HPLC-MS/MS法测定注射用盐酸雷尼替丁中的N-亚硝基二甲胺  

Determination of N-nitrosodimethylamine in Ranitidine hydrochloride injection by HPLC-MS/MS

作　　者：姚永青 杨博涵 李洁 李茜 刘英 YAO Yongqing;YANG Bohan;LI Jie;LI Qian;LIU Ying(Henan Chemical Quality Evaluation and Control Engineering Technology Research Center,Henan Provincial Institute for Drug and Medical Device Control,Zhengzhou,Henan,450018 P.R.China)

机构地区：[1]河南省药品医疗器械检验院河南省化学药品质量评价与控制工程技术研究中心,河南郑州450018

出　　处：《华西药学杂志》2025年第2期175-177,共3页West China Journal of Pharmaceutical Sciences

基　　金：河南省重点研发与推广专项(科技攻关,编号:232102320288)。

摘　　要：目的采用HPLC-MS/MS测定注射用盐酸雷尼替丁中的遗传毒性杂质N-亚硝基二甲胺。方法采用ACE EXCEL3 C_(18)-AR色谱柱(100 mm×4.6 mm,3μm),以0.1%甲酸水溶液和0.1%甲酸的甲醇溶液为流动相,梯度洗脱,柱温40℃;质谱采用大气压化学电离源,正离子扫描模式,监测模式为多反应监测。结果N-亚硝基二甲胺0.4960~99.2015 ng·mL^(-1)与峰面积线性关系良好(r=0.9998),平均回收率97.90%,RSD=1.70%(n=9);3批样品中N-亚硝基二甲胺的含量为0.013~0.015μg·g^(-1)。结论所用方法简便快速、专属性强、准确度好、灵敏度高,可有效控制注射用盐酸雷尼替丁中的N-亚硝基二甲胺,同时为其他药物中N-亚硝基二甲胺的控制提供了参考。OBJECTIVE To determine genotoxic impurity N-nitrosodimethylamine in ranitidine hydrochloride for injection by HPLC-MS/MS.METHODS The analytes were separated on a ACE EXCEL3 C18-AR column(100 mm×4.6 mm,3μm).0.1%formic acid was used as mobile phase A,methanol containing 0.1%formic acid was used as mobile phase B,and the gradient elution method was used.The flow rate was set at 0.5 mL·min-1,with the column temperature of 40℃.Multiple reaction monitoring scanning was employed for the quantification with APCI source in positive mode.RESULTS The linearity of NDMA in the range of 0.4960-99.2015 ng·mL^(-1)was good(r=0.9998),and the average recovery was 97.90%with the RSD of 1.70%(n=9).The concentrations of NDMA in the 3 batches of samples were 0.013-0.015μg·g^(-1).CONCLUSION The new method is simple,accurate,sensitive,which can be used for the determination of NDMA in Ranitidine hydrochloride injection and provide reference for the control of NDMA in other drugs.

关 键 词：盐酸雷尼替丁 高效液相色谱质谱联用法 梯度洗脱 遗传毒性杂质 N-亚硝基二甲胺 多反应监测 

分 类 号：R917[医药卫生—药物分析学]