高效液相色谱-串联质谱法同时检测厄贝沙坦原料药及其片剂中3种N-亚硝胺类基因毒性杂质  

Simultaneous detection of 3 N-nitrosamine genotoxic impurities in irbesartan

作　　者：徐艳梅 韩彬 闫凯 高燕霞 XU Yan-mei;HAN Bin;YAN Kai;GAO Yan-xia(Hebei Institute for Drug Control,Shijiazhuang 050000,China)

机构地区：[1]河北省药品医疗器械检验研究院,石家庄050000

出　　处：《药物分析杂志》2021年第4期720-725,共6页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立厄贝沙坦原料及其片剂中3种N-亚硝胺类基因毒性杂质N-亚硝基二甲胺(NDMA)、N-亚硝基二乙胺(NDEA)和N-亚硝基-N-甲基-4-氨基丁酸(NMBA)的高效液相色谱-串联质谱(LC-MS/MS)检测方法。方法:采用C18色谱柱,以甲醇-水(0.1%甲酸)为流动相,梯度洗脱,流速0.3 mL·min^(-1),以APCI源正离子多反应监测(MRM)模式,进行MS/MS检测。结果:3种N-亚硝胺类基因毒性杂质在各自的线性范围内具有良好的线性关系,相关系数r≥0.9977;NDMA、NDEA和NMBA加样回收率分别为102.1%、98.1%和102.6%;检测下限和定量下限的范围分别为0.08~0.31 ng·mL^(-1)和0.27~1.03 ng·mL^(-1)。检测4批原料药及3批厄贝沙坦制剂,均未检出NDMA、NDEA和NMBA。结论:该方法可用于检测厄贝沙坦原料及制剂中的NDMA、NDEA和NMBA。Objective:To establish a high performance liquid chromatography-tandem mass spectrometry method for simultaneous detection of N-nitrosamine genotoxic impurities named N-nitrosodimethylamine(NDMA),N-nitrosodiethylamine(NDEA)and N-nitroso-N-methyl-4-aminobutyric acid(NMBA)in irbesartan and its tablets.Methods:NDMA,NDEA and NMBA were separated on a C18 chromatographic column with methanol and 0.1%formic acid as mobile phase under gradient elution at a flow rate of 0.3 mL·min^(-1).Mass data acquisition was performed with multiple reaction monitoring(MRM)in positive APCI mode.Results:All the 3 marker substances showed good linearity(r>0.9977)in the test ranges.The average recoveries of NDMA,NDEA and NMBA were 102.1%,98.1%,and 102.6%,respectively.The LODs and LOQs for the compounds ranged from 0.08 to 0.31 ng·mL^(-1)and from 0.27 to 1.03 ng·mL^(-1),respectively.Four batches of irbesartan and three batches of its tablets were tested,and NDMA,NDEA and NMBA were not detected.Conclusion:The method can be used to detect NDMA,NDEA and NMBA in irbesartan and its tablets.

关 键 词：液相色谱-质谱法 厄贝沙坦 N-亚硝基二甲胺 N-亚硝基二乙胺 N-亚硝基-N-甲基-4-氨基丁酸 血管紧张素Ⅱ受体拮抗剂 基因毒性杂质 安全监测 

分 类 号：R917[医药卫生—药物分析学]