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.

中文翻译：

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用于测定醋酸阿比特龙中五种潜在遗传毒性杂质的灵敏 GC-MS/MS 方法的开发和验证

开发了一种灵敏且选择性的气相色谱-串联质谱法，用于鉴定和定量五种潜在的遗传毒性杂质（PGI），即氯甲烷、2-氯丙烷、2-溴丙烷、4-氯-1-丁醇和硫酸二乙酯，在醋酸阿比特龙中。该方法根据国际协调委员会 (ICH) 指南进行了验证。在 30-480 ng/mL（2-氯丙烷、2-溴丙烷、4-氯-1-丁醇和硫酸二乙酯）和 90-1440 ng/mL（氯甲烷）的浓度范围内建立了线性关系。每个 PGI 的相关系数＞0.995。五个 PGI 的萃取回收率范围为 90.49 至 106.79%。定量限、检出限、准确度、精密度、