(Ph Eur monograph 1094)
C24H29ClO4 416.9 427-51-0
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.
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.
B, C, D, E.
by infrared absorption spectrophotometry (2.2.24), comparing with the spectrum obtained
with cyproterone acetate CRS.
by thin-layer chromatography (2.2.27), using a TLC silica gel F254
Dissolve 20 mg of the substance to be examined in methylene
chloride R and dilute to 10 ml with the same solvent.
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.
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.
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).
gives the reaction of acetyl (2.3.1).
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.
Examine by liquid chromatography (2.2.29).
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
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
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.
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.
Store protected from light.
A. R =
B. R =
Action and use