GC-MS/MS法测定卡格列净中基因毒杂质正溴丁烷的含量

Determination of 1-bromobutane in Canagliflozin by GC-MS/MS

目的:建立气相色谱-串联质谱(GC-MS/MS)法测定卡格列净中基因毒杂质正溴丁烷的含量。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:210℃,进样体积1μL,线速度,采用不分流高压进样。质谱条件:EI源,离子源温度:200℃;溶剂延时:3.0 min,检测电压:0.6 kV,以多反应监测(MRM)模式检测。结果:正溴丁烷浓度在10~1000 ng·mL^(-1)浓度范围内,线性关系良好(r>0.999),加样回收率(n=3)的范围为96.2%~101.2%,RSD范围为2.005%~2.307%,检测下限为0.2 ng·mL^(-1),定量下限为1.0 ng·mL^(-1)。结论:本方法专属性较强,灵敏度高,稳定性好,可适用于对基因毒杂质正溴丁烷的定量,为卡格列净的安全性提供了质量控制。

Objective:To establish a GC-MS/MS method for the determination of 1-bromobutane in Canagliflozin.Methods:An Agilent DB-624 capillary column(6%cyanide propylbenzene-94%dimethylsiloxane copolymer,0.32 mm×30m,1.8μm)was used for separating the analytes by programmed heating.The inlet temperature was 210℃.MS condition:Ionization mode was EI.Electron energy was 70 eV,and the source temperature was 200℃.The analytes were detected with MS/MS in multiple reaction monitoring(MRM)mode.Results:It showed good linearity with regression coefficients no less than 0.999 in the concentration range of 10~1000 ng·mL^(-1).The average recoveries were 92.12%-96.43%,and RSD range was 2.125%-3.532%.The lower limits of detection was 0.2 ng·mL^(-1),The lower limits of detection was 1.0 ng·mL^(-1).Conclusion:The memod showed strong specificity,high sensitivity,high separation and good stability which could be reliably and effectively used in the determination of 1-bromobutane in Canagliflozin,and provided a guarantee for the quality control of Canagliflozin.