GC-MS法测定盐酸苯海索原料药中遗传毒性杂质氯代环己烷  

GC-MS method for the determination of the genotoxic impurity chlorocyclo⁃hexane in trihexyphenidyl hydrochloride bulk drug

作　　者：殷丽宁 张煜 胡一桥[1] 詹新安 YIN Lining;ZHANG Yu;HU Yiqiao;ZHAN Xin'an(School of Life Sciences,Nanjing University,Nanjing 210093;Hisun Pharmaceutical(Hangzhou)Co.,Ltd.,Hangzhou 311404,China)

机构地区：[1]南京大学生命科学学院,南京210093 [2]海正药业(杭州)有限公司,杭州311404

出　　处：《中国药科大学学报》2022年第1期79-85,共7页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.31872755,No.81872811);江苏省杰出青年基金资助项目(No.BK20190007);中央高校基础研究基金资助项目(No.02141438473)。

摘　　要：建立一种GC-MS分析方法用于盐酸苯海索原料药中遗传毒性杂质氯代环己烷的含量测定。采用SH-RXI-5SILMS毛细管柱(0.25 mm×30 m,0.25μm),以60℃恒温程序运行6 min;进样口温度180℃,进样分流比为10∶1,进样量为1.0μL;质谱检测器采用SIM检测模式,检测器电压为0.3 kV,接口温度240℃,选择性监测m/z 82离子。氯代环己烷在59.72~1493 ng/mL范围内与峰面积呈现良好的线性关系(r=0.9999);检测限和定量限浓度分别为17.92和59.72 ng/mL;该方法日内和日间精密度良好(RSD≤5.0%)且耐用性良好(RSD≤1.65%)。本法适用于盐酸苯海索中遗传毒性杂质氯代环己烷的痕量检测,可为盐酸苯海索原料药的质量控制提供理论依据。Gas chromatography-mass spectrometry(GC-MS) method was established for trace analysis of thepotential genotoxic impurity chlorocyclohexane in trihexyphenidyl hydrochloride bulk drug,utilizing an RXI-5 SIL MS column at isothermal temperature of 60 ℃ for the entire 6-minute run time.The inlet temperature was180 ℃ and a split ratio of 10∶1 was used with the injection volume of 1.0 μL.The selective ion monitoring modewas set at m/z 82 for chlorocyclohexane with a detector voltage of 0.3 kV and an ion source temperature of 240 ℃.The method was verified with respect to specificity,limit of detection(LOD),limit of quantitation(LOQ),accuracy,precision and robustness.Good linear correlation was achieved with coefficient r of 0.999 9 in the concentrationrange of 59.72-493 ng/m L.The intra-and inter-day precision was satisfactory(RSD ≤ 5.0%) and robust(RSD ≤1.65%).The proposed method in this study can be adequately adopted as a tool for quality assurance of trihexy-phenidyl hydrochloride in routine test of potential genotoxic impurity.

关 键 词：盐酸苯海索 氯代环己烷 遗传毒性杂质 GC-MS 痕量检测 

分 类 号：R917[医药卫生—药物分析学]