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 30–480 ng/mL (2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate) and 90–1440 ng/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.

Quantitative Determination of Four Potential Genotoxic Impurities in the Active Pharmaceutical Ingredients in TSD-1 Using UPLC-MS/MS

“…Molecules 2022, 27, 4129 2 of 9 issued relevant guidelines on the control of PGIs in active pharmaceutical ingredients (APIs) [11][12][13]. The manufacture of APIs may produce PGIs; so, trace amounts of PGIs in drugs must be monitored and regulated to ensure public safety [14][15][16][17]. TSD-1 is synthesized from 4-nitrobenzenesulfonyl chloride.…”

“…To ensure the safety of drug use, the European Drug Administration (EMA), the United States Food and Drug Administration (FDA), and the International Council of Harmonization (ICH) issued relevant guidelines on the control of PGIs in active pharmaceutical ingredients (APIs) [11][12][13]. The manufacture of APIs may produce PGIs; so, trace amounts of PGIs in drugs must be monitored and regulated to ensure public safety [14][15][16][17]. TSD-1 is synthesized from 4-nitrobenzenesulfonyl chloride.…”