crystalline powder, is odorless or has a slight, characteristic
odor and is tasteless.
Tolutamide is soluble in ethanol, slightly soluble in
Identification (1) Boil 0.2 g of Tolbutamide with 8
mL of diluted sulfuric acid (1 in 3) under a redux condenser for 30 minutes. Cool the solution in ice-water,
collect the precipitated crystals, recrystallize from water and dry at 105 C for 3 hours: the crystals melt between 135 C and 139 C.
(2) To the filtrate obtained in (1) add about 20 mL
of a solution of sodium hydroxide (1 in 5) to make alkaline and heat: an ammonia-like odor is perceptible.
Assay Weigh accurately about 0.3 g of Tolazoline

Hydrochloride, dissolve in 100 mL of anhydrous acetic
acid, add 25 mL of mercuric acetate TS and titrate with
Endpoint Detection method in Titrimetry). Perform a
Purity (1) AcidTo 3.0 g of Tolbutamide, add 150

mL of water, warm at 70 C for 5 minutes, allow to
stand for 1 hour in ice-water and filter. To 25 mL of the
filtrate, add 2 drops of methyl red TS and 0.20 mL of
0.1 mol/L sodium hydroxide VS: a yellow color is observed.
(2) ChlorideTo 40 mL of the filtrate obtained in
(1), add 6 mL of dilute nitric acid and water to make 50
than 0.011%).
50 mL. Perform the test. Prepare the control solution
more than 0.021%).
(4) Heavy metalsProceed with 2.0 g of Tolbutamide according to Method 2 and perform the test. Prepare the control solution with 2.0 mL of standard lead

= 19.668 mg of C10H12N2HCl.

hours).
Detection reagentDissolve 0.5 g of Potassium

Iodide in 50 mL of water (A). Dissolve 1.5 g of soluble
starch in 50 mL of soluble starch (B). To 10 mL each of
A and B solution, add 3 mL of ethanol upon the use.

Assay Weigh accurately about 0.5 g of Tolbutamide,
previously dried and dissolve in 30 mL of neutralized
ethanol. Add 20 mL of water and titrate with 0.1 mol/L
sodium hydroxide VS (indicator: 3 drops of phenolphthalein TS).

= 27.035 mg of C12H18N2O3S
ment.
Tolbutamide Tablets. Weigh accurately a portion of the
powder, equivalent to about 0.5 g of tolbutamide
(C12H18N2O3S), dissolve in 50 mL of neutralized ethanol, add 25 mL of water and titrate with 0.1 mol/L sodium hydroxide VS (indicator: 3 drops of phenolphthalein TS).
Tolbutamide Tablets

= 27.035 mg of C12H18N2O3S
Tolbutamide Tablets contain not less than 95.0% and

not more than 105.0% of the labeled amount of tolbutamide (C12H18N2O3S: 270.35).

Tablets, with Tolbutamide.
Identification Weigh a quantity of powdered Tolbutamide Tablets, equivalent to 0.5 g of tolbutamide according to the labeled amount, add 50 mL of chloroform, mix with shaking and filter. Evaporate the filtrate
to dryness and proceed with the residue as directed in
the Identification under Tolbutamide.
Dissolution Test Take 1 tablet of Tolbutamide Tablets and perform the test at 100 revolutions per minute
according to the Method 2 under the Dissolution Test,
using 900 mL of phosphate buffer solution, pH 7.4.
Take 20 mL or more of the dissolved solution after 30
minutes from the start of the test and filter through a
membrane filter (less than 0.8 m in pore size). Discard
the first 10 mL of the filtrate, pipet exactly V mL of the
subsequent filtrate, add water to make exactly V ' mL of
a solution containing about 10 g of tolbutamide
(C12H18N2O3S) per mL according to the labeled amount
weigh accurately about 50 mg of Tolbutamide RS, previously dried at 105 C for 3 hours, dissolve in 10 mL
of methanol and add phosphate buffer solution, pH 7.4,
to make exactly 100 mL. Pipet exactly 2 mL of this solution, add water to make exactly 100 mL and use this
solution as the standard solution. Determine the absorbances, AT and AS, of the test solution and the standard
The dissolution rate of Tolbutamide Tablets after 30
minutes should be not less than 80%.
Dissolution rate (%) to labeled amount of tolbutamide

90
1
AT
V'
(C12H18N2O3S) = WS A V C 5
S
WS: Amount (mg) of Tolbutamide RS,
C: Labeled amount (mg) of tolbutamide
(C12H18N2O3S) per tablet.
Tolfenamic Acid
CH3
CO2H
H
N
Cl
C14H12ClNO2 : 261.70
Tolfenamic Acid, when dried, contains not less than
99.0% and not more than 101.0% of tolfenamic acid
(C14H12ClNO2),
Description Tolfenamic Acid is a white or pale yellow, crystalline powder.
Tolfenamic Acid is soluble in dimethylformamide,
slightly soluble in ethanol or in dichloromethane, and
Tolfenamic Acid dissolves in dilute sodium hydroxide
TS.
Melting pointAbout 213.
Identification (1) Dissolve 10 mg each of Tolfenamic acid and Tolfenamic acid RS in a mixture of methanol and 1 mol/L hydrochloric acid TS (99 : 1) to make
100 mL, respectively. To 5.0 mL of this solution add a
mixture of methanol and 1 mol/L hydrochloric acid TS
(99 : 1) to make 50 mL. Determine the absorption spectra of these solutions as directed under the Ultra-visible
(2) Determine the infrared spectra of solutions of
Tolfenamic Acid and Tolfenamic Acid RS as directed
in the potassium bromide disk method under the Infrared
(3) Dissolve 25 mg of Tolfenamic Acid in the mixure of dichloromethane and methanol (3 : 1) to make 10
mL, and use this solution as the test solution. Separately, dissolve 25 mg of Tolfenamic Acid RS in the mix-
KP 9 955
ure of dichloromethane and methanol (3 : 1) to make 10

mL, and use this solution as the standard solution. Perform the test with these solutions as directed under the
thin-layer chromatography. Spot 10 L each of the test
gel with fluorescent indicator for the thin-layer chromatography. Develop the plate with a mixture of toluene,
dioxane, glacial acetic acid (90 : 25 : 1) to a distance of
about 15 cm, air-dry the plate. Examine under ultraviolet light (main wavelength : 254 nm). The principal
spots from the test solution and the standard solution
show same color and same Rf value.
Purity (1) CopperPlace 1.0 g of Tolfenamic acid
in a silica crucible, moisten with sulfuric acid, heat cautiously on a flame for 30 minutes and then heat slowly
to about 650. Continue ignition until particles have
disappeared. Allow to cool, dissolve the residue in 0.1
mol/L hydrochloric acid TS and dilute to 25.0 mL with
the same acid, and use this solution as the test solution.
Dilute standard Copper stock solution with 0.1 mol/L
hydrochloric acid TS to appropriate concentration, and
directed under the Atomic absorption Spectrophotometry. Assay the concentration of copper in the test solution (10 ppm).
Gas : Combustible gas acetylene
Supporting gas air
Lamp : Copper hollow-cathode lamp
avelength : 324.8 nm
(2) Related substancesDissolve 50.0 mg of the

substance in 5 mL of ethanol and dilute to 50.0 mL
with the mobile phase, and use this solution as the test
solution. Separately, dissolve 25 mg of Tolfenamic Acid related substance I (2-chlorobenzoic acid) and 25 mg
of Tolfenamic Acid related substance II (3-chloro-2methylaniline) in 5 mL of ethanol and add the mobile
phase to make exactly 50 mL, and use this solution as
the standard solution (1). Add the mobile phase to 1.0
mL of the test solution, to make exactly 50 mL, add the
mobile phase to 1.0 mL of this solution to make 10.0
mL, and use this solution as the standard solution (2).
Perform the test with each 20 L of the test solution
conditions. The peak area of related substance (1) obtained from the test solution is not more than the peak
area of the corresponding peak obtained from standard
solution (1) (0.1%), related substance (2) is not more
than half the peak area of the corresponding peak obtained from standard solution (1) (0.05%). The peak
area other than the principal peak from the test solution
is not more than the peak area of the principal peak obtained from standard solution (2) (0.1%), the total area
other than the principal peak from the test solution is
not more than 5 times the peak areas of the principal
peak obtained from the standard solution (2) (0.5%).
The peaks smaller than 0.1 times the peak area of the
principal peak obtained from the standard solution (2)

are excepted.
Detector : An Ultraviolet absorption photometer
5m in particle diameter octadecylsilanized silica gel
for liquid chromatography.
Mobile phase : A mixture of ethanol, water and glacial acetic acid (650 : 320 : 2).
System suitability
with the test solution and the standard solution according to the above operating conditions: the relative retention times of related substance I and II to the retention times of tolfenamic acid (about 15 minutes) are
0.25 and 0.34, respectively, with the resolution between
the related substance I peak and the related substance II
peak being not less than 2.5.
Loss on Drying Not more than 0.5 % (1 g, 105 , a
constant mass).
Residue on Drying Not more than 0.1 % (1 g).
Assay Weigh accurately about 0.2 g of Tolfenamic
Acid, previously dried, dissolve in 100 mL of ethanol,
with sonicator and titrate with 0.1 mol/L sodium hydroxide VS (indicator: 0.1 mL of phenol red TS). Perform the blank determination, and make any necessary
correction.

= 26.171 mg of C14H12ClNO2

Tolnaftate
S
NCO
CH3
H3C
C19H17NOS: 307.41
Tolnaftate, when dried, contains not less than 98.0%
and not more than 101.0% of tolnaftate (C19H17NOS).
Description Tolnaftate is a white powder and is odorless.
Tolnaftate is freely soluble in chloroform, sparingly soluble in ether, slightly soluble in methanol or in ethanol

Identification (1) To 0.2 g of Tolnaftate, add 20 mL
of potassium hydroxide ethanol TS and 5 mL of water
and heat under a reflux condenser for 3 hours. After
cooling, to 10 mL of this solution, add 2 mL of glacial
acetic acid and shake with 1 mL of lead acetate TS: a
black precipitate is produced.
Tolnaftate and Tolnaftate RS in methanol (1 in 100000)
(3) Determine the infrared spectra of Tolnaftate and
Tolnaftate RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
Melting Point
drying).
Between 111 C and 114 C (after
Purity (1) Heavy metalsCarbonize 1.0 g of Tolnaftate by gentle heating. After cooling, add 5 mL of nitric
acid and 1 mL of sulfuric acid and heat until white
fumes are evolved. After cooling, add 2 mL of nitric acid and heat until white fumes are evolved. After cooling,
add 2 mL of nitric acid and 0.5 mL of perchloric acid
and heat gradually until white fumes are evolved. Repeat this procedure twice and heat until white fumes are
no longer evolved. Incinerate the residue by igniting
between 500 C and 600 C for 1 hour. Proceed according to Method 2 and perform the test with 50 mL of the
test solution so obtained. Prepare the control solution as
follows: to 11 mL of nitric acid, add 1 mL of sulfuric
acid, 1 mL of perchloric acid and 2 mL of hydrochloric
acid, proceed in the same manner as the test solution
and add 2.0 mL of standard lead solution and water to
make 50 mL (not more than 20 ppm).
(2) Related substancesDissolve 0.50 g of Tolnaftate in 10 mL of chloroform and use this solution as the
chloroform to make exactly 100 mL. Pipet 5.0 mL of
this solution, add chloroform to make exactly 100 mL
10 L each of the test solution and the standard solution on a plate of silica gel with fluorescent indicator
toluene to a distance of about 10 cm and air-dry the
plate. Allow the plate to stand in iodine vapor for 5 minutes and examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot
at a pressure not exceeding 0.67 kPa, 65 C, 3 hours).
Residue on Ignition Weigh accurately 2.0 g of Tolnaftate and carbonize by gradual heating. Moisten the
substance with 1 mL of sulfuric acid, heat gradually until white fumes are no longer evolved and ignite between 450 C and 550 C for about 2 hours to constant
mass: the residue is not more than 0.1%.
Assay Weigh accurately about 50 mg each of Tolnaftate and Tolnaftate RS, previously dried, dissolve each
in 200 mL of methanol by warming in a water-bath,
cool and add methanol to make exactly 250 mL. Pipet
5.0 mL each of the solutions, to each add methanol to
make exactly 100 mL and use these solutions as the test
solution and the standard solution, respectively. Determine the absorbances, AT and AS , of the test solution and the standard solution, respectively, at 257 nm
Amount (mg) of tolnaftate (C19H17NOS)

A
= amount (mg) of Tolnaftate RS T
AS
Tolnaftate Cream
Tolnaftate Cream contains not less than 90.0% and not
more than 110.0% of tolnaftate (C19H17NOS: 307.41).
Creams, with Tolnaftate.
Identification Evaporate 10 mL of the next-to-final

chloroform solution prepared in the Assay on a steambath just to dryness, dissolve the residue in 1 mL of alcohol and use this solution as the test solution. Proceed
as directed in Identification (2) under Tolnaftate.
Assay Weigh accurately a portion of Tolnaftate
Cream, equivalent to about 10 mg of tolnaftate
(C19H17NOS) in a separatory funnel and add 75 mL of
chloroform. Wash the chloroform solution with 25 mL
of 0.1 mol/L sodium hydroxide TS, two 25 mL volumes
of 0.1 mol/L hydrochloric acid TS and 25 mL of water.
Filter the chloroform layer through a chloroformwashed cotton and dilute with chloroform to make exactly 100 mL. Pipet exactly 5 mL of this solution, dilute with chloroform to make exactly 50 mL and use
this solution as the test solution. Separately, weigh accurately a portion of Tolnaftate RS, previously dried (in
vacuum, 65 C, 3 hours), dissolve in chloroform to
make solution having a known concentration of about
10 g per mL and use this solution as the standard solution. Perform the test with the test solution and the
standard solution at about 258 nm using chloroform as
the blank and determine the absorbances, AT and AS, for
KP 9 957

AT
Amount (mg) of tolnaftate (C19H17NOS) = C A
S
C: Concentration (g/mL) of Tolnaftate RS in the
standard solution.
Tolnaftate Topical Solution

Tolnaftate Solution contains not less than 90.0% and
not more than 110.0% of the labeled amount of tolnaftate (C19H17NOS: 307.41).
Method of preparntion Prepare as directed under
Liquids and Solutions, with Tolnaftate.
Identification (1) Spot 1 drop of Tolnaftate Solution
on filter paper. Spray platinic chloride-potassium
iodide TS on the paper: a pale yellow color is observed
in the spot.
(2) To a volume of Tolnaftate Solution, equivalent
to 20 mg of tolnaftate according to the labeled amount,
add chloroform to make 10 mL and use this solution as
the test solution. Separately, dissolve 20 mg of Tolnaftate RS in 10 mL of chloroform and use this solution as
test solution and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with toluene to a distance
of about 12 cm and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spot
from the test solution and that from the standard solution show the same Rf value.
Assay Pipet a volume of Tolnaftate Solution, accurately measured, equivalent to about 20 mg of tolnaftate (C19H17NOS), add 4.0 mL of the internal standard
solution, then add chloroform to make exactly 50 mL
weigh accurately about 0.4 g of tolnaftate RS, previously dried (in vacuum at a pressure not exceeding 0.67
kPa, 65 C, 3 hours) and dissolve in chloroform to
make exactly 100 mL. Pipet exactly 5 mL of this solution, add 4.0 mL of the internal standard solution, then
add chloroform to make exactly 50 mL and use this solution as the standard solution. Perform the test with 10
the following conditions and calculate the ratios, QT
and QS, of the peak area of tolnaftate to that of the internal standard for the test solution and the standard solution, respectively.
Amount (mg) of tolnaftate (C19H17NOS)

1
QT
= amount (mg) of tolnaftate RS Q 20
S
Interal standard solutionA solution of diphenylphthalate in chloroform (3 in 200).
inside diameter and 15 to 30 cm in length, packed with
(5m to 10 m in particle diameter).
about 25 C.
Mobile phase: A mixture of methanol and water (7 :
3).
time of tolnaftate is about 14 minutes.
System suitablilty
operating conditions, the internal standard and Tolnaftate are eluted in this order with the resolution between
Tolperisone Hydrochloride
H
H 3C
COCCH 2
HCl
CH 3
and enantiomer
C16H23NOHCl: 281.82
Tolperisone Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of tolperisone hydrochloride (C16H23NOHCl).
Description Tolperisone Hydrochloride is a white
crystalline powder and has a slight characteristic odor.
Tolperisone Hydrochloride is very soluble in glacial
acetic acid, freely soluble in water or in ethanol, soluble in acetic anhydride, slightly soluble in acetone,
Tolperisone Hydrochloride is hygroscopic.
Melting pointBetween 167 C and 174 C.
pHDissolve 1.0 g of Tolperisone Hydrochloride
4.5 and 5.5.
Identification (1) Dissolve 0.2 g of Tolperisone Hydrochloride in 2 mL of ethanol, add 2 mL of mdinitrobenzene TS and 2 mL of sodium hydroxide TS
and heat: a red color is observed.
(2) To 5 mL of a solution of Tolperisone Hydrochloride (1 in 20), add 2 to 3 drops of iodine TS: a redbrown precipitate is produced.
(3) Dissolve 0.5 g of Tolperisone Hydrochloride in
5 mL of water, add 2 mL of ammonium TS and filter.
Acidify 5 mL of the filtrate with dilute nitric acid: the
solution responds to the Qualitative Tests for chloride.
Torsemide
N
H
N
H
N
CH3
1%
Absorbance E 1cm (257nm): Between 555 and 585

(after drying, 5 mg, ethanol, 500 mL).
1.0 g of Tolperisone Hydrochloride in 10 mL of water:
(2) SulfatePerform the test using 4.0 g of Tolperisone Hydrochloride. Prepare the control solution with
than 0.005%).
(3) Heavy metalsProceed with 1.0 g of Tolperisone Hydrochloride according to Method 2 and perform the test. Prepare the control solution with 2.0 mL
(4) Piperidine hydrochlorideDissolve 0.20 g of
Tolperisone Hydrochloride in water to make exactly 10
dissolve 20 mg of Piperidine Hydrochloride RS in water to make exactly 1000 mL and use this solution as
the standard solution. Transfer exactly 5 mL each of the
test solution and the standard solution to different separatory funnels, add 0.1 mL each of a solution of cupric
sulfate (1 in 20), then add 0.1 mL each of strong ammonia water and exactly 10 mL each of a mixture of
isooctane and carbon disulfide (3 : 1) and shake vigorously for 30 minutes. Immediately after allowing to
stand, separate the isooctane-carbon disulfide mixture
layer and dry with anhydrous sodium sulfate. Perform
as directed under the Ultraviolet-visible Spectrophotometry: the absorbance of the test solution at 438 nm is
not more than that of the standard solution.
Assay Weigh accurately about 0.5g of Tolperisone
mixture of acetic anhydride and anhydrous acetic acid
(7 : 3) and titrate with 0.1 mol/L perchloric acid VS

NH
CH3
CH3
C16H20N4O3S : 348.42
Torsemide contains not less than 98.0% and not more
than 102.0% of torsemide (C16H20N4O3S), calculated
Description Torsemide is a white, crystalline powder.
Torsemide is slightly soluble in ehtanol or in methanol,
very slightly soluble in acetone or in chloroform, and
practically insoluble in water or in ether.
Torsemide and Torsemide RS, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
(2) The retention time of the principal peak obtained from the test solution in the Assay corresponds
to the retention time of the principal peak obtained
Purity (1) Heavy metalsProceed with 1.0 g of Torsemide according to Method 2 and perform the test.
(2) Related substancesUse the test solution in the
Assay. Separately, weigh accurately about 8 mg each of
Torsemide related substance I, {4-[(3-methylphenyl)
amino]-3-pyridinesulfonamide} RS, Torsemide related
Compound II {N-[(n-butylamino)carbonyl]-4-[(3methylphenyl)amino]-3-pyridinesulfoneamide} RS and
Torsemide
related
Compound
III,
{N[ethylamino)carbonyl]-4-[(3-methylphenyl)amino]-3pyridinesulfoneamide} RS, add 30 mL of methanol,
sonicate for not less than 8 minutes. Add 45 mL of 0.02
mol/L potassium phosphate buffer, cool to room temperature, dilute with mobile phase to make exactly 100
mL. Quantitatively dilute a portion of this solution with
mobile phase to obtain a solution having a known concentration of about 0.0019 mg per mL, and use this solution as the standard solution. Perform the test with 20
the following operating conditions in the Assay, measure the peak areas of the related substance I, the related
KP 9 959
substance II and the related substance III by using the

automatic integration method, calculate the amount
(mg) of the related substances by equation 1: the relative substance I is not more than 0.5%, the related substance II is not more than 0.3%, the relative substance
III is not more than 0.2%. Calculate the each amount
(mg) of any other related substances by equation (2).
The value is not more than 0.1%, the sum of amount
(mg) of these substances is not more than 0.2%, and the
amount of total related substances containing the related substance I, the related substance II and the related substance III is not more than 1.0%.
Amount (mg) of related substances
C A
= 100 S T
(1)
CT AS
CS : Concentration (mg/mL) of each the related substance in the standard solution.
CT : Concentration (mg/mL) of Torsemide in the test
solution.
AS : Peak area of each the related substance obtained
AT : Peak area of each the related substance obtained from the test solution.
Any other related substances (mg)

A
= 100 i
(2)
AS
Ai : Peak area other than the related substance I,
II and III obtained from the test solution.
AS : Sum of peak areas of total peaks obtained from
the test solution.
System suitability
System performance : Weigh about 3 mg each of
Torsemide RS and Torsemide related substance I RS,
dissolve in 3 mL of methanol, with sonication for not
less than 8 minutes. add 4.5 mL of 0.02 mol/L Potassium dihydrogen phosphate bufffer, cool to room temperature, dilute with mobile phase to make exactly 10
mL. When the procedure is run with 20 L of this solution according to the operating conditions as directed in
the Assay, the resolution of peaks between Torsemide
and Torsemide related substance I is not less than 1.0,
and the symmetry factor is not more than 2.0.
times with 20 L of standard solution according to the
operating conditions as directed under the Assay, the
relative standard deviation of the peak area of Torsemide is not more than 10.0%.
Water Not more than 0.8% (1 g, volumetric titrimetry, direct titration).
Assay Weigh accurately about 38 mg of Torsemide,

add 30 mL of methanol, and dissolve with sonication
for not less than 8 minutes. Add 45 mL of 0.02 mol/L
potassium dihydrogen phosphate buffer, dilute with
mobile phase to make exactly 100 mL. and use this solution as the test solution. Separately, weigh accurately
about 19 mg of Torsemide RS, dissolve in 15 mL of
methanol, with sonication for not less than 8 minutes.
Add 22.5 mL of 0.02 mol/L potassium dihydrogen
phosphate buffer, dilute with mobile phase to make exactly 50 mL, and use this solution as the standard solution. Perform the test with each 20 L of the test solution and the standard solution as directed under the
Liquid Chromatography according to the following operating conditions, measure the peak areas of torsemide
obtained from each solutions, AT and AS .
Amount (mg) of torsemide (C16H20N4O3S)

A
= 100C T
AS
C : Concentration (mg/mL) of Torsemide in the standard solution.
Operation conditions
Mobile phase : A mixture of 0.02 mol/L potassium
dihydrogen phosphate buffer solution and methanol
(3:2).
Flow rate : 1.5 mL/minute.
System suitability
operating conditions, symmetry factor is not more than
2.0.
above operating conditions, the relative standard deviation of the peak area of torsemide is not more than
2.0%.
0.02 mol/L Potassium phosphate buffer Dissolve
2.7 g of potassium dihydrogen phosphate in about 900
mL of water. Adjust with phosphoric acid to pH of 3.5,
and dilute with water to make 1000mL.
Tramadol Hydrochloride
CH3
H3C
N
H
HCl
HO
OCH3
and enantiomer
C16H25NO2HCl : 299.84
Tramadol Hydrochloride contains not less than 99.0%

and not more than 101.0% of tramadol hydrochloride
(C16H25NO2HCl), calculated on the anhydrous basis.
Description Tramadol Hydrochloride is a white,
crystalline powder.
Tramadol Hydrochloride is very soluble in water or in
methanol, and practically insoluble in acetone.
Tramadol Hydrochloride and Tramadol Hydrochloride
under Infrared Spectrophotometry: both spectra exhibit
(2) Perform the test with, as directed under Thinlayer Chromatography for the Related Substance I in
Purity test as directed under the Thin-layer Chromatography: the spot from the test solution (2) shows the
same Rf values as the spot from the test solution (1)
(3) A solution of Tramadol Hydrochloride (1 in 50)
responds to the Qualitative Test (2) for chlorides.
Melting Point Between 180 and 184.
D : Between -0.10
and +0.10 (1.0 g, water, 20 mL, 100 mm)
Purity (1) Clarty and color of solutionDissolve
1.0 g of Tramadol Hydrochloride in 20 mL of water:
the solution is colorless and clear.
(2) AcidityDissolve 1.0 g of Tramadol Hydrochloride in 20 mL of water, add 0.1 mL of methyl red TS
to 10 mL of this solution, add 0.2 mL of 0.01 mol/L
hydrochloric acid VS: a red color is produced. Not
more than 0.4 mL of 0.01 mol/L sodium hydroxide is
required to change the color of the solution to yellow.
(3) Heavy metalsProceed with 1.0 g of Tramadol
Hydrochloride according to the method 1, and perform
(4) Related substance IWeigh 0.1 g of Tramadol

Hydrochloride, dissolve in 2 mL of methanol, and use
this solution as the test solution (1). Pipet exactly 1 mL
of this solution, add methanol to make exactly 10 mL,
and use this solution as the test solution (2). Separately,
weigh 50 mg of Tramadol Hydrochloride RS, dissolve
in methanol to make 10 mL, and use this solution as the
standard solution (1). Weigh 10 mg of Tramadol Hydrochloride related substance (I) RS {(2RS)-2[(dimethylamino)methyl]cyclohexanone}, dissolve in
10 mL of methanol, pipet exactly 1 mL of this solution,
add methanol to make 10 mL, and use this solution as
the standard solution (2). Weigh 5 mg of Tramadol Hydrochloride related substance (II) RS {(1RS,2RS)-2[(dimethylamino)methyl]-1-(3-methoxyphenyl) cyclohexanol}, dissolve in 1 mL of the standard solution (1),
and use this solution as the standard solution (3). Perform the test with the test solution and the standard solutions as directed under the Thin-layer Chromatography. Spot 10 L each of the test solution and the standard solutions on a plate of silica gel with fluorescent
indicator for thin-layer chromatography. Develop 2/3
of the plate. Saturate the plate for 20 minutes with concentrated ammonia. For this, add concentrated ammonia to one trough of a twin trough tank. Just before developing, add a mixture of concentrated ammonia, isopropanol and toluene (1 : 19 : 80) to the distance of
about and 10 cm, air-dry the plate. Place the plate in the
chromatographic tank, ensuring that the layer of silica
gel is oriented towards the middle of the tank. Expose
the plate to iodine vapour for 1 hour, examine under ultraviolet light (main wavelength: 254 nm). The spot of
the related substance (I) obtained from test solution (1)
is not more intense and not greater than the spot obtained from standard solution (2) (0.2%). When 2 spots
in the chromatogram obtained from standard solution
(3) are crearly separated, it is effective.
(5) Related substance II Weigh 0.15 g of Tramadol Hydrochloride, dissolve in the mobile phase to
solution. Pipet 2.0 mL of the test solution, add the mobile phase to make 10 mL, pipet 1.0 mL of this solution,
add the mobile phase to make 100 mL, and use this solution as the standard solution. Perform the test with
each 20 L of the test solution and the standard solution as directed under the Liquid Chromatography according to the following operating conditions, and
measure the peak areas of each solution according to
the automatic integration method. The peak area of the
related substance (II) obtained from the test solution is
not greater than 0.5 times the principal peak area of obtained from the standard solution (0.2%), the peak area
other than the principal peak is not more than 0.5 times
the principal peak obtained from the standard solution
(0.1%), the total area of peaks other than the principal
peak is not more than 2 times the peak area of the principal peak obtained from the standard solution (0.4%).
The peaks less than 0.1 times the peak area of the principal peak obtained from the standard solution are excepted.
KP 9 961
Detector : An Ultraviolet absorption photometer
inside dismeter and about 25 cm in length, packed
with base-deactivated octadecylsilanized silica gel for
the Liquid Chromatography (5 m in particle diameter).
Column temperature : A room temperature
Mobile phase : A mixture of a mixture of water and trifluoro acetic acid (0.2 : 100), and acetonitrile (705 : 295)
System suitability
System performance : Dissolve 5 mg of Tramadol related substance II RS in 4 mL of test solution, add
the mobile phase to make 100 mL. When the procedure
is run with 20 L of this solution, as directed under the
Tramadol related substance II peak and Tramadol peak
Water Not more than 0.5 % (1 g, volumetric titration,
direct titration).
Assay Weigh accurately about 0.18 g of Tramadol
Hydrocholride, dissolve in 25 mL of glacial acetic acid,
add 10 mL of acetic anhydride, mix, and titrate with 0.1
mol/L perchloric acid (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank
determination and make any necessary correction.
1 mL of 0.1 mol/L perchloric acid = 29.984 mg of

C16H25NO2HCl
Tranexamic Acid
HOOC
CH2NH2
C8H15NO2: 157.21
Tranexamic Acid, when dried, contains not lest than
99.0% and not more than 101.0% of tranexamic Acid
(C8H15NO2).
Description Tranexamic Acid is a white crystal or
Tranexamic Acid is freely soluble in water or in glacial
acetic acid, very slightly soluble in ethanol, and practically insoluble in ether.
Tranexamic Acid dissolves in sodium hydroxide TS.
Identification Determine the infrared spectra of Tra-
nexamic Acid and Tranexamic Acid RS, as directed in

Spectrophotometry: both spectra exhibit the similar intensities of absorption at the same wavenumbers.
pH Dissolve 1.0 g of Tranexamic Acid in 20 mL of
1.0 g of Tranexamic Acid in 20 mL of water: the solution is clear and colorless.
(2) ChloridePerform the test with 1.0 g of Tranexamic Acid. Prepare the control solution with 0.40
0.014%).
(3) Heavy metalsDissolve 2.0 g of Tranexamic
Acid in water to make 20 mL, and use this solution as
the test stock solution. To 12 mL of the test stock solution add 2 mL of hydrochloric acid-ammonium acetate
butler solulion. pH 3.5, mix, add 1.2 mL of thioacetamide TS, mix immediately, and use this solution as tle
test solution. Separately, proceed in the same manner as
above with a mixture of 1 mL of Standard Lead Solution, 2 mL of the test stock solution and 9 mL of water,
and use the solution so obtained as the standard solution. Separately, proceed in the same manner with a
mixture of 10 mL of water and 2 mL of the test stock
solution, and use the solution so obtained as the control
solution. Conform that the color of the standard solution is slightly darker than that of the control solution.
Compare the test solution and the standard solution 2
minutes after they are prepared: the color of the test solution is not more intense than that of the standard solution (not more than 10 ppm).
Tranexamic Acid according to Method 1 and perform
(5) Related substancesDissolve 0.20 g of Tranexamic Acid in water to make exactly 20 mL, and use
the test solution, and add water to make exactly 100
mL. Pipet exactly 1 ml. of this solution. add water to
make exactly 10 mL and use this solution as the standard solution. Perform the test with exactly 20 L each
of the test solution and test standard solution as directed under Liquid Chromatography according to the
the automatic integration method: the area multiplied
by relative response factor 1.2 of the peak, having the
relative retention time of about 1.5 with respect to tranexarnic acid, is not more than 2/5 of the peak area of
tranexamic acid from the standard solution, and the
area of the peak, having the relative retention time of
about 2.1 with respect to tranexamic acid, is not more
than 1/5 of the peak area of tranexamic acid from the
standard solution. The area of each peak other than tranexamic acid and other than the peaks mentioned above
is not more than 1/5 of the peak area of tranexamic acid
from the standard solution. For this comparison. use the
areas of the peaks, having the relative retention time of
about 1.1 and about 1.3, after multiplying by their relative response factors 0.005 and 0.006, respectively. The
total area of the peaks other than tranexamic acid is not
more than the peak area of tranexamic acid from the
standard solution.
System suitability
of the standard solution add water to make exactly 25
mL. Confirm that the peak area of tranexamic acid obtained from 20 L of this solution is equivalent to 14%
to 26% of that from 20 L of the standard solution.
System suitability under the Assay.
above operating conditions, the relative standard deviation of the peak area of tranexamic acid is not more
than 7%.
as the retention time of tranexamic acid beginning after
the solvent peak.
ic acid (1 in 10), add water to make 600 mL, and add

400 mL of methanol.
time of tranexamic acid is about 20 minutes.
System suitability
System performance: To 5 mL of the standard
solution add 1 mL of a solution of 4-(aminomethyl)
benzoic acid (1 in 10,000) and water to make 50 mL.
when the procedure is run with 20 L of this solution
under the above operating condition,, tranexamic acid
and 4-(aminomethyl)benzoic acid are eluted in this order with the resolution between these peaks being not
less than 5.
times with 20 L of the standard solution tinder the
above operating conditions, the relative standard deviation of the peak area of tranexamic acid is not more
than 0.6%.
Trapidil
C 2H 5
N

hours).
C 2H 5
N
N
N

Assay Weigh accurately about 50 mg each of Tranexamic Acid and Tranexamnic Acid RS, previously
dried, dissolve in water to make exactly 25 mL, and use
these solutions as the test solution and standard solution. Perform the test with exactly 20 L each of the
tranexamic acid from the test solution and the standard
Amount (mg) of tranexamic acid (C8H15NO2)

AT
= amount (mg) of Tranexamic Acid RS A
S
particle diameter).
about 25 C.
Mobile phase: Dissolve 11.0 g of sodium dihydrogen phosphate in 500 mL of water, and add 5 mL of
triethylamine and 1.4 g of sodium lauryl sulfate. Adjust
the pH to 2.5 with phosphoric acid or diluted phosphor-
H 3C
C10H15N5: 205.26
Trapidil, when dried, contains not less than 98.5% and
not more than 101.0% of trapidil (C10H15N5).
Description Trapidil is a white to pale yellowish
Trapidil is very soluble in water or in methanol, freely
soluble in ethanol, in acetic anhydride and in glacial
acetic acid and sparingly soluble in ether.
pHDissolve 1.0 g of Trapidil in 100 mL of water:
Identification (1) To 5 mL of a solution of Trapidil
(1 in 50), add 3 drops of Dragendorff's TS: an orange
color is observed.
Trapidil and Trapidil RS (1 in 125000) as directed under the Ultraviolet-visible Spectrophotometry: both
spectra exhibit the similar intensities of absorption at
Melting Point
1%
Absorbance E 1cm
(after drying, 20 mg, water, 2500 mL).
KP 9 963
2.5 g of Trapidil in 10 mL of water: the solution is clear
and colorless to pale yellow.
(2) ChloridePerform the test with 0.5 g of Trapidil. Prepare the control solution with 0.25 mL of 0.01
mo1/L hydrochloric acid VS (not more than 0.018%).
(3) AmmoniumPlace 50 mg of Trapidil in a
glass-stoppered Erlenmeyer flask, thoroughly moisten
with 10 drops of sodium hydroxide TS and stopper the
flask. Allow it to stand at 37 C for 15 minutes: the gas
evolved does not change moistened red litmus paper to
blue.
(4) Heavy metalsDissolve 1.0 g of Trapidil in 40
mL of water and add 1.5 mL of dilute hydrochloric acid,
2 mL of dilute acetic acid and water to make 50 mL.
Perform the test using this solution as the test solution.
standard lead solution, add 2 mL of dilute acetic acid
and water to make 50 mL (not more than 10 ppm).
Trapidil according to Method 1 and perform the test
(6) Related substancesDissolve 0.10 g of Trapidil in 4 mL of methanol and use this solution as the test
solution. Pipet exactly 1 mL of the test solution and add
methanol to make exactly 20 mL. Pipet exactly 1 mL of
this solution, add methanol to make exactly 100 mL
20 L each of the test solution and the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chloroform,
ethanol and glacial acetic acid (85 : 13 : 2) to a distance
of about 10 cm and air-dry the plate. Allow the plate to
stand in iodine vapor for 60 minutes: the spots other
Assay Weigh accurately about 0.2 g of Trapidil,
previously dried, dissolve in 20 mL of glacial acetic
acid and titrate with 0.1 mol/L perchloric acid VS
(potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination
Each mL of 0.1 mol/L percholic acid VS

=20.526 mg of C10H15N5
Triamcinolone
O
HO
CH3
CH2OH
OH
OH
CH3
H
F
C21H27FO6: 394.43
Triamcinolone, when dried, contains not less than
97.0% and not than 103.0% of triamcinolone
(C21H27FO6).
Description Triamcinolone is a white, crystalline
Triamcinone is freely soluble in dimethylformamide,
slightly soluble in methanol, in ethanol or in acetone,
and practically insoluble in water, in isopropanol or in
ether.
Identification (1) Dissolve 1 mg of Triamcinolone in
6 mL of ethanol, add 5 mL of 2,6-di-tert-butyl-p-cresol
TS and 5 mL of sodium hydroxide TS and heat in a water-bath for 30 minutes under a reflux condenser: a redpurple color is observed.
(2) Add 5 mL of water and 1 mL of Fehling's TS to
10 mg of Triamcinolone and heat: a red precipitate is
produced.
(3) Proceed with 10 mg of Triamcinolone as directed under Oxygen Flask Combustion Method, using
a mixture of 0.5 mL of 0.01 mol/L sodium hydroxide
TS and 20 mL of water as the absorbing liquid. When
combustion is completed, shake vigorously so as to absorb the gas evolved: the solution responds to the Qualitative Tests for fluoride.
(4) Determine the infrared spectra of Triamcinolone
and Triamcinolone RS, previously dried, as directed in
Spectrophotometry: both spectra exhibit the similar intensities of absorption at the same wavenumbers. If any
differences appear, dissolve 0.1 g each of Triamcinolone and Triamcinolone RS in 7 mL of a mixture of
isopropanol and water (2 : 1) by warming. Cool the solutions in ice-water, filter the crystals produced, wash
with two 10 mL volumes of water, dry and repeat the
test on the residues.
D : Between +65 and
+71 (after drying, 0.1 g, dimethylformamide, 10 mL,
100 mm).
Purity Heavy metalsProceed with 0.5 g of Triamcinolone according to Method 2 and perform the test.

Loss on drying Not more than 2.0% (0.5 g, in vacuum, P2O5, 60 C, 3 hours).
Triamcinolone Acetonide
O
Residue on Ignition Not more than 0.3% (0.5 g, platinum crucible).
HO
Amount (mg) of triamcinolone (C21H27FO6)

QT
= amount (mg) of Triamcinolone RS Q
S
Internal standard solutionDissolve 15 mg of methyl parahydroxybenzoate in a solution of ascorbic acid
in methanol (1 in 1000) to make 100 mL.
particle diameter).
about 25 C.
(3 : 1).
time of triamcinolone is about 10 minutes.
System suitability
operating conditions, triamcinolone and the internal
standard are eluted in this order with the resolution between these peaks being not less than 2.0.
above operating conditions, the relative standard deviation of the ratio of the peak area of triamcinolone to
tight containers.
CH2OH
O
CH3
Assay Dissolve about 20 mg each of Triamcinolone

and Triamcinolone RS, previously dried and accurately
weighed, in a solution of ascorbic acid in methanol (1
in 1000) to make exactly 50 mL. Pipet exactly 5 mL
each of these solutions, add 5.0 mL each of the internal
standard solution, add a solution of ascorbic acid in methanol (1 in 1000) to make exactly 20 mL and use these
respectively. Perform the test with 10 L each of the
peak height of triamcinolone to that of the internal
standard, for the test solution and the standard solution,
respectively.
CH3
CH3
CH3
H
F
C24H31FO6: 434.50
Triamcinolone Acetonide, when dried, contains not less
than 97.0% and not more than 103.0% of triamcinolone
acetonide (C24H31FO6).
Description Triamcinolone Acetonide is a white,
Triamcinolone Acetonide is sparingly soluble in dehydrated ethanol, in acetone or in dioxane, slightly soluble in methanol or in ethanol, and practically insoluble in water or in ether.
Identification (1) Dissolve 2 mg of Triamcinolone
Acetonide in 40 mL of ethanol, add 5 mL of 2,6-di-tertbutyl-p-cresol TS and 5 mL of sodium hydroxide TS
and heat in a water-bath under a reflux condenser for
20 minutes: a green color is observed.
(2) Add 5 mL of water and 1 mL of Fehling's TS to
10 mg of Triamcinolone Acetonide and heat: a red precipitate is produced.
(3) Proceed with 10 mg of Triamcinolone Acetonide as directed under Oxygen Flask Combustion Method, using a mixture of 0.5 mL of 0.01 mol/L sodium
hydroxide TS and 20 mL of water as the absorbing liquid. When combustion is completed, shake vigorously
so as to absorb the gas evolved: the solution responds
to the Qualitative Tests for fluoride.
(4) Determine the ultraviolet absorption spectra of
solutions of Triamcinolone Acetonide and Triamcinolone Acetonide RS in ethanol (1 in 100000) as directed under the Ultraviolet-visible Spectrophotometry:
(5) Determine the infrared spectra of Triamcinolone
Acetonide and Triamcinolone Acetonide RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same
wavenumbers. If any differences appear, dissolve 0.1 g
each of Triamcinolone Acetonide and Triamcinolone
Acetonide RS in 20 mL of ethanol, respectively, evaporate to dryness and repeat the test on the residues.
[ ] 20
D : Between +100
KP 9 965
and +107 (after drying, 0.1 g, dioxane, 10 mL, 100

mm).
Purity (1) Heavy metalsProceed with 0.5 g of Triamcinolone Acetonide according to Method 2 and perform the test. Prepare the control solution with 1.5 mL
(2) Related substancesDissolve 40 mg of Triamcinolone Acetonide in 4 mL of acetone and use this solution as the test solution. Pipet exactly 1 mL of the test
mixture of chloroform and methanol (93 : 7) to a distance of about 10 cm and air-dry the plate. Examine
Residue on Ignition Not more than 0.2% (0.5 g, platinum crucible).
Assay Dissolve about 20 mg each of Triamcinolone
Acetonide and Triamcinolone Acetonide RS, previously dried and accurately weighed, in methanol to make
exactly 50 mL. Pipet exactly 10 mL each of these solutions, add exactly 10 mL each of the internal standard
solution, then add the mobile phase to make exactly 50
standard solution, respectively. Perform the test with 20
the following conditions and calculate the ratios, QT
and QS, of the peak height of triamcinolone acetonide
to that of the internal standard, respectively.
Amount (mg) of triamcinolone acetonide (C24H31FO6)

QT
= amount (mg) of Triamcinolone Acetonide RS Q
S
Internal standard solutionA solution of prednisolone in methanol (1 in 5000).
particle diameter).
(3 : 1).
time of triamcinolone acetonide is about 13 minutes.
System suitability
operating conditions, the internal standard and triamcinolone acetonide are eluted in this order with the resolution between these peaks being not less than 6.0.
the ratios of the peak height of triamcinolone acetonide

tight containers.
Triamterene
H2N
NH2
N
N
NH2
Cl2Hl1N7: 253.26
Triamterene, when dried, contains not less than 98.5%
and not more than 101.0% of triamterene (Cl2Hl1N7).
Description Triamterene is a yellow, crystalline
Triamterene is sparingly soluble in dimethylsulfoxide,
very slightly soluble in glacial acetic acid, and practically insoluble in water, in ethanol or in ether.
Triamterene dissolves in nitric acid or in sulfuric acid,
but does not dissolve in dilute nitric acid, in dilute sulfuric acid or in dilute hydrochloric acid.
Identification (1) To 10 mg of Triamterene, add 10
mL of water, heat and filter after cooling: the filtrate
shows a purple fluorescence. To 2 mL of the filtrate,
add 0.5 mL of hydrochloric acid: the fluorescence disappears.
(2) The filtrate obtained in (1) responds to the Qualitative Tests for primary aromatic amines.
(3) Dissolve 10 mg each of Triameterene and Triameterene RS in 100 mL of glacial acetic acid. To 10
mL each of these solutions, add water to make 100 mL.
Determine the absorption spectra of these solutions as
Purity (1) Heavy metalsProceed with 1.0 g of Triamterene according to Method 2 and perform the test.

Triamterene according to Method 3 and perform the
(3) Related substancesDissolve 0.10 g of Triamterene in 20 mL of dimethylsulfoxide. Pipet exactly 2
mL of this solution, add methanol to make exactly 50
mL and use this solution as the test solution. Pipet exactly 1 mL of the test solution, add methanol to make
mixture of ethyl acetate, strong ammonia water and
methanol (9 : 1 : 1) to a distance of about 10 cm and
air-dry the plate. Examine the plate under ultraviolet
hours).
Assay Weigh accurately about 0.15 g of Triamterene,
previously dried and dissolve in 100 mL of glacial acetic acid by warming, cool and titrate with 0.05 mol/L
perchloric acid VS (indicator: 2 drops of methylrosaniline chloride TS). Perform a blank determination and

= 12.663 mg of Cl2Hl1N7
Tribenoside
O
H
O
CH3
O
O
OH
C isomer
C29H34O6 : 478.58
Tribenoside is a mixture of - and -anomers.
Tribenoside contains not less than 96.0% and not more
than 102.0 % of tribenoside (C29H34O6).
Description Tribenoside is a yellowish to pale yellow,

clear viscous liquid.
Tribenoside is very soluble in dichloromethane, in methanol or in acetone, and practically insoluble in water.
Identification Determine the infrared spectra of Tribenoside and Tribenoside RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
-40.0 (0.4 g, methanol 20 mL, 100 mm).
4.0 g of Tribenoside in methanol to make 20 mL: the
solution is clear, and perform the test with this solution
as directed under the Ultraviolet-visible Spectrophotometry at 420 nm: the absorbance is not more than 0.1%.
(2) Heavy metalsProceed with 1.0 g of Tribenoside according to the Method 2 and perform the test.
(3) Related substancesDissolve 1.0 g of Tribenoside in to make 25.0 mL, and use this solution as the
test solution (1). Dissolve 50.0 mg of Tribenoside in a
mixture of acetonitrile and water (95 : 5) to make exactly 50 mL, and use this solution as the test solution
(2). Separately, dissolve 25.0 mg of benzaldehyde and
30.0 mg of Tribenoside related substance I RS [3,5,6tri-O-benzyl-1,2-O-(1-methylethylidene)--dglucofuranose] in acetonitrile to make exactly 100 mL.
Add 2.5 mL of water and acetonitrile to 20 mL of this
solution to make exactly 50 mL, and use this solution
as the standard solution (1). Dissolve 50.0 mg of Tribenoside RS in a mixture of acetonitrile and water (95 :
5) to make exactly 50 mL, and use this solution as the
standard solution (2). Dissolve 12.0 mg of benzyl ether in a mixture of acetonitrile and water (95 : 5) to
make exactly 100 mL, and use this solution as the
standard solution (3). Perform the test with each 20 L
of the test solution and the standard solutions, as directed under the Liquid Chromatography according to
the following operating conditions: The peak area of related substance I obtained from the test solution is not
greater than 1.7 times the peak area of the related substance I RS corresponding peak in the chromatogram
obtained from standard solution (1) (0.5%), The peak
area of the related substance (II) obtained from the test
solution is not greater than 2 times peak area of benzaldehyde obtained from the standard solution (3) (0.5%);
if the area of the peak of the related substance (II) obtained from the test solution is greater than the peak
area of benzaldehyde peak obtained from the standard
solution (1), dilute properly the test solution to obtain
an area equal to or smaller than the area of the peak obtained from the standard RS. The peak area of the related substance (III) obtained from the test solution is
KP 9 967
not greater than the peak area of the principal peak obtained from the standard solution (3) (0.3%), the peak
area other than the related substances is not greater than
the peak area of the related substance (I) RS obtained
from standard solution (1) (0.3%). The total peak area
of peaks other than the principal peak obtained from
test solution is not more than 6.7 times the peak of the
related substance (I) RS obtained from standard solution (1) (2.0%). Disregard any peak less than 0.17 times
the area of the peak due to impurity A obtained from
the standard solution (1) (not more than 0.05%).
Detector : An ultraviolt-visible absorption photometer (wavelength: 254 nm)
octadecylsilanized silica gel for the liquid chromatography (3 m in particle diameter).
Mobile phase : Control the step or concentration
gradient by mixing mobile phase A and mobile phase B.
Mobile phase A - 0.1 vol% phosphoric acid
Mobile phase B - acetonitrile
Time (min)
0 ~ 40
40 ~ 55
55 ~ 56
56 ~ 60
Mobile phase A
(vol%)
55 10
10
10 55
55
Mobile phase B
(vol%)
45 90
90
90 45
45

Retention time : The relative retention time of isomer, related substance II, IV, III and I to the isomer of Tribenoside (retention time about 18 minutes),each, are 1.1, 0.2, 0.6, 0.8 and 1.4, respectively.
System suitability
with the standard solution (2) according to the above
operating conditions, the resolution between the peak
of -isomer and the peak of -isomer is not less than
3.0.
Assay Proceed with each 20 L of the test solution
(2) and the standard solution (2) in Related Substances,
as directed under the Liquid Chromatography according to the operating conditions for the related substances, determine the peak area, AT , AT , AS
and AS , of -isomer and -isomer of Tribenoside.

Amount (mg) of tribenoside (C29H34O6)
= Amount (mg) of Tribenoside RS
( AT + AT )/( AS + AS )
Packaging and Storage Under nitrogen, in a tight
containers.
Trichlormethiazide
H2NO 2S
O2
S
NH
Cl
N
H
CHCl 2
H
and enantiomer
C8H8Cl3N3O4S2: 380.66
Trichlormethiazide, when dried, contains not less than
98.0% and not more than 101.0% of trichlormethiazide
(C8H8Cl3N3O4S2).
Description Trichlormethiazide is a white powder.
Trichlormethiazide is freely soluble in NNdimethylformamide or in acetone, slightly soluble in in
acetonitrile or in ethanol, and practically insoluble in
water.
A Solution of Trichlormethiazide in aceton (1 in 50)
of solutions of Trichiormethiazide and Trichiormethiazide RS in ethanol (3 in 250000) as directed under the
Trichlormethiazide and Trichlormethiazide RS as directed in the potassium bromide disk method under the
(3) Perform the test with Trichiormethiazide as directed under the Flame Coloration Test (2): a green
color appears.
Purity (1) ChlorideDissolve 1.0 g of Trichlormethiazide in 30 mL of acetone, add 6 mL of dilute nitric
acid and water to make 50 mL and perform the test using this solulion as the test solution. Prepare the control
solution as follows: to 1.0 mL of 0.01 mol/L hydrochloric acid VS, add 30 mL of acetone, 6 mL of dilute nitiric acid and water to make 50 mL (not more than
0.036%).
(2) SulfateDissolve 1.0 g of Trichlormethiaside
in 30 mL of acetone, add 1 mL of dilute hydrochloric
acid and water to make 50 mL and perform the test using this solution as the test solution. Prepare the control
solution as follows: to 1.0 mL of 0.005 mol/L sulfuric
acid VS, add 30 mL of acetone, 1 mL of dilute hydrochloric acid and water to make 50 mL (not more
than 0.048%).
(3) Heavy metalsProceed with 1.0 g of Trichlormethiazide according to Method 2 and perform the test.

Trichlormethiazide according to Method 3 and perform
the test (not more than 3.3 ppm).
(5) Related substancesDissolve 25 mg of Trichlormethiazide in 50 mL of acetoiihrile, and use this solution as the test solution. Perform the test with 10 L
of the test solution as directed under the Liquid Chromatography according to the following conditions, determine each peak area by the automatic integration
method, and calculate the amount of related substances
by the area percentage method: the amount of 4-amino6-chlorobenzene-l,3-disulfonamide, having the relative
retention time of about 0.3 with respect to trichlormethiazide, is not more than 2.0%, and the total amount of
the related substances is not more than 2.5%.
(wavelength: 268 nmn).
about 25 C.
Control the gradient by mixing the mobile phases A
and B as directed in the following table.
Mobile phase A: A mixture of diluted phosphoric
acid (1 in 1000) and acetonitrile (3:1).
Mobile phase B: A mixture of acetonitrile and diluted phosphoric acid (1 in 1000) (3:1).
(minutes)
0 to 10
10 to 20
Mobile phase
A (vol%)
100
100 0
Mobile phase
B (vol%)
0
0 100
Flow rate: 1.5 mL per minute

long as the retention time of trichlormethiazide beginning after the solvent peak.
System suitability
of the test solution, add acctonitrile to make exactly 50
rnL, and use this solution as the solution for system suitability test. Pipet 1 mL of the solution, and add acetonitrile to make exactly 20 mL. Confirm that the peak
area of trichlormethiazide obtained from 10 L of this
solution is equivalent to 3.5% to 6.5% of that of trichlormethiazide obtained from 10 L of the solution for
system suitability test.
System performance: To 5 mL of the solution for
system suitability test add 5 mL of water, and warm in
a water bath at 60 C for 30 minutes. When the procedure is run with 10 L of this solution, after cooling,
under the above operating conditions, 4-amino-6chlorobenzene-1,3-disulfonamide and trichlormethiazide are eluted in this order, the relative retention time
of 4-amino-6-chlorobenzene-1,3-disulfonamide with
respect to trichlormethiazide is about 0.3, and the num-
ber of theoretical plates and the symmetry factor of the

peak of trichlormethiazide are not less than 5000 and
not more than 1.2, respectively.
times with 10 L of the solution for system suitability
test under the above operating conditions, the relative
standard deviation of the peak area of trichlormethiazide is not more than 2.0%.
hours)
Assay Weigh accurately about 25 mg each of Trichlormethiazide and Trichlormethiazide RS, previously
dried, and dissolve in exactly 20 mL of the internal
standard solution. To exactly 1 mL each of these solutions add acetonitrile to make exactly 20 mL, and use
these solutions as the test solution and the standard solution. Perform the test with 10 L each of the test solution and standard solution as directed under liquid
and determine the ratios, QT and QS of the peak area of
trichlormethiazide to that of the internal standard.
Amount (mg) of trichlormethiazide (C8H8Cl3N3O4S2) =

QT
amount (mg) of Trichlormethiazide RS Q
S
Internal standard solutionA solution of 3nitrophenol in acetonitrile (1 in 800).
about 25 C.
Mobile phase: A mixture of diluted phosphoric acid
(1 in 1000) and acetonitrile (3 : 1).
time of trichlormethiazide is about 8 minutcs.
System suitability
with l0 L of the standard solution under the above operating conditions, the internal standard and trichlormethiazide are eluted in this order with the resolution between these peaks being not less than 2.0.
above operating conditions, the relative standard deviation of the ratio of the peak area of trichlormethiazide
KP 9 969
Triclofos Sodium
Cl
Cl
Cl
OPO 3HNa
Monosodium Trichloroethyl Phosphate

C2H3Cl3NaO4P: 251.37
Triclofos Sodium, when dried, contains not less than
97.0% and not more than 102.0% of Triclofos Sodium
(C2H3Cl3NaO4P) and not less than 41.0% and not more
than 43.2% of chlorine (Cl: 35.45).
Description Triclofos Sodium is a white, crystalline
powder.
Triclofos Sodium is freely soluble in water, slightly soluble in ethanol and practically insoluble in ether.
Triclofos Sodium is hygroscopic.
Triclofos Sodium and Triclofos Sodium RS as directed
in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) To 0.5 g of Triclofos Sodium, add 10 mL of nitric acid, evaporate in a water-bath to dryness and ignite further over a flame. Dissolve the residue in 5 mL
of water and filter, if necessary: the filtrate responds to
the Qualitative Tests for sodium salt.
(3) To 0.1 g of Triclofos Sodium, add 1 g of anhydrous sodium carbonate and heat for 10 minutes. After cooling, dissolve the residue in 40 mL of water, filter, if necessary and render the filtrate acidic with dilute
nitric acid: the solution responds to the Qualitative
Tests (2) for chloride. The remainder of the filtrate responds to the Qualitative Tests (1) for chloride and to
the Qualitative Tests for phosphate.
pH Dissolve 1.0 g of Triclofos Sodium in 50 mL of
1.0 g of Triclofos Sodium in 50 mL of water: the solution is clear and colorless.
(2) ChloridePerform the test with 0.20 g of Triclofos Sodium. Prepare the control solution with 1.0 mL
0.178%).
(3) Heavy metals Prepare the test solution with
1.0 g of Triclofos Sodium according to Method 1 and
(4) ArsenicProceed with 1.0 g of Triclofos Sodium according to Method 1 and perform the test (not
more than 2 ppm).
(5) Free phosphoric acidWeigh accurately about
0.3 g of Triclofos Sodium, previously dried, dissolve in

the test solution. Pipet exactly 5 mL each of the test solution and standard phosphoric acid solution, add 2.5
mL of ammonium molybdate-sulfuric acid TS and 1
mL of 1-amino-2-naphthol-4-sulfonic acid TS, shake,
add water to make exactly 25 mL and allow to stand at
20 C for 30 minutes. Perform the test with the test solution and the standard solution, using a solution obtained in the same manner with 5 mL of water as the
blank, as directed under the Ultraviolet-visible Spectrophotometry. Determine the absorbances at 740 nm,
AT and AS, of the test solution and standard phosphoric
acid solution, respectively: the content of the free
phosphoric acid is not more than 1.0% .
Content (%) of the free phosphoric acid (H3PO4)
1
AT
= A W 257.8
S
W: Amount (mg) of Triclofos Sodium taken.
100 C, 3 hours).
Assay
(1) Triclofos SodiumWeigh accurately
about 0.2 g of Triclofos Sodium, previously dried,
place in a Kjeldhal flask, add 2 mL of sulfuric acid and
2.5 mL of nitric acid and heat until brown gas are not
evolved. After cooling, add 1 mL of nitric acid, heat
until white fumes are produced and cool. Repeat this
procedure until the solution becomes colorless. Transfer this solution to a flask using 150 mL of water, add
50 mL of molybdenum trioxide-citric acid TS, heat
gently to boil, add gradually 25 mL of quinoline TS
with stirring and heat in a water-bath for 5 minutes. After cooling, filter the precipitate and wash repeatedly
with water until the washing does not indicate acidity.
Transfer the precipitate to a flask using 100 mL of water, add exactly 50 mL of 0.5 mol/L sodium hydroxide
VS, dissolve and titrate with 0.5 mol/L hydrochloric acid VS until the color of the solution changes from purple to yellow (indicator: 3 drops of phenolphthaleinthymol blue TS). Perform a blank determination and
make any necessary corrections.

= 4.834 mg of C2H3Cl3NaO4P
(2) ChlorineWeigh accurately about 10 mg of
Triclofos Sodium, previously dried, perform the test
according to the procedure of determination for chlorine as directed under the Oxygen Flask Combustion
Method, using 1 mL of 1 mol/L sodium hydroxide TS
and 20 mL of water as the absorbing liquid.
Triclofos Sodium Syrup

Monosodium Trichloroethyl Phosphate Syrup
Triclofos Sodium Syrup contains not less than 90.0%
triclofos sodium (C2H3Cl3NaO4P: 251.37).
excess silver nitrate with 0.02 mol/L ammonium thiocyanate VS (indicator: 2 to 3 drops of ferric ammonium sulfate TS). Perform a blank determination and
make any necessary corrections.
= 1.6758 mg of C2H3Cl3NaO4P
Packaging and Storage Preserve in tight containers,
in a cold place.

Syrups, with Triclofos Sodium.
Identificatlon (1) Weigh a volume of Triclofos Sodium Syrup, equivalent to 0.25 g of triclofos sodium
according to the labeled amount, add 40 mL of water,
shake well, add 5 mL of diluted sulfuric acid (3 in 50)
and extract with 25 mL of isoamyl alcohol. Take 5 mL
of the extract, evaporate on a water-bath to dryness and
add 1 mL of diluted sulfuric acid (1 in 2) and 1 mL of a
solution of potassium permanganate (1 in 20) to the residue. Heat in a water-bath for 5 minutes, add 7 mL of
water and then add a solution of oxalic acid (1 in 20)
until the color of the solution disappears. To 1 mL of
this solution, add 1 mL of pyridine and 1 mL of a solution of sodium hydroxide (1 in 5) and heat in a waterbath, while shaking, for 1 minute: a pale red color is
observed in the pyridine layer.
(2) Take 10 mL of the extract obtained in (1), evaporate on a water-bath to dryness, add 1 g of anhydrous
sodium carbonate to the residue and heat for 10 minutes. After cooling, dissolve the residue in 40 mL of
water, filter, if necessary and render the filtrate acidic
with dilute nitric acid: the solution responds to the Qualitative Tests (2) for chloride. The remainder of the filtrate responds to the Qualitative Tests (1) for chloride
and to the Qualitative Tests for phosphate.
pH

requirement.
Assay Weigh accurately a volume of Triclofos Sodium Syrup, equivalent to about 0.13 g of triclofos sodium according to the labeled amount, add 15 mL of
water, 1 mL of sodium hydroxide TS and 15 mL of
ether, shake for 1 minute and separate the water layer.
Wash the ether layer with 1 mL of water and combine
the washing with above water layer. To this solution,
add 2.5 mL of diluted sulfuric acid (3 in 50) and extract
with four 10 mL volumes of isoamyl alcohol. Combine
the isoamyl alcohol extracts and add isoamyl alcohol to
make exactly 50 mL. Measure exactly 10 mL of this
solution and dilute with 10 mL of potassium hydroxide-ethanol TS. Place in a glass ampule, fire-seal, mix
and heat at 120 C for 2 hours in an autoclave. After
cooling, transfer the contents to a flask, add 20 mL of
diluted nitric acid (63 in 500) and exactly 25 mL of
0.02 mol/L silver nitrate VS, shake well and titrate the
Triclosan
Cl
OH
O
Cl
Cl
C12H7Cl3O2 : 289.54
Triclosan contains not less than 97.0% and not more
than 103.0% of triclosan (C12H7Cl3O2), calculated on
Description Triclosan is a white, crystalline powder.
Triclosan is very soluble in methanol, in ethanol or in
acetone, slightly soluble in hexane, and practically insoluble in water.
Melting pointabout 57 C.
Triclosan and Triclosan RS as directed in the potassium
bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wave numbers.
(2) The retention time of the principal peak obtained from the test solution corresponds to the retention time of the principal peak obtained from the standard solution.
Triclosan according to Method I and perform the test.
(2) Related substancesPerform the test with
about 0.5 L of the test solution in the Assay as directed under the Gas Chromatography according to the
following operating conditions. Inject the test solution,
increase the column temperature by 20 C per minute
to 140 C, then increase column temperature by 4 C
per minute to 240 C, maintain this temperature for not
less than 5 minutes, and measure the peak area of
chromatogram obtained from the above, calculate the
percentage of each related substance; each related substance is not more than 0.1 %, total related substance is
not more than 0.5%.
KP 9 971
Detector, column, mobile phase, flow rate and system suitability; perform as directed in the operating
conditions in the Assay.
(3) Monochlorophenols and 2,4-dichlorophenol

0.25 g of Triclosan, exactly weighed, dissolve in 20
mL of acetonitrile, add water to make exactly 25 mL,
weigh accurately 5 mg of 4-chlorophenol and 1 mg of
2,4-dichlorophenol, respectively, dissolve in 50 mL of
acetonitrile, add water, to make exactly 100 mL. Pipet exactly 1.0 mL of this solution, add a mixture of
acetonitrile and water (1 : 1) to make exactly 100 mL,
and use this solution as the standard solution. Perfrm
standard solution as directed under the Liquid Chromatography according to the following operating conditions: the peak areas of 4-chlorophenol and 2,4dichlorophenol obtained from the test solution are not
larger than the peak areas of 4-chlorophenol and 2,4dichlorophenol obtained from the standard solution.
Detector : An electrochemical detector (electrode
1 : -0.45 V, electrode 2 : -0.75 V)
octadecylsilanized silica gel for the Liquid Chromatography (3 to 10 m in particle size diameter).
Mobile phase : A mixture of acetonitrile and phosphate buffer solution (1 : 1).
System suitability
deviation of the peak area obtained from 2,4dichlorophenol is not more than 9.0%.
Phosphate buffer solutionDissolve 1.38 g of anhydrous sodium dihydrogen phosphoric acid and 1.42 g
of sodium monohydrogen phosphoric acid, dissolve in
water to make 1000 mL.
(4) 1,3,7-trichlorodibenzo-p-dioxin, 2,8-dichloro

dibenzo-p-dioxin, 2,8-dichlorodibenzofuran and 2,4,8trichlorodibenzofuranTrasfer about 2.0 g of Triclosan, accurately weighed, to a stoppered centrifuge tube,
add 5 mL of 2 mol/L potassium hydroxide, and shake
for 10 minutes to dissolve. Add 3 mL of n-hexane,
shake for 10 minutes, and allow the phases to separate.
Transfer the organic layer to a suitable container. Add 3
mL of n-hexane to the aqueous layer, shake for 10 minutes, and allow the phases to separate. Transfer the
organic layer to the previous extract, discard the
aqueous layer. Add 3 mL of 2 mol/L potassium hydroxide to the combined organic layers, shake for 10
minutes, and allow the phases to separate. Discard the
aqueous layer, add another 3 mL of 2 mol/L potassium
hydroxide to the combined organic layers, shake for 10

minutes, and allow the phases to separate. Transfer the
organic layer to a suitable container, and evaporate
with the aid of a stream of nitrogen to dryness. Dissolve the residue in 1.0 mL of methanol, and use this
solution as the test solution. Separately, transfer exactly
weighed 5 mg of 2,8-dichlorodibenzofuran and 10 mg
of 2,4,8-trichlorodibenzofuran, respectively, to a 100
mL-volumetric flask, add exactly measured 5 mg of
1,3,7-trichlorodibenzo-p-dioxin and a quantity equivalent to about 10 mg of 2,8-dichlorodibenzo-p-dioxin,
and dissolve in methanol to make exactly 100 mL. Pipet 1.0 mL of this solution, add methanol to make exactly 100 mL, and use this solution as the standard solution. Perform the test with 20 L each of the test solution and the standard solution as directed under the
Liquid Chromatography according to the following operating conditions: the peak areas of 2,8dichlorodibenzofuran, 2,8-dichlorodibenzo-p-dioxin,
2,4,8-trichlorodibenzofuran and 1,3,7-trichlorodibenzop-dioxin obtained from the test solution is not larger
than each peak area obtained from the standard solution.
inside dismeter and about 25 cm in length, packed with
octadecylsilanized silica gel for the Liquid Chromatography (3 to 10 m in partical diameter).
Mobile phase : A mixture of acetonitrile, water and
glacial acetic acid (70 : 30 : 0.1).
System suitability
with 20 L of standard solution according to the above
operating conditions, the relative retention times of
peaks obtained from 2,8-dichlorodibenzofuran, 2,8dichlorodibenzo-p-dioxin,
2,4,8-trichlorobenzofuran
and 1,3,7-trichlorodibenzo-p-dioxin are about 0.59,
0.71, 0.88 and 1.0, respectively.
deviation of peak areas obtained from 2,8dichlorodibenzo-p-dioxin is not more than 15.0%.
5) 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,
7,8-tetrachlorodibenzofuran (extremely toxic)
Transfer about 30 g of Triclosan, accurately weighed,
to a separatory funnel, add 30 L of the internal standard solution, dissolve in 200 mL of 1 mol/L sodium
hydroxide TS, extract 4 times with 30 mL each of nhexane, and combine all the extracts, Wash the combined extracts with 20 mL of water, extract the washing
with 15 mL of n-hexane, add the extract to the other
combined extracts, add about 3 g of anhydrous sodium
sulfate to the combined extracts, allow to stand for 30
minutes, quantitatively transfer to a an appropriate
round-bottom flask, and distile, using a distillation ap-
paratus until about 1 mL remains. Transfer this solution

to the top of chromatographic column A, and elute with
50 mL of n-hexane. Tranfer the eluates to the top of
chromatographic column B, and elute with 30 mL of a
mixture of n-hexane and dichloromethane (98 : 2), discard the elutes. Elute with 40 mL of a mixture of nhexane and dichloromethane (1 : 1), collect the eluates
in a round-bottom flask. Distill the combined eluates,
using a distillation apparatus until about 1 mL remains.
Further concentrate this solution with the aid of a
stream of nitrogen to about 50 L, evaporate at room
temperature to dryness, and dissolve in 10 L of 2,2,4trimethylpentane, and use this solution as the test solution.
Perform the test with 1 L of the test solution as directed under the Gas Chromatography with high quality
Mass Spectrometry, measure the peak areas at mass-tocharge ratios of 319.90, 321.89, 331.88, 333.93, 303.90,
305.90 and 317.94. The peak area for 2,3,7,8tetrachlorodibenzo-p-dioxin at a mass-to-charge ratio
of 319.90 is not larger than the peak area of the associated internal standard at a mass-to-charge ratio of
331.88; the peak area for 2,3,7,8-tetrachloro dibenzofuran at a mass-to-charge ratio of 303.90 is not larger
than the peak area of the associated internal standard at
a mass-to-charge ratio of 315.94.
Detector: A high-resolution mass Spectrograph
(electron-impact ionization).
Column: A capillary column, about 0.25 mm in inside diameter and about 60 m in length, coated with
cyanopolysiloxane.
Mobile phase: helium
Column temperature: Initially the temperature of
the column is equilibrated at 80, then, 1 minute after
the injection, the temperature is increased at a rate of
20 per minute to 220, then increased at a rate of
2 per minute to 270, and maintained at 270 for
not less than 20 minutes.
Signal-to-noise ratio: not less than 50 at a mass-tocharge ratio of 321.89.
Stationary phase ATake about 10 g of silica gel
in a suitable containers, add about 3 mL of 1 mol/L sodium hydroxide TS.
Stationary phase BTake about 60 g of silica gel
in a suitable containers, add about 74 mL of sulfuric acid.
Column A for the chromatographyTransfer 5.1 g
of stationary phase A, 0.5 g of silica gel, 6.2 g of stationary phase B, 3.2 g of sodium sulfuric acid in the
column, 10 mm in inside diameter, for chromatograph,
add 50 mL of n-hexane, wash, discard the eluate.
Column B for the chromatographyTransfer 2.5 g
of alumina and 2.5 g of sulfuric acid in the column, 6
mm in inside diameter, for chromatograph, add 30 mL
of n-hexane, wash, discard the eluate.
Internal standard solutionTransfer accurately
measured quantities of 2,3,7,8-tetrachlorodibenzo-p-
dioxin, 13C-labeled and 2,3,7,8- tetrachlorodibenzofuran, 13C- labeled in nonane, and dilute qustitatively, and
stepwise if necessary, with 2,2,4-trimethylpentane to
obtain a solution having known concentrations of about
1.0 pg of each per 1L .
Water not more than 0.1 % (1 g, volumetric titratioin,
direct titration).
Residue of Ignition not more than 0.1 % (1 g).
Assay Weigh accurately about 40 mg each of Triclosan and Triclosan RS, dissolve in dichloromethane to
make exactly 10 mL, and use these solutions as the test
solution and the standard solution, respectively. Perform the test with o.5 L each of test solution and standard solution as directed under the Gas Chromatography according to the following operating conditions,
calculate the peak areas, AT and AS of triclosan obtained from each solution
Amount (mg) of triclosan (C12H7Cl3O2)

A
= amount (mg) of Triclosan RS T
AS
Detector: A hydrogen Flame ionization detector
Column: A tube, about 0.53 mm in inside diameter
and about 15 m in length, packed with 50 % of phenyl
and 50 % methylpolysiloxan.
Injection port temperature: Maintain at 34 C and is increased rapidly to 200 C of the injection.
Column temperature: After the injection, increase
the column temperature by 20 C per minute to 140 C,
then increase column temperature by 4 C per minute
to 240 C, and maintain this temperature for not less
than 5 minutes.
Detector temperature: 260 C
Carrier gas: helium (6 psi)
System suitability
times with 0.5 L of standard solution according to the
above operating conditions, the relative standard deviation of peak areas obtained from triclosan is not more
than 2.0%.
Packaging and Storage Preserve in light resistant,
tight containers.
Triflusal
COOH
F3C
COCH3
KP 9 973
C 10 H 7 F 3 O 4 : 248.16
Triflusal contains not less than 98.5% and not more
than 101.5% of triflusal (C 10 H 7 F 3 O 4 ), calculated on the
dried basis.
Description Triflusal is a white powder.
Triflusal is very soluble in ethanol, soluble in dichloromethane, and practically insoluble in water.
Melting pointAbout 118 (with decomposition)
Identification (1) Mix about 5 mg of Triflusal and 45
mg of magnesium oxide and ignite them in a crucible
until an almost white residue is obtained. Allow to cool,
add 1 mL of water, 0.05 mL of phenolphthalein TS and
about 1 mL of dilute hydrochloric acid to render the solution colorless. Filter. To a freshly prepared mixture of
0.1 mL of alizarin S TS and 0.1 mL of zirconyl nitrate
TS, add 1.0 mL of the filtrate. Mix, allow to stand for 5
minutes and compare the color of the solution with that
of a blank prepared in the same manner. The test solution is yellow and the blank is reds.
(2) Weigh 0.2 g of Triflusal, add 2.0 mL of dilute
sodium hydroxide TS. Heat to boiling and maintain
boiling for 15 minutes. Allow to cool and add 25.0 mL
of dilute sulfuric acid. A crystalline precipitate is
formed. Filter, , wash the precipitate with water and dry
at 100 to 105. The crystals melt between 176
and 178.
(3) Dissolve 50.0 mg each of Triflusal and Triflusal
RS in ethanol to make exactly 100 mL. Add ethanol to
1.0 mL of this solution to make exactly 20 mL. Determine the absorption spectra of these solutions as directed under the Ultraviolet-visible Spectrophotometry:
(4) Determine the infrared spectra of Triflusal and
Triflusal RS as directed in potassium bromide disk method under the Infrared absorption Spectrophotometry:
about 1.0 g of Triflusal in ethanol to make 20 mL: the
solution is clear.
(2) Heavy metals Weigh 2.0 g of Triflusal, dissolve in 9 mL of ethanol, add water to make 20 mL,
add 2 mL of dilute acetic acid and a mixture of ethanol
and water (9 : 6) to make 50 mL, and perform the test
using this solution as the test solution.
Prepare the cotrol solution as follows: add 2 mL of dilute acetic acid and a mixture of ethanol and water (9 :
6) to 2.0 mL of lead standard solution to make 50 mL
(3) Triflusal related substance Weigh exactly
0.1 g of Triflusal, dissolve in the mobile phase to make
exactly 25 mL, and use this solution as the test solution. Separately, weigh exactly 40 mg of Triflusal related substance I (2-acetoxyterephthalic acid) RS, dissolve in the mobile phase to make exactly 100 mL, add
the mobile phase to 1.0 mL of this solution to make exactly 100 mL, and use this solution as the standard solution. Perform the test with 20 L each of the test solution and the standard solution as directed under the
Liquid Chromatography according to the following operating conditions. The peak area of 2acetoxyterephthalic acid obtained from the test solution
is not greater than the area of principal peak obtained
from the standard solution (not more than 0.1%).
aminopropylsilanized silica gel for the liquid chromatography (5 m in particle diameter).
Mobile phase : A mixture of acetonitrile and 0.05
mol/L phosphate buffer solution (pH 4.5) (75 : 25).
System suitability
When the procedure is run with 20 L of the
mixture of the same volumes of the test solution and
the standard solution, according to the above operating
conditions, the retention times of Triflusal and 2acetoxyterephthalic acid are about 2.4 and 5 minutes,
respectively.
(4) Triflusal related substance IIDissolve 0.1 g
of Triflusal in 15 mL of ethanol. Add 15 mL of cold
water and 0.5 mL of 5 w/v% ferric ammonium sulfate
solution. Allow to stand for 1 minute. This solution is
not more intensely colored than that of a control solution as the follows: dissolve 10.0 mg of Triflusal related substance (II) [4-(trifluoromethylsalicylic acid)]
in ethanol to make exactly 100 mL. To 3 mL of this solution, add 0.1 mL of glacial acetic acid, 0.5 mL of 0.5
w/v% ferric ammonium sulfate solution, 12 mL of
ethanol and 15 mL of water.
Loss on Drying Not more than 0.5% (1 g, vacuum,
diphosphorus pentaoxide).
Assay Weigh accurately about 0.2 g of Triflusal, dissolve in 50 mL of ethanol, and titrate with 0.1 mol/L
sodium hydroxide (potentiometric titration, Endpoint

= 24.82 mg of C 10 H 7 F 3 O 4
Packaging and Storage Store in an tight containers,
at a temperature not more than 25 C.
Trihexyphenidyl Hydrochloride
HO
CH2CH2
1 mL of 1 mol/L hydrochloric acid VS by warming,

cool and add water to make 100 mL. Determine the absorbance of this solution at 247 nm as directed under
the Ultraviolet-visible Spectrophotometry: the absorbance is not more than 0.50.
hours).
HCl
and enantiomer
C20H31NOHCl: 337.93
Trihexyphenidyl Hydrochloride, when dried, contains
not less than 98.5% and not more than 101.0% of trihexyphenidyl hydrochloride (C20H31NOHCl).
Description
Trihexyphenidyl Hydrochloride is a
white crystalline powder, is odorless and has a bitter
taste.
Trihexyphenidyl Hydrochloride is soluble in ethanol,
sparingly soluble in glacial acetic acid, slightly soluble
in water, very slightly soluble in acetic anhydride, and
Identification (1) Dissolve 1 g of Trihexyphenidyl
Hydrochloride in 100 mL of water by warming, cool
and use this solution as the test solution. To 5 mL of the
test solution, add 1 mL of a solution of picric acid in
chloroform (1 in 50) and shake vigorously: a yellow
(2) To 20 mL of the test solution obtained in (1),
add 2 mL of sodium hydroxide TS: a white precipitate
is produced. Collect the precipitate, wash with a small
volume of water, recrystallize from methanol and dry in
a desiccator (in vacuum, silica gel) for 2 hours: the
crystals so obtained melt between 113 C and 117 C.
(3) The test solution obtained in (1) responds to the
Qualitative Tests (2) for chloride.
pH Dissolve 1.0 g of Trihexyphenidyl Hydrochloride
in 100 mL of water by warming and cool: the pH of
1.0 g of Trihexyphenidyl Hydrochloride in 100 mL of
water by warming: the solution is clear and colorless.
(2) Heavy metalsDissolve 1.5 g of Trihexyphenidyl Hydrochloride in 60 mL of water by warming in a
water-bath at 80 C, cool and filter. To 40 mL of the filtrate, add 2 mL of dilute acetic acid and water to make
50 mL and perform the test using this solution as the
test solution. Prepare the control solution with 2.0 mL
of standard lead solution, 2 mL of dilute acetic acid and
water to make 50 mL (not more than 20 ppm).
(3) PiperidylpropiophenoneDissolve 0.10 g of
Trihexyphenidyl Hydrochloride in 40 mL of water and
Assay Weigh accurately about 0.5 g of Trihexyphenidyl Hydrochloride, previously dried, dissolve in 50
acid (1 : 1) and titrate with 0.1 mol/L perchloric aciddioxane VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any necessary correction.
Each mL of 0.1 mol/L perchloric acid-dioxane VS

Trihexyphenidyl Hydrochloride
Tablets
Trihexyphenidyl Hydrochloride Tablets contain not less
amount of trihexyphenidyl hydrochloride (C20H31NO
HCl: 337.93).
Tablets, with Trihexyphenidyl Hydrochloride.
Identification (1) Weigh a portion of powdered Trihexyphenidyl Hydrochloride Tablets, equivalent to 0.1
g of trihexyphenidyl hydrochloride according to the labeled amount, add 30 mL of chloroform, shake and filter. Evaporate the filtrate on a water-bath to dryness.
Dissolve the residue in 10 mL of water by warming,
cool and use this solution as the test solution. With 5
mL of the test solution, proceed as directed in the Identification (1) under Trihexyphenidyl Hydrochloride.
(2) Weigh a portion of powdered Trihexyphenidyl
Hydrochloride Tablets, equivalent to 10 mg of trihexyphenidyl hydrochloride according to the labeled
amount, add 5 mL of chloroform, shake, filter and use
the filtrate as the test solution. Separately, dissolve 20
mg of trihexyphenidyl hydrochloride RS in 10 mL of
chloroform and use this solution as the standard solution. Perform the test with the test solution and the
mixture of chloroform and methanol (9 : 1) to a dis-
KP 9 975
tance of about 10 cm and air-dry the plate. Spray evenly platinic chloride-potassium iodide TS on the plate:
the spots from the test solution and standard solution
show a blue-purple color and the same Rf value.
(3) The test solution obtained in (1) responds to the
Qualitative Tests (2) for chloride.
Dissolution Test Perform the test with 1 tablet of Trihexyphenidyl Hydrochloride Tablets at 50 revolutions
per minute according to Method 2 under the Dissolution Test, using 900 mL of diluted phosphate buffer solution, pH 6.8 (1 in 2). Take 30 mL or more of the dissolved solution after 30 minutes from the start of the
test and filter through a membrane filter with a pore
of the filtrate and use the subsequent filtrate as the test
Trihexyphenidyl Hydrochloride RS, previously dried at
105 C for 3 hours and dissolve in diluted phosphate
buffer solution, pH 6.8 (1 in 2) to make exactly 100 mL.
Pipet exactly 2 mL of this solution, add diluted phosphate buffer solution, pH (1 in 2) to make exactly 100
exactly 20 mL each of the test solution, the standard solution and diluted phosphate buffer solution, pH 6.8 (1
in 2), add exactly 1 mL of diluted acetic acid (1 in 10),
immediately add 5.0 mL of bromocresol green-sodium
hydroxide-acetic acid-sodium acetate TS and shake.
Then, add exactly 10 mL each of dichloromethane,
shake well, centrifuge and take the dichloromethane
layer. Determine the absorbances, AT, AS and AB, for
the test solution, the standard solution, and the diluted
phosphate buffer solution, respectively, of these dichloromethane layers at 415 nm as directed under the Ultraviolet-visible Spectrophotometry, using dichloromethane as a blank.
The dissolution rate of Trihexyphenidyl Hydrochloride
Tablets in 30 minutes should be not less than 70%.

of trihexyphenidyl hydrochloride (C20H31NOHCl)
AT-AB
1
= WS A -A C 18
S B
WS: Amount (mg) of Trihexyphenidyl Hydrochloride RS,
C: Labeled amount (mg) of Trihexyphenidyl Hydrochloride in 1 tablet.
To one tablet of Trihexyphenidyl Hydrochloride Tablets,
add 2 mL of dilute hydrochloric acid and 60 mL of water, disintegrate by vigorous shaking for 10 minutes and
warm in a water-bath with occasional shaking for 10
minutes. Cool, add 2 mL of methanol and add water to
make exactly V mL of the solution containing about 20
g of trihexyphenidyl hydrochloride per mL. Centrifuge, if necessary and use the supernatant liquid as the
test solution. Separately, dissolve about 20 mg of trihexyphenidyl hydrochloride RS (previously determine

the loss on drying at 105 C for 3 hours) in methanol to
make exactly 20 mL. Pipet exactly 2 mL of this solution, add 2 mL of dilute hydrochloric acid and water to
make exactly 100 mL and use this solution as the standard solution. Pipet exactly 10 mL each of the test solution and the standard solution, transfer to glassstoppered centrifuge tubes, add exactly 10 mL of bromocresol purple-dibasic potassium phosphate-citric acid TS and 15 mL of chloroform, stopper tightly, shake
well and centrifuge. Pipet exactly 10 mL each of the
chloroform layers, add chloroform to make exactly 50
mL. Determine the absorbances, AT and AS, of these solutions obtained from the test solution and the standard
solution at 408 nm as directed under Ultraviolet-visible
Spectrophotometry, respectively.
Amount (mg) of trihexyphenidyl hydrochloride
(C20H31NOHCl) = amount (mg) of Trihexyphenidyl
Hydrochloride RS, calculated on the dried basis
AT
V
A 1000
S
Trihexyphenidyl Hydrochloride Tablets. Weigh accurately a portion of the powder, equivalent to about 5 mg
of trihexyphenidyl hydrochloride (C20H31NOHCl), dissolve in 2 mL of dilute hydrochloric acid and 60 mL of
water by warming in a water-bath for 10 minutes with
occasional shaking. After cooling, add 2 mL of methanol and water to make exactly 100 mL and use this solution as the test solution. Dissolve about 50 mg of Trihexyphenidyl Hydrochloride RS (previously determine
the loss on drying at 105 C for 3 hours), weighed accurately, in methanol and add methanol to make exactly
20 mL. Pipet exactly 2 mL of this solution, add 2 mL of
dilute hydrochloric acid and water to make exactly 100
exactly 10 mL each of the test solution and the standard
solution into glass-stoppered centrifuge tubes, add exactly 10 mL each of bromocresol purple-dibasic potassium phosphate-citric acid TS and 15 mL each of chloroform, stopper tightly, shake thoroughly and centrifuge. Pipet exactly 10 mL each of the chloroform layers
and add chloroform to make exactly 50 mL. Determine
the absorbances, AT and AS, of these solutions obtained
from the test solution and the standard solution at 408
nm as directed under Ultraviolet-visible Spectrophotometry, respectively.
Amount (mg) of trihexyphenidyl hydrochloride

(C20H31NOHCl) = amount (mg) of Trihexyphenidyl
Hydrochloride RS, calculated on the dried basis
1
AT
A 10
S
Trimetazidine Hydrochloride
CH3O
CH3O
CH2
NH
2HCl
dard solution.
direct titration).
OCH3
C14H22N2O32HCl: 339.26
Trimetazidine Hydrochloride contains not less than
98.0% and not more than 101.0% of trimetazidine hydrochloride (C14H22N2O32HCl), calculated on the anhydrous basis.
Description Trimetazidine Hydrochloride is a white,
Trimetazidine Hydrochloride is very soluble in water or
in formic acid, soluble in methanol and practically insoluble in ether.
pHDissolve 1.0 g of Trimetazidine Hydrochloride in 20 mL of water: the pH of this solution is between 2.3 and 3.3.
of solutions of Trimetazidine Hydrochloride and Trimetazidine Hydrochloride RS in 0.1 mol/L hydrochloric
acid TS (1 in 6250) as directed under the Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared spectra of Trimetazidine
Hydrochloride and Trimetazidine Hydrochloride RS as
(3) A solution of Trimetazidine Hydrochloride (1 in
Trimetazidine Hydrochloride according to Method 2
ppm).
(2) Related substancesDissolve 0.5 g of Trimetazidine Hydrochloride in 10 mL of water and use this
test solution, add water to make exactly 100 mL and
mixture of cyclohexane and diethylamine (1 : 1) to a
distance of about 10 cm, air-dry the plate and then dry.
After cooling, examine under ultraviolet light (main
spot and the spot of the starting point from the test solution are not more intense than the spot from the stan-
Assay Weigh accurately about 0.12 g of Trimetazidine Hydrochloride, dissolve in 5 rnL of formic acid,
add exactly 15 mL of 0.1 mol/L perchioric acid VS, and
heat at 90 C to 100 C for 30 minutes. After cooling,
add 45 mL of glacial acetic acid, and titrate the excess
perchioric acid with 0.1 mol/L sodium acetate VS (potentiometric titration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any

= 16.963 mg of C14H22N2O32HCl
Trimethadione
H3C
H3C
N
O
CH3
C6H9NO3: 143.14
Trimethadione, when dried, contains not less than
98.0% and not more than 101.0% of trimethadione
(C6H9NO3).
Description Trimethadione is a white crystal or crystalline powder and has a camphor-like odor.
Trimethadione is very soluble in ethanol or in chloroform, freely soluble in ether, and soluble in water.
Identification (1) To 5 mL of a solution of Trimethadione (1 in 50), add 2 mL of barium hydroxide TS: a
precipitate is produced immediately.
(2) Determine the infrared spectra of solution of
Trimethadione and Trimethadione RS in chloroform (1
in 50) as the test solution using a 0.1 mm fixed sodium
chloride cell, as directed in the solution method under
Melting Point
Purity Heavy metalsProceed with 2.0 g of Trimethadione according to Method 1 and perform the test.
KP 9 977
6 hours).
Assay Weigh accurately about 0.4 g of Trimethadione, previously dried, in a stoppered Erlenmyer flask,
dissolve in 5 mL of ethanol, add exactly measured 50
mL of 0.1 mol/L sodium hydroxide VS, stopper and allow to stand for 15 minutes with occasional shaking.
Titrate the excess sodium hydroxide with 0.1 mol/L
hydrochloric acid VS (indicalor: 4 drops of cresol red

= 14.314 mg of C6H9N03
not exceeding 30 C.
Trimethadione Tablets
Trimethadione Tablets contain not less than 94.0% and
not more than 106.0% of the labeled amount of trimethadione (C6H9NO3: 143.14).
Tablets, with Trimethadione.
Identification (1) Weigh a portion of powdered Trimethadione Tablets, equivalent to 1 g of Trimethadione
according to the labeled amount, add 10 mL of petroleum benzin and shake frequently for 15 minutes. Decant, remove the petroleum benzin, add another 10 mL
of petroleum benzin and repeat the extraction in the
same manner. To the residue, add 25 mL of ether, allow to stand for 20 minutes with occasional shaking,
filter, evaporate the filtrate at room temperature and dry
the residue in a desiccator (silica gel) for 6 hours: the
residue melts between 44 C and 47 C. Proceed with
this residue as directed in the Identification under Trimethadione.
(2) Determine the infrared spectrum of a solution of
the dried residue in (1) in chloroform (1 in 50) using a
0.1 mm fixed sodium chloride cell, as directed in the
solution method under the Infrared Spectrophotometry:
it exhibits absorption at the wavenumbers of about
2960 cm-1, 1814 cm-1, 1735 cm-1, 1445 cm-1, 1394 cm-1,
1290 cm-1, 1100 cm-1 and 1055 cm-1.
ment.

Trimethadione Tablets. Weigh accurately a portion of
the powder, equivalent to about 1 g of trimethadione
(C6H9NO3), add 50 mL of ethanol and boil gently for

15 minutes under a reflux condenser. Filter the warm
ethanol solution into a volumetric flask through a glass
filter (G4) and wash the residue with three 10 mL volumes of warm ethanol. Combine the washings with the
filtrate in the flask, cool and add ethanol to make exactly 100 mL. Pipet exactly 25 mL of the solution into a
stoppered Erlenmeyer flask, add 25 mL of water and
exactly 30 mL of 0.1 mol/L sodium hydroxide VS,
stopper, allow to stand for 15 minutes with occasional
shaking and titrate the excess sodium hydroxide with
0.1 mol/L hydrochloric acid VS (indicator: 4 drops of
cresol red TS). Perform a blank determination and
= 14.314 mg of C6H9NO3
not exceeding 30 C.
Trimetoquinol Hydrochloride
Hydrate
OCH3
CH2
OCH3
HCl
H2O
HO
NH
OCH3
HO
Tretoquinol Hydrochloride
C19H23NO5HClH2O: 399.87
Trimetoquinol Hydrochloride Hydrate contains not less
than 98.0% and not more than 101.% of trimetoquinol
hydrochloride (C19H23NO5HCl: 381.85), calculated on
Description Trimetoquinol Hydrochloride is a white
Trimetoquinol Hydrochloride Hydrate is freely soluable
in methanol, and sparingly soluble in water or in ethanol.
after drying, in vacuum, at 105 C, for 4 hours).
of solutions of Trimetoquinol Hydrochloride Hydrate
and Trimetoquinol Hydrochloride Hydrate RS in 0.01
mol/L hydrochloric acid TS (1 in 2000) as directed under the Ultraviolet-visible Spectrophotometry: both
same wavelengths.
(4) Determine the infrared spectra with Trimetoquinol Hydrochloride Hydrate and Trimetoquinol Hy-
drochloride Hydrate RS as directed in the potassium

(5) A solution of Trimetoquinol Hydrochloride Hydrate (1 in 50) responds to the Qualitative Tests (1) for
chloride.
D : Between -17 and
-20, (calculated on the dried basis, 0.25 g, water,
warming and cooling, 25 mL, 100 mm).
pH Dissolve 1.0 g of Trimetoquinol Hydrochloride
Hydrate in 100 mL of water by warming and cool: the
0.10 g of Trimetoquinol Hydrochloride Hydrate in 10
mL of water by warming: the solution is clear and colorless.
(2) SulfatePerform the test with 0.5 g of Trimetoquinol Hydrochloride Hydrate. Prepare the control
solution with 0.40 mL of 0.005 mol/L sulfuric acid VS
(3) Heavy metalsProceed with 1.0 g of Trimetoquinol Hydrochloride Hydrate according to Method 2
ppm).
(4) Related substancesDissolve 50 mg of Trimetoquinol Hydrochloride Hydrate in 50 mL of the mobile
phase and use this solution as the test solution. Pipet
exactly 1 mL of this solution, add the mobile phase to
test solution and the standard solution, as directed under the Liquid Chromatography according to the following conditions. Determine each peak area of both
solutions by the automatic integration method: the total
area of the peaks other than that of trimetoquinol from
the test solution is not larger than the peak area of trimetoquinol from the standard solution.
about 40 C.
Mobile phase: Dissolve 2 g of potassium dihydrogen phosphate and 2 g of sodium 1-pentane sulfonate in
1000 mL of water. Adjust with phosphoric acid to a pH
between 2.8 and 3.2, filter through a membrane filter
(0.4 m in pore size) and add 200 mL of acetonitrile to
800 mL of the filtrate.
time of trimetoquinol is about 7 minutes.

System suitability
exactly 20 mL. Confirm that the peak area of trimetoquinol obtained from 20 L of this solution is equivalent to 7% to 13% of that of trimetoquinol obtained
from 20 L of the standard solution.
System performance: Dissolve 5 mg of Trimetoquinol Hydrochloride Hydrate and 1 mg of procaine
hydrochloride in 50 mL of the mobile phase. When the
above operating conditions, procaine and trimetoquinol
above operating conditions, the relative standard deviation of the peak area of trimetoquinol is not more than
2.0%.
the retention time of trimetoquinol after the solvent
peak.
Water 3.5 ~ 5.5% (0.3 g, volumetric titration, direct
titration).
Assay Weigh accurately about 0.5 g each of Trimetoquinol Hydrochloride Hydrate, dissolve in 2 mL of 0.1
mol/L hydrochloric acid VS and 70 mL of dehydrated
ethanol with thorough shaking and titrate with 0.1
mol/L potassium hydroxide-ethanol VS (potentiometric

Trioxsalen
CH3
O
CH 3
CH 3
C14H12O3: 228.25
Trioxsalen contains not less than 97.0% and not more
than 103.0% of trioxsalen (C14H12O3), calculated on the
dried basis.
KP 9 979
Description Trioxsalen is a white to grayish white
crystalline powder and is orderless.
Trioxsalen is slightly soluble in water, slightly soluble
in chloroform and practically insoluble in ethanol.
of solutions of Trioxsalen and Trioxsalene RS in chloroform (1 to 200000) as directed under the Ultravioletvisible Spectrophotometry: both absorption spectra exhibit maxima and minima at the same wavelengths.
(2) Determine the infrared spectra of Trioxsalene
and Trioxsalen RS, dried at 105 C for 6 hours, as directed in the paste method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
(3) The retention time of the principal peak obtained from the test solution as directed in the Assay
Purity Related substancesProceed with the test solution as directed under the Assay: the total peak area
of any peaks other than the principal peak is not more
than 2.0% of the total peak area of all the peaks and the
peak area of the peak with relative retention time to trioxsalene of about 0.75 is not more than 1.5% of the total peak area of all peaks.
hours).
Assay Weigh accurately about 0.1 g each of Trioxsalen and Trioxsalen RS, previously dried at 105 C for 6
hours, dissolve each in tetrahydrofuran to make exactly
100 mL. Filter these solutions, transfer exactly 5 mL
each of the filtrate, dilute with the mobile phase to
solution and the standard solution, respectively. Perform the test with 20 L each of the test solution and
conditions. Determine the peak areas, AT and AS, of trioxslen for the test solution and the standard solution,
respectively.
Amount (mg) of trioxsalen (C14H12O3)

AT
= Amount (mg) of Trioxsalen RS A
S
octadesylsilanized silica gel for liquid chromatography
(70 : 30).
System suitability
operating conditions, the symmetry factor for trioxsalene peak is not more than 2.0.
the peak area of trioxsalen is not more than 2.0%.
Tripelennamine Hydrochloride
CH2
CH2CH2N(CH3)2
HCl
C16H21N3HCl: 291.82
Tripelennamine Hydrochloride contains not less than
98.0% and not more than 100.5% of tripelennamine
hydrochloride (C16H21N3HCl), calculated on the dried
basis.
Description Tripelennamine Hydrochloride is a white
crystalline powder.
Tripelennamine Hydrochloride is very soluble in water,
in ethanol and in chloroform, sparingly soluble in acetone and practically insoluble in benzene, in ether or in
ethyl acetate.
Tripelennamine Hydrochloride is slowly darkened by
light.
A solution of Tripelennamine Hydrochloride is neutral.
Identification (1) Weigh 50 mg each of the Tripelennamine Hydrochloride and Tripelennamine Hydrochloride RS, dissolve in 25 mL of 0.01 mol/L hydrochloric
acid TS and transfer to a separatory funnel. Add 2 mL
of 1 mol/L sodium hydroxide and 4 mL of carbon disulfide, shake for 2 minutes, filter with a dried filter paper
and place the filtrate in a stoppered flask. Determine
the infrared spectra of the test solution and the standard
solution as directed in the solution method under the
Infrared Spectrophotometry, using carbon disulfide as a
blank (1 mm cell, wavelength 7 m to 15 m): both
same wavelengths.
(2) A solution of Tripelennamine Hydrochloride (1
50 mg of Tripelennamine Hydrochloride, dissolve in
mobile phase to make exactly 100 mL and use this solution as the test solution. Perform the test with 10 L
of the test solution as directed under the Liquid Chromatography according to the following conditions. Determine each peak area from the test solution by the automatic integration method and calculate their amount
by the area percentage: the amount of which the relative retention time is 0.70 is not more than 0.3%, the
amount of which the relative retention time is 1.37 is
not more than 0.2%, the amount of the others is not
more than 0.1% and the total area of the peaks other
than the principal peak is not more than 1.0%.
Detector, column, mobile phase, flow rate and system suitability: proceed as directed in the operating
conditions in the Assay.
Melting Point

hours).
with 10 L of the system suitability solution under the

above operating conditions, benzaldehye and 2aminobenzylpyridine are eluted in this order with the
above operating conditions, the relative standard deviation of the peak area of tripelennamine is not more than
1.0%.
Benzaldehyde solutionDissolve 1.0 mL of benzaldehyde in mobile phase to make 100 mL. Pipet 5 mL
of this solution, diluted with mobile phase to make 100
mL and mix with shaking.
System suitability solutionWeigh about 50 mg of
2-benzylaminopyridine, dissolve in 10 mL of methanol,
diluted with mobile phase to make 100 mL and mix
with shaking. Pipet 5.0 mL of this solution, add 5.0 mL
of benzaldehyde solution, diluted with mobile phase to
make 100 mL and mix with shaking.

Assay Dissolve about 50 mg each of Tripelennamine
Hydrochloride and Tripelennamine Hydrochloride RS,
accurately weighed, in a mobile phase to make exactly
100 mL and use these solution as the test solution and
the standard solution, respectively. Perform the test
according to the following operating conditions. Determine the peak areas, AT and AS, of tripelennamine
Amount (mg) of tripelennamine hydrochloride

(C16H21N3HCl) = amount (mg) of Tripelennamine
AT
Hydrochloride RS A
S
octadesylsilanized silica gel for liquid chromatography
about 35 C.
Mobile phase: To 530 mL of methanol, add 1.0 mL
of N,N-dimethyloctyl amine and mix well with shaking.
To this solution, add 430 mL of sodium 1octanesulfonate solution (0.029 mol/L), mix and adjust
the pH to 3.0 with phosphoric acid.
System suitability
Tropicamide
CH 2OH
CCONCH 2
H
CH 2CH 3
and enantiomer
C17H20N2O2: 284.35
Tropicamide, when dried, contains not less than 98.5%

and not more than 101.0% of tropicamide
(C17H20N2O2).
Description
Tropicamide is a white, crystalline
powder, is odorless and has a bitter taste.
Tropicamide is freely soluble in ethanol or in chloroform, slightly soluble in water or in ether, and practically insoluble in petroleum ether.
Tropicamide dissolves in dilute hydrochloric acid.
pHThe pH of a solution of Tropicamide (1 in
Identification (1) To 5 mg of Tropicamide, add 0.5
mL of a solution of ammonium vanadate in sulfuric acid (1 in 200) and heat: a blue-purple color is observed.
(2) Dissolve 5 mg of Tropicamide in 1 mL of ethanol and 1 mL of water, add 0.1 g of 2,4dinitrochlorobenzene and heat in a water-bath for 5 minutes. Cool and add 2 to 3 drops of a solution of sodium hydroxide (1 in 10) and 3 mL of ethanol: a redpurple color is observed.
1%
Absorbance E1cm
(after drying, 5 mg, 2 mol/L hydrochloric acid TS, 200
KP 9 981
mL).
L-Tryptophan,
Melting Point
Purify (1) ChlorideDissolve 1.0 g of Tropicamide

in 30 mL of ethanol, add 6 mL of dilute nitric acid and
water to make 50 mL and perform the test using this
solution as the test solution. Prepare the control solution with 0.45 mL of 0.01 mol/L hydrochloric acid VS,
30 mL of ethanol, 6 mL of dilute nitric acid and add
(2) Heavy metalsDissolve 1.0 g of Tropicamide
in 30 mL of ethanol, add 2 mL of dilute acetic acid and
water to make 50 mL and perform the test using this
solution as the test solution. Prepare the control solution with 2.0 mL of standard lead solution, 30 mL of
ethanol, 2 mL of dilute acetic acid and water to make
50 mL (not more than 20 ppm).
(3) N-Ethyl--picolylamineDissolve 0.10 g of
Tropicamide in 5 mL of water by heating, add 1 mL of
a solution of acetaldehyde (1 in 20) and shake well.
Add 1 to 2 drops of sodium nitroprusside TS and 1 to 2
drops of sodium bicarbonate TS and shake: no blue
color is observed.
(4) Tropic acidTo 10 mg of Tropicamide, add 5
mg of sodium borate and 7 drops of pdimethylaminobenzaldehyde TS and heat on a waterbath for 3 minutes. Cool in ice-water and add 5 mL of
acetic anhydride: no red-purple color is observed.
Assay Weigh accurately about 0.5 g of Tropicamide,

= 28.435 mg of C17H20N2O2
tight containers.
L-Tryptophan
H
N
H
CH2
CO2H
NH2
Cl1Hl2N2O2: 204.23

and not more than 101.0% of L-tryptophan
(Cl1Hl2N2O2).
Description L-Tryptophan is a white to yellowish
white crystal or crystalline powder, is odorless and has
a slightly bitter taste.
L-Tryptophan is freely soluble in formic acid, slightly
soluble in water, very slightly soluble in ethanol and
L-Tryptophan dissolves in dilute hydrochloric acid.
Identification Determine the infrared spectra of LTryptophan and L-Tryptophan RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities
D : Between -30.0
and -33.0. Weigh accurately about 0.25 g of LTryptophan, previously dried and dissolve in 20 mL of
water by warming. After cooling, add water to make
exactly 25 mL and determine the specific rotation of
the solution in a 100 mm cell.
pH Dissolve 1.0 g of L-Tryptophan in 100 mL of water by warming and cool: the pH of this solution is between 5.4 and 6.4.
Purity (1) Clarity of solution Dissolve 0.20 g of LTryptophan in 10 mL of 2 mol/L hydrochloric acid TS:
the solution is clear.
(2) ChlorideDissolve 0.5 g of L-Tryptophan in 6
mL of dilute nitric acid and add water to make 50 mL.
Perform the test using this solution as the test solution.
(3) Sulfate Dissolve 0.6 g of L-Tryptophan in 40
mL of water and 1 mL of dilute hydrochloric acid and
add water to make 50 mL. Perform the test using this
solution as the test solution. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not
more than 0.028%).
(4) AmmoniumPerform the test with 0.25 g of LTryptophan. Prepare the control solution with 5.0 mL
of standard ammonium solution (not more than 0.02%).
(5) Heavy metalsProceed with 1.0 g of LTryptophan according to Method 4 and perform the test.
(6) ArsenicDissolve 1.0 g of L-Tryptophan in 3
mL of 1 mol/L hydrochloric acid TS and 2 mL of water
by heating and perform the test (not more than 2 ppm).
(7) Related substances Dissolve 0.30 g of LTryptophan in 1 mL of 1 mol/L hydrochloric acid TS,
add water to make 50 mL and use this solution as the
test solution. Pipet exactly 1 mL of the test solution and
add water to make exactly 50 mL. Pipet exactly 5 mL

directed under the Thin-layer Chromatography, Spot 5
on a plate of silica gel for thin-layer chromatography.
Develop the plate with a mixture of n-butanol, water
and glacial acetic acid (3 : 1 : 1) to a distance of about
10 cm and air-dry the plate at 80 C for 30 minutes.
Spray evenly a solution of ninhydrin in acetone (1 in
50) on the plate and heat at 80 C for 5 minutes: the
hours).
Residue on Igntion Not more than 0.1% (1 g).
Assay Weigh accurately about 0.2 g of L-Tryptophan,
previously dried, dissolve in 3 mL of formic acid, add
changes from orange-yellow through yellowish green
to green (indicator: 0.5 mL of -naphtholbenzeine TS).
correction.

= 20.423 mg of C11H12N2O2
tight containers.
Tubocurarine Chloride
Hydrochloride Hydrate
CH3
N
HO
CH2
OCH3
H
Cl
HCl
5H2O
H
HO
CH2
CH3O
N
O
H 3C
CH3
Tubocurarine Hydrochloride
C37H41ClN2O6HCl5H2O: 771.72
Tubocurarine Chloride Hydrochloride Hydrate contains
not less than 98.0% and not more than 101.0% of tubocurarine chloride hydrochloride (C37H41ClN2O6HCl:
Description Tubocurarine Chloride Hydrochloride
Hydrate is a white crystal or crystalline powder and is
odorless.
Tubocurarine Chloride Hydrochloride Hydrate is spa-
ringly soluble in water or in ethanol, slightly soluble in

glacial acetic acid, and practically insoluble in ether or
in chloroform.
pHThe pH of a solution of Tubocurarine Chloride Hydrochloride Hydrate (1 in 100) is between 4.0
and 6.0.
Identification (1) To 20 mL of a solution of Tubocurarine Chloride Hydrochloride Hydrate (1 in 2000), add
0.2 mL of sulfuric acid and 2 mL of a solution of potassium iodate (1 in 100), shake and heat in a water-bath
for 30 minutes: a yellow color is observed.
(2) To 1 mL of a solution of Tubocurarine Chloride
Hydrochloride Hydrate (1 in 100), add 1 mL of a solution of Reinecke salt TS (1 in 100): a red precipitate is
produced.
Tubocurarine Chloride Hydrochloride Hydrate and Tubocurarine Chloride Hydrochloride Hydrate RS (3 in
(4) A solution of Tubocurarine Chloride Hydrochloride Hydrate (1 in 50) responds to the Qualitative Tests
(2) for chloride.
D : Between +210
and +220 (calculated on the dried basis, 0.1 g, , water,
10 mL, after allowing to stand for 3 hours, 100 mm).
0.10 g of Tubocurarine Chloride Hydrochloride Hydrate in 10 mL of ethanol: the solution is clear and colorless.
(2) Chloroform-soluble substancesWeigh accurately about 0.2 g of Tubocurarine Chloride Hydrochloride Hydrate, calculated on the dried basis, add 200 mL
of water and 1 mL of a saturated solution of sodium bicarbonate and extract with three 20 mL volumes of
chloroform. Combine the chloroform extracts, wash
with 10 mL of water, filter the chloroform solution
through absorbent cotton into a tared beaker, wash the
absorbent cotton with two 5 mL volumes of chloroform
and combine the filtrate and the washings. Evaporate
the chloroform in a water-bath and dry the residue at
105 C for 1 hour: the mass of the residue is not more
than 2.0% of the mass of Tubocurarine Chloride Hydrochloride Hydrate taken. Add 10 mL of water to the
residue: the residue does not dissolve. Add 1 mL of hydrochloric acid and stir: the residue dissolves.
Assay Weigh accurately about 0.5 g of Tubocurarine
Chloride Hydrochloride Hydrate, add 20 mL of glacial
KP 9 983
acetic acid and dissolve by warming in a water-bath.

After cooling, add 60 mL of acetic anhydride and titrate
correction.
tight containers
loride Injection.
Tubocurarine Chloride
Hydrochloride Injection
Tubocurarine Hydrochloride Injection
Tubocurarine Chloride Hydrochloride Injection is an
aqueous solution for injection. Tubocurarine Chloride
Hydrochloride Injection contains not less than 93.0%
and not more than 107.0% of the labeled amount of tubocurarine chloride hydrochloride hydrate (C37H41Cl
N2O6HCl5H2O: 771.72).
Method of Preparation Prepare as directed under Injections, with Tubocurarine Chloride Hydrochloride
Hydrate.
Description Tubocurarine Chloride Hydrochloride
Injection is a clear, colorless liquid.
Identification (1) To a volume of Tubocurarine Chloride Hydrochloride Injection, equivalent to 10 mg of
tubocurarine chloride hydrochloride hydrate according
to the labeled amount, add water to make 20 mL and
proceed as directed in the Identification (1) under Tubocurarine Chloride Hydrochloride Hydrate.
(2) Proceed with a volume of Tubocurarine Chloride Injection, equivalent to 3 mg of Tubocurarine
Chloride Hydrochloride Hydrate according to the labeled amount, as directed in the Identification (2) under
Tubocurarine Chloride Hydrochloride Hydrate.
(3) To a volume of Tubocurarine Chloride Hydrochloride Injection, equivalent to 3 mg of Tubocurarine
Chloride Hydrochloride Hydrate according to the labeled amount, add water to make 100 mL and determine the absorption spectrum of the solution as directed under the Ultraviolet-visible Spectrophotometry:
it exhibits a maximum between 279 nm and 281 nm
and a minimum between 253 nm and 257 nm.
[ ] 20
D

: Between +0.35
and +0.42 (200 mm), calculated with reference to the
value of solution containing 1 mg of Tubocurarine
Chloride Hydrochloride Hydrate per mL, according to
the labeled amount of Tubocurarine Chloride Hydroch-
Assay Measure exactly a volume of Tubocurarine

Chloride Hydrochloride Injection, equivalent to about
15 mg of tubocurarine chloride hydrochloride hydrate
(C37H41Cl N2O6HCl5H2O), add water to make exactly
500 mL and use this solution as the test solution. Separately, weigh accurately about 15 mg of Tubocurarine
Chloride Hydrochloride Hydrate RS (previously dry in
the same manner as directed under Tubocurarine Chloride Hydrochloride Hydrate and determine the loss on
drying), dissolve in water to make exactly 500 mL and
absorbances, AT and AS, of the test solution and the
standard solution at 280 nm as directed under the Ultraviolet-visible Spectrophotometry, respectively.
Amount (mg) of tubocurarine chloride hydrochloride

hydrate (C37H41ClN2O6HCl5H2O) = amount (mg) of
Tubocurarine Chloride Hydrochloride Hydrate RS,
AT
when dried A 1.1321
S
hermetic containers under nitrogen atmosphere.
Tulobuterol Hydrochloride
OH
CCH 2NHC(CH 3 ) 3
HCl
H
Cl
C12H18ClNOHCl: 264.19
Tulobuterol Hydrochloride, when dried, contains not
less than 98.5% and not more than 101.0% of tulobuterol hydrochloride (C12H18ClNOHCl).
Description Tulobuterol Hydrochloride is a white
Tulobuterol Hydrochloride is very soluble in methanol,
freely soluble in water, in ethanol or in glacial acetic
acid, sparingly soluble in acetic anhydride, and very
A solution of Tulobuterol Hydrochloride (1 in 20)

of solutions of Tulobuterol Hydrochloride and Tulobuterol Hydrochloride RS (1 in 2500) as directed under
(2) Determine the infrared spectra of Tulobuterol
Hydrochloride and Tulobuterol Hydrochloride RS, previously dried, as directed in the potassium bromide disk
same wavenumbers.
(3) A solution of Tulobuterol Hydrochloride (1 in
1.0 g of Tulobuterol Hydrochloride in 10 mL of water:
(2) Heavy metalsProceed with 2.0 g of Tulobuterol Hydrochloride according to Method 1 and perform
(3) Related substancesDissolve 0.30 g of Tulobuterol Hydrochloride in 5 mL of methanol and use this
test solution, add methanol to make exactly 50 mL and
directed under the Thin-layer Chromatography. Use a
plate of silica gel with a fluorescent indicator for thinlayer chromatography previously developed with the
upper-layer of a mixture of ethyl acetate and strong
ammonia water (200 : 9) to the top of the plate and airdried. Spot 5 L each of the test solution and the standard solution on the plate. Develop the plate with the
upper layer of a mixture of ethyl acetate and strong
ammonia water (200 : 9) to a distance of about 10 cm
principal spot and the spot of the starting point from the
standard solution.
Assay Weigh accurately about 0.5 g of Tulobuterol
3) and titrate with 0.1 mol/L perchloric acid VS (potentiometric titrration, Endpoint Detection Method in Titrimetry). Perform a blank determination and make any

= 26.419 mg of C12H18ClNOHCl
Ubidecarenone
O
CH3
CH3
H3CO
9
H3CO
CH3
CH3
O
C59H90O4: 863.34
Ubidecarenone contains not less than 98.0% and not
more than 101.0% of ubidecarenone (C59H90O4), calculated on the anhydrous basis.
Description Ubidecarenone is a yellow to orange
crystalline powder, is odorless and has no taste.
Ubidecarenone is soluble in ether, very slightly soluble
in dehydrated ethanol and practically insoluble in water.
Ubidecarenone is gradually colored by light.
Identification (1) Dissolve 50 mg of Ubidecarenone
in 1 mL of ether and add 10 mL of dehydrated ethanol.
To 2 mL of this solution, add 3 mL of dehydrated ethanol and 2 mL of dimethyl malonate, then add dropwise
1 mL of a solution of potassium hydroxide (1 in 5) and
mix: a blue color is observed.
(2) Determine the infrared spectra of Ubidecarenone and Ubidecarenone RS as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
Ubidecarenone according to Method 4 and perform the
(2) Related substancesDissolve 50 mg of Ubidecarenone in 50 mL of dehydrated ethanol by warming
at about 50 C for 2 minutes, cool and use this solution
as the test solution. To exactly 1 mL of the test solution,
add dehydrated ethanol to make exactly 100 mL and
test with 5 L each of the test solution and the standard
according to the following conditions. Determine each
peak area of both solutions by the automatic integration
method: the total area of peaks other than the principal
peak from the test solution is not larger than the principal peak area from the standard solution.
KP 9 985
phase, flow rate and selection of column: Proceed as directed in the operating conditions in the Assay.
Detection sensitivity: Adjust the detection sensitivity so that the peak height of Ubidecarenone obtained
and 40 mm.
Time span of measurement: About twice of the retention time of Ubidecarenone after the solvent peak.

above operating conditions, the relative standard deviation of the peak area of Ubidecarenone is not more than
0.8%.
tight containers.
Undecylenic Acid

direct titration).
CH2
Amount (mg) of ubidecarenone (C59H90O4)

= amount (mg) of Ubidecarenone RS,
A
AS
about 35 C.
Mobile phase: A mixture of methanol and dehydrated ethanol (13 : 7).
time of Ubidecarenone is about 10 minutes.
System suitability
System performance: Dissolve each 10 mg of
Ubidecarenone and Ubidecarenone RS in 20 mL of dehydrated ethanol by warming at about 50 C for 2 minutes. After cooling, when the procedure is run with 5
L of the system suitability solution under the above
operating conditions, Ubidecarenone RS and Ubidecarenone are eluted in this order with the resolution between their peaks being not less than 4.0.
CHCH2(CH2)6CH2CO2H
C11H20O2.: 184.28

Assay Weigh accurately about 50 mg of Ubidecarenone and Ubidecarenone RS (previously determine the
water content), dissolve each in 40 mL of dehydrated
ethanol by warming at about 50 C for 2 minutes, cool,
add dehydrated ethanol to make exactly 50 mL each
and use this solution as the test solution and the standard solution, respectively. Perform the test with 5 L
the following conditions and determine peak areas,
AT and AS , of Ubidecarenone of for the test solution
and the standard solution, respectively.
Undecylenic Acid contains not less than 97.0% and not

more than 100.5% of undecylenic acid (C11H20O2).
Description Undecylenic Acid is a colorless or pale
yellow color liquid and has characteristic odor.
Undecylenic Acid is miscible with ethanol, with ether,
with chloroform, with benzene or with fixed and volatile oils.
Undecylenic acid is practically insoluble in water.
Identification (1) To 1 mL of Undecylenic Acid, add
1 mL of potassium permanganate TS dropwise: the
permanganate color disappears.
(2) Place 3 mL of Undecylenic Acid and 3 mL of
freshly distilled aniline and heat for 10 minutes with
reflux condenser. After cooling, add 10 mL of ethanol
and 10 mL of ether and transfer to a separatory funnel.
Wash the ether solution with four 20 mL volumes of
water and discard the water washings. Heat in a steambath until the odor of ether no longer is perceptible,
then a portion of activated carbon, mix and filter. Evaporate the filtrate to dryness and recrystallize the residue from 70% ethanol: it melts between 66 o C and
67.6 o C .
Refractive index
Specific gravity
nD25 : Between 1.447 and 1.448.

25
: Between 0.910 and 0.913.
d 25
Iodine Value Between 131 and 138.

Congealing Range Not lower than 21
C.
Purity (1) Water soluble acidsShake 5 mL of Undecylenic Acid with 5 mL of water and filter the water
layer through a filter paper previously moistened with
water. Add 1 drop of methyl orange and titrate with
0.01 mol/L sodium hydroxide: not more than 1.0 mL of
0.01 mol/L sodium hydroxide is required to match the
color produced by 1 drop of methyl orange in 5 mL of
water.
(2) Heavy metalsProceed with 1.0 g of Undecylenic Acid according to Method 2 and perform the test.
Assay Weigh accurately about 0.75 g of Undecylenic
Acid, dissolve in 50 mL of ethanol, add 3 drops of phenolphthalein TS and titrate with 0.1 mol/L sodium hydroxide VS (indicator: 3 drops of phenolphthalein TS).
The end point of the titration is only when a pale red
color persists for not less than 30 seconds. Perform a

= 18.428 mg of C11H20O2
tight containers.
Urokinase
Urokinase is an enzyme, obtained from human urine,
that activates plasminogen and has the molecular
weight of about 54000. Urokinase is a solution using a
suitable buffer solution as the solvent.
Urokinase contains not less than 60000 units per mL
and not less than 120000 units per mg of protein.
Description Urokinase is a clear, colorless liquid.
Identification (1) Dissolve 70 mg of fibrinogen in 10
mL of phosphate buffer solution, pH 7.4, add 1 mL of
solution of thrombin containing 10 units per mL in Isotonic Sodium Chloride Injection, mix, place in a Petri
dish about 90 mm in inside diameter and keep horizontally until the solution is coagulate. On the surface,
drop 10 L of Urokinase containing 100 units per mL
in gelatin-tris buffer solution and stand overnight: lysis
circle is appeared.
(2) Dissolve 1.0 g of powdered agar in 100 mL of
boric acid-sodium hydroxide buffer solution, pH 8.4,
by warming and pour the solution into a Petri dish until
the height comes to about 2 mm. After cooling, make
two wells of 2.5 mm in diameter with the space of 6
mm. To each well, place separately 10 L of Urokinase
containing 30000 units per mL in Isotonic Sodium
Chloride Injection and 10 L of anti-urokinase serum
and stand overnight: a clear precipitated line is appeared.
Purity (1) Heavy metals Proceed with 2.0 mL of
Urokinase according to Method 2 and perform the test.

(2) Blood group substances Dilute Urokinase
with Isotonic Sodium Chloride Injection so that each
mL of the solution contains 12000 units and use this solution as the test solution. To anti-A type antibody for
blood typing, add Isotonic Sodium Chloride Injection
to dilute each 32, 64, 128, 256, 512 and 1024 times,
place separately 25 L each of these solutions in six
wells on the first and second lane of a V-shaped 96-well
microplate. Next, add 25 L of the test solution into the
six wells on the first lane and 25 L of Isotonic Sodium
Chloride Injection into the six wells of the second lane,
mix and allow to stand for 30 min. To each well, add 50
L of A-type erythrocyte suspension, mix, allow to
stand for 2 hours and compare the agglutination of
erythrocyte in both lanes: dilution factor of anti-A type
antibody of the wells which show the agglutination is
equal in both lanes. Perform the same test with anti-A
type antibody for blood typing and A-type erythrocyte
suspension.
Abnormal Toxicity Dilute Urokinase with Isotonic
Sodium Chloride Injection so that each mL of the solution contains 12000 units and use this solution as the
test solution. Inject 5.0 mL of the test solution into the
peritoneal cavity of each of 2 or more of wellnourished, healthy guinea pigs weighing about 350 g
and inject 0.5 mL of the test solution into peritoneal
cavity of each 2 or more of well-nourished, healthy
mice aged about 5 weeks. Observe the conditions of the
animals for more than 7 days: all the animals exhibit no
abnormalities.
High Molecular Weight Urokinase Dilute Urokinase with gelatin-phosphate buffer solution so that each
mL of the solution contains 10000 units and use this solution as the test solution. Perform the test with 100 L
of the test solution as directed under the Liquid Chromatography according to the following conditions. Determine the areas of two peaks eluted closely at about
35 minutes having smaller retention time, Aa and
larger retention time, Ab , by the automatic integration
method: the value, Aa /( Aa + Ab ) , is not less than 0.85.
Apparatus: Use a pumping system for the mobile
phase, a sample injection port, a column, a pumping
system for the reaction reagent, a reaction coil, a reaction chamber, a spectrofluorometer and a recorder. Attach a 3-way tube to the outlet for the mobile phase of
the column, connect the pumping system for the reaction reagent and the reaction coil, and join outlet of the
reaction coil to the spectrofluorometer.
Detector: Spectrofluorometer (excitation wavelength: 365 nm, fluorescence wavelength: 460 nm).
diameter and 60 cm in length, packed with porous silica
gel for liquid chromatography (10 m to 12 m in par-
KP 9 987
ticle diameter).
about 20 C.
Reaction coil: A stainless steel column, 0.25 mm in
inside diameter and 150 cm in length.
Reaction coil temperature: 37 C.
Mobile phase: Gelatin-phosphate buffer solution.
Flow rate of mobile phase: 0.5 mL/minute.
Reaction reagent: 7-(Glutarylglycyl-L-arginyl amino)-4-methylcoumarin TS.
Flow rate of reaction reagent: 0.75 mL/minute.
Selection of column: Adjust the pH of Urokinase to
7.5 with sodium hydroxide TS, allow to stand at 37 C
for over 24 hours and add gelatin-phosphate buffer solution to make the solution containing 20000 units per
mL. Proceed with 100 L of this solution under the
above operating conditions and calculate the resolution.
Use a column giving elution of high molecular weight
Urokinase (54000), low molecular weight Urokinase
(33000) in this order with the resolution between their
Assay (1) Urokinase Pipet 1.0 mL of Urokinase,
dilute exactly with gelatin-tris buffer solution so that
each mL of the solution contains about 30 units and use
this solution as the test solution. Add exactly 2 mL of
gelatin-tris buffer solution to contents of one ample of
high molecular weight Urokinase RS to dissolve, pipet
1.0 mL of this solution, dilute exactly with gelatin-tris
buffer solution so that each mL of the solution contains
about 30 units and use this solution as the standard solution. Place 1.0 mL of L-pyrgluta-myl-glycyl-Larginine-p-nitroaniline hydrochloride TS in two siliconcoated test tubes, about 10 mm in inside diameter,
warm in a water-bath at 35 0.2 C for 5 minutes, add
separately 0.50 mL each the test solution and the standard solution, warm in a water-bath at 35 0.2 C for
exactly 30 minutes and then add 0.50 mL of diluted
glacial acetic acid (2 in 5). Determine the absorbances,
AT and AS, of these solutions at 405 nm as directed under the Ultraviolet-visible Spectrophotometry, using
water as the blank. Separately, place 1.0 mL of Lpyroglutamylglycyl-L-arginine-p-nitroaniline hydrochloride TS in two test tubes, add 0.50 mL of diluted glacial acetic acid (2 in 5) and 0.50 mL each of the test solution and the standard solution. Determine the absorbances, ATO and ASO , of these solutions at 405 nm as
the same manner, using water as the blank.
Amount (units) of Urokinase =
AT ATO
ab
AS ASO
a: Amount (units) of Urokinase in 1 mL of the standard solution,

b: Total volume (mL) of the test solution.
(2) Protein Measure exactly a volume of Urokinase, equivalent to about 15 mg of protein and perform
the test as directed under the Nitrogen Determination.

= 0.87544 mg of protein
Store at -20 C or below.
Ursodeoxycholic Acid
H
CO2H
H3C
CH3
CH3
HO
OH
H
Ursodesoxycholic Acid
C24H40O4: 392.57
Ursodeoxycholic Acid, when dried, contains not less
than 98.5% and not more than 101.0% of ursodeoxycholic acid (C24H40O4).
Description Ursodeoxycholic Acid is a white crystal
or powder, is odorless and has a bitter taste.
Ursodeoxycholic Acid is freely soluble in glacial acetic
acid, in ethanol, or in dehydrated ethanol, slightly soluble in chloroform, very slightly soluble in ether and
Ursodeoxycholic Acid dissolves in sodium hydroxide
TS.
Identification Dissolve 10 mg of Ursodeoxycholic
Acid, add 1 mL of sulfuric acid and 1 drop of formalin
and allow to stand for 5 minutes. To the solution, add 5
mL of water: a blue-green suspended substance is produced.
D : Between +59.0
and +62.0 (after drying, 1.0 g, dehydrated ethanol, 25
mL, 100 mm).
Purity (1) OdorTo 2.0 g of Ursodeoxycholic Acid,
add 100 mL of water and boil for 2 minutes: no odor is
perceptible.
(2) ChlorideDissolve 2.0 g of Ursodeoxycholic
Acid in 20 mL of glacial acetic acid with shaking, add
water to make 200 mL, shake thoroughly and allow to
stand for 10 minutes. Filter this solution, discard the
first 10 mL of the filtrate and use the subsequent filtrate
as the test solution. To 40 mL of the test solution, add 6
mL of dilute nitric acid and water to make 50 mL. Per-
form the test using this solution as the test solution.

hydrochloric acid, add 4 mL of glacial acetic acid, 6
mL of dilute nitric acid and water to make 50 mL (not
more than 0.022%).
(3) SulfateTo 40 mL of the test solution obtained
in (2), add 1 mL of dilute hydrochloric acid and water
to make 50 mL and perform the test using this solution
as the test solution. Prepare the control solution as follows: to 0.40 mL of 0.005 mol/L sulfuric acid VS, add
4 mL of glacial acetic acid, 1 mL of dilute hydrochloric
(4) Heavy metalsProceed with 1.0 g of Ursodeoxycholic Acid according to Method 2 and perform
(5) BariumTo the solution obtained in (1), add 2
mL of hydrochloric acid, boil for 2 minutes, cool, filter
and wash with water until the last washing makes 100
mL. To 10 mL of the solution, add 1 mL of dilute sulfuric acid: no turbidity is produced.
Ursodeoxycholic Acid according to Method 3 and perform the test (not more than 2 ppm).
(7) Related substancesDissolve 50 mg of Urosodeoxycholic Acid in a mixture of chloroform and ethanol (9 : 1) to make exactly 25 mL and use this solution
as the test solution. Separately, dissolve 75 mg of chenodeoxycholic acid RS in a mixture of chloroform and
ethanol (9 : 1) to make exactly 50 mL and use this solution as the standard solution (1). Dissolve 25 mg of lithocholic acid RS in a mixture of chloroform and ethanol (9 : 1) to make exactly 50 mL. To exactly 1 mL of
this solution, add a mixture of chloroform and ethanol
(9 : 1) to make exactly 10 mL and use this solution as
the standard solution (2). Perform the test with the test
solution and the standard solutions (1) and (2) as directed under Thin-layer Chromatography. Spot 10 L
each of the test solution and the standard solutions (1)
and (2) on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chloroform,
acetone and glacial acetic acid (7 : 2 : 1) to a distance
of about 10 cm and air-dry the plate. Dry the plate at
120 C for 30 minutes, immediately, spray evenly a solution of molybdenic phosphoric acid in acetone (1 in
5) on the plate and heat at 120 C for 2 to 3 minutes:
the spot from the test solution, corresponding to that
from the standard solution (1), is not more intense than
the spot from the standard solution (1) and the spot other than the principal spot and the above spots from the
hours).
Assay Weigh accurately about 0.5 g of Ursodeoxycholic Acid, previously dried and dissolve in 40 mL of
neutralized ethanol and 20 mL of water. Add 2 drops of

phenolphthalein TS, titrate with 0.1 mol/L of sodium
hydroxide and titrate again after adding 100 mL of
freshly boiled and cooled water near the end point.
= 39.257 mg of C24H40O4
L-Valine
H
(CH3)2CH
CO2H
NH2
C5H11NO2: 117.15
L-Valine,
when dried, contains not less than 98.5% and

not more than 101.0% of L-valine (C5H11NO2).
Description L-Valine is a white crystal or crystalline

powder, is odorless or has a faint characteristic odor
and has a slightly sweet taste, which becomes bitter.
L-Valine is freely soluble in formic acid, soluble in water and practically insoluble in ethanol or in ether.
L-Valine dissolves in dilute hydrochloric acid.
Identification (1) To 5 mL of a solution of L-Valine
(1 in 5000), add 1 mL of ninhydrin TS. Heat for 3 minutes in a water-bath: a blue-purple color is observed.
(2) Dissolve 0.3 g of L-Valine in 10 mL of water by
warming, add 10 drops of dilute hydrochloric acid and
2 mL of sodium nitrite TS: an effervescence is produced and a colorless gas evolves.
D : Between +26.5
and + 29.0(after drying, 2 g, 6 mol/L hydrochloric acid
TS, 25 mL, 100 mm).
pH Dissolve 0.5 g of L-Valine in 20 mL of water: the
0.5 g of L-Valine in 20 mL of water: the solution is
(2) Chloride Proceed with 0.5 g of L-Valine. Prepare the control solution with 0.30 mL of 0.01 mol/L
hydrochloric acid VS (not more than 0.021%).
(3) Sulfate Proceed with 0.6 g of L-Valine. Prepare the control solution with 0.35 mL of 0.005 mol/L
sulfuric acid VS (not more than 0.028%).
(4) Ammonium Proceed with 0.25 g of L-Valine.
ammonium solution (not more than 0.02%).
(5) Heavy metalsProceed with 1.0 g of L-Valine
KP 9 989

(6) ArsenicProceed with 1.0 g of L-Valine according to Method 2 and perform the test (not more
than 2 ppm).
(7) Related substancesDissolve 0.10 g of LValine in 25 mL of water and use this solution as the
water to make exactly 50 mL. Pipet 5.0 mL of this solution, add water to make exactly 20 mL and use this solution as the standard solution. Perform the test with
plate with a mixture of n-butanol, water and glacial
acetic acid (3 : 1 : 1) to a distance of about 10 cm and
air-dry the plate. Spray evenly a solution of ninhydrin
in acetone (1 in 50) on the plate and heat at 80 C for 5
minutes: the spots other than the principal spot form the
standard solution.
hours).
Assay Weigh accurately about 0.12 g of L-Valine,
previously dried and dissolve in 3 mL of formic acid,

= 11.715 mg of C5H11NO2
Vancomycin Hydrochloride
HO
HO
NH2
OH
CH3
H3C
O
O
HO
O
Cl
O
O
H
OH
HO
Cl
O
H
O
H
HN
N
H
H
N
O
O
H
N
N
H
H
N
H
N
H
NH2
Description Vancomycin Hydrochloride is a white to

light brown powder, is odorless, and has a little bit of
bitter taste.
Vancomycin Hydrochloride is freely soluble in water,
very slightly soluble in ethanol, and practically insoluble in ether.
Identification (1) Weigh about 10 mg of Vancomycin
Hydrochloride, dissolve in 2 mL of water, and add 1mL
of 1 mol/L sodium hydroxide TS and one drop of cupric sulfate solution (1 in 10): red-purple to purple color develops.
(2) Weigh about 10 mg of Vancomycin Hydrochloride, dissolve in 2 mL of water, and add 2mL of anthrone TS and shake: a red to dark brown color develops.
(3) Weigh about 20 mg of Vancomycin Hydrochloride, dissolve in 10 mL of water, and add one drop of
silver nitrate TS: the solution turns to turbid.
(4) Weigh about 10 mg of Vancomycin Hydrochloride, dissolve in water and make to 100 mL. Determine
the absorption spectrum of this solution as directed under Ultraviolet-visible Spectrophotometry, it exhibits
maximum between 279 nm and 284 nm.
of Vancomycin Hydrochloride in 10 mL of water is
Purity (1) Heavy metalsProceed with 1 g of Vancomycin Hydrochloride according to Method 2 and
(2) Vancomycin factor AWeigh 0.1 g of Vancomycin Hydrochloride, dissolve in 0.1 mol/L hydrochloric acid TS, make to exactly 50 mL and use this solution as the test solution. Perform the test with the test
solution as directed under Thin-layer Chromatography.
Spot 2 L of each solution on a plate of silica gel for
thin-layer chromatography, develop the plate with the
mixture of methanol, acetonitrile and 10 % ammonia
water (6:3:3) as the developing solvent mixture to a
distance of about 10 cm, and air-dry the plate. Place the
plate in the vapor of iodine for 20 minutes: the spot for
vancomycin A ( Rf about 0.1) is not detected.
CH3
H
O
H3C
HOOC
Vancomycin Hydrochloride is the hydrochloride of a

glycopeptides substance having antibacterial activity
produced by the growth of Streptomyces orientalis.
Vancomycin Hydrochloride contains not less than 900
g (potency) per mg of vancomycin (C66H75Cl2N9O24:
CH3
Sterility Test It meets the requirement, when Vancomycin Hydrochloride is used in a sterile preparation.
HCl
OH
HO
OH
C66H75Cl2N9O24HCl: 1485.72

vancomycin, when Vancomycin Hydrochloride is used
in a sterile preparation.

of Vancomycin Hydrochloride for Injection in 10 mL of

Assay The Standard curve method (1) Agar media for seed and base layerPeptone
6.0 g Meat extract
1.5 g
Yeast extract
3.0 g Agar
15.0 g
Water
1000 mL
Mix all the ingredients, and sterilize. Adjust the pH
of the solution so that it will be 5.8 to 6.0 after sterilization.
(3) Cylinder plate- Prepare according to the method
I 5 as directed under Microbial Assay for Antibiotics.
Use 10 mL for base layer.
(4) Weigh accurately an appropriate amount of
Vancomycin Hydrochloride, dissolve in sterile purified
water to make the solution so that contains 1 mg (potency) and pipet exactly an appropriate amount of this
solution and dilute to make solutions so that each mL
contains 10.0 g (potency) and use this solution as the
test solution. Separately, Weigh accurately an appropriate amount of Vancomycin Hydrochloride RS, dissolve
in sterile purified water to make the solution so that
each mL contains 1 mg (potency), and use this solution
as the standard stock solution. Keep the standard solution at not exceeding 5 C and use within 7 days. In use,
pipet exactly an appropriate amount of this standard
stock solution and dilute in sterile purified water to
make the solutions so that each mL contains 6.4, 8.0,
10.0, 12.5, and 15.6 g (potency) per mL, and use these
solutions as the standard solutions. Also use the solution containing 10.0 g (potency) per mL as the standard mid-diluted solution. Perform the test with these
solutions according to the Standard curve method (II 4)
Sterility Test It meets the requirement, when Vancomycin Hydrochloride is used in a sterile preparation.
Vancomycin Hydrochloride
for Injection
Vancomycin Hydrochloride for Injection is a preparation for injection which is dissolved before use.
Vancomycin Hydrochloride for Injection contains not
less than 90.0 % and not more than 120.0 % of the labeled amount of vancomycin (C66H75Cl2N9O24:
1449.25).
Method of Preparation Prepare as directed under Injection, with Vancomycin Hydrochloride.
Identification Perform the tests according to the
Identification 1), 2), and 4) under Vancomycin Hydrochloride.

vancomycin, when it is used in a sterile preparation.
ment.
Assay The Standard curve method Perform the test
according to the Assay under Vancomycin Hydrochloride. In the test, weigh accurately the contents of not
less than 10 Vancomycin Hydrochloride for Injection.
Weigh an appropriate amount of the content, according
to labeled content, dissolve in sterile purified water to
make a solution so that each mL contain 1 mg (potency). Pipet exactly an appropriate amount of this solution and dilute to make a solution so that each mL contains 10.0 g (potency) and use this solution as the test
solution.
Vasopressin Injection
Vasopressin Injection is an aqueous solution for injection. Vasopressin Injection contains synthetic vasopressin or the pressor principle, vasopressin, obtained from
the posterior lobe of the pituitary of healthy cattles and
pigs, from which the majority of the oxytocic principle,
oxytocin, has been removed.
Vasopressin Injection contains not less than 85.0% and
not more than 120.0% of the labeled vasopressin units.
Method of Preparation Prepare as directed under Injections, with vasopressin prepared by synthesis or obtained from the posterior lobe of the pituitary.
Description Vasopressin Injection is a clear and colorless liquid, is odorless or has a slight, characteristic
odor.
Purity Oxytocic principleWhen tested by the following procedure, Vasopressin Injection contains not
more than 0.6 oxytocin units for each determined 10
KP 9 991
vasopressin units.
Standard stock solutionDissolve 200 Units of
Oxytocin RS, according to the labeled Units, in exactly
10 mL of diluted glacial acetic acid (1 in 400). Pipet 1
mL of this solution, and add diluted glacial acetic acid
(1 in 400) to make exactly 10 mL. Store in a cold place,
avoiding freezing. Use within 6 months from the date
of preparation.
Standard solutionDilute the standard stock solution with Isotonic Sodium Chloride Injection so that
each mL of the solution contains 0.020 oxytocin units.
Test solutionAssume oxytocin units are equivalent to 6/100 of the determined vasopressin units. Dilute Vasopressin Injection with Isotonic Sodium Chloride Injection so that each mL of the resulting solution
is expected to contain 0.020 oxytocin unit.
ApparatusUse the apparatus for the uterus contraction test, equipped with a thermostatic bath. Maintain a temperature of the bath at 37 C to 38 C with a
variation of not more than 0.1 C during the course of
the test. Use a 100-mL Magnus' chamber for suspending the uterus vertically.
Test animalUse healthy, virgin and metestrus
guinea pigs weighing between 175 g and 350 g. They
have been bred under conditions where they have been
completely isolated from the sight and smell of males
since the time of weaning.
ProcedureImmerse the Magnus' chamber in the
bath maintained at a constant temperature, add LockeRinger's solution to the chamber and introduce oxygen
into the solution at a moderate rate. Sacrifice a guinea
pig by means of a blow on the head, immediately remove the uterus from the body, suspend it in toe chamber and connect one horn of the uterus to the lever with
a thread. If necessary, weigh the lever provided that the
weight is not changed throughout the Assay. Start the
Assay after 15 to 30 minutes when the uterus is completely relaxed. Administer the same quantities, 0.1 to
0.5 mL, of the test solution and the sample solution to
the Magnus' chamber alternately twice with regular intervals of between 10 and 20 minutes to contract the
uterus, finally administer the standard solution in a
quantity which is 25% larger than the preceding doses
and measure the height of every contraction. The mean
height of uterus contraction caused by the standard solution is equal to or higher than that caused by the test
solution. The height of contraction caused by the increased dose of the standard solution is distinctly higher than those caused by the preceding doses of the standard solution.

Assay (1) Test animalsUse healthy male rats
weighing between 200 g and 300 g.
(2) Standard stock solutionDissolve 200 Units of
Oxytocin RS, according to the labeled Units, in exactly
10 mL of diluted glacial acetic acid (1 in 400). Pipet 1
mL of this solution, and add diluted glacial acetic acid
(1 in 400) to make exactly 10 mL. Store in a cold place,
avoiding freezing. Use within 6 months from the date
of preparation.
(3) Standard solutionDilute the standard stock
solution with Isotonic Sodium Chloride Injection so
that 0.2 mL of the obtained solution causes blood pressure increases of between 35 mmHg and 60 mmHg in
test animals when injected according to (4) and designate this solution as the high-dose standard solution
( S H ). Then dilute this solution with Isotonic Sodium
Chloride Injection, 1.5 to 2.0 times by volume and designate as the low-dose standard solution ( S L ).
(4) Test solutionDilute an accurately measured
volume of Vasopressin Injection with Isotonic Sodium
Chloride Injection so that the obtained solution contains the same concentration in units as the high-dose
standard solution based on the labeled units and designate it as the high-dose test solution ( TH ). Then dilute
this solution with Isotonic Sodium Chloride Injection
1.5 to 2.0 times by volume and designate as the lowdose sample solution ( TL ). Make the concentration ratio of S H to S L equal to the ratio of TH to TL .
When the sensitivity of an animal is changed, adjust the
concentration of SH and TH before the next set of assay
is started. However, keep the same ratio of S H to S L
and TH to TL as in the primary set.
(5) Dose of injectionAlthough 0.2 mL of each
solution is usually injected, the dose of injection can be
determined based from preliminary tests or experiences.
Inject the same volume throughout a set of tests.
(6) ProcedureInject subcutaneously 0.7 mL of a
solution of urethane (1 in 4) per 100 g of body weight
to anesthetize the test animals and cannulate the trachea.
Under artificial respiration (about 60 strokes per
minute), remove a part of the second cervical vertebra,
cut off the spinal cord and destroy the brain through the
foramen magnum. Insert cannula filled with Isotonic
Sodium Chloride Injection into the femoral vein.
Through this cannula, inject the solution prepared by
dissolving 200 heparin units of heparin sodium in 0.1
mL of Isotonic Sodium Chloride Injection per 100 g of
body wight and then immediately inject 0.3 mL of Isotonic Sodium Chloride Injection. Insert a cannula into a
carotid artery and connect the cannula to a manometer
for blood pressure measurement with vinyl tube. The
cannula and the vinyl tube have previously been filled
with Isotonic Sodium Chloride Injection. Inject all
standard and the test solutions at regular intervals of 10
to 15 minutes into the femoral vein through the cannula
followed by 0.3 mL of the Isotonic Sodium Chloride

Injection when the blood pressure increases caused by
each solution returns to the original level. Measure the
height of blood pressure increases within 0.67 kPa on
the kymogram. Maintain a constant temperature between 20 C and 25 C during the assay.
In advance, make four pairs from S H , S L , TH , TL
as follows.
Randomize the order of injection for pairs, but keep the
order of injection within pairs as indicated.
Pair 1: S H , TL ,
Pair 3: TH , S L ,
Pair 2: S L , TH ,
Pair 4: TL , S H .
Carry out this Assay using the same animals throughout

a set of four pairs of observations. Perform this assay
with two sets. If necessary, however, use the different
animals for both sets of tests.
(7) CalculationSubtract increases of blood pressure caused by the low dose from those caused by the
high dose in the Pairs 1, 2, 3 and 4 of each set and obtain the responses y1 , y2 , y3 and y4 , respectively.
Sum up y1 , for each set to obtain Y1 and obtain Y2 ,
Y3 and Y4 in the same way.
Y Y Y
y + b
f
4 4f
s2 =
n
y 2 : Sum of each squares of y1, y2, y3 and y4 of
2
each group.
Y = Y12 + Y22 + Y32 + Y42

Y : Multiply the sum of y1, y2, y3 and y4 of one
group and sum all of each group.

n = 3( f 1)
t 2 : Value of the table of Assay Method for insulin

2
for injection, to n of calculating s .
Packaging and Storage Preserve in hermetic containers, store at a cold place and avoid freezing.
Expiration Date 36 months after preparation
Verapamil Hydrochloride
OCH3
CN
Units in 1 mL of Vasopressin Injection = antilog M

b
units in 1 mL of high-dose standard solution
a
IYa
M =
Yb
I = log
SH
T
= log H
SL
TL
Ya = Y1 + Y2 + Y3 Y4
Yb = Y1 + Y2 + Y3 + Y4
a: Volume (mL) of Vasopressin Injection sampled,
b: Total volume (mL) of the high-dose sample solution, prepared by diluting with Isotonic Sodium Chloride Injection.
Compute L (P = 0.95) by the following equation and

confirm L to be 0.15 or less. If L exceeds 0.15, repeat
the test, improving the conditions of the assay or increasing the number of sets until L reaches 0.15 or less.
L = 2 (C 1)(CM 2 + I 2 )
C=
f = number of sets
Yb2
Yb2 4 fs 2 t 2
CH3O
CH3O
CH3
CCH2CH2CH2NCH2CH2
OCH3
HCl
CH(CH3)2
Iproveratril Hydrochloride
C27H38N2O4HCl: 491.06
Verapamil Hydrochloride, when dried, contains not less

than 98.5% and not more than 101.0% of verapamil
hydrochloride (C27H38N2O4HCl).
Description Verapamil Hydrochloride is a white,
Verapamil Hydrochloride is freely soluble in methanol,
in glacial acetic acid or in chloroform, soluble in ethanol or in acetic anhydride, sparingly soluble in water
Identification (1) To 2 mL of a solution of Verapamil
Hydrochloride (1 in 50), add 5 drops of Reinecke salt
Verapamil Hydrochloride and Verapamil Hydrochloride
RS in 0.01 mol/L hydrochloric acid TS (1 in 50000) as
directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(3) Determine the infrared spectra of Verapamil
Hydrochloride and Verapamil Hydrochloride RS, previously dried, as directed in the potassium bromide disk
same wavenumbers.
(4) A solution of Verapamil Hydrochloride (1 in 50)
KP 9 993
= 49.11 mg of C27H38N2O4HCl


pH Dissolve 1.0 g of Verapamil Hydrochloride in 20

mL of freshly boiled and cooled water by warming and
cool: the pH of this solution is between 4.5 and 6.5.
1.0 g of Verapamil Hydrochloride in 20 mL of water by
warming: the solution is clear and colorless
(2) Heavy metalsProceed with 1.0 g of Verapamil
Verapamil Hydrochloride according to Method 3 and
(4) Related substancesDissolve 0.50 g of Verapamil Hydrochloride in 10 mL of chloroform and use
test solution, add chloroform to make exactly 100 mL
and use this solution as the standard stock solution. Pipet 5.0 mL of the standard stock solution, add chloroform to make exactly 100 mL and use this solution as
the standard solution (1). Separately, pipet 5.0 mL of
the standard stock solution, add chloroform to make
exactly 50 mL and use this solution as the standard solution (2). Perform the test with the test solution and
the standard solutions (1) and (2) as directed under
test solution and the standard solutions (1) and (2) on
two plates of silica gel for thin-layer chromatography.
With the one plate, develop the plate with a mixture of
cyclohexane and dimethylamine (17 : 3) to a distance
of about 15 cm, air-dry the plate, heat at 110 C for 1
hour and cool. Examine immediately after spraying
evenly ferric chloride-iodine TS on the plate: the three
spots, having more intense color in the spots than the
principal spot and the original point from the test solution, are not more intense than the spot from the standard solution (1) in color. With another plate, develop
the plate with a mixture of toluene, methanol, acetone
and glacial acetic acid (14 : 4 : 1 : 1) and perform the
test in the same manner.
hours).
Assay Weigh accurately about 0.7 g of Verapamil
Vigabatrin
H
NH2
H2C
COOH
and enantiomer
C6H11NO2 : 129.16
Vigabatrin contains not less than 98.0% and not more

than 102.0% of vigabatrin (C6H11NO2), calculated on
an anhydrous basis.
Description Vigabatrin is a white powder.
Vigabatrin is very soluble in water.
spectra of Vigabatrin and Vigabatrin RS as directed in
(2) In the Assay, the retention time of the principal
peak from the test solution is the same as that from the
standard solution.
0.5 (2 g, water, 10 mL, 100 mm).
Purity (1) Heavy metals Proceed the test with 2.0
g of Vigabatrin according to Method 2. Prepare the
(2) EthanolDissolve 2 g of Vigabatrin, accurately weighed, in 10 mL of a solution containing 0.0025%
of 1,2-dichloroethane (internal standard) in water in a
20 mL-sized headspace vial. Heat the vial at 60 C for
30 minutes, and use the solution as the test solution.
Separately, prepare a solution containing 0.025% of
dehydrated ethanol and 0.0025% of 1,2-dichloro-ethane
in water . Use water as the blank. ). Perform the test
with the blank solution, the test solution and the standard solution as directed under the head-space Gas
Using the chromatograms obtained with the test solution and the standard solution, determine the ratios of
the peak area of Vigabatrin to that of ethanol, and calculate the content of ethanol in the portion of Vigabatrin: not more than 0.6% of ethanol is found.
Detector: A flame ionization detector.
Column: A fused-silica column 0.32 mm inside diameter and 60 m in length, coated with a 1.0 m film
of bonded methylsilicone for gas chromatography.
Carrier gas: Helium
Injector temperature: 150 C.

Column temperature: Maintain an initial temperature at 35 C for 12 minutes, and increase to 175 C at
a constant rate of 10 C per minute.
(3) Related substancesThe sum of the related
substances determined by methods [I] and [II] described below is not more than 0.5%.
[I] Dissolve 0.4 g of Vigabatrin in the mobile phase
to make 100 mL, and use this solution as the test solution. Separately, dissolve 4.0 mg of 3-aminopent-4-ene1,1-dicarboxylic acid RS in the 100 mL of the mobile
phase. Dilute 5.0 mL of this solution with the mobile
phase to exactly 50 mL, and use this solution as the
standard solution (1). Dissolve 4.0 mg of 5-vinyl-2pyrrolidone RS in the mobile phase to make exactly
100 mL. Dilute 5.0 mL of this solution with the mobile
phase to 50 mL, and use this solution as the standard
solution (2). Dissolve 4.0 mg of (E)-4-amino-2ethylidenebutyric acid hydrochloride RS in the mobile
phase to make exactly 100 mL. Dilute 5.0 mL of this
solution with the mobile phase to 50 mL, and use this
solution as the standard solution (3). Dissolve 2.0 mg
of 5-vinyl-2-pyrrolidone RS and 0.40 g of Vigabatrin
RS in the mobile phase to make exactly 100 mL, and
the test with 20 L each of the test solution, the standard solutions (1), (2), and (3) as directed under the
conditions. Determine the area of each peak by the automatic integration method. The areas of any peaks corresponding to 5-vinyl-2-pyrrolidone and (E)-4-amino2-ethylidenebutyric acid obtained from the test solution
are not greater than the areas of the peaks from the
standard solutions (2) and (3), respectively (not more
than 0.1% of each); the area of any other secondary
peak is not greater than the area of the peak from the
standard solution (1) (not more than 0.1%). Calculate
the percentage content of 5-vinyl-2-pyrrolidone and
(E)-4-amino-2-ethylidenebutyric acid using the areas of
the peaks from the standard solutions (2) and (3) respectively and of any other impurity from the peak
from the standard solution (1) taking, for the purposes
of calculation, that this peak is equivalent to 0.1%, and
hence determine the sum of the contents of total related
substances.
Column: Two stainless steel columns connected to
each other in series.
Column 1: A stainless steel column about 4.6 mm
inside diameter and 25 cm in length, packed with silica
of which surface is modified with chemically-bonded
hexylsilyl groups (5 m in particle diameter).
Column 2: A stainless steel column about 4.6 mm
inside diameter and 25 cm in length, packed with cation
exchange resin (10 m in particle diameter).
Mobile phase: A mixture of water, acetonitrile, and
phosphate buffer solution (950 : 25 : 25).

System suitability
operating conditions, 5-vinyl-2-pyrrolidone and vigabatrin are eluted in this order with the resolution between
the peaks of 5-vinyl-2-pyrrolidone and vigabatrin being
not less than 1.5.
Time span of measurement: 2 times as long as
the retention time of vigabatrin.
Phosphate buffer solution: Dissolve 58.5 g of sodium dihydrogen phosphate in water, add 23 mL of
phosphoric acid, and dilute with water to 1000 mL.
[II] Dissolve 20.0 mg of Vigabatrin in 10 mL of
water to make exactly 10 mL. To 1 mL of this solution,
add 2 mL of a solution prepared by dissolving 7.7 g of
boric acid in water, adjusting to pH 7.7 with 50% sodium hydroxide solution and diluting to 250 mL with
water. Add 3 mLof a solution of 0.16% (9fluorenyl)methyl chloroformate in acetone, mix and allow to stand for 5 minutes. Add 3 mL of ethyl acetate,
shake vigorously for a few seconds, and allow to separate. Use the lower layer as the test solution and proceed the test within 8 hours of preparation. Separately,
dissolve 2.0 mg of 4-aminobutyric acid and 0.2 g of
Vigabatrin in water to make 100 mL. Using 1 mL of
this solution, prepare the standard solution in the same
manner. Perform the test with 25 L of the test solution
Determine the peak area of 4-aminobutyric acid by the
automatic integration method: the content of 4aminobutyric acid in the portion of Vigabatrin is not
more than 0.2%.
Column: A stainless steel column about 4.6 mm inside diameter and 25 cm in length, packed with 5 m
silica gel particles of which surface of which is modified by chemically-bonded phenyl groups.
Mobile phase: A mixture of sodium acetate buffer
solution and acetonitrile (75 : 25).
System suitability
operating conditions, (9-fluorenyl)methanol, 4aminobutyric acid, and vigabatrin are eluted in this order and their corresponding retention times are about 6
minutes, 9 minutes, and 14 minutes, respectively with
the resolution between the peaks of the derivatives of
4-aminobutyric acid and (9-fluoreny)methanol being
not less 2.
Sodium acetate buffer solution: Dissolve 8.2 g of
anhydrous sodium acetate in water, adjust the pH to 4.2
with glacial acetic acid and dilute to 2 L with water.
KP 9 995
Water Not more than 0.5% (0.3 g, dehydrated methanol, 50 mL, volumetric titration, direct titration).
Assay Dissolve 0.2 g each of Vigabatrin and Vigabatrin RS, accurately weighed, in water to make 100 mL.
Use these solutions as the test solution and the standard
in the Liquid Chromatography according to the following conditions. Calculate the peak areas, AT and AS ,
of vigabatrin of these solutions.
Amount (mg) of vigabatrin (C6H11NO2) = amount (mg)

A
of Vigabatrin RS T
AS
Column: A stainless steel column about 4.6 mm inside diameter and 25 cm in length, packed with 10 m
cation exchange resin.
Mobile phase: A mixture of phosphate buffer solution, methanol, and acetonitrile (1000:40:4).
System suitability
System performance: Dissolve 2.0 mg of 5-vinyl2-pyrrolidone RS and 0.2 g of Vigabatrin RS in water
to make 100 mL. When the procedure is run with 20
L of this solution, 5-vinyl-2-pyrrolidone and vigabatrin are eluted in this order and the resolution between
the peaks of 5-vinyl-2-pyrrolidone and vigabatrin being
not less than 1.5.
Phosphate buffer solutionDissolve 3.4 g of potassium dihydrogen phosphate in water, adjust the solution pH to 2.8 by phosphoric acid, and dilute with water
to 1000 mL.
Vinblatine Sulfate
OH
N
CH2CH3
H2SO4
H
N
N
H
CH3O
CH3O
CH2CH3
H
N
H
CH3 HO
CH3
OCH3 O
C46H58N4O9H2SO4: 909.05
Vinblastine Sulfate contains not less than 96.0% and

not more than 102.0% of vinblastine sulfate
(C46H58N4O9H2SO4), calculated on the dried basis.
Description Vinblastine Sulfate is a white to pale
yellow powder.
Vinblastine Sulfate is soluble in water, sparingly soluble in methanol and practically insoluble in ethanol or
ether.
Vinblastine Sulfate is hygroscopic.
of the solutions of Vinblastine Sulfate and Vinblastine
Sulfate RS (1 in 50000) as directed under the Ultraviolet-visible Spectrophotometry: both spectra exhibit similar intensities of absorption at the same wavelengths.
(2) Determine the infrared spectra of Vinblastine
Sulfate and Vinblastine Sulfate RS as directed in the
Spectrophotometery: both spectra exhibit similar intensities of absorption at the same wavenumbers..
(3) A solution of Vinblastine Sulfate (1 in 100) responds to the Qualitative Tests for sulfate.
D : between -28 and 35 (0.20 g, calculated on the dried basis, methanol, 10
mL, 100 mm).
pH Dissolve 15 mg of Vinblastine Sulfate in 10 mL
10 mg of Vinblastine Sulfate in 10 mL of water: the solution is clear and colorless.
(2) Related substancesDissolve about 4 mg of
Vinblastine Sulfate in 10 mL of water and use this solution as the test solution. Pipet 1.0 mL of the test solution, add water to make exactly 25 mL and use this solution as the standard solution. Perform the test with 20
these solutions by the automatic integration method:
the area of any peak other than the main peak is not
larger than 1/4 of the peak area of vinblastine from the
standard solution, and the total area of peaks other than
the main peak is not larger than 3/4 of the peak area of
vinblastine from the standard solution.
System suitability
system suitability in the Assay.
Test for required detectability: To exactly 2.5 mL
of the standard solution, add water to make exactly 100

mL. Confirm that the peak area of vinblastine obtained
from 200 L of this solution is equivalent to 1.7 to3.3%
of that from 200 L of the standard solution.
above operating conditions, the relative standard deviation of the peak area of vinblastine is not more than
1.5%.
long as the retention time of vinbalstine beginning after
the solvent peak.
Loss on Drying Perform the test with about 10 mg of
Vinblastine Sulfate as directed in Method 2 under the
Thermal Analysis according to the following conditions: not more than 15.0%.
water. When the procedure is run with 20 L of this solution under the above operating conditions, vincristine
and vinblastine are eluted in this order with a resolution
between their peaks being not less than 4.
above operating conditions, the relative standard deviation of the peak area of vinblastine is not more than
1.0%.
Packaging and Storage Preserve in light resistant,
ight containers. Store at not exceeding 20 C.
Vinblatine Sulfate for Injection
Heating rate: 5 C/minute
Temperature range: room temperature to 200 C
Atmospheric gas: dried Nitrogen
Flow rate of atmospheric gas: 40 mL/minute
Vinblastine Sulfate for Injection is a preparation for injection which is reconstituted before use. When dried,
Vinblastine Sulfate for Injection contains not less than
of vinblastine sulfate (C46H58N4O9H2SO4: 909.07).
Assay Weigh accurately about 10 mg of Vinblastine

Sulfate and Vinblastine Sulfate RS (previously determinethe loss on drying in the same manner as Vinblastine Sulfate), dissolve in water to make exactly 25 mL,
and use these solutions as the test solution and the
exactly 20 L each of the test solution and the standard
solution as directed under the Liguid Chromatography
according to the following conditions, and determine
the peak areas, AT and AS , of vinbalstine.
Method of Preparation Prepare as directed under Injections, with Vinblastine Sulfate.
Amount (mg) of vinblastine sulfate

(C46H58N4O9H2SO4)
= Amount (mg) of Vinblastine Sulfate RS (calculated
A
on the dried basis) T
AS
particle diameter).
about 25 C.
Mobile phase: To 7 mL of diethylamine, add water
to make 500 mL and adjust the pH 7.5 with phosphoric acid. To 380 mL of this solution, add 620 mL of
a mixture of methanol and acetonitrile (4 : 1).
time of vinblastine is about 8 minutes.
System suitability
Vinblastine Sulfate and Vincristine Sulfate in 25 mL of
Description Vinblastine Sulfate for Injection is a

white to pale yellow, light mass or powder.
Vinblastine Sulfate for Injection is freely soluble in water.
The pH of its aqueous solution (1 in 1000) is 3.5 to 5.0.
Identification Proceed as directed in the Identification (1) under Vinblastine Sulfate.
Purity Related substancesDissolve 4 mg of Vinblastine Sulfate for Injection in 10 mL of water and use
test solution, add water to make exactly 25 mL and use
according to the following conditions. Determine each
peak area of these solutions by the automatic integration method: the area of any peak other than the main
peak of the test solution is not larger than 1/2 of the
peak area of vinblastine from the standard solution, and
the total area of any peaks other than the main peak
from the test solution is not larger than 2 times the peak
area of vinblastine from the standard solution.
Perform as directed in the operating conditions in
Purity (2) under Vinblastine Sulfate.
System suitability
Perform as directed in the system suitability in
Purity (2) under Vinblastine Sulfate.
KP 9 997
Bacterial Endotoxins Less than 10 EU/mg
Dissolve 1 Vinblastine Sulfate Injection in wate to
make exactly V mL so that each mL contains abut 0.4
mg of vinblastine sulfate (C46H58N4O9H2SO4) according to the labeled amount, and use this solution as the
test solution. Separately, weigh accurately about 10 mg
of Vinblastine Sulfate RS (previously determine the
loss on drying in the same manner as Vinblastine Sulfate), dissole in water to make exactly 25 mL, and use
this solution as the standard solution. Proceed as directed in the Asay under Vinblastine Sulfate.
Amount (mg ) of vinblastine sulfate

(C46H58N4O9H2SO4)
= Amount of Vinblastine Sulfate RS (calculated on the
A
25
dried basis) T
AS V
Assay Take an amount of Vinblastine Sulfate for Injection, equivalent to 0.10 g of vinblastine sulfate
(C46H58N4O9H2SO4), dissolve each content with a suitable amount of water, transfer into a 100-mL volumetric flask, wash each container with water, transfer the
washings into the volumetric flask, and add water to
make exactly 100 mL. Pipet 10 mL of this solution, add
water to make exactly 25 mL, and use this solution as
mg of Vinblastine Sulfate RS (previously determine the
loss on drying in the same manner as Vinblastine Sulfate), dissolve in water to make exactly 25 mL, and use
this solution as the standard solution. Proceed as directed in the Assay under Vinblastine Sulfate.
Amount (mg) of vinblastine sulfate

(C46H58N4O9H2SO4) =
Amount (mg) of Vinblastine Sulfate RS (calculated on
A
the dried basis) T 10
AS
hermetic containers and store at a cold place.
Vincristine Sulfate
OH
N
CH2CH3
H2SO4
H
N
N
H
CH3O
CH3O
CH2CH3
H
N
OHC
H
HO
CH3
OCH3 O
C46H56N4O10H2SO4: 923.04
Vincristine Sulfate contains not less than 95.0% and not
more
than
105.0%
of
vincristine
sulfate
(C46H56N4O10H2SO4), calculated on the dried basis.
Description Vincristine Sulfate is a white to pale yellowish white powder.
Vincristine Sulfate is very soluble in water and practically insoluble in ethanol or in ether.
Vincristine Sulfate is hygroscopic.
D : between +28.5
and +35.5 (0.20 g, calculated on the dried basis, water,
10 mL, 100 mm).
Identification (1) Dissolve 5 mg of Vincristine Sulfate in 2 mL of ceric ammonium sulfate-phosphoric acid TS: a blue-purple color is observed.
(2) Determine the absorption spectra of the solutions of Vincristine Sulfate and Vincristine Sulfate RS
(3) Dissolve 20 mg of Vincristine Sulfate in 10 mL
of sodium chloride TS, adjust the solution with ammonia TS to a pH between 9 and 10 and extract with two 5
mL volumes of chloroform. Wash the combined chloroform extracts with a small portion of sodium chloride
TS, add a small portion of anhydrous sodium sulfate
and allow to stand for several minutes. Filter through a
pledget of absorbent cotton, evaporate the filtrate under
reduced pressure to dryness and dissolve the residue in
a small volume of chloroform. Determine the infrared
spectra of this solution and Vincristine Sulfate RS in
chloroform as directed in the solution method under the
(4) A solution of Vincristine Sulfate (1 in 100) responds to the Qualitative Tests for sulfate.

pH Dissolve 10 mg of Vincristine Sulfate in 10 mL of
25 mg of Vincristine Sulfate in 10 mL of water: the solution is clear and colorless.
(2) Related substancesDissolve 25 mg of Vincristine Sulfate in 10 mL of water and use this solution
these solutions by the automatic integration method:
the total area of the peaks other than the principal peak
of the test solution is not larger than the peak area of
vincristine from the standard solution and the area of
any peak other than the principal peak of the test solution is not larger than 2/5 of the peak area of vincristine
octylsilanized silica gel for liquid chromatography (5
Mobile phase: Use methanol as the mobile phase A
and a mixture of water and diethylamine (197 : 3) adjusted with phosphoric acid to a pH of 7.5 as the mobile
phase B. Run a mixture of the mobile phase A and the
mobile phase B (31 : 19) for 24 minutes after injection
of the test solution and run a mixture of the mobile
phase A and the mobile phase B for subsequent 30 minutes, increasing the composition ratio of the mobile
phase A by 1% per minute. For subsequent 4 minutes,
run a mixture of the mobile phase A and the mobile
phase B, decreasing the composition ratio of the mobile
phase A by 7.5% per minute, then continue running a
(31 : 19).
time of vincristine is about 19 minutes.
Selection of column: Dissolve 10 mg each of Vincristine Sulfate and Vinblastine Sulfate in 100 mL of
water. Proceed with 20 L of this solution under the
above operating conditions. Vincristine and vinblastine
Detection sensitivity: Adjust the detection sensitivity so that the peak height of vincristine from 20 L of
the standard solution is between 5 mm and 15 mm.
as the retention time of vincristine after the solvent
peak.
Loss on Drying Not more than 12.0% (50 mg, in vacuum, 105 C, 2 hours).
Assay Weigh accurately about 10 mg of Vincristine
Sulfate, dissolve in acetic acid-sodium acetate buffer
solution, pH 5.0, to make exactly 50 mL. Pipet 5.0 mL
of this solution, add acetic acid-sodium acetate buffer
solution, pH 5.0, to make exactly 50 mL. Determine the
absorbance (A) of this solution, using the blank buffer
solution as control, at a maximum wavelength at about
Amount (mg) of vincristine sulfate

A
(C46H56N4O10H2SO4) = 177 5000
hermetic containers and store at a cold place
Vinorelbine Tartrate
O
OH
OH
HO
CH3
H
N
H
OH
H
N
CH3
H3CO
O
H
CH3O
N
CH3
CH3
HO
H3CO
C45H54N4O82C4H6O6 : 1079.11
Vinorelbine Tartrate contains not less than 98.0% and
not more than 102.0% of vinorelbine tartrate
(C45H54N4O82C4H6O6), calculated on the anhydrous
basis.
Description Vinorelbine Tartrate occurs as a white to
yellow or bright brown amorphous powder.
Vinorelbine Tartrate is freely soluble in water.
Identification (1) Dissolve 50 mg of Vinorelbine
Tartrate in 1 mL of water. To 0.1 mL of this solution,
add 0.1 mL of 10 % potassium bromide solution, 0.1
mL of 2% resorcinol solution, and 3 mL of sulfuric acid.
Heat on a hot water bath for 5 to 10 minutes until a
dark blue color develops. Allow to cool, and pour the
solution into water. The color changes to red.
(2) Dissolve 10 mg each of Vinorelbine Tartrate and
Vinorelbine Tartrate RS in 5 mL of water, add 0.5 mL
of 5 mol/L sodium hydroxide, and extract with 5 mL of
methylene chloride. Filter the organic extracts through
anhydrous sodium sulfate, and evaporate the organic
KP 9 999
extracts to about 0.5 mL. Use these solutions as the test
solution and the standard solution. Determine the infrared absorption spectra of these solutions as directed in
(3) The retention time of the major peak obtained
from the test solution corresponds to that from the
standard solution (2), as obtained in the test for related
substances in the Purity.
of Vinorelbine Tartrate in 50 mL of water is between
3.3 and 3.8.
0.1 g of Vinorelbine Tartrate in 10 mL of water: the solution is clear. Determine the absorbance of this solution as directed under the Ultraviolet-visible Spectrophotometery: its absorption, determined at 420 nm using water as the blank, is not more than 0.03.
(2) Related substancesDissolve 35 mg of Vinorelbine Tartrate, accurately weighed, in the mobile
phase to make exactly 25 mL, and use this solution as
the test solution. Separately, dissolve 35 mg of Vinorelbine Tartrate, accurately weighed, in the mobile phase
standard solution (1). Pipet 1.0 mL of the standard solution (1), and dilute with the mobile phase to 50 mL. Pipet 1 mL of this solution, dilute with the mobile phase
again to 100 mL, and use this solution as the standard
solution (2). Perform the test with 20 L each of the
test solution and the standard solution (2) as directed
under the Liquid Chromatography, determine their major peak areas by the automatic integration method, and
calculate the percentage of each related substance in the
portion of Vinorelbine Tartrate. The photodegradation
product is not more than 0.3%, any individual impurity
or coeluted impurities comprising an individual peak is
not more than 0.2%, and total impurities, excluding the
photodegradation product, is not more than 0.7%. Disregard any peak areas less than or equal to one-half of
the peak area obtained for vinorelbine from the standard solution (2).
A
Amount (%) of each related substance = 100 i
AS
Ai is the peak area for each impurity obtained from
the test solution.
AS is the sum of all the peak areas obtained from
the test solution.
about 40 C.
Mobile phase: Dissolve 1.22 g of sodium 1decanesulfonate in 620 mL of methanol. Add 380 mL
of phosphate buffer.
System suitability
System performance: Dissolve accurately
weighed quantities of Vinorelbine Tartrate RS and Vinorelbine Related Substance I RS in water to obtain a
solution having known concentrations of about 1.4 mg
per mL and 0.01 mg per mL, respectively. Expose a
portion of this solution in a suitable xenon lamp apparatus capable of supplying a dose of 1600 KJ/m2 between 310 and 800 nm at a power of 500 W/m2 for
about one hour, in order to generate an additional photodegradation product (3,4,7,8-tetradehydro-3,4dideoxy-3,6-epoxy-6,7-dihydro-Cnorvincaleukoblastine) having a relative retention time
of about 0.8. When the procedure is run with 20 L of
retention time for vinorelbine is about 13.5 minutes, the
relative retention times are about 0.8 for the photodegradation product and 1.2 for vinorelbine related substance I, and the resolution between the peaks of vinorelbine tartrate and vinorelbine related substance I is
not less than 1.1.
long as the retention time of vinorelbine.
Phosphate bufferDissolve 6.9 g of monobasic
sodium phosphate in 900 mL of water. Adjust with
phosphoric acid to a pH of 4.2, and dilute with water to
1000 mL.
direct titration)
Residue on Ignition
Not more than 0.1% (1 g)
Assay Dissolve about 0.35 g of Vinorelbine Tartrate,

accurately weighed, in 40 mL of glacial acetic acid, and
correction.
Each mL of 0.1 mol/L perchloric acid VS = 53.96 mg

of C45H54N4O82C4H6O6.
Packaging and Storage Preserve in tight, lightresistant containers. Store in a freezer.
Vitamin A Oil
Vitamin A Oil is the fatty oil obtained from fresh livers
and pyloric caeca of marine animals, or this fatty oil, its
concentrate, vitamin A or its fatty acid esters diluted
with cod liver oils or vegetable oils, containing not less
than 30000 Vitamin A units per g. Vitamin A Oil may

contain suitable antioxidant.
Vitamin A Oil contains not less than 90.0% and not
more that 120.0% of the labeled units of vitamin A.
Description Vitamin A Oil is yellow to yellow-brown
clear or slightly turbid oil, is odorless or has a faint,
Decomposition of Vitamin A Oil is accelerated upon
exposure to air or light.
Identification Dissolve Vitamin A Oil in chloroform,
prepare a solution of 30 Vitamin A units per mL according to the labeled units, pipet 1 mL of the solution and
add 3 mL of antimony trichloride TS: the color of the
solution changes immediately to blue, which fades rapidly.
Purity (1) AcidDissolve 1.2 g of Vitamin A Oil in
30 mL of a mixture of neutralized ethanol and ether (1 :
1), boil gently for 10 minutes under a reflux condenser,
cool and add 5 drops of phenolphthalein TS and 0.60
mL of 0.1 mol/L sodium hydroxide VS: a red color develops.
(2) RancidityNo unpleasant odor of rancid oil is

perceptible by warming Vitamin A Oil.
(3) Related substancesVitamin A Oil meets the
conditions determined as directed in Method 1 under
the Vitamin A Assay, or its f value determined as directed in Method 2 under the Vitamin A Assay is not
less than 0.85.
Assay Proceed as directed under the Vitamin A Assay.
Packaging and Storage Preserve in light-resistant
and almost well-filled or under nitrogen atmosphere,
tight containers.
Vitamin A Oil Capsules

Vitamin A Capsules
Vitamin A Oil Capsules contain not less than 90.0%
and not more than 130.0% of the labeled units of Vitamin A.
Capsules, with Vitamin A Oil.
Description The content of Vitamin A Oil Capsules
conforms to the requirement of Description under Vitamin A Oil.
Indentification Proceed the test with the content of
Vitamin A Oil Capsules as directed in the Identification
under Vitamin A Oil.
Assay Weigh accurately 20 Vitamin A Oil Capsules,

cut open, transfer the oil contents, mix well and proceed with the oil as directed under Vitamin A Assay.
Wash the capsules with a small amount of ether, allow
to stand at room temperature to evaporate the ether and
weigh accurately. Calculate the weight of Vitamin A Oil
from the difference between the weights before and after the above-described procedure. Calculate the Vitamin A units per 1 capsule from the weight and the Vitamin A units of the oil.
Warfarin Potassium
O
O
H
C
OK
CH2COCH3
C19H15KO4: 346.42
Warfarin Potassium, when dried, contains not less than
98.0% and not more than 102.0% of warfarin potassium (C19H15KO4).
Description Warfarin Potassium is a white crystalline
powder.
Warfarin Potassium is very soluble in water, freely soluble in ethanol.
Warfarin Potassium dissolves in sodium hydroxide TS.
Warfarin Potassium is colored to light yellow by light.
The solution of Warfarin porassium in water (1 in 10)
has no optical rotation.
of the solutions of Warfarin Potassium and Warfarin
Potassium RS, respectively, in 0.02 mol/L sodium hydroxide TS (1 in 100000) as directed under Ultravioletvisible Spectrophotometry: both spectra exhibit similar
(2) Determine the infrared spectra of Warfarin Potassium and Warfarin Potassium RS, previously dried,
same wavenumbers.
(3) The solution of Warfarin potassium in water (1
in 250) responds to the Qualitative Tests for potassium
salts.
pH Dissolve 1.0 g of Warfarin Potassium in 100 mL
of water: the pH of the solution is between 7.2 and 8.3.
Purity (1) Alkaline colored substancesDissolve
about 1.0 g of Warfarin Potassium in sodium hydroxide
KP 9 1001
TS (1 in 20) to make exactly 10 mL. Determine the absorbance of this solution at 385 nm within 15 minutes
as directed under the Ultraviolet-visible Spectrophotometry, using sodium hydroxide TS (1 in 20) as a blank.
The absorbance is not more than 0.20.
(2) Heavy metalsDissolve about 2.0 g of Warfarin Potassium in 30 mL of ethanol, add 2 mL of dilute
acetic acid and ethanol to make 50 mL and perform the
test. Prepare the control solution with 2.0 mL of standard lead solution and add 2 mL of dilute acetic acid
and ethanol to make 50 mL (not more than 10 ppm).
(3) Related SubstancesDissolve about 0.10 g of
Warfarin Potassium, weighed accurately, in 100 mL of
mixture solution of watermethanol (3 : 1) and use this
test solution, dilute with mixture solution of watermethanol (3 : 1) to exactly 100 mL, and use this solution as the standard solution. Perform the test with
exactly 20 L each of the test and standard solutions as
the automatic integration method: the area of any peak
other than warfarin is not greater than 1/10 times the
peak area of warfarin obtained with the standard solution. The total area of all peaks other than warfarin obtained with the test solution is not greater than 1/2
times the peak area of warfarin with the standard solution.
phase, and flow rate : proceed as directed in the operation conditions under the Assay.
System suitability
Test for required detectability: Pipet exactly 1 mL of
the standard solution, dilute with mixture solution of
watermethanol (3 : 1) to exactly 20 mL. Confirm that
the peak area of warfarin obtained with 20 L of this
solution is equivalent to 3.5 to 6.5% of that with 20 L
of the standard solution.
System performance: Dissolve 20 mg of propyl parahydroxybenzoate in 50 mg of methanol, dilute with water to exactly 200 mL. Mix 5 mL of this solution and 4
mL of Warfarin Potassium in mixture solution of watermethanol (3 : 1) (1 in 2000), and dilute with mixture
solution of watermethanol (3 : 1) to 100 mL. When the
above operating condition, propyl parahydroxybenzoate and warfarin are eluted in this order with resolution between these peaks and the symmetry factor being not less than 7 and not more than 1.5, respectively.
with 20 L of the standard solution under the above operating conditions, the relative standard deviation of the
peak area of warfarin is not more than 2.0%.
the retention time of warfarin beginning after the solvent peak.
hours).
Assay Weigh accurately about 25 mg each of Warfarin Potassium and Warfarin Potassium RS, previously
dried, dissolve separately in and dilute with the mixture
solution of watermethanol (3 : 1) to make exactly 50
mL each. Pipet exactly 10 mL each of these solution,
dilute with the mixture solution of watermethanol (3 :
1) to make exactly 50 mL, and use the solutions as the
Perform the test with exactly 20 L each of the test solution and the standard solutions as directed under Liquid Chromatography according to the following conditions, and determine each peak area, AT and AS , of
warfarin by the automatic integration method.
Amount (mg) of Warfarin Potassium = amount (mg) of

A
Warfarin Potassium RS T
AS
diameter and 25 cm in length, packed with octadecylsilanized silica gel for Liquid Chromatography (5 m in
particle diameter).
about 40 C.
Mobile phase: A mixture solution of wateracetonitrileglacial acetic acid (68 : 32 : 1)
time of warfarin is about 10 minutes.
System suitability
with 20 L of the standard solution under the above operating condition, the number of theoretical plates and
the symmetry factor of the peak of warfarin are not less
than 8000 and not more than 1.5, respectively.
above operating conditions, the relative standard deviation of the peak area of warfarin is not more than 1.0%.
tight containers.
Warfarin Potassium Tablets

Warfarin Potassium Tablets contains not less than
of warfarin potassium (C19H15KO4: 346.42).
Tablets, with Warfarin Potassium.

of the solution T2 obtained in the Assay, using 0.02
mol/L potassium hydroxide TS as the blank, as directed
under Ultraviolet-visible Spectrophotometry: it exhibits
a maximum between 306 nm and 310 nm, and a minimum between 258 nm and 262 nm. Separately, determine the absorption spectrum of the solution T1 obtained in the Assay, using 0.02 mol/L hydrochloric acid
TS as the blank, as directed under Ultraviolet-visible
nm and 285 nm and between 303 nm and 307 nm, and
a minimum between 243 nm and 247 nm.
(2) Weigh a portion of powdered Warfarin Potassium Tablets, equivalent to 10 mg of Warfarin Potassium according to the labeled amount, dissolve in 10
mL of acetone by shaking and filter the liquid. Evaporate acetone from the filtrate on a water-bath. Add 10
mL of ether and 2 mL of dilute hydrochloric acid to the
residue and mix by shaking. The aqueous layer responds to the Qualitative Tests (1) for potassium salts.
Uniformity of Dosage Units It meets requirements
of the Content Uniformity Test when the test is performed according to the following method. Weigh a
portion of powdered Warfarin Potassium Tablets,
equivalent to 1 tablet of Warfarin Potassium Tablets,
add 40 mL of water and shake vigorously for 30 minutes. Add water to make exactly V mL of this solution
containing about 20 g of warfarin potassium
(C19H15KO4) per mL and filter the solution. Discard the
first 5 mL of the filtrate and use the subsequent filtrate
40 mg of Warfarin Potassium RS, previously dried at
105 C for 3 hours and add water to make exactly 100
mL. Pipet exactly 5 mL of this solution, add water to
make exactly 100 mL and use this solution as the standard solution. Pipet exactly 20 mL each of the test solution and the standard solution, add 0.05 mol/L of hydrochloric acid TS to make exactly 25 mL each and use
these solutions as T1 and S1 solutions, respectively.
Separately, pipet exactly 20 mL each of the test solution and the standard solution, add 0.05 mol/L of potassium chloride reagent to make exactly 25 mL each and
use these solutions as T2 and S2 solutions, respectively.
Determine the absorbances, AT and AS , of T1 and S1
solutions at the wavelength of 272 nm as directed under
the Ultraviolet-visible Spectrophotometry, using T2 and
S2 solutions as the blank, respectively.
Amount (mg) of warfarin potassium (C19H15KO4) =

A
V
amount (mg) of Warfarin Potassium RS T
AS 2000
Warfarin Potassium Tablets. Weigh accurately a portion
of the powder, equivalent to about 4 mg of warfarin po-
tassium (C19H15KO4), add 80 mL of water, shake well

for 15 minutes and add water to make exactly 100 mL.
Filter this solution, discard the first 10 mL of the filtrate
and use the subsequent filtrate as the test solution. Separately, weigh accurately about 80 mg of Warfarin Potassium RS, previously dried at 105 C for 3 hours and
add water to make exactly 100 mL. Pipet exactly 5a mL
use this solution as the standard solution. Pipet exactly
10 mL each of the test solution and the standard solution and add 0.02 mol/L of hydrochloric acid TS to
each of these solutions to make T1 and S1 solutions, respectively. Separately, pipet exactly 10 mL each of the
test solution and the standard solution, add 0.02 mol/L
of potassium hydroxide TS to make exactly 20 mL each
and use these solutions as T2 and S2 solutions, respectively. Determine the absorbances, AT and AS, of T1 and
S1 solutions at the wavelength of 272 nm as directed
T2 and S2 solutions as the blank, respectively.
Amount (mg) of warfarin potassium (C19H15KO4) =
A
1
amount (mg) of Warfarin Potassium RS T
AS 2
tight containers.
Xenon (133Xe) Injection

Xenon (133Xe) Injection is an aqueous solution for injection containing xenon-133 (l33Xe) in the form of solution. Xenon (133Xe) Injection conforms to the requirements of Xenon (133Xe) Injection in the korean
Pharmaceutical Codex (Third Edition, 2007).
Description Xenon (l33Xe) Injection is a clear, colorless liquid.
Xylitol
HOH 2C
OH
OH
OH
CH2OH
C5H12O5: 152.15
Xylitol, when dried, contains not less than 98.0% and
not more than 101.0% of xylitol (C5H12O5).
Description Xylitol is a white crystalline powder, is
odorless and has a sweet taste.
Xylitol is very soluble in water and practically insoluble in ethanol.
Xylitol is hygroscopic.
KP 9 1003
Identification (1) To 1 mL of a solution of Xylitol (1
in 2), add 2 mL of ferrous sulfate TS and 1 mL of a solution of sodium hydroxide (1 in 5): a blue-green color
is observed without turbidity.
(2) Determine the infrared spectra of Xylitol and
Xylitol RS, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry: both spectra exhibit similar intensities of
pH Dissolve 5.0 g of Xylitol in 10 mL of freshly
boiled and cooled water: the pH of this solution is between 5.0 and 7.0.
Melting Point Between 93.0 C and 95.0 C .
Purity (1) Clarity and color of solutionDissolve 5
g of Xylitol in 10 mL of water: the solution is clear and
colorless.
(2) ChloridePerform the test with 2.0 g of Xylitol.
(3) SulfatePerform the test with 4.0 g of Xylitol.
mol/L sulfuric acid VS (not more than 0.006%).
(4) Heavy metalsProceed with 4.0 g of Xylitol
(5) NickelDissolve 0.5 g of Xylitol in 5 mL of
water, add 3 drops of dimethylglyoxime TS and 3 drops
of ammonia TS and allow to stand for 5 minutes: no
red color is produced.
Xylitol according to Method 1 and perform the test (not
more than 1.3 ppm).
(7) SugarsDissolve 5.0 g of Xylitol in 15 mL of
water, add 4.0 mL of dilute hydrochloric acid and heat
on a water-bath for 3 hours under a reflux condenser.
After cooling, neutralize with sodium hydroxide TS
(indicator: 2 drops of methyl orange TS). Then add water to make 50 mL, transfer 10 mL of this solution to a
flask, add 10 mL of water and 40 mL of Fehlings TS,
boil gently for 3 minutes and allow to stand to precipitate cuprous oxide. Remove the supernatant liquid
through a glass filter (G4) and wash the precipitate with
warm water until the last washing does not show alkalinity. Filter these washings through the glass filter
mentioned above, dissolve the precipitate in the flask in
20 mL of ferric sulfate TS, filter the solution through
the glass filter mentioned above, wash with water,
combine the washings with the filtrate, heat at 80 C
and titrate with 0.1 mol/L potassium permanganate VS:
not more than 1.0 mL of 0.1 mol/L potassium permanganate VS is consumed.
P2O5, 24 hours).
Assay Weigh accurately about 0.2 g of Xylitol, previously dried, dissolve in water to make exactly 100
mL. Pipet 10.0 mL of this solution into an iodine flask,
add exactly 50 mL of potassium periodate TS and heat
on a water-bath for 15 minutes. After cooling, add 2.5 g
of potassium iodide, stopper immediately, shake well,
allow to stand for 5 minutes in a dark place and titrate
with 0.1 mol/L sodium thiosulfate VS (indicaor: 3 mL
of starch TS). Perform a blank determination and make

= 1.9018 mg of C5H12O5
Xylitol Injection
Xylitol Injection is an aqueous solution for injection.
Xylitol Injection contains less than 95.0% and not more
than 105.0% of the labeled amount of xylitol (C5H12O5:
152.15).
Method of Preparation Prepare as directed under Injections, with Xylitol.
No preservative may be added.
Desciption Xylitol Injection is a clear, colorless liquid and has a sweet taste.
Identification Measure a volume of Xylitol Injection,
equivalent to 0.1 g of Xylitol according to the labeled
amount, add water to make 10 mL and use this solution
as the test solution. Separately, dissolve 0.1 g of Xylitol
RS in 10 mL of water and use this solution as the standard solution. Perform the test with the test solution
and the standard solution as directed under the Thinlayer chromatography. Spot 2 L each of the test solution and the standard solution on a plate of silica gel for
mixture of ethanol, strong ammonia water and water
(25 : 4 : 3) to a distance of about 10 cm and air dry the
plate. Spray evenly silver nitrate-ammonia TS and dry
at 105 C for 15 minutes: the spots from the test solution and the standard solution show a blackish brown
color and the same Rf value.
pH

Bacterial Endotoxins Less than 0.50 EU / mL.

Insoluble Particulate Matter for Injections Test It
Assay Measure exactly a volume of Xylitol Injection,
equivalent to about 5 g of xylitol (C5H12O5) according
to the labeled amount, add 5.0 mL of the internal standard solution, add water to make exactly 25 mL and use
this solution as the test solution. Separately, measure
exactly about 0.5g of Xylitol RS after drying in a dessicator (in vacuum, P2O5) for 24 hours, add 5.0 mL of the
internal standard solution, add water to make exactly
and the standard solution, as directed under the Liquid
Chromatography and calculate the ratios, QT and QS
of the peak area of Xylitol to that of the internal standard for the test solution and the standard solution, respectively.
Amount(mg) of xylitol (C5H12O5)

Q
= Amount (mg) of Xylitol RS T
QS
Internal standard solutionA solution of white
sugar (5 in 50).
inside diameter and about 15 to 30 cm in length,
packed with strong acidic ion exchange resin (the calcium form of the sulfonated styrene divinylbenzene copolymer, 9 m in particle diameter).
(75 : 25).
time of xylitol is about 5 minutes.
System suitability
operating conditions: xylitol and the internal standard
are eluted in this order ; A resolution between their
peaks is not less than 2.0.
the ratios of the peak area of xylitol is not more than
1.0%.
tainers.
Dried Yeast
Dried Yeast is dried and powdered cells of yeast belonging to Saccharomyces.

Dried Yeast contains not less than 0.4 g of protein and
not less than 100 g of thiamine compounds [as thiamine hydrochloride (C12H17ClN4OS.HCl: 337.27)] per
1 g.
Description Dried Yeast occurs as a pale yellowish
white to brown powder and has a characteristic odor
and taste.
Identification Dried Yeast, when examined under a
microscope, shows isolated cells, spheroidal or oval in
shape, and 6 m to 12 m in length.
Purity (1) RancidityDried Yeast is free from any
unpleasant or rancid odor or taste.
(2) StarchAdd iodine TS to Dried Yeast, and examine microscopically: no or only a few granules are
tinted blackish purple.
Loss on Drying Not more than 8.0 % (1 g, 100C, 8
hours).
Ash Not more than 9.0 % (1 g, proceed as directed in
the Ash under the Crude Drugs).
Assay (1) Protein Weigh accurately about 50 mg of
Dried Yeast and perform the test as directed under the
Nitrogen Determination.
Amount(mg) of protein in 1 g of Dried Yeast = amount

1
(mg) of nitrogen (N) 6.25 amount (g) of sample
(2) Thiamine Weigh accurately about 1 g of Dried
Yeast, add 1 mL of dilute hydrochloric acid and 80 mL
of water, and heat in a water-bath at 80 to 85
for 30 minutes with occasional shaking. After cooling,
add water to make exactly 100 mL, and centrifuge for
10 minutes. Pipet 4.0 mL of supernatant liquid, add exactly 5 mL of acetic acid-sodium acetate TS and exactly 1 mL of enzyme TS, and allow to stand at 45 ~
50 for 3 hours. Place exactly 2 mL of this solution
onto a chromatographic column prepared by pouring
2.5 mL of a weakly acidic CM-bridged cellulose cation
exchanger (H type) (40 m to 110 m in particle diameter) into a chromatographic tube about 1 cm in inside diameter and about 17 cm in length, and elute at
the flow of about 0.5 mL per minute. Wash the upper
part of the column with a small amount of water, and
wash the column with two 10 mL portions of water at
the flow rate of about 1 mL per minute. Elute the column with two 2.5 mL portions of diluted phosphoric
acid (1 in 50) at the flow rate of about 0.5 mL of per
minute, and combine the eluate. To a eluate add 1.0 mL
of the internal standard solution and 10 mg of sodium
KP 9 1005
1-octanesulfonate, and after dissolving, use this solution as the test solution. Separately, weigh accurately
about 15 mg of the Thiamine Hydrochloride RS (determine the water content in the same manner as for
Thiamine Hydrochloride), dissolve in 0.001 mol/L hydrochloric acid TS to make exactly 100 mL. Pipet 1.0
mL of this solution, and add the mobile phase to make
exactly 100 mL. Pipet 1.0 mL of this solution, and add
1.0 mL of the internal standard solution and 3.0 mL of
the mobile phase, and use this solution as the standard
conditions, and calculate the ratios, QT and QS , of
the peak area of thiamine to that of the internal standard.
Amount (g) of thiamine in 1 g of Dried Yeast
= amount (mg) of Thiamine Hydrochloride RS,
Q
Qs
1
amount (g) of the sample 12.5
Internal standard solution Dissolve 0.01 g of
phenacetin in acetonitrile to make 100 mL, and to 1 mL
of this solution add diluted acetonitrile (1 in 5) to make
100 mL.
Detector: An ultraviolet absorption photometer (wavelength: 254 nm).
about 40 .
Mobile phase: Dissolve 2.7 g of potassium dihydrogenphosphate in 1000 mL of water, and adjust the
pH to 3.5 with diluted phosphoric acid (1 in 10). Dissolve 1.6 g of sodium 1-octanesulfonate in 800 mL of
this solution, and add 200 mL of acetonitrile.
time of thiamine is about 8 minutes.
operating conditions, thiamine and the internal standard
Zinc Chloride
Zinc Chloride contains not less than 97.0% and not

more than 101.0% of zinc chloride (ZnCl2).
Description Zinc Chloride is a white, crystalline
powder, rods or masses and is odorless.
Zinc Chloride is very soluble in water and freely soluble in ethanol. Its solution may sometimes be slightly
turbid and the solution becomes clear on addition of a
small amount of hydrochloric acid.
pHThe pH of an aqueous solution of Zinc Chloride (1 in 2) is between 3.3 and 5.3.
Zinc Chloride is deliquescent.
Identification A solution of Zinc Chloride (1 in 30)
responds to the Qualitative Tests for zinc salt and for
chloride.
about 1.0 g of Zinc Chloride in 10 mL of water and 2
drops of hydrochloric acid: the solution is clear and colorless.
(2) SulfatePerform the test with 2.0 g of Zinc
Chloride. Prepare the control solution with 0.40 mL of
(3) AmmoniumDissolve 0.5 g of Zinc Chloride
in 5 mL of water and warm with 10 mL of a solution of
sodium hydroxide (1 in 6): the evolving gas does not
change moistened red litmus paper to blue.
(4) Heavy metalsDissolve 0.5 g of Zinc Chloride
in 5 mL of water in a Nessler tube, shake thoroughly
with 15 mL of potassium cyanide TS, add 1 drop of sodium sulfide TS, allow to stand for 5 minutes and immediately observe from the top downward against a
white background: the solution has no more color than
the following control solution (not more than 50 ppm).
Control solutionTo 2.5 mL of standard lead solution, add 3 mL of water and 15 mL of potassium cyanide TS, shake thoroughly and add 1 drop of sodium
sulfide TS.
(5) Alkali earth metals and alkali metalDissolve
2.0 g of Zinc Chloride in 120 mL of water, add ammonium sulfide TS to complete precipitation and add water to make 200 mL. shake thoroughly and filter
through dry filter paper. Discard the first 20 mL of the
filtrate, take the following 100 mL of the filtrate, evaporate with 3 drops of sulfuric acid to dryness and heat
the residue strongly at 600 C to constant mass: the
weight is not more than 10.0 mg.
of Zinc Chloride according to Method 1 and perform
(7) OxychlorideShake gently 0.25 g of Zinc
Chloride with 5 mL of water and 5 mL of ethanol and
add 0.30 mL of 1 mol/L hydrochloric acid VS: the solution is clear.
ZnCl2: 136.32
Assay Weigh accurately about 0.3 g of Zinc Chloride

and add 0.4 mL of dilute hydrochloric acid and water to
make exactly 200 mL. Measure exactly 20 mL of the
solution, add 80 mL of water, 2 mL of ammoniaammonium chloride buffer solution, pH 10.7 and titrate
with 0.01 mol/L disodium ethylenediaminetetraacetate
VS (indicator: 40 mg of eriochrome black T-sodium
chloride indicator).
Each mL of 0.01 mol/L disodium ethylenediaminetetraacetate VS = 1.3630 mg of ZnCl2
Zinc Oxide
ZnO: 81.41
Zinc Oxide, when ignited, contains not less that 99.0%
and not more than 101.0% of zinc oxide (ZnO).
Description Zinc Oxide is a white, amorphous
Zinc Oxide is practically insoluble in water, in ethanol,
in glacial acetic acid or in ether.
Zinc Oxide dissolves in dilute hydrochloric acid or in
Zinc Oxide gradually absorbs carbon dioxide from air.
Identification (1) Ignite Zinc Oxide: a yellow color
is observed and disappears on cooling.
(2) A solution of Zinc Oxide in dilute hydrochloric
acid (1 in 10) responds to the Qualitative Tests for zinc
salt.
Purity (1) Carbonate and clarity and color of solutionTo 2.0 g of Zinc Oxide, add 10 mL of water, mix
with shaking, add 30 mL of dilute sulfuric acid and heat
in a water-bath with stirring: no effervescence occurs
and the solution obtained is clear and colorless.
(2) AlkaliTo 1.0 g of Zinc Oxide, add 10 mL of
water and boil for 2 minutes. After cooling, filter
through a glass filter (G3) and to the filtrate, add 2
drops of phenolphthalein TS and 0.20 mL of 0.1 mol/L
hydrochloric acid VS: the solution is colorless.
(3) SulfateTo 0.5 g of Zinc Oxide, add 40 mL of
water, mix with shaking and filter. To 20 mL of the filtrate, add 1 mL of dilute hydrochloric acid and water to
make 50 mL and perform the test using this solution as
0.096%).
(4) IronDissolve 1.0 g of Zinc Oxide in 50 mL of
dilute hydrochloric acid (1 in 2), dissolve 0.1 g of ammonium persulfate in this solution and extract with 20
mL of methyl isobutyl ketone. Add 30 mL of acetic acid-sodium acetate buffer solution for Iron Limit Test,
pH 4.5, to the methyl isobutyl ketone layer, extract
again and use the layer of the buffer solution as the test
solution. Separately, perform the test in the same manner with 1.0 mL of standard iron solution and use the
layer so obtained as the control solution. Add 2 mL
each of ascorbic acid solution for Iron Limit Test (1 in
100) to the test solution and the control solution, respectively, mix, allow to stand for 30 minutes, add 5
mL of an ethanol solution of ,'-dipyridyl (1 in 200)
and water to make 50 mL. After allowing to stand for
30 minutes, compare the color of the both liquids
against a white backgound: the color of the liquid from
the test solution is not stronger than that from the control solution (not more than 10 ppm).
(5) LeadTo 2.0 g of Zinc Oxide, add 20 mL of
water, then add 5 mL of glacial acetic acid with stirring
and heat in a water-bath until dissolved completely.
Cool and add 5 drops of potassium chromate TS: no
turbidity is produced.
(6) ArsenicDissolve 0.5 g of Zinc Oxide in 5 mL
of dilute hydrochloric acid, use this solution as the test
solution and perform the test (not more than 4 ppm).
Loss on Ignition Not more than 1.0% (1 g, 850 C, 1
hour).
Assay Weigh accurately about 0.8 g of Zinc Oxide,
previously ignited at 850 C for 1 hour, dissolve in 2
mL of water and 3 mL of hydrochloric acid and add
water to make exactly 100 mL. Pipet 10.0 mL of this
solution, add 80 mL of water, then add a solution of sodium hydroxide (1 in 50) until a slight precipitate is
produced. Add 5 mL of ammonia-ammonium chloride
buffer solution, pH 10.7 and titrate with 0.05 mol/L
disodium ethylenediaminetetraacetate VS (indicator: 40
Each mL of 0.05 mol/L disodium ethylenediaminetetraacetate VS = 4.069 mg of ZnO

Zinc Sulfate Hydrate

ZnSO47H2O: 287.58
Zinc Sulfate contains not less than 99.0% and not more
than 102.0% of zinc sulfate hydrate (ZnSO47H2O).
Description Zinc Sulfate hydrate is a colorless crystal or a white, crystalline powder, is odorless and has an
astringent, characteristic taste.
Zinc Sulfate hydrate is very soluble in water and practically insoluble in ethanol or ether.
The pH of a solution of Zinc Sulfate hydrate (1 in 20) is
Zinc Sulfate hydrate effloresces in dry air.
Identification A solution of Zinc Sulfate hydrate (1
KP 9 1007
in 20) responds to the Qualitative Tests for zinc salt and
for sulfate.
Purity (1) AcidDissolve 0.25 g of Zinc Sulfate hydrate in 5 mL of water and add 1 drop of methyl orange
TS: no red color is observed.
(2) Heavy metalsDissolve 1.0 g of Zinc Sulfate
hydrate in 10 mL of water contained in a Nessler tube.
Add 20 mL of potassium cyanide TS and mix well. Add
2 drops of sodium sulfide TS and allow the mixture to
stand for 5 minutes. Observe vertically against a white
background, the color of the solution is not more intense than the following control solution (not more than
10 ppm).
Description Zinc Undecylenate is a white fine powder.

Zinc Undecylenate is practically insoluble in water or
in ethanol.
Control solutionTo 1.0 mL of standard lead solution, add 10 mL of water and 20 mL of potassium cyanide TS and mix well. Add 2 drops of sodium sulfide
TS.
Identification (1) Acidify 5 g of Zinc Undecylenate

with 25 mL of 1 mol/L sulfuric acid, add 20 mL of water and extract in a separatory funnel with two 25 mL
volumes of ether. Evaporate the ether solution until the
odor of ether no longer is perceptible. Add 1 mL of potassium permanganate dropwise to this residue: the
permanganate color disappears.
(2) Perform the test according to the Identification
(2) under Undecylenic Acid with 3mL of residue of
Undecylenic Acid obtained in Identification (1).
(3) Dissolve about 100 mg of Zinc Undecylenate in
a mixture of 10 mL of water and 1 mL of ammonium
hydroxide and add 2-3 drops of sodium sulfide: a white,
flocculent precipitate of zinc sulfide is produced.
(3) Alkalies and alkaline earthsDissolve 2.0 g of

Zinc Sulfate hydrate in 150 mL of water, add a suitable
amount of ammonium sulfide TS to complete the precipitation and add water to make exactly 200 mL.
Shake well and filter through a dry filter paper. Discard
the first 20 mL of the filtrate, take exactly 100 mL of
the subsequent filtrate, evaporate to dryness and ignite
as directed under the Residue on ignition: the mass of
the residue is not more than 5.0 mg.
of Zinc Sulfate hydrate according to Method 1 and perform the test (not more than 2 ppm).
Purity Alkalies and alkaline earthsBoil 1.50 g of

Zinc Undecylenate with a mixture of 50 mL of water
and 10 mL of hydrochloric acid, filter while hot and
wash the separated acid with about 50 mL of hot water.
Render the combined filtrate and washings alkaline
with ammonium hydroxide TS, add ammonium sulfide
to precipitate the zinc completely, dilute with water to
make exactly 200 mL, mix and filter. To 100 mL of the
clear filtrate, add 0.5 mL of sulfuric acid. Evaporate to
dryness and ignite over a low flame to constant mass:
the weight of the residue does not exceed 7.5 mg (not
more than 1.0%).
Assay Weigh accurately about 0.3 g of Zinc Sulfate

hydrate and dissolve in water to make exactly 100 mL.
Measure exactly 25 mL of this solution, add 100 mL of
water and 2 mL of ammonia-ammonium chloride buffer solution, pH 10.7 and titrate with 0.01 mol/L disodium ethylenediaminetetraacetate VS (indicator: 40

hours).

= 2.8756 mg of ZnSO47H2O
Zinc Undecylenate
CH 2
CHCH 2(CH 2)6CH 2CO 2
Zn
C22H38O4Zn: 431.94
Zinc Undecylenate contains not less than 98.0% and
not more than 102.0% of zinc undecylenate
(C22H38O4Zn), calculated on the dried basis.
Assay Weigh accurately about 1 g of Zinc Undecylenate, boil with 50.0 mL of 0.05 mol/L sulfuric acid VS
for 10 minutes, or until the undecylenic acid layer is
clear, adding water, if necessary, to maintain the original volume. Cool, transfer the mixture to a separatory
funnel and add water to make 250 mL. Extract with
two 100 mL volumes of hexane, wash the combined
extracts with water until the last washing is neutral to
litmus, add the washings to the original water layer and
evaporate on a water-bath to about 100 mL and cool
(indicator: 3 drops of methyl orange TS). Titrate the
VS. Perform a blank determination and make any necessary correction.

= 21.597 mg of C22H38O4Zn

from the standard solution (1). The test is not valid unless the chromatogram from the standard solution (2)
shows two clearly separated spots.
(3) Dissolve about 0.1 g of Zolpidem Tartrate in 1
mL of warm methanol. 0.1 mL of the solution responds
to the Qualitative Test for 3) of tartrates.
Zolpidem Tartrate
CH3
CO2
H
HO2C
N
N
H3C
OH
CH3
OH
H3C
C42H48N6O8 : 764.87
Zolpidem Tartrate contains not less than 98.5% and not
more than 101.0% of zolpidem tartrate (C42H48N6O8),
Description Zolpidem Tartrate is a white crystalline
powder.
Zolpidem Tartrate is sparingly soluble in methanol,
slightly soluble in water, and practically insoluble in
dichloromethane.
Zolpidem Tartrate is hygroscopic.
Identification (1) Dissolve 0.10 g each of Zolpidem
Tartrate and Zolpidem Tartrate RS in 10 mL of 0.1
mol/L hydrochloric acid TS and add 10 mL of water.
Add dropwise 1 mL of 3.4 w/v% ammonia water with
stirring. Filter and collect the resulting precipitate.
Wash each precipitate with water and then dry at 100 to
105 C for 2 hour to obtain test precipitate and reference precipitate, respectively. Determine the infrared
spectra of the precipitates as directed in the potassium
bromide disk method under the Infrared Spectrophotometry, respectively: both spectra exhibit similar intensities of absorption at the same wavenumbers.
(2) Dissolve 50 mg of Zolpidem Tartrate in 5 mL of
methanol, add 0.1 mL of diethylamine and methanol to
make 10 mL, and use this solution as the test solution.
Separately, dissolve 50 mg of Zolpidem Tartrate RS in
5 mL of methanol, add 0.1 mL of diethylamine and methanol to make 10 mL, and use this solution as the
standard solution (1). Also dissolve 50 mg of Flunitrazepam RS in dichloromethane to make 10 mL. Mix 1
mL of the solution with 1 ml of the standard solution
(1), and use this solution as the standard solution (2).
test solution and the standard solutions (1) and (2) on a
plate of silica gel with fluorescent indicator for thinlayer chromatography. Develop the plate with the mixture of ethyl acetate, cyclohexane and diethylamine
(45 : 45 : 10) to a distance of about 12 cm and air-dry
the plate. Examine under ultraviolet light (main wavelength: 254 nm). The Rf value of principal spot in the
chromatogram obtained with the test solution is the
same as that of the principal spot in the chromatogram
Purity (1) Clarity and color of solutionMix 0.25 g

of Zolpidem Tartrate with 0.125 g of tartaric acid, dissolve the mixture in 20 mL of water and add to make
25 mL. The solution is clear
(2) Related substancesDissolve 25.0 mg of Zolpidem Tartrate in the mobile phase to make exactly 50
dissolve 5 mg of Zolpidem Related Substance I {N,NDimethyl-2-[7-methyl-2-(4-methylphenyl)imidazo[1,2a]pyridin-3-yl]acetamide} RS in the mobile phase to
make exactly 50 mL and use this solution as the standard solution (1). Separately, dissolve 5 mg of Zolpidem Tartrate in the mobile phase to make exactly 50
mL. To 10 mL of this solution, add 10 mL of the standard solution (1) and use this solution as the standard
solution (2). Also dilute 2.0 mL of the test solution
with mobile phase to exactly 100 mL, to 1.0 mL of this
solution add mobile phase to make exactly 10 mL and
the test with exactly 20 L each of the test solution and
the standard solution (3) as directed under Liquid
and determine each peak area by the automatic integration method: in the chromatogram from the test solution, the total area of all peaks other than the principal
peak is not greater than the peak area of the principal
peak in the chromatogram from th standard solution (3)
(0.2%). Disregard any peak with an area less than 0.1
times that of the principal peak in the chromatogram
from the standard solution (3).
Mobile phase: A mixture of phosphate buffer solution, methanol and acetonitrile (59 : 23 : 18)
System suitability
operating condition and adjusted the sensitivity of the
system so that the height of the peak of zolpidem related substance I is at least 50% of the full scale of the
recorder, the resolution between the peaks of zolpidem
related substance I and zolpidem tartrate is not less than
2.0.
phosphate buffer solutionAdjust 0.56 w/v% solution of phosphoric acid to pH 5.5 with triethylamine.
KP 9 1009
Water not more than 3.0% (0.5 g, volumetric titration, direct titration).
Assay Weigh accurately about 0.30 g of Zolpidem
Tartrate and dissolve in a mixture of 20 mL of glacial
acetic acid and 20 mL of acetic anhydride. Titrate with
Endpoint Detection Method in Titrimetry). Carry out a
blank titration.
Each ml of 0.1 mol/L perchloric acid VS

= 38.24 mg of C42H48N6O8.
tight containers.

5.monograph - Part I (J Z)

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5.monograph - Part I (J Z)

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KP 9 539

RS, dissolve in 10 mL of methanol, and add 0.06 mol/L

Description Josamycin Propionate is a white to light

540 Monographs, Part I

pH The pH of a solution obtained by dissolving 0.1 g

Bacterial Endotoxins Less than 0.50 EU per mg of

Residue on Ignition Not more than 1.0 % (1 g).

Loss on Drying Not more than 4.0 % (0.1 g, in vacuum, 60 C, 3 hours).

Perform the test (not more than 0.021%).

Packaging and Storage Preserve in tight containers.

(3) SulfateDissolve 0.5 g of Kainic Acid in 40

Control solutionAdd 5 mL of sodium carbonate

Loss on Drying Between 6.5% and 8.5% (1 g, 105

542 Monographs, Part I

Identification (1) Weigh accurately an appropriate

a: Amount (mg) of Kallidinogenase in 1 mL of the

(4) ProteaseWeigh accurately an appropriate

544 Monographs, Part I

Not more than 3.0% (0.5g,

and 0.05 mol/L phosphate buffer solution, pH 7.0 to

( AS6 AS2 ) ( A06 A02 ) a b

W S : Amount (Units) of Kallidinogenase Reference Standard

Packaging and Storage Preserve in tight containers

Packaging and Storage Preserve in tight containers.

pH Dissolve 1.0 g of Ketamine Hydrochloride in 10

Between 148 C and 152 C .

Specific Optical Rotation [ ]20

546 Monographs, Part I

Loss on Drying Not more than 0.5% (1 g, in vacuum,

It meets the require-

Assay Weigh accurately and powder not less than 20

Purity (1) Clarity and color of solutionDissolve

solution. Pipet exactly 1 mL of the test solution and add

548 Monographs, Part I

with a mixture of dichloromethane, acetone and glacial

(C15H13NO3C4H11NO3), calculated on the dried basis.

550 Monographs, Part I

peak in the test solution, AT , and the standard solution, A S .

Amount (mg) of lactose monohydrate (C12H22O11H2O)

552 Monographs, Part I

Ai : Peak area of lamivudine enantiomer

solutions and calculate the content of residual solvents

C: Concentration (g/mL) of salicylic acid in the

respectively, with the resolution between lamivudine

Packaging and Storage

Water Not more than 0.2% (1 g, coulometric titration).

Amount (mg) of lamivudine (C8H11N3O3S)

554 Monographs, Part I

side C (C49H76O20: 985.12).

weigh accurately about 5.0 mg of Lanatoside C RS,

Packaging and Storage

556 Monographs, Part I

Flow rate: 0.8 mL/min.

corresponds to that from the standard solution.

Ai : Area of each related substance peak obtained

558 Monographs, Part I

Flow rate: 1.0 mL/min.

Specific Optical Rotation [ ]20