LC-MS/MS法测定盐酸二甲双胍缓释片中N-亚硝基二甲胺及其产生原因初探  

Determination of N-Nitrosodimethylamine in Metformin Hydrochloride Sustained-release Tablets by LC-MS/MS and Preliminary Study on Its Causes

作　　者：张一平 鲍梦娟 贾永娟 夏学军[1,2] ZHANG Yiping;BAO Mengjuan;JIA Yongjuan;XIA Xuejun(Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050;Beijing Key Lab.of Drug Delivery Technology and Novel Formulations,Beijing 100050;Beijing Harmony Health Medical Diagnostic Co.,Ltd.,Beijing 100176)

机构地区：[1]中国医学科学院北京协和医学院药物研究所,北京100050 [2]药物传输技术及新型制剂重点实验室,北京100050 [3]北京和合医学诊断技术股份有限公司,北京100176

出　　处：《中国医药工业杂志》2021年第11期1504-1509,共6页Chinese Journal of Pharmaceuticals

摘　　要：建立了液相色谱串联质谱(LC-MS/MS)法测定盐酸二甲双胍(1)缓释片中N-亚硝基二甲胺(NDMA)的含量,对其进行方法学验证并考察1缓释片、1原料药和1缓释片中辅料在多种破坏条件下NDMA的产生情况。结果显示,各项方法学考察结果均良好。在光照条件下,1缓释片的辅料和1缓释片中NDMA均有所增加;在碱性条件和氧化条件下,1原料药、1缓释片的辅料和1缓释片中NDMA均有所增加。1缓释片中的NDMA可能是由于在缓释片的制备工艺或贮存过程中,原料药自身、原料药与辅料之间以及不同辅料之间的相互作用产生的,因此在生产和贮存过程中需注意避免光照、强碱性和氧化条件。A LC-MS/MS method was established to determine the content of N-nitrosodimethylamine(NDMA)in metformin hydrochloride(1)sustained-release tablets.The methodologies were validated and used and used to investigate the NDMA formation in 1 sustained-release tablets,the bulk drug and the excipients of 1 sustained-release tablet under various stress conditions.The results of various methodological investigations were good.The contents of NDMA in 1 sustained-release tablets and its excipients increased under light condition.And under the alkaline and oxidative conditions,the contents of NDMA increased in the bulk drug,1 sustained-release tablet excipients and 1 sustained-release tablets.The formation of NDMA in 1 sustained-release tablets might be due to the interactions between the drug substance itself,the drug substance and excipients,as well as different excipients during the processes of preparation and storage.Therefore,in the process of production and storage,care should be taken to avoid light,strong alkaline and oxidizing conditions.

关 键 词：液相色谱串联质谱 N-亚硝基二甲胺 基因毒性杂质 盐酸二甲双胍缓释片 

分 类 号：R917[医药卫生—药物分析学]