LC-MS/MS法测定厄贝沙坦中基因毒性杂质N-亚硝基二甲胺和N-亚硝基二乙胺  

Determination of N-nitrosodimethylamine and N-nitrosodiethylamine in irbesartan by liquid chromatography-tandem mass spectrometry

作　　者：张岩琛 王玲娜 刘晓强 ZHANG Yan-chen;WANG Ling-na;LIU Xiao-qiang(Changzhou Food and Drug Supervision and Inspection Center,Changzhou 213000,China)

机构地区：[1]常州市食品药品监督检验中心,常州213000

出　　处：《中国新药杂志》2021年第6期569-576,共8页Chinese Journal of New Drugs

摘　　要：建立同时检测厄贝沙坦中N-亚硝基二甲胺(NDMA)和N-亚硝基二乙胺(NDEA)的液质联用(liquid chromatography-tandem mass spectrometry,LC-MS/MS)方法。选择大气压电离串联四极杆质谱(APCI+MRM)模式进行检测,流动相为0.1%甲酸水溶液-0.1%甲酸甲醇溶液梯度洗脱。结果表明该方法专属性良好,标准曲线线性范围分别为1~120 ng·mL^(-1)(NDMA)和0.4~48 ng·mL^(-1)(NDEA);检测限浓度分别为0.5 ng·mL^(-1)(NDMA)和0.2 ng·mL^(-1)(NDEA);精密度RSD均<3.0%;准确度为96.1%~106.2%,重复性良好;样品的提取回收率分别为102.5%(NDMA)和99.9%(NDEA);对照溶液在进样器和0℃下放置24 h后稳定。该方法简单灵敏准确,可以较好地满足厄贝沙坦原料药生产中基因毒性杂质NDMA和NDEA的检验。To develop a liquid chromatography-tandem mass spectrometry method for simultaneous detection of N-nitrosodimethylamine(NDMA)and N-nitrosodiethylamine(NDEA)in irbesartan.APCI(+)MRM mode was selected for detection.Gradient elution was conducted with mobile phase consisting of 0.1%formic acid solution and methanol containing 0.1%formic acid.The method had good specificity.Good linearity was obtained for NDMA and NDEA in the range of 1~120 ng·mL^(-1)and 0.4~48 ng·mL^(-1),respectively.The limits of detection(LOD)were 0.5 ng·mL^(-1)and 0.2 ng·mL^(-1)for NDMA and NDEA.The relative standard deviation(RSD)of peak area was less than 3.0%.The accuracy was 96.1%~106.2%and repeatability was good.The average percent recovery was 102.5%and 99.9%for NDMA and NDEA,respectively.All samples were stable after being stored for 24 h in auto-injection sampler or at 0℃.This method is simple,sensitive and accurate,and can be used for limit test and quantitation of NDMA and NDEA in irbesartan.

关 键 词：液相色谱串联质谱 厄贝沙坦 基因毒性杂质 N-亚硝基二甲胺 N-亚硝基二乙胺 

分 类 号：R917[医药卫生—药物分析学]