Flavoxate Hydrochloride

(Ph. Eur. monograph 1692)

C₂₄H₂₆ClNO₄        427.9        3717-88-2

Action and use

Anticholinergic.

Preparation

Flavoxate Tablets

DEFINITION

2-(Piperidin-1-yl)ethyl 3-methyl-4-oxo-2-phenyl-4H-1-benzopyran-8-carboxylate hydrochloride.

Content

99.0 per cent to 101.0 per cent (dried substance).

CHARACTERS

Appearance

White or almost white, crystalline powder.

Solubility

Slightly soluble in water, sparingly soluble in methylene chloride, slightly soluble in ethanol (96 per cent).

IDENTIFICATION

A. Infrared absorption spectrophotometry (2.2.24).

Comparison: flavoxate hydrochloride CRS.

B. It gives reaction (a) of chlorides (2.3.1).

TESTS

Related substances

Liquid chromatography (2.2.29). Use freshly prepared solutions.

Solvent mixture: Mix 20 volumes of a 0.4 g/L solution of potassium dihydrogen phosphate R adjusted to pH 3.0 with phosphoric acid R and 80 volumes of acetonitrile R.

Test solution: Dissolve 10.0 mg of the substance to be examined in the solvent mixture and dilute to 10.0 mL with the solvent mixture.

Reference solution (a): Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture.

Reference solution (b): Dilute 1.0 mL of reference solution (a) to 10.0 mL with the solvent mixture.

Reference solution (c): Dissolve 6.0 mg of flavoxate impurity A CRS and 3.0 mg of flavoxate impurity B CRS in the solvent mixture, add 2.0 mL of the test solution and dilute to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to
20.0 mL with the solvent mixture.

Column:

— size: l = 0.25 m, Ø = 4.6 mm;

— stationary phase: spherical end-capped octadecylsilyl silica gel for chromatography R (5 μm).

Mobile phase:

— mobile phase A: 0.435 g/L solution of dipotassium hydrogen phosphate R adjusted to pH 7.5 with phosphoric acid R;

— mobile phase B: acetonitrile R;

Flow rate: 0.8 mL/min.

Detection: Spectrophotometer at 254 nm.

Injection: 10 μL.

Relative retention: With reference to flavoxate (retention time = about 10 min): impurity A = about 0.2; impurity B = about 0.8.

System suitability: Reference solution (c):

— resolution: minimum 4.0 between the peaks due to impurity B and flavoxate.

Limits:

— impurity A: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (c) (0.3 per cent);

— impurity B: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (c) (0.15 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 of unspecified impurities: not more than 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent);

— disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).

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

In order to avoid overheating in the reaction medium, mix thoroughly throughout and stop the titration immediately after the end-point has been reached.

Dissolve 0.350 g in 10 mL of anhydrous formic acid R and add 40 mL of acetic anhydride R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20).

1 mL of 0.1 M perchloric acid is equivalent to 42.79 mg of C₂₄H₂₆ClNO₄.

STORAGE

Protected from light.

IMPURITIES

Specified impurities A, B.

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 for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use) C.

A. 3-methyl-4-oxo-2-phenyl-4H-1-benzopyran-8-carboxylic acid,

B. ethyl 3-methyl-4-oxo-2-phenyl-4H-1-benzopyran-8-carboxylate,

C. 1-methylethyl 3-methyl-4-oxo-2-phenyl-4H-1-benzopyran-8-carboxylate.