GC-MS法测定维格列汀中3种基因毒性杂质  

Determination of three genotoxic impurities in vildagliptin by GC-MS

作　　者：常艳 刘清梁 薛志旗 CHANG Yan;LIU Qing-liang;XUE Zhi-qi(Research and Development Center of China Resources DOUBLE-CRANE Pharmaceutical Co.,Ltd.,Beijing 100102,China)

机构地区：[1]华润双鹤药业股份有限公司研究与发展中心,北京100102

出　　处：《中国新药杂志》2022年第3期277-284,共8页Chinese Journal of New Drugs

摘　　要：目的:建立一种GC-MS检测维格列汀中基因毒性杂质氯乙酸甲酯、氯乙酸乙酯和氯乙酸异丙酯含量的方法。方法:采用VF-624ms毛细管柱(30 m×0.25 mm,1.4μm);进样口温度220℃;柱流速1.0 mL·min^(-1);进样方式用分流进样,分流比5∶1;载气为氦气;检测器为质谱检测器;离子化方式为EI;溶剂延迟4 min;检测方式为选择离子模式(SIM);外标法计算。结果:空白溶剂和维格列汀均不干扰氯乙酸甲酯、氯乙酸乙酯和氯乙酸异丙酯的检测;氯乙酸甲酯、氯乙酸乙酯和氯乙酸异丙酯在一定范围内线性良好,r均>0.990;定量下限分别为0.02402,0.02436,0.02415μg·mL^(-1);加样回收率良好,平均加样回收率(n=9)分别为99%,99%和99%;RSD分别为1.3%,1.4%和1.2%;室温条件下,对照品溶液和加标样品溶液在28.5和24 h内稳定性良好。结论:该方法灵敏度高、专属性和准确度好,可用于维格列汀中氯乙酸甲酯、氯乙酸乙酯和氯乙酸异丙酯检测。Objective:To establish a GC-MS method for the determination of three genotoxic impurities of methyl chloroacetate,ethyl chloroacetate and isopropyl chloroacetate in vildagliptin.Methods:An VF-624 ms column(30 m×0.25 mm,1.4μm)was adopted for separation with a injector temperature of 220℃.The carrier gas flow rate was set at 1.0 mL·min^(-1) with a split ratio of 5∶1.Helium as used as the carrier gas,and the time of solvent delay was 4 min.EI,SIM and external standard method were used in MS analysis.Results:Blank solvent and vildagliptin caused no interference.The assay of methyl chloroacetate,ethyl chloroacetate and isopropyl chloroacetate were linear over the certain range(r>0.990).The limits of quantitation(LOQ)were 0.02402,0.02436 and 0.02415μg·mL^(-1).The average recoveries of methyl chloroacetate,ethyl chloroacetate and isopropyl chloroacetate were 99%,99% and 99% with RSD of 1.3%,1.4% and 1.2%.The control solution and the labeled sample solution have good stability within 28.5 h and 24 h at room temperature.Conclusion:The method is sensitive,selective,and accurate,which can be used to detect the three genotoxic impurities,methyl chloroacetate,ethyl chloroacetate and isopropyl chloroacetate,in vildagliptin.

关 键 词：维格列汀 氯乙酸甲酯 氯乙酸乙酯 氯乙酸异丙酯 GC-MS 基因毒性杂质 

分 类 号：R917[医药卫生—药物分析学]