BP右美沙芬
Dextromethorphan Hydrobromide
General Notices
(Ph Eur monograph 0020)
Second identification A, C, D.
A. It complies with the test for specific optical rotation (see Tests).
B. Infrared absorption spectrophotometry (2.2.24).
Preparation Discs.
Comparison dextromethorphan hydrobromide CRS.
C. Thin-layer chromatography (2.2.27).
Test solution Dissolve 25 mg of the substance to be examined in methanol R and dilute to 10 ml with the same solvent.
Reference solution Dissolve 25 mg of dextromethorphan hydrobromide CRS in methanol R and dilute to 10 ml with the same solvent.
Plate TLC silica gel G plate R.
Mobile phase concentrated ammonia R, methylene chloride R, methanol R, ethyl acetate R, toluene R (2:10:13:20:55 V/V/V/V/V).
Application 5 μl.
Development Over 2/3 of the plate.
Drying In air.
Detection Spray with potassium iodobismuthate solution R2.
Results The principal spot in the chromatogram obtained with the test solution is similar in position and size to the principal spot in the chromatogram obtained with the reference solution.
D. It gives reaction (a) of bromides (2.3.1).
TESTS
Solution S
Dissolve 1.0 g in alcohol R and dilute to 20 ml with the same solvent.
Appearance of solution
Solution S is clear (2.2.1) and colourless (2.2.2, Method II).
Acidity or alkalinity
Dissolve 0.4 g in carbon dioxide-free water R with gentle heating, cool and dilute to 20 ml with the same solvent. Add 0.1 ml of methyl red solution R and 0.2 ml of 0.01 M sodium hydroxide. The solution is yellow. Not more than 0.4 ml of 0.01 M hydrochloric acid is required to change the colour of the indicator to red.
Specific optical rotation (2.2.7)
+ 28 to + 30 ( anhydrous substance).
Dissolve 0.200 g in 0.1 M hydrochloric acid and dilute to 10.0 ml with the same acid.
Related substances
Liquid chromatography (2.2.29).
Liquid chromatography (2.2.29).
Test solution Dissolve 10.0 mg of the substance to be examined in the mobile phase and dilute to 10.0 ml with the mobile phase.
Reference solution (a) Dissolve 2 mg of dextromethorphan impurity A CRS in 2 ml of the test solution and dilute to 25.0 ml with the mobile phase.
Reference solution (b) Dilute 1.0 ml of the test solution to 200.0 ml with the mobile phase. Column:
— size: l = 0.25 m, ? = 4.6 mm,
— stationary phase: octadecylsilyl silica gel for chromatography R (5 μm).
Mobile phase Dissolve 3.11 g of docusate sodium R in a mixture of 400 ml of water R and 600 ml of acetonitrile R. Add 0.56 g of ammonium nitrate R. Adjust to apparent pH 2.0 with glacial acetic acid R.
Flow rate 1.0 ml/min.
Detection Spectrophotometer at 280 nm.
Injection 20 μl.
Run time Twice the retention time of dextromethorphan.
Relative retention With reference to dextromethorphan (retention time = about 21.9 min): impurity B = about 0.44; impurity C = about 0.85; impurity D = about 0.90; impurity A = about 1.13.
System suitability Reference solution (a):
— resolution: minimum 1.5 between the peaks due to impurity A and dextromethorphan. Limits:
— correction factor: for the calculation of content, multiply the peak area of impurity C by 0.2,
— any impurity: not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.5 per cent), and not more than 1 such peak has an area greater than half the area of the principal peak in the chromatogram obtained with reference solution (b) (0.25 per cent),
— total: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (b) (1 per cent),
— disregard limit: 0.1 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).
N,N-Dimethylaniline
Maximum 10 ppm.
Dissolve 0.5 g with heating in 20 ml of water R. Allow to cool, add 2 ml of dilute acetic acid R and 1 ml of a 10 g/l solution of sodium nitrite R and dilute to 25 ml with water R. The solution is not more intensely coloured than a reference solution prepared at the same time in the same manner using 20 ml of a 0.25 mg/l solution of dimethylaniline R.
Water (2.5.12)
4.0 per cent to
5.5 per cent, determined on 0.200 g.
Sulphated ash (2.4.14)
Maximum 0.1 per cent, determined on 1.0 g.
ASSAY
Dissolve 0.300 g in a mixture of 5.0 ml of 0.01 M hydrochloric acid and 20 ml of alcohol R. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20). Read the volume added between the 2 points of inflexion.
1 ml of 0.1 M sodium hydroxide is equivalent to 35.23 mg of C18H26BrNO.
STORAGE
Protected from light.
IMPURITIES
A. R1 = CH3, R2 = H, X = H2: ent-3-methoxymorphinan,
B. R1 = H, R2 = CH3, X = H2: ent-17-methylmorphinan-3-ol,
C. R1 = R2 = CH3, X = O: ent-3-methoxy-17-methylmorphinan-10-one,