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General Notices

(Ph. Eur. monograph 0516)

C22H23NO7413.4128-62-1

Action and use

Opioid receptor agonist; cough suppressant.

Ph Eur

DEFINITION

(3S)-6,7-Dimethoxy-3-[(5R)-4-methoxy-6-methyl-5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinolin-5-yl]isobenzofuran-1(3H)-one.

Content

99.0 per cent to101.0 per cent (dried substance).

CHARACTERS

Appearance

White or almost white, crystalline powder or colourless crystals.

Solubility

Practically insoluble in water, soluble in acetone, slightly soluble in ethanol (96 per cent) . It dissolves in strong acids; on dilution of the solution with

water, the base may be precipitated.

IDENTIFICATION

First identification C, E

Second identification A, B, D, E

A.Specific optical rotation (see Tests).

B.

Melting point (2.2.14): 174 C to 177 C.

C.Infrared absorption spectrophotometry(2.2.24).

Comparison noscapine CRS.

D.Thin-layer chromatography (2.2.27).

Test solution Dissolve 25 mg of the substance to be examined in acetone Rand dilute to 100 mL with the same solvent.

Reference solution Dissolve 25 mg of noscapine CRSin acetone Rand dilute to 100 mL with the same solvent.

Plate TLC silica gel plate R.

Status: You are viewing the legally effective version.

Noscapine

BP 2016

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Mobile phase concentrated ammonia R, ethanol (96 per cent) R, acetone R, toluene R(1:3:20:20 V/V/V/V).

Application 10 L.

Development Over 2/3 of the plate.

Drying In air.

Detection Spray with dilute potassium iodobismuthate solution R.

Results The principal spot in the chromatogram obtained with the test solution is similar in position, colour and size to the principal spot in the

chromatogram obtained with the reference solution.

E.To 20 mg add 10 mL of water Rand shake. It does not dissolve.

TESTS

Appearance of solution

The solution is clear (2.2.1) and not more intensely coloured than reference solution Y6(2.2.2, Method II).

Dissolve 0.2 g in acetone Rand dilute to 10 mL with the same solvent. Examine immediately after dissolution.

Specific optical rotation (2.2.7)

+ 42 to + 48 (dried substance).

Dissolve 0.500 g in 0.1 M hydrochloric acidand dilute to 25.0 mL with the same acid.

Related substances

Liquid chromatography(2.2.29).

Test solution Dissolve 20.0 mg of the substance to be examined in 8 mL of methanol R, with the aid of ultrasound, and dilute to 10.0 mL with the same

solvent.

Reference solution (a) Dilute 1.0 mL of the test solution to 20.0 mL with methanol R. Dilute 1.0 mL of this solution to 10.0 mL with methanol R.

Reference solution (b) Dissolve 5 mg ofpapaverine hydrochlorideRin the mobile phase and dilute to 50.0 mL with the mobile phase. Dilute 1.0 mL ofthe solution to 10.0 mL with the mobile phase.

Reference solution (c) Dissolve 1.5 mg ofpapaverine hydrochlorideRin 10 mL of the test solution and dilute to 25 mL with the mobile phase.

Column:

size: l= 0.125 m, = 4.6 mm;

stationary phase: nitrile silica gel for chromatography R(5 m).

Mobile phase methanol R,phosphate buffer solution pH 6.0 R1(350:650 V/V).

Flow rate 1 mL/min.

Detection Spectrophotometer at 240 nm.

Injection 10 L.

Run time 2.5 times the retention time of noscapine.

Relative retention With reference to noscapine(retention t ime = about 10 min): impurity A = about 1.3.

System suitability: reference solution (c):

resolution: minimum 2 between the peaks due to noscapineand impurity A.

Limits:

impurity A: not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.5 per cent);

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any other impurity: for each impurity, not more than 0.4 times the area of the principal peak in the chromatogram obtained with reference solution

(a) (0.2 per cent);

sum of impurities other than A: not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per

cent);

disregard limit: 0.1 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).

Loss on drying(2.2.32)

Maximum 1.0 per cent, determined on 0.500 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

Dissolve 0.350 g in 40 mL of anhydrous acetic acid R, warming gently. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically

(2.2.20).

1 mL of 0.1 M perchloric acidis equivalent to 41.34 mg of C22H23NO7.

STORAGE

Protected from light.

IMPURITIES

A.1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline (papaverine).

Ph Eur

Crown Copyright 20

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