采用改良LC-MS/MS法评估枸橼酸铋雷尼替丁及其制剂中NDMA含量  

Content Evaluation of NDMA in Ranitidine Bismuth Citrate and its Preparations by a Modified LC-MS/MS Method

作　　者：张岩琛 刘晓强 黄海伟[2] 刘旻虹 余洁 Zhang Yanchen;Liu Xiaoqiang;Huang Haiwei;Liu Minhong;Yu Jie(Changzhou Food,Drug and Fiber Supervision and Inspection Center,Jiangsu Changzhou 213002,China;National Institutes for Food and Drug Control)

机构地区：[1]常州市食品药品纤维质量监督检验中心,江苏常州213002 [2]中国食品药品检定研究院

出　　处：《中国药师》2021年第7期272-276,共5页China Pharmacist

摘　　要：目的:采用改良LC-MS/MS法评估枸橼酸铋雷尼替丁及其制剂中N-亚硝基二甲胺(NDMA)含量。方法:使用Waters Atlantis T3-C_(18)柱(150 mm×4.6 mm,5μm),流动相A为0.1%甲酸的水溶液,流动相B为0.1%甲酸的乙腈溶液,流速为0.9ml·min^(-1),梯度洗脱,柱温为40℃,进样量为20μl。采用大气压化学电离源(APCI),选择反应检测扫描模式(MRM),以75.20→43.05为定量离子,75.20→58.10为定性离子测定盐酸雷尼替丁、枸橼酸铋雷尼替丁、枸橼酸铋钾原料药、枸橼酸铋雷尼替丁胶囊以及复方雷尼替丁制剂中NDMA含量。结果:分别考察了3个生产企业的制剂、其原料药中的NDMA含量以及制剂生产过程中3个批次的NDMA增量,数值不一,其中E企业的增量不明显,F企业的增量在限度的50%70%,G企业的增量在限度的50%150%。结论:枸橼酸铋雷尼替丁制剂工艺过程中可能产生NDMA,导致制剂中NDMA含量增加。各生产企业应对自己自身制剂工艺导致的NDMA增量进行工艺评估,必要时停产或进行工艺优化。Objective:To evaluate the content of NDMA in ranitidine bismuth citrate and its preparations by a modified LC-MS/MS method.Methods:A Waters Atlantis T3-C_(18)(150 mm×4.6 mm,5μm)column was adopted for the determination with gradient elution.Mobile phase A was 0.1%formic acid in water,and mobile phase B was 0.1%formic acid in acetonitrile at a flow rate of 0.9 ml·min^(-1).The column temperature was 40℃,and the injection volume was 20μl.APCI source and MRM mode were used for the determination of NDMA in ranitidine hydrochloride,bismuth citrate ranitidine,bismuth potassium citrate,bismuth citrate ranitidine capsules and compound ranitidine preparations with 75.20→43.05 as the quantitative ions and 75.20→58.10 as the qualitative ions.Results:The preparations from three manufacturing companies,NDMA content in the raw materials,and NDMA increments of three batches in the production process of the preparations were investigated.The increase of company E was not obvious,while the increase of company F was 50%-70%of the limit,and that of company G was 50%-150%of the limit.Conclusion:NDMA content in the preparations may be increased by the preparation process of ranitidine bismuth citrate preparations.Each manufacturer should conduct process evaluation on the increment of NDMA caused by its own preparation process,and stop production or optimize the process if necessary.

关 键 词：液质联用 枸橼酸铋雷尼替丁 制剂工艺 N-亚硝基二甲胺 

分 类 号：TQ460.72[医药卫生—药物分析学]