Action and use
Dopamine receptor antagonist; neuroleptic.
DEFINITION
Zuclopenthixol Acetate Injection is a sterile solution of Zuclopenthixol Acetate in a suitable vegetable oil.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of zuclopenthixol acetate, C24H27ClN2O2S
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, protected from light, using the following solutions.
(1) Dilute a volume of the injection with ethanol (96%) to contain 0.5% w/v of Zuclopenthixol Acetate.
(2) 0.5% w/v of zuclopenthixol acetate dihydrochloride BPCRS in ethanol (96%).
(3) 0.5% w/v each of zuclopenthixol acetate dihydrochloride BPCRS and zuclopenthixol decanoate dihydrochloride BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a silica gel F254 precoated plate (Merck silica gel 60 F254 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 5 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, 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
3 volumes of diethylamine and 90 volumes of cyclohexane.
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 to that in the chromatogram obtained with solution (2).
B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).
TESTS
Related substances
Carry out the method for thin-layer chromatography, Appendix III A, protected from light, using the following solutions.
(1) Dissolve a quantity of the injection containing 0.10 g of Zuclopenthixol Acetate in sufficient dichloromethane to produce 50 mL.
(2) 0.0010% w/v of 2-chlorothioxanthone BPCRS in dichloromethane.
(3) 0.0020% w/v of zuclopenthixol hydrochloride BPCRS in dichloromethane containing a few drops of diethylamine.
(4) 0.00040% w/v of zuclopenthixol hydrochloride BPCRS in dichloromethane containing a few drops of diethylamine.
(5) 0.00020% w/v of zuclopenthixol hydrochloride BPCRS in dichloromethane containing a few drops of diethylamine.
CHROMATOGRAPHIC CONDITIONS
(a) Use a silica gel F254 precoated plate (Merck silica gel 60 F254 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 5 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air, spray with a mixture of equal volumes of sulfuric acid and absolute ethanol, heat at 110° for 5 minutes and examine under ultraviolet light (365 nm).
MOBILE PHASE
10 volumes of diethylamine, 40 volumes of dichloromethane and 50 volumes of cyclohexane.
LIMITS
In the chromatogram obtained with solution (1):
any spot corresponding to 2-chlorothioxanthone is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%);
any spot corresponding to zuclopenthixol is not more intense than the spot in the chromatogram obtained with solution (3) (1%);
any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (4) (0.2%);
and not more than one other secondary spot spot is more intense than the spot in the chromatogram obtained with solution (5) (0.1%).
trans-Isomer
Carry out the method for liquid chromatography, Appendix III D, protected from light, using the following solutions.
(1) Dissolve a quantity of the injection containing 20 mg of Zuclopenthixol Acetate in 25 mL of dichloromethane and dilute to 50 mL with dichloromethane.
(2) Dissolve 23 mg of trans-clopenthixol acetate dihydrochloride BPCRS (equivalent to 20 mg of trans-clopenthixol acetate) in sufficient dichloromethane containing a few drops of diethylamine to produce 50 mL; dilute 1 mL of the resulting solution to 100 mL with dichloromethane.
(3) Mix equal volumes of solution (1) and undiluted solution (2).
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 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 50 μL of each solution.
MOBILE PHASE
0.08 of a volume of 13.5M ammonia, 45 volumes of dichloromethane, 45 volumes of n-heptane and 50 volumes of acetonitrile.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the principal peaks is at least 2.6.
LIMITS
In the chromatogram obtained with solution (1): the area of any peak corresponding to trans-clopenthixol acetate is not greater than the area of the peak in the chromatogram obtained with solution (2) (1%).
ASSAY
Prepare a 0.2% w/v solution of cis-flupenthixol propionate dihydrochloride BPCRS (internal standard) in dichloromethane.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dissolve a quantity of the injection containing 20 mg of Zuclopenthixol Acetate in 25 mL of dichloromethane, add 5 mL of the internal standard solution and dilute to 50 mL with dichloromethane.
(2) Dissolve 20 mg of zuclopenthixol acetate dihydrochloride BPCRS in 25 mL of dichloromethane containing a few drops of diethylamine, add 5 mL of the internal standard solution and dilute to 50 mL with dichloromethane.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under trans-Isomer may be used.
DETERMINATION OF CONTENT
Determine the weight per mL of the injection, Appendix V G, and calculate the content of C24H27ClN2O2S using the declared content of C24H27ClN2O2S in zuclopenthixol acetate dihydrochloride BPCRS.
STORAGE
Zuclopenthixol Acetate Injection should be protected from light.
