气相色谱-质谱法测定替格瑞洛中间体中基因毒性杂质1-溴丙烷

Determination of genotoxic impurity 1-bromopropane in intermediate of Ticagrelor by gas chromatography-mass spectrometry

建立气相色谱-质谱法测定替格瑞洛中间体[4,6-二氯-2-(丙硫基)-5-氨基嘧啶(DCPA)]中潜在基因毒性杂质1-溴丙烷。样品以N,N-二甲基甲酰胺溶解后直接进样,经Agilent DB-5MS毛细管色谱柱(30 m×0.25 mm,0.25μm)分离,采用选择离子扫描(SIM)模式定量分析。1-溴丙烷的质量浓度在131.8~1 758 ng/mL范围内与色谱峰面积线性关系良好,相关系数为0.999 8,检出限为0.40μg/g,定量限为1.32μg/g。样品加标平均回收率为91.8%,测定结果的相对标准偏差为2.9%(n=6)。该方法简单便捷、专属性强、灵敏度高,可为卤代烃类基因毒性杂质的痕量检测提供方法参考。

A method for the determination of potential genotoxic impurity 1-bromopropane in the intermediate[4,6-dichloro-2-(propylthio)-5-aminopyrimidine(DCPA)]of Ticagrelor by gas chromatography-mass spectrometry was established.The sample was dissolved in N,N-dimethylformamide and directly injected,separated by DB-5MS chromatography column(30 m×0.25 mm,0.25μm),and quantitatively analyzed using selective ion monitoring(SIM)mode.The mass concentration of 1-bromopropane had a good linear relationship with the chromatographic peak area in the range of 131.8-1758 ng/mL,the correlation coefficient was 0.9998,the detection limit was 0.40μg/g,and the quantitative limit was 1.32μg/g.The average recovery of sample spiking was 91.8%,and the relative standard deviation of the determination results was 2.9%(n=6).The developed method is simple and convenient,with strong specificity and high sensitivity,which can provide a method reference for the trace detection of halogenated hydrocarbon genotoxic impurities.