Cyproterone Acetate

(Ph Eur monograph 1094)

 

C24H29ClO4 416.9 427-51-0

 

Ph Eur


 

 

Definition

 

Cyproterone acetate contains not less than 97.0 per cent and not more than the equivalent of 103.0 per cent of 6-chloro-3,20-dioxo-1b,2b-dihydro-3¢H-cyclopropa[1,2]pregna-1,4,6-trien-17-yl acetate, calculated with reference to the dried substance.

 

Characters

 

A white or almost white, crystalline powder, practically insoluble in water, very soluble in methylene chloride, freely soluble in acetone, soluble in methanol, sparingly soluble in ethanol.

 

It melts at about 210C.

 

Identification

 

First identification

 

A.

 

Second identification

 

B, C, D, E.

 

A.    Examine by infrared absorption spectrophotometry (2.2.24), comparing with the spectrum obtained with cyproterone acetate CRS.

 

B.    Examine by thin-layer chromatography (2.2.27), using a TLC silica gel F254 plate R.

 

Test solution

 

Dissolve 20 mg of the substance to be examined in methylene chloride R and dilute to 10 ml with the same solvent.

 

Reference solution

 

Dissolve 10 mg of cyproterone acetate CRS in methylene chloride R and dilute to 5 ml with the same solvent.

 

Apply to the plate 5 ml of each solution. Develop over a path of 15 cm using a mixture of equal volumes of cyclohexane R and ethyl acetate R. Allow the plate to dry in air. Repeat the development. Allow the plate to dry in air. Examine in ultraviolet light at 254 nm. The principal spot in the chromato-gram obtained with the test solution is similar in position and size to the principal spot in the chromatogram obtained with the reference solution.

 

C.    To about 1 mg add 2 ml of sulphuric acid R and heat on a water-bath for 2 min. A red colour develops. Cool. Add the solution cautiously to 4 ml of water  R and shake. The solution becomes violet.

 

D.    Incinerate about 30 mg with 0.3 g of anhydrous sodium carbonate R over a naked flame for about 10 min. Cool and dissolve the residue in 5 ml of dilute nitric acid R. Filter. To 1 ml of the filtrate add 1 ml of water  R. The solution gives reaction (a) of chlorides (2.3.1).

 

E.    It gives the reaction of acetyl (2.3.1).

 

Tests

 

Specific optical rotation (2.2.7)

 

Dissolve 0.25 g in acetone R and dilute to 25.0 ml with the same solvent. The specific optical rotation is +152 to +157, calculated with reference to the dried substance.

 

Related substances

 

Examine by liquid chromatography (2.2.29).

 

Test solution

 

Dissolve 10.0 mg of the substance to be examined in acetonitrile R and dilute to 10.0 ml with the same solvent.

 

Reference solution (a)

 

Dilute 1.0 ml of the test solution to 100.0 ml with acetonitrile R.

 

Reference solution (b)

 

Dissolve 5 mg of medroxyprogesterone acetate CRS in acetonitrile R and dilute to 50.0 ml with the same solvent. Dilute 1.0 ml of the solution to 10.0 ml with reference solution (a).

 

The chromatographic procedure may be carried out using:

 

a stainless steel column 0.125 m long and 4.6 mm in internal diameter packed with octadecylsilyl silica gel for chromatography R (3 mm),

 

as mobile phase at a flow rate of 1.5 ml/min a mixture of 40 volumes of acetonitrile R and 60 volumes of water  R,

 

as detector a spectrophotometer set at 254 nm.

 

Inject 20 ml of reference solution (a) and 20 ml of reference solution (b). Adjust the sensitivity of the system so that the height of the principal peak in the chromatogram obtained with reference solution (a) is at least 50 per cent of the full scale of the recorder. The test is not valid unless, in the chromatogram obtained with reference solution (b), the resolution between the peak corresponding to cyproterone acetate and the peak corresponding to medroxyprogesterone acetate is at least 3.0.

 

Inject 20 ml of the test solution. Continue the chromato-graphy for twice the retention time of cyproterone acetate. In the chromatogram obtained with the test solution, the sum of the areas of all the peaks, apart from the principal peak, is not greater than 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent). Disregard any peak with an area less than 0.05 times that of the principal peak in the chromatogram obtained with reference solution (a).

 

Loss on drying (2.2.32)

 

Not more than 0.5 per cent, determined on 1.000 g by drying at 80C at a pressure not exceeding 0.7 kPa.

 

Sulphated ash (2.4.14)

 

Not more than 0.1 per cent, determined on 1.0 g.

 

Assay

 

Dissolve 50.0 mg in methanol  R and dilute to 50.0 ml with the same solvent. Dilute 1.0 ml of the solution to 100.0 ml with methanol  R. Measure the absorbance (2.2.25) at the maximum at 282 nm.

 

Calculate the content of C24H29ClO4 taking the specific absorbance to be 414.

 

Storage

 

Store protected from light.

 

Impurities

 

A.    R = H: 3,20-dioxo-1b,2b-dihydro-3¢H-cyclopropa[1,2]pregna-1,4,6-trien-17-yl acetate,

 

B.    R = OCH3: 6-methoxy-3,20-dioxo-1b,2b-dihydro-3¢H-cyclopropa[1,2]pregna-1,4,6-trien-17-yl acetate.

 

 

 


Ph Eur

 

Action and use

 

Antiandrogen

 

Preparation

 

Cyproterone Tablets.