Cyclizine

C ₁₈ H ₂₂ N ₂      266.4      82-92-8

Histamine H₁ receptor antagonist; antihistamine.

Cyclizine Injection

Cyclizine is 1-benzhydryl-4-methylpiperazine. It contains not less than 98.5% and not more than 101.0% of C₁₈H₂₂N₂, calculated with reference to the dried substance.

A white or creamy white, crystalline powder.

Practically insoluble in water. It dissolves in most organic solvents and in dilute acids.

A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of cyclizine (RS 075).

B. The light absorption, Appendix II B, in the range 220 to 350 nm of a freshly prepared 0.002% w/v solution in 0.05m sulfuric acid exhibits a maximum at 227 nm with a series of ill-defined maxima between 258 and 272 nm. The absorbance at 227 nm is about 0.87.

C. Melting point, about 107°, Appendix V A.

Shake 1 g with 25 mL of carbon dioxide-free water for 5 minutes and filter. The pH of the filtrate is 7.6 to 8.6, Appendix V L.

A 1.0% w/v solution in ether and a 1.0% w/v solution in 2m hydrochloric acid are clear, Appendix IV A.

Dissolve 0.20 g in 2 mL of methanol and dilute to 30 mL with 2m nitric acid. 15 mL of the resulting solution complies with the limit test for chlorides, Appendix VII (500 ppm).

Carry out the method for thin-layer chromatography, Appendix III A, using silica gel G as the coating substance and as the mobile phase the lower layer obtained after shaking together a mixture of 2 volumes of 13.5m ammonia, 8 volumes of methanol and 90 volumes of dichloromethane and allowing the layers to separate. Apply separately to the plate 20 µL of each of four freshly prepared solutions in methanol containing (1) 2.0% w/v of the substance being examined, (2) 0.010% w/v of the substance being examined, (3) 0.010% w/v of N-methylpiperazine and (4) 0.10% w/v of each of the substance being examined and hydroxyzine hydrochloride BPCRS. After removal of the plate, allow it to dry in air and expose to iodine vapour for 10 minutes. Any spot corresponding to N-methylpiperazine in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (3) (0.5%). Any other secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%). The test is not valid unless the chromatogram obtained with solution (4) shows two clearly separated spots.

When dried to constant weight at 80°, loses not more than 1.0% of its weight. Use 1 g.

Not more than 0.1%, Appendix IX A.

Carry out Method I for non-aqueous titration, Appendix VIII A, using 0.1 g and determining the end point potentiometrically. Each mL of 0.1m perchloric acid VS is equivalent to 13.32 mg of C₁₈H₂₂N₂.