Atmospheric Pressure Photoionization Applied to Quantitation of Cyproterone Acetate in Human Plasma

Cyproterone acetate [6-chloro-1beta,2beta-dihydro-17alpha-hydroxy- 3'H-cyclopropa(1,2)-pregna-1,4,6-triene-3,20-dione acetate] is a powerful antiandrogen used in the treatment of women suffering from disorders associated with androgenization such as hirsutism and acne. A fast, sensitive, and robustness method is developed for the determination and quantitation of cyproterone acetate in human blood plasma by liquid chromatography coupled with tandem mass spectrometry. Cyproterone acetate is extracted from 0.2 mL human plasma by liquid-liquid extraction. The method has a chromatographic run of 4.5 min, using a C18 analytical column (100- yen 2.1-mm i.d.), and the linear calibration curve over the range is linear from 1 to 500 ng/mL (r2 > 0.994). The between-run precision, based on the relative standard deviation replicate quality controls, is 96.2% (3 ng/mL), 97.5% (120 ng/mL), and 99.1% (400 ng/mL). The between-run accuracy was +/- 2.7%, 3.1%, and 4.8% for the previously mentioned concentrations, respectively. The method is employed in a bioequivalence study of two tablet formulations of cyproterone acetate (100 mg).