Action and use
Antiandrogen.
Definition
Cyproterone Tablets contain Cyproterone Acetate.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of cyproterone acetate, C24H29ClO4
95.0 to 105.0% of the stated amount.
Identification
A. Shake a quantity of the powdered tablets containing 0.1 g of Cyproterone Acetate with 20 mL of
dichloromethane, filter through a glass-fibre filter paper (Whatman GF/C is suitable) and evaporate the filtrate to dryness using a rotary evaporator and a water bath at 40°. The
infrared absorption spectrum of the residue,
Appendix II A, is concordant with the
reference spectrum of cyproterone acetate
(RS 395).
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
Dissolution
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.
test conditions
(a) Use Apparatus 2, rotating the paddle at 75 revolutions per minute.
procedure
(1) After 45 minutes withdraw a sample of the medium and filter. Measure the
absorbance of the filtered medium, suitably diluted with the dissolution medium, if necessary, to produce a solution containing the equivalent of 0.0011% w/v of cyproterone acetate, at the maximum at 285 nm,
Appendix II B using dissolution medium in the reference cell.
determination of content
Calculate the total content of cyproterone acetate, C24H29ClO4, in the medium from the absorbances obtained and using the declared content of C24H29ClO4, in cyproterone acetate BPCRS.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 0.1 g of Cyproterone Acetate with 50 mL of a 4:1 mixture of
acetonitrile and
water for 5 minutes, dilute to 100 mL with
water and filter through a glass-fibre filter (Whatman GF/C is suitable).
(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase.
(4) Dilute 1 volume of solution (2) to 10 volumes with the mobile phase.
chromatographic conditions
(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
40 volumes of acetonitrile and 60 volumes of water.
When the chromatograms are recorded under the prescribed conditions the retention time of cyproterone acetate is about 22 minutes.
system suitability
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the two principal peaks is at least 3.0.
limits
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than half the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the sum of the areas of all the secondary peaks is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.5%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.1%).
Assay
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Shake a quantity of the powdered tablets containing 50 mg of Cyproterone Acetate with 50 mL of a 4:1 mixture of
acetonitrile and
water for 5 minutes, dilute to 100 mL with the same solvent mixture and filter through a glass-fibre filter (Whatman GF/C is suitable); dilute 1 volume of the filtrate to 10 volumes with the mobile phase.
chromatographic conditions
The chromatographic procedure described under Related substances may be used.
system suitability
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the two principal peaks is at least 3.0.
determination of content
Calculate the content of C24H29ClO4 in the tablets, using the declared content of C24H29ClO4 in cyproterone acetate BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed in the monograph for Cyproterone Acetate and the following:
1. 6β-Chloro-7α,17α-dihydroxy-1α,2α-methylenepregna-4-ene-3,20-dione (chlorohydrin derivative)
2. 17α-Hydroxy-6-chloro-1α-chloromethylpregna-4,6-diene-3,20-dione (1-chloromethyl derivative)
3. 1α,2α-Methylene-3,6,20-trioxopregna-4-en-17α-yl acetate
4. 17α-Hydroxy-6-chloro-1α,2α-methylenepregna-4,6-diene-3,20-dione (cyproterone)
