JP XVIII Official Monographs / Nicotinic Acid Injection 1419

with water to make 50 mL (not more than 0.019z). Assay Measure exactly a volume of Nicotinic Acid Injec-
(4) Nitro compounds—Dissolve 1.0 g of Nicotinic Acid tion, equivalent to about 0.1 g of nicotinic acid (C6H5NO2),
in 8 mL of sodium hydroxide TS, and add water to make 20 and add the mobile phase to make exactly 100 mL. Pipet 10
mL: the solution has no more color than Matching Fluid A. mL of this solution, add exactly 10 mL of the internal stand-
(5) Heavy metals <1.07>—Proceed with 1.0 g of Nicotinic ard solution, then add the mobile phase to make 100 mL,
Acid according to Method 2, and perform the test. Prepare and use this solution as the sample solution. Separately,
the control solution with 2.0 mL of Standard Lead Solution weigh accurately about 0.1 g of Nicotinic Acid RS, previ-
(not more than 20 ppm). ously dried at 1059C for 1 hour, and dissolve in the mobile
phase to make exactly 100 mL. Pipet 10 mL of this solution,
Loss on drying <2.41> Not more than 0.5z (1 g, 1059C,
add exactly 10 mL of the internal standard solution, then
1 hour).
add the mobile phase to make 100 mL, and use this solution
Residue on ignition <2.44> Not more than 0.1z (1 g). as the standard solution. Perform the test with 10 mL each of
the sample solution and standard solution as directed under
Assay Weigh accurately about 0.3 g of Nicotinic Acid, pre-
Liquid Chromatography <2.01> according to the following
viously dried, dissolve in 50 mL of water, and titrate <2.50>
conditions, and calculate the ratios, QT and QS, of the peak
with 0.1 mol/L sodium hydroxide VS (indicator: 5 drops of
area of nicotinic acid to that of the internal standard.
phenolphthalein TS).
Amount (mg) of nicotinic acid (C6H5NO2)
Each mL of 0.1 mol/L sodium hydroxide VS
＝ M S × QT / QS
＝ 12.31 mg of C6H5NO2
MS: Amount (mg) of Nicotinic Acid RS taken
Containers and storage Containers—Well-closed contain-
ers. Internal standard solution—A solution of caffeine in the
mobile phase (1 in 1000).
Operating conditions—
Nicotinic Acid Injection Detector: An ultraviolet absorption photometer (wave-
length: 260 nm).
ニコチン酸注射液 Column: A stainless steel column 4.6 mm in inside diame-
ter and 15 cm in length, packed with octadecylsilanized silica
gel for liquid chromatography (5 mm in particle diameter).
Nicotinic Acid Injection is an aqueous injection.
Column temperature: A constant temperature of about
It contains not less than 95.0z and not more
359C.
than 110.0z of the labeled amount of nicotinic acid
Mobile phase: Dissolve 1.1 g of sodium 1-octane sulfonate
(C6H5NO2: 123.11).
in a mixture of 0.05 mol/L sodium dihydrogenphosphate TS
Method of preparation Prepare as directed under Injec- (pH 3.0) and methanol (4:1) to make 1000 mL.
tions, with Nicotinic Acid. It may contain Sodium Car- Flow rate: Adjust so that the retention time of caffeine is
bonate or Sodium Hydroxide as a solubilizer. about 9 minutes.
System suitability—
Description Nicotinic Acid Injection is a clear, colorless
System performance: When the procedure is run with 10
liquid.
mL of the standard solution under the above operating con-
pH: 5.0 – 7.0
ditions, nicotinic acid and the internal standard are eluted in
Identification (1) To a volume of Nicotinic Acid Injec- this order with the resolution between these peaks being not
tion, equivalent to 0.1 g of Nicotinic Acid, add 0.3 mL of less than 10.
dilute hydrochloric acid, and evaporate on a water bath to 2 System repeatability: When the test is repeated 6 times
mL. After cooling, collect the crystals formed, wash with with 10 mL of the standard solution under the above operat-
small portions of ice-cold water until the last washing shows ing conditions, the relative standard deviation of the ratios
no turbidity on the addition of silver nitrate TS, and dry at of the peak area of nicotinic acid to that of the internal
1059C for 1 hour: the crystals melt <2.60> between 2349C standard is not more than 1.0z.
and 2389C. With the crystals, proceed as directed in the
Containers and storage Containers—Hermetic containers.
Identification (1) under Nicotinic Acid.
(2) Dissolve 0.02 g of the dried crystals obtained in (1) in
water to make 1000 mL, and determine the absorption spec-
trum as directed under Ultraviolet-visible Spectrophotome-
try <2.24>: it exhibits a maximum between 261 nm and 263
nm, and a minimum between 235 nm and 239 nm. Sepa-
rately, determine the absorbances of this solution, A1 and
A2, at each wavelength of maximum and minimum absorp-
tion, respectively: the ratio A2/A1 is between 0.35 and 0.39.
Bacterial endotoxins <4.01> Less than 3.0 EU/mg.
Extractable volume <6.05> It meets the requirement.
Foreign insoluble matter <6.06> Perform the test according
to Method 1: it meets the requirement.
Insoluble particulate matter <6.07> It meets the require-
ment.
Sterility <4.06> Perform the test according to the Mem-
brane filtration method: it meets the requirement.

The JP Drugs are to be tested according to the provisions given in the pertinent monographs, General Notices, General Rules for Crude Drugs,
General Rules for Preparations, and General Tests for their conformity to the Japanese Pharmacopoeia. (See the General Notices 5.)