Zuclopenthixol Tablets

General Notices

Action and use

Dopamine receptor antagonist; neuroleptic.

Definition

Zuclopenthixol Tablets contain Zuclopenthixol Hydrochloride.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of zuclopenthixol, C22H25ClN2OS

95.0 to 105% of the stated amount.

Identification

A. The light absorption, Appendix II B, in the range 205 to 350 nm of solution A prepared in the Assay exhibits maxima at 230, 268 and 325 nm.
B. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Shake a quantity of the tablets containing the equivalent of 8.7 mg of zuclopenthixol with 10 mL of methanol, centrifuge and use the supernatant liquid.
(2) 0.1% w/v of zuclopenthixol hydrochloride BPCRS in methanol.
(3) 0.1% w/v each of zuclopenthixol hydrochloride BPCRS and trans-clopenthixol hydrochloride BPCRS.
chromatographic conditions
(a) Use as the coating silica gel F254 (Merck silica gel 60 F254 plates are suitable).
(b) Use the mobile phase as described below in an unsaturated tank.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in air, spray with a 1% w/v solution of sodium molybdate in sulfuric acid, heat at 110° for 20 minutes and examine in daylight.
mobile phase

2 volumes of 13.5m ammonia, 2 volumes of propan-1-ol, 40 volumes of toluene and 60 volumes of acetone.

system suitability

The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated spots.

confirmation

The principal spot in the chromatogram obtained with solution (1) corresponds in position and colour to that in the chromatogram obtained with solution (2).

Tests

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions in a mixture of equal volumes of methanol and a phosphate buffer of pH 6.5 prepared by dissolving 2.56 g of potassium dihydrogen orthophosphate and 1.08 g of dipotassium hydrogen orthophosphate in 1000 mL of water and adjusting the pH if necessary to 6.5 ± 0.05 using potassium hydroxide or orthophosphoric acid.

(1) Shake a quantity of the powdered tablets containing the equivalent of 20 mg of zuclopenthixol with 35 mL of the phosphate buffer pH 6.5 until complete disintegration, add 65 ml of methanol, mix with the aid of ultrasound for 5 minutes, dilute to 200 ml with the solvent mixture, centrifuge and use the supernatant liquid.
(2) Dilute 1 volume of solution (1) to 100 volumes with the same solvent mixture.
(3) 0.00010% w/v of zuclopenthixol hydrochloride BPCRS and 0.000010% w/v of 2-chlorothioxanthone BPCRS in the solvent mixture.
chromatographic conditions
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5 µm) (Waters Symmetry C8 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use a column temperature maintained at 45°.
(e) Use a detection wavelength of 270 nm.
(f) Inject 50 µL of each solution.
mobile phase

A 0.077% w/v solution of dodecyltrimethylammonium bromide in a mixture of 18 volumes of methanol, 32 volumes of acetonitrile and 50 volumes of the phosphate buffer pH 6.5.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks corresponding to zuclopenthixol and 2-chlorothioxanthone is at least 2.5.

limits

In the chromatogram obtained with solution (1):

the area of any secondary peak is not greater than the area of the peak in the chromatogram obtained with solution (2) (1%);

the sum of the areas of any secondary peaks is not greater than 2.5 times the area of the peak in the chromatogram obtained with solution (2) (2.5%).

trans-Isomer

Carry out the method for liquid chromatography, Appendix III D, protected from light, using the following solutions.

(1) Shake a quantity of the powdered tablets containing the equivalent of 20 mg of zuclopenthixol in 10 mL of water for 10 minutes with the aid of ultrasound and filter (Whatman GF/C is suitable); to 5 mL of the filtrate add 25 mL of the mobile phase, shake thoroughly for 1 minute and dilute to 50 mL with the mobile phase; use the upper layer.
(2) Prepare a 0.004% w/v solution of trans-clopenthixol hydrochloride BPCRS in water, shake 5 mL of this solution with 25 mL of the mobile phase for 1 minute and dilute to 50 mL with the mobile phase; use the upper layer.
(3) Dissolve 10 mg of zuclopenthixol hydrochloride BPCRS in 5 mL of a 0.004% w/v solution of trans-clopenthixol hydrochloride BPCRS, add 25 mL of the mobile phase, shake thoroughly for 1 minute, dilute to 50 mL with the mobile phase and use the upper layer.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with silica gel for chromatography (5 µm) (Spherisorb S 5W is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
mobile phase

0.2 volumes of water, 0.3 volumes of 13.5m ammonia, 15 volumes of propan-2-ol and 85 volumes of n-heptane.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3) shows a similar resolution to that in the reference chromatogram supplied with trans-clopenthixol hydrochloride BPCRS.

LIMITS

In the chromatogram obtained with solution (1):

the area of any peak corresponding to trans-clopenthixol hydrochloride is not greater than 2.5 times the area of the peak in the chromatogram obtained with solution (2) (5%).

Assay

Weigh and powder 20 tablets. To a quantity of the powder containing the equivalent of 20 mg of zuclopenthixol add 40 mL of 0.1m hydrochloric acid, heat on a water bath for 30 minutes, shaking occasionally, cool, dilute to 200 mL with water and shake thoroughly. Centrifuge some of the resulting solution and dilute 20 mL of the supernatant liquid to 200 mL with water and mix (solution A). Prepare a reference standard in the following manner. Dissolve 25 mg of zuclopenthixol hydrochloride BPCRS, in 40 ml of 0.1m hydrochloric acid, dilute to 200 mL with water and shake thoroughly. Dilute 20 mL of the resulting solution to 200 mL with water and mix (solution B). Measure the absorbance, Appendix II B, of solution B and solution A at 230 nm using 0.002m hydrochloric acid in the reference cell. Calculate the content of C22H25ClN2OS using the absorbances at the maximum at 230 nm and the declared content of C22H25ClN2OS in zuclopenthixol hydrochloride BPCRS.

Labelling

The quantity of active ingredient is stated in terms of the equivalent amount of zuclopenthixol.

IMPURITIES

The impurities limited by the requirements of this monograph include those shown under Zuclopenthixol Hydrochloride.