Edition: BP 2025 (Ph. Eur. 11.6 update)
General Notices
(Ph. Eur. monograph 1347)
C20H24ClNS,H2O 363.9 7081-40-5
Action and use
Anticholinergic.
Ph Eur
DEFINITION
Metixene hydrochloride contains not less than 98.0 per cent and not more than the equivalent of 102.0 per cent of (RS)-1-methyl-3-[(9H-thioxanthen-9-yl)methyl]piperidine hydrochloride, calculated with reference to the dried substance.
CHARACTERS
A white or almost white, crystalline or fine crystalline powder, soluble in water, soluble in ethanol (96 per cent) and in methylene chloride.
IDENTIFICATION
A. Examine by infrared absorption spectrophotometry (2.2.24), comparing with the spectrum obtained with metixene hydrochloride CRS.
B. It gives reaction (a) of chlorides (2.3.1).
TESTS
Appearance of solution
Dissolve 0.40 g in methanol R and dilute to 20.0 mL with the same solvent. The solution is clear (2.2.1) and not more intensely coloured than reference solution Y6 (2.2.2, Method I).
pH (2.2.3)
Dissolve 0.18 g in carbon dioxide-free water R heating if necessary at about 50 °C, cool and dilute to
10.0 mL with the same solvent. The pH of the solution, measured immediately, is 4.4 to 5.8.
Related substances
Examine by thin-layer chromatography (2.2.27), using a TLC silica gel plate R. Carry out the test rapidly and protected from light.
Test solution Dissolve 50 mg of the substance to be examined in methylene chloride R and dilute to 5.0 mL with the same solvent.
Reference solution (a) Dissolve 5 mg of metixene hydrochloride CRS in methylene chloride R and dilute to 100.0 mL with the same solvent.
Reference solution (b) Dissolve 20 mg of thioxanthene CRS in 50 mL of methylene chloride R. Dilute 1.0 mL of the solution to 20.0 mL with methylene chloride R.
Reference solution (c) Dissolve 5 mg of thioxanthone CRS in 50 mL of methylene chloride R. Dilute 1.0 mL of the solution to 20.0 mL with methylene chloride R.
Reference solution (d) Dilute 4 mL of reference solution (a) to 10.0 mL with methylene chloride R.
Apply to the plate as narrow bands 5 μL of each solution. Develop over a path of 10 cm using a mixture of 10 volumes of glacial acetic acid R, 10 volumes of methanol R and 80 volumes of methylene chloride R. Dry the plate in a stream of cold air. Spray with a mixture of 1 volume of sulfuric acid R and 9 volumes of alcohol R and heat at 100 °C for 10 min. Allow the plate to cool and examine in ultraviolet light at 365 nm. Thioxanthene shows orange fluorescence and thioxanthone shows greenish-blue fluorescence. Any band corresponding to thioxanthene in the chromatogram obtained with the test solution is not more intense than the band in the chromatogram obtained with reference solution (b) (0.2 per cent); any band corresponding to thioxanthone in the chromatogram obtained with the test solution is not more intense than the band in the chromatogram obtained with reference solution (c) (0.05 per cent); any band, apart from the principal band and the bands corresponding to thioxanthene and thioxanthone, is not more intense than the band in the chromatogram obtained with reference solution (a) (0.5 per cent) and at most one such band is more intense than the band in the chromatogram obtained with reference solution (d) (0.2 per cent). The test is not valid unless the bands in the chromatograms obtained with reference solutions (b) and (c) are clearly visible and differentiated.
Loss on drying (2.2.32)
Not less than 4.0 per cent and not more than 6.0 per cent, determined on 0.500 g by drying in an oven at 138-142 °C.
Sulfated ash (2.4.14)
Not more than 0.1 per cent, determined on 1.0 g.
ASSAY
Dissolve 0.250 g in a mixture of 5.0 mL of 0.01 M hydrochloric acid and 50 mL of alcohol R. Carry out a potentiometric titration (2.2.20), using 0.1 M sodium hydroxide. Read the volume added between the 2 points of inflexion.
1 mL of 0.1 M sodium hydroxide is equivalent to 34.59 mg of C20H24ClNS.
STORAGE
Store protected from light.
IMPURITIES
A. 9H-thioxanthene,
B. 9H-thioxanthen-9-one (thioxanthone).
Ph Eur
