高效液相色谱-串联质谱法同时测定3种N-亚硝胺类基因毒性杂质  

Simultaneous Determination of Three Genotoxic Nitrosamine Impurities in Irbesartan by HPLC-MS/MS

作　　者：徐艳梅 韩彬 郝丽娟 高燕霞 XU Yanmei;HAN Bin;HAO Lijuan;GAO Yanxia(Hebei Institute for Drug and Medical Device Control,Shijiazhuang 050011,China)

机构地区：[1]河北省药品医疗器械检验研究院,石家庄050011

出　　处：《医药导报》2022年第11期1672-1676,共5页Herald of Medicine

基　　金：河北省中央引导地方科技发展资金项目(216Z4802G)。

摘　　要：目的建立高效液相色谱-串联质谱(HPLC-MS/MS)法同时测定厄贝沙坦原料药中3种N-亚硝胺类基因毒性杂质(N-亚硝基乙基异丙胺、N-亚硝基二异丙胺和N-亚硝基二丁胺)。方法采用Agilent 120 PFP色谱柱(100 mm×2.1 mm,2.7μm),流动相为甲醇(A)-0.1%甲酸(B),梯度洗脱,流速0.4 mL·min^(-1),柱温40℃;采集模式为正离子,监测模式为质谱多反应监测。结果N-亚硝基乙基异丙胺、N-亚硝基二异丙胺和N-亚硝基二丁胺在各自线性范围内线性关系良好(R^(2)≥0.9997),平均加样回收率分别为95.13%,92.00%和93.96%,RSD分别为4.22%,3.25%和3.60%。结论该方法简单、快速,灵敏度高,准确性强,重复性好,可用于厄贝沙坦原料药中N-亚硝胺类基因毒性杂质的检测。Objective To establish an HPLC-MS/MS method for the determination of three genotoxic N-nitrosamine impurities(N-nitrosoethyl isopropylamine,N-nitroso diisopropylamine and N-nitroso dibutylamine)in irbesartan simultaneously.Methods Agilent120 PFP column(100 mm×2.1 mm,2.7μm)was applied.The mobile phase was methanol(A)-0.1%formic acid(B)at a flow rate of 0.4 mL·min^(-1) with gradient elution.The column temperature was set as 40℃.And positive ion was used as the acquisition mode.The multiple reaction monitoring(MRM)was used as the monitoring mode.Results N-nitrosoethylisopropylamine,N-nitrosodiisopropylamine and N-nitrosodibutylamine had a good linear relationship within their respective linear ranges(R^(2)≥0.9997).The average recoveries were 95.13%,92.00%and 93.96%,respectively;and RSD were 4.22%,3.25%and 3.60%,respectively.Conclusion The method is simple,rapid,sensitive,accurate,and reproducible,which can be used for the detection of N-nitrosamine genotoxic impurities in irbesartan.

关 键 词：厄贝沙坦 基因毒性杂质 N-亚硝基乙基异丙胺 N-亚硝基二异丙胺 N-亚硝基二丁胺 

分 类 号：R972[医药卫生—药品] R927.1[医药卫生—药学]