EUROPEAN PHARMACOPOEIA 11.

0 Terbutaline sulfate

– impurity E : not more than 0.5 times the area of the

principal peak in the chromatogram obtained with
reference solution (b) (0.05 per cent) ;
– unspecified impurities : for each impurity, not more than the
area of the principal peak in the chromatogram obtained
with reference solution (b) (0.10 per cent) ;
– total : not more than 3 times the area of the principal peak
in the chromatogram obtained with reference solution (b)
(0.3 per cent) ;
– disregard limit : 0.5 times the area of the principal peak in E. (2E,4E)-4-(4,4-dimethylpent-2-yn-1-ylidene)-N,N′-
the chromatogram obtained with reference solution (b) dimethyl-N,N′-bis(naphthalen-1-ylmethyl)pent-2-ene-1,5-
(0.05 per cent). diamine,
Loss on drying (2.2.32) : maximum 0.5 per cent, determined
on 1.000 g by drying in an oven at 105 °C.
Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on
1.0 g.
ASSAY F. (2Z)-N,6,6-trimethyl-N-(naphthalen-2-ylmethyl)hept-2-
Dissolve 0.250 g in 50 mL of ethanol (96 per cent) R, add en-4-yn-1-amine (cis-isoterbinafine).
5 mL of 0.01 M hydrochloric acid. Titrate with 0.1 M sodium
hydroxide determining the end-point potentiometrically 01/2020:0690
(2.2.20). Read the volume added between the 2 points of
inflexion.
1 mL of 0.1 M sodium hydroxide is equivalent to 32.79 mg of
C21H26ClN.
STORAGE TERBUTALINE SULFATE
Protected from light.
Terbutalini sulfas
IMPURITIES
Specified impurities : B, E.
Other detectable impurities (the following substances would,
if present at a sufficient level, be detected by one or other of
the tests in the monograph. They are limited by the general
acceptance criterion for other/unspecified impurities and/or
by the general monograph Substances for pharmaceutical use
(2034). It is therefore not necessary to identify these impurities C24H40N2O10S Mr 548.6
for demonstration of compliance. See also 5.10. Control of [23031-32-5]
impurities in substances for pharmaceutical use): A, C, D, F.
DEFINITION
Bis[5-[(1RS)-2-(tert-butylamino)-1-hydroxyethyl]benzene-
1,3-diol] sulfate.
Content : 98.5 per cent to 101.0 per cent (dried substance).
CHARACTERS
A. N-methyl-C-(naphthalen-1-yl)methanamine, Appearance : white or almost white, crystalline powder.
Solubility : freely soluble in water, slightly soluble in ethanol
(96 per cent), practically insoluble in heptane.
It shows polymorphism (5.9).
IDENTIFICATION
A. Infrared absorption spectrophotometry (2.2.24).
B. (2Z)-N,6,6-trimethyl-N-(naphthalen-1-ylmethyl)hept-2- Comparison : terbutaline sulfate CRS.
en-4-yn-1-amine (cis-terbinafine), If the spectra obtained in the solid state show differences,
dissolve the substance to be examined and the reference
substance separately in aldehyde-free methanol R, evaporate
to dryness and record new spectra using the residues.
B. 5 mL of solution S (see Tests) gives reaction (a) of sulfates
(2.3.1).
C. (2E)-N,6,6-trimethyl-N-(naphthalen-2-ylmethyl)hept-2-
en-4-yn-1-amine (trans-isoterbinafine), TESTS
Solution S. Dissolve 1.0 g in carbon dioxide-free water R and
dilute to 50.0 mL with the same solvent.
Appearance of solution. Solution S is clear (2.2.1) and its
absorbance (2.2.25) at 400 nm in a 2 cm cell is not greater
than 0.11.
Acidity. To 10 mL of solution S add 0.05 mL of methyl red
D. (2E)-N,6,6-trimethyl-N-[(4-methylnaphthalen-1- solution R. Not more than 1.2 mL of 0.01 M sodium hydroxide
yl)methyl]hept-2-en-4-yn-1-amine (4-methylterbinafine), is required to change the colour of the indicator to yellow.

General Notices (1) apply to all monographs and other texts 4155
Terconazole EUROPEAN PHARMACOPOEIA 11.0

Optical rotation (2.2.7): − 0.10° to + 0.10°, determined on

solution S.
Related substances. Liquid chromatography (2.2.29).
Test solution. Dissolve 75.0 mg of the substance to be
examined in the mobile phase and dilute to 50.0 mL with the A. 3,5-dihydroxybenzoic acid (α-resorcylic acid),
mobile phase.
Reference solution (a). Dissolve 7.5 mg of terbutaline
impurity C CRS and 22.5 mg of terbutaline sulfate CRS in the
mobile phase and dilute to 50 mL with the mobile phase.
Dilute 1 mL of the solution to 100 mL with the mobile phase.
Reference solution (b). Dilute 1.0 mL of the test solution to
100.0 mL with the mobile phase. Dilute 1.0 mL of this solution B. (4RS)-2-tert-butyl-1,2,3,4-tetrahydroisoquinoline-4,6,8-
to 10.0 mL with the mobile phase. triol,
Column :
– size : l = 0.15 m, Ø = 4.6 mm ;
– stationary phase : base-deactivated end-capped octadecylsilyl
silica gel for chromatography R (5 μm).
Mobile phase : prepare a 0.050 M ammonium formate solution
as follows : dissolve 3.15 g of ammonium formate R in about C. 2-(tert-butylamino)-1-(3,5-dihydroxyphenyl)ethan-1-one,
980 mL of water for chromatography R, adjust to pH 3.0 by
adding about 8 mL of anhydrous formic acid R and dilute to
1000 mL with water for chromatography R. Dissolve 4.23 g
of sodium hexanesulfonate R in 770 mL of the 0.050 M
ammonium formate solution, then add 230 mL of methanol R.
Flow rate : 1.0 mL/min.
Detection : spectrophotometer at 276 nm.
Injection : 20 μL. D. 2-[benzyl(tert-butyl)amino]-1-(3,5-dihydroxyphen-
Run time : 6 times the retention time of terbutaline. yl)ethan-1-one.
Identification of impurities : use the chromatogram obtained
with reference solution (a) to identify the peak due to 01/2012:1270
impurity C.
Relative retention with reference to terbutaline (retention
time = about 10 min): impurity C = about 0.9.
System suitability : reference solution (a) :
– resolution : minimum 2.0 between the peaks due to TERCONAZOLE
impurity C and terbutaline.
Calculation of percentage contents :
Terconazolum
– for each impurity, use the concentration of terbutaline
sulfate in reference solution (b).
Limits :
– unspecified impurities : for each impurity, maximum
0.10 per cent ;
– total : maximum 0.2 per cent ;
C26H31Cl2N5O3 Mr 532.5
– reporting threshold : 0.05 per cent. [67915-31-5]
Loss on drying (2.2.32) : maximum 0.5 per cent, determined
on 1.000 g by drying in an oven at 105 °C for 3 h. DEFINITION
1-[4-[[(2RS,4SR)-2-(2,4-Dichlorophenyl)-2-[(1H-1,2,4-
ASSAY triazol-1-yl)methyl]-1,3-dioxolan-4-yl]methoxy]phenyl]-4-(1-
Dissolve 0.400 g in 70 mL of anhydrous acetic acid R with methylethyl)piperazine.
heating. Titrate with 0.1 M perchloric acid, determining the Content : 99.0 per cent to 101.0 per cent (dried substance).
end-point potentiometrically (2.2.20).
CHARACTERS
1 mL of 0.1 M perchloric acid is equivalent to 54.86 mg Appearance : white or almost white powder.
of C24H40N2O10S.
Solubility : practically insoluble in water, freely soluble in
IMPURITIES methylene chloride, soluble in acetone, sparingly soluble in
ethanol (96 per cent).
Other detectable impurities (the following substances would, It shows polymorphism (5.9).
if present at a sufficient level, be detected by one or other of
the tests in the monograph. They are limited by the general IDENTIFICATION
acceptance criterion for other/unspecified impurities and/or First identification : A.
by the general monograph Substances for pharmaceutical use
(2034). It is therefore not necessary to identify these impurities Second identification : B, C.
for demonstration of compliance. See also 5.10. Control of A. Infrared absorption spectrophotometry (2.2.24).
impurities in substances for pharmaceutical use): A, B, C, D. Comparison : terconazole CRS.

4156 See the information section on general monographs (cover pages)