Development and Validation of a Sensitive GC-MS/MS Method for the Determination of Five Potential Genotoxic Impurities in Abiraterone Acetate.

Abstract

A sensitive and selective gas chromatography-tandem mass spectrometry method was developed for the identification and quantification of five potential genotoxic impurities (PGIs), i.e., chloromethane, 2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate, in abiraterone acetate. The method was validated according to the International Council for Harmonisation (ICH) guidelines. The linearity was established for the concentration range of 30-480ng/mL (2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate) and 90-1440ng/mL (chloromethane). The correlation coefficient of each PGIs was >0.995. The extraction recoveries ranged from 90.49 to 106.79% for the five PGIs. The quantitation limit, detection limit, accuracy, precision, repeatability and stability of the method demonstrated that the method was an adequate quality control tool for quantitation and identification of chloromethane, 2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate at trace levels in drug substances and drug products.