GC-MS/MS法测定缬沙坦氨氯地平片(Ⅰ)中亚硝胺类基因毒性杂质  

Determination of N-nitrosamines Genotoxic Impurities in VaIsartan and Amlodipine Tablets(Ⅰ)by GC-MS/MS

作　　者：林秋婕 傅俊 陈露 许文佳 陈赞民 Lin Qiujie;Fu Jun;Chen Lu;Xu Wenjia;Chen Zhanmin(Hainan Inspection and Testing Research Institute,Haikou 570216,China)

机构地区：[1]海南省检验检测研究院,海南海口570216

出　　处：《广东化工》2024年第17期158-160,共3页Guangdong Chemical Industry

摘　　要：建立气相色谱-串联质谱法(GC-MS/MS)同时测定缬沙坦氨氯地平片(Ⅰ)中2个基因毒性杂质N-亚硝基二甲胺(NDMA)和N-亚硝基二乙胺(NDEA)的含量。采用Agilent DB-WAXms(30 m×0.25 mm,0.25μm)毛细管柱进行分离,程序升温,载气流速3 mL/min,进样体积3μL。质谱分析采用电子轰击(EI)离子源,多反应监测模式,外标法定量。结果表明,NDMA、NDEA及相邻色谱峰之间的分离度好,NDMA浓度在0.25 ng/mL~100 ng/mL、NDEA浓度在0.1 ng/mL~50 ng/mL范围内,线性关系良好。NDMA和NDEA的定量限分别为0.2 ng/mL和0.3 ng/mL,检测限分别为0.07 ng/mL和0.1 ng/mL。精密度、重复性、稳定性试验的RSD均小于8%,NDMA的平均回收率为91.2%~98.1%,NDEA的平均回收率为89.9%~96.3%,本方法简便快捷,专属性强,灵敏度、准确度高、线性范围宽,可用于测定缬沙坦氨氯地平片(Ⅰ)中NDMA和NDEA的含量。s:A gas chromatography-tandem mass spectrometry(GC-MS/MS)method was established for the determination of two genotoxic impurities,N-nitrosodimethylaminen(NDMA)and N-nitrosodiethylaminen(NDEA),in valsartan and amlodipine tablets(I).The separation was carried out on an Agilent DB-WAXms(30 m×0.25 mm,0.25μm)capillary column with programmed temperature increase,carrier gas flow rate of 3 mL/min and injection volume of 3μL.The mass spectrometry analysis was performed using an electron bombardment(EI)ion source in multiple reaction monitoring(MRM)mode,and quantified by external standard method.The results showed that the separation between NDMA,NDEA and adjacent peaks was good,and the linearity was good in the ranges of 0.25 ng/mL~100 ng/mL for NDMA and 0.1 ng/mL~50 ng/mL for NDEA.The limits of quantification(LOQ)for NDMA and NDEA were 0.2 ng/mL and and 0.3 ng/mL respectively,and the limits of detection(LOD)were 0.07 ng/mL and The RSD of precision,reproducibility and stability tests were less than 8%,and the average recoveries were 91.2%~98.1%for NDMA and 89.9%~96.3%for NDEA.The method is sensitive,exclusive,with high recovery,wide linear range,easy and fast to operate,and can be used for the determination of NDMA and NDEA in valsartan and amlodipine tablets(Ⅰ).

关 键 词：气相色谱-串联质谱法 基因毒性杂质 N-亚硝基二甲胺:N-亚硝基二乙胺 缬沙坦氨氯地平片(Ⅰ) 

分 类 号：R917[医药卫生—药物分析学]