Action and use
Dopamine receptor antagonist; neuroleptic.
DEFINITION
Zuclopenthixol Decanoate Injection is a sterile solution of Zuclopenthixol Decanoate in a suitable vegetable oil.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of zuclopenthixol decanoate, C32H43ClN2O2S
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions, protected from light.
(1) Dilute a volume of the injection with ethanol (96%) to contain 0.5% w/v of Zuclopenthixol Decanoate.
(2) 0.5% w/v of zuclopenthixol decanoate dihydrochloride BPCRS in ethanol (96%).
(3) 0.5% w/v each of zuclopenthixol decanoate dihydrochloride BPCRS and zuclopenthixol acetate dihydrochloride BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel F254 (Merck silica gel 60 F254 plates are suitable). Before use, heat the plate at 110° for 30 minutes.
(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, 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
3 volumes of diethylamine and 90 volumes of cyclohexane as the mobile phase, using an unlined tank.
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 peak due to zuclopenthixol decanoate 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 acetonitrile, protected from light.
(1) Dilute the injection to contain 0.50% w/v of Zuclopenthixol Decanoate.
(2) 0.015% w/v of zuclopenthixol hydrochloride BPCRS.
(3) 0.0025% w/v of 2-chlorothioxanthone BPCRS.
(4) 0.005% w/v of trans-clopenthixol decanoate dihydrochloride BPCRS.
(5) 0.015% w/v of zuclopenthixol hydrochloride BPCRS, 0.0025% w/v of 2-chlorothioxanthone BPCRS and 0.005% w/v of trans-clopenthixol decanoate dihydrochloride BPCRS in solution (1).
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Waters Symmetry C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 270 nm.
(f) Inject 20 μL of each solution.
(g) For solution (1), allow the chromatography to proceed for twice retention time of the principal peak.
MOBILE PHASE
0.1 volume of orthophosphoric acid, 26 volumes of 0.02M dioctyl sodium sulfosuccinate (prepared by dissolving 8.89 g of dioctyl sodium sulfosuccinate in 500 mL of water, stirring for 6 to 8 hours and diluting to 1000 mL with water) and 74 volumes of ethanol (96%).
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (5) shows clearly separated peaks.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to zuclopenthixol is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (3%);
the area of any peak corresponding to 2-chlorothioxanthone is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.5%);
the area of any peak corresponding to trans-clopenthixol decanoate is not greater than the area of the principal peak in the chromatogram obtained with solution (4) (1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions solutions in acetonitrile protected from light.
(1) Dilute a volume of the injection to contain 0.50% w/v of Zuclopenthixol Decanoate.
(2) 0.57% w/v of zuclopenthixol decanoate dihydrochloride BPCRS.
(3) 0.015% w/v of zuclopenthixol hydrochloride BPCRS, 0.0025% w/v of 2-chlorothioxanthone BPCRS and 0.005% w/v of trans-clopenthixol decanoate dihydrochloride BPCRS in solution (1).
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) shows clearly separated peaks.
DETERMINATION OF CONTENT
Calculate the content of C32H43ClN2O2S using the declared content of C32H43ClN2O2S in zuclopenthixol decanoate dihydrochloride BPCRS. Each mg of zuclopenthixol decanoate dihydrochloride is equivalent to 0.8852 mg of zuclopenthixol decanoate.
STORAGE
Zuclopenthixol Decanoate Injection should be protected from light.
