采用不同方法评估二甲双胍原料药及其制剂中N-亚硝胺二甲胺含量  

Different methods to evaluate the content of N-nitrosodimethylamine in metformin and its preparations

作　　者：张岩琛 刘晓强 黄海伟[2] 刘旻虹 汪嘉丽 ZHANG Yan-chen;LIU Xiao-qiang;HUANG Hai-wei;LIU Min-hong;WANG Jia-li(Changzhou Food、Drug and Fibre Supervision and Inspection Center,Changzhou 213002,China;National Institutes for Food and Drug Control,Beijing 102629,China)

机构地区：[1]常州市食品药品纤维质量监督检验中心,常州213002 [2]中国食品药品检定研究院,北京102629

出　　处：《药物分析杂志》2021年第6期1036-1040,共5页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:探讨采用不同方法评估二甲双胍原料药及其制剂中N-亚硝胺二甲胺含量。方法:分别采用LC-MS/MS法及GC-MS/MS法测定4个厂家的二甲双胍固体制剂及其所用二甲双胍原料药中N-亚硝胺二甲胺含量,比较结果差异并分析制剂工艺的NDMA增量。结果:对未检出的样品(原料或制剂),2种检测方法结果无差异。对检出的样品,LC-MS/MS检测结果均高于GC-MS/MS检测结果0.003μg·g^(-1)左右。生产企业E制剂工艺增量约为0.03μg·g^(-1),且不同批次差异较大。生产企业F制剂工艺增量为0,且不同批次较稳定。生产企业G、H制剂工艺增量约为0.009μg·g^(-1),且不同批次较稳定。结论:LC-MS/MS法及GC-MS/MS法测定二甲双胍原料药及其固体制剂中NDMA含量无明显差异,辅料中若含有亚酸硝盐可导致制剂中产生NDMA。Objective:To evaluate the content of N-nitrosodimethylamine(NDMA)in metformin and its preparation by different methods.Methods:LC-MS/MS and GC-MS/MS methods were used to determine the content of NDMA in the solid preparations of metformin from four manufacturers and their metformin APIs.The difference of the results was compared and the NDMA increment of the preparation process was analyzed.Results:There was no difference between the two methods when no N-nitrosodimethylamine was detected in the samples(raw materials or preparations).For the positive samples,the results of LC-MS/MS were all about 0.003μg·g^(-1)higher than those of GC-MS/MS.The process increment was about 0.03μg·g^(-1)for samples from company E,and there were great differences among different batches.There were no process increment for samples from company F,and different batches were stable.The process increment for samples from companies G and H was about 0.009μg·g^(-1),and different batches were stable.Conclusion:There was no significant difference between LC-MS/MS and GC-MS/MS in the determination of NDMA in metformin APIs and their solid preparations.If there are nitrates in the excipients,NDMA can be produced in the preparations.

关 键 词：液质联用法 气质联用法 二甲双胍 N-亚硝基二甲胺 制剂工艺 

分 类 号：R917[医药卫生—药物分析学]