UPLC-MS/MS联用技术测定厄贝沙坦中N-亚硝基二甲胺与N-亚硝基二乙胺  

Determination of N-nitrosodimethylamine and N-nitrosodiethylamine in Irbesartan by UPLC-MS/MS Technique

作　　者：陈可心 高珣 李军毅 李辉辉 刘钦伟 闫占宽 CHEN Ke-xin;GAO Xun;LI Jun-yi;LI Hui-hui;LIU Qin-wei;YAN Zhan-kuan(Jiangsu Ocean University,Jiangsu Lianyungang 222005;Jiangsu Yuanchuang Pharmaceutical R&d Co.,Ltd.,Jiangsu Lianyungang 222042,China)

机构地区：[1]江苏海洋大学,江苏连云港222005 [2]江苏原创药物研发有限公司,江苏连云港222042

出　　处：《广州化工》2022年第24期100-104,共5页GuangZhou Chemical Industry

摘　　要：开发并验证了一种定量分析厄贝沙坦中2种基因毒性杂质的超高效液相色谱-串联质谱(UPLC-MS/MS)方法。采用Agilent ZORBAX Eclipse plus C18色谱柱(3.0 mm×100 mm, 1.8μm),0.1%甲酸水溶液-甲醇为流动相梯度洗脱,大气压化学电离、正离子平行反应监测模式(APCI+PRM)进行检测,结果显示N-亚硝基二甲胺(NDMA)和N-亚硝基二乙胺(NDEA)在0.225~1.5 ng/mL浓度范围内线性关系良好,检测限(LOD)为0.022 ng/mL、0.044 ng/mL,供试品加标溶液回收率为78%~103%。所建立的方法灵敏、准确,可满足对厄贝沙坦中2种N-亚硝胺类基因毒性杂质的检测。To develop an ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous quantitative analysis of two genotoxic impurities in Irbesartan, N-nitrosodimethylamine(NDMA) and N-nitrosodiethylamine(NDEA) were separated on a Agilent ZORBAX Eclipse Plus C18column(3.0 mm×100 mm, 1.8 μm) with mobile phase consisting of 0.1% formic acid solution and methanol under gradient elution. Atmospheric pressure chemical ionization, positive ion parallel reaction monitoring mode(APCI +PRM) mode was selected for detection. Good linearities were obtained for NDMA and NDEA in the concentration range of 0.225~1.5 ng/mL, and the limits of detection were 0.022 ng/mL and 0.044 ng/mL. The recoveries were 78%~104%. The method is sensitive and accurate, and can be used for the determination of two n-nitrosamines genotoxic impurities in Irbesartan.

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

分 类 号：R917[医药卫生—药物分析学]