GC-MS/MS法测定苯甲酸阿格列汀中基因毒杂质2-氰基氯苄和邻二溴甲基苯腈的含量  

Simultaneous determination of genotoxic impurities 2-cyanobenzyl chloride and 2-dibromomethyl-benzonitrile in alogliptin benzoate by GC-MS/MS

作　　者：葛雪松 赵毅 卓静 孙桐 张新勇 GE Xuesong;ZHAO Yi;ZHUO Jing;SUN Tong;ZHANG Xinyong(Suqian Institute for Food and Drug Control,Suqian 223800,China)

机构地区：[1]江苏省宿迁市食品药品检验所,江苏宿迁223800

出　　处：《中国药品标准》2022年第1期95-100,共6页Drug Standards of China

摘　　要：目的:建立气相色谱-串联质谱法(GC-MS/MS)同时测定苯甲酸阿格列汀中基因毒杂质邻二溴甲基苯腈和2-氰基氯苄的含量。方法:采用6%氰丙基苯-94%二甲基硅氧烷(Agilent DB-624,30 m×0.32 mm,1.8μm)色谱柱,程序升温;进样口温度:260℃,进样体积1μL,线速度,5∶1分流比进样。质谱条件:EI源,离子源温度:250℃;溶剂延时:1.5 min,检测电压:0.6 kV,以多反应监测(MRM)模式检测。结果:2-氰基氯苄和邻二溴甲基苯腈浓度在20~1000 ng·mL^(-1)浓度范围内,线性关系良好(r>0.997),加样回收率(n=3)为95.8%~104.2%,RSD为2.125%~3.532%,检测下限分别为3.0 ng·mL^(-1)和8.0 ng·mL^(-1),定量下限分别为8.0 ng·mL^(-1)和13.0 ng·mL^(-1)。测定样品9份,均未检出2-氰基氯苄和邻二溴甲基苯腈。结论:本法可同时对2-氰基氯苄和邻二溴甲基苯腈进行定量,为苯甲酸阿格列汀的安全性提供了质量保障。Objective:To established a GC-MS/MS method for the simultaneous determination of 2-cyanobenzyl chloride and 2-dibromomethyl-benzonitrile in alogliptin benzoate.Methods:The method was performed on a DB-624 capillary column(6%cyanide propylbenzene-94%dimethylsiloxane copolymer,0.32 mm×30 m,1.8μm)with programed temperature.The injector temperature was controlled at 260℃,the injection volume was 1μL and the split ratio was 5∶1.The source temperature was 250℃,solvent delayed 1.5min and the electron energy was 0.6 kV.The analyses were detected by the multiple reaction monitoring(MRM)in the EI mode.Results:Both analytes showed good linearity with regression coefficients of no less than 0.997 in the concentration range of 20-1000 ng·mL^(-1).The average recoveries were 95.8%-104.2%with RSD range of 2.125%-3.532%.The lower detection limit values were 3.0 ng·mL^(-1) and 8.0 ng·mL^(-1),respectively.The lower limits of quantification were 8.0 ng·mL^(-1) and 13.0 ng·mL^(-1),respectively.2-cyanobenzyl chloride and 2-dibromomethylbenzonitrile were not detected in 9 samples.Conclusion:The method can simultaneously quantify 2-cyanobenzyl chloride and 2-dibromomethylbenzonitrile,and provide the quality assurance for the safety of alogliptin benzoate.

关 键 词：气相色谱-串联质谱法 苯甲酸阿格列汀 2-氰基氯苄 邻二溴甲基苯腈 

分 类 号：R921.2[医药卫生—药学]