HPLC-MS/MS法测定西咪替丁片中11种N-亚硝胺类基因毒性杂质  

Determination of 11 N-nitrosamine Impurities in Cimetidine Tablets by HPLC-MS/MS

作　　者：李钰鑫 扈麟 李晓燕 郑金凤 马晓宁 李帅 陈鸿玉 刘雁鸣 文庆 Li Yuxin;Hu Lin;Li Xiaoyan;Zheng Jinfeng;Ma Xiaoning;Li Shuai;Chen Hongyu;Liu Yanming;Wen Qin(Hunan Institute for Drug Control and Texting,Changsha 410001,China;NMPA Key Laboratory for Pharmaceutical Excipients Engineering,Technology Research,Changsha 410001,China;Hunan Drug Inspection Center,Changsha 410001,China)

机构地区：[1]湖南省药品检验检测研究院,湖南长沙410001 [2]国家药品监督管理局药用辅料工程技术研究重点实验室,湖南长沙410001 [3]湖南省药品审核查验中心,湖南长沙410001

出　　处：《广东化工》2024年第17期152-154,共3页Guangdong Chemical Industry

基　　金：湖南省自然科学基金科药联合基金项目(2024JJ8164)。

摘　　要：目的:建立高效液相色谱-串联质谱法(HPLC-MS/MS)同时测定西咪替丁片中11种N-亚硝胺类基因毒性杂质(N-亚硝基二甲胺、N-甲基-N-亚硝苯胺、N-亚硝基二乙醇胺、(2S)-N-亚硝基降烟碱、N-亚硝基二正丙胺、N-亚硝基吗啉、N-亚硝基哌啶、N-亚硝基二正丁胺、N-亚硝基二异丙胺、N-亚硝基-N-乙基异丙胺、N-亚硝基二乙胺)。方法采用ACE EXCEL 3 C18-AR色谱柱(4.6 mm×150 mm,3μm),以0.1%甲酸溶液(A)-甲醇(B)为流动相,梯度洗脱,流速0.8 mL·min^(-1),离子源为APCI离子源,以正离子模式采集。结果:11种N-亚硝胺类基因毒性在1 ng·mL^(-1)~500 ng·mL^(-1)范围内线性关系良好,回收率在80.81%~105.13%,RSD均小于4.0%。结论:该方法操作简单、灵敏度高、重现性好,可用于西咪替丁片中11种N-亚硝胺类基因毒性杂质的质量控制。Objective:To determine 11 N-nitrosamine impurities in Cimetidine tablets by HPLC-MS/MS.Methods The separation of impurities was performed by ACE EXCEL3 C18-AR(4.6 mm×250 mm,3μm)with the mobile phase 0.1%formic acid solution(A)-methanol solution(B)by gradient at a flow rate was 0.8 mL·min^(-1).Multiple reaction monitoring was performed on a triple mass spectrometer equipped with an APCI source in the positive mode.Results Under the selected conditions,the calibration curves were in good linearty at 1 ng∙mL^(-1)~500 ng∙mL^(-1) for 11 N-nitrosamine impurities.The recoveries were within 80.81%~105.13%with RSD under 4.0%.Conclusion The present method has the advantages of simple operation,highly sensitive and good reproducibility,and can simultaneously determine 11 N-nitrosamine impurities in ranitidine hydrochloride capsules.

关 键 词：西咪替丁片 N-亚硝胺 基因毒性杂质 

分 类 号：R917[医药卫生—药物分析学]