盐酸二甲双胍中基因毒杂质N-亚硝基二甲胺检测方法的建立  

Method development for determination of genotoxic impurities N-dimethylnitrosamine in metformin hydrochloridey HPLC-MS/MS

作　　者：张龙浩 于颖洁 袁松[1] 周露妮 黄海伟[1] 何兰[1] ZHANG Long-hao;YU Ying-jie;YUAN Song;ZHOU Lu-ni;HUANG Hai-wei;HE Lan(National Institutes for Food and Drug Control,NMPA Key Labboraltory for Qualiy Research and Evaluation of Chemical Drugs,Beijing 102629,China)

机构地区：[1]中国食品药品检定研究院国家食品药品监督管理局化学药品研究与评价重点实验室,北京102629

出　　处：《药物分析杂志》2022年第7期1195-1200,共6页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立高效液相色谱-三重四极杆质谱(HPLC-MS/MS)法测定盐酸二甲双胍原料药和制剂中N-亚硝基二甲胺(NDMA)。方法:采用Phenomenex ACE Excel 3 C_(18)-AR色谱柱(100 mm×4.6 mm,3μm),以0.1%甲酸水-0.1%甲酸甲醇为流动相,梯度洗脱,流速0.5 mL·min^(-1),柱温40℃,进样量5μL;质谱离子化方式为APCI,正离子模式,多反应监测(MRM),NDMA的定量离子对为m/z 75.0→43.0,定性离子对为m/z 75.0→58.0。结果:NDMA质量浓度在1~100 ng·mL^(-1)范围内,线性关系良好;检测限为0.25 ng·mL^(-1);30批样品的测定结果NDMA的含量为0~0.46μg·g^(-1)。结论:本方法可用于测定盐酸二甲双胍原料药和制剂中NDMA含量。Objective:To establish a high-performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-MS/MS)method for the determination of N-dimethylnitrosamine(NDMA)in metformin hydrochloride drug substance and its products.Methods:The drugs were separated by Phenomenex ACE Excel 3 C_(18)-AR column(100 mm×4.6 mm,3μm)with the mobile phases of 0.1%formic acid-water and 0.1%formic acid-methanol in gradient elution.The flow rate was 0.5 mL·min^(-1),and the column temperature was 40℃.The injection volume was 5μL.The electrospray ionization source with positive ion mode was used for analyzing drugs in the multiple reaction monitoring mode.The transitions of m/z 75.0→43.0 and m/z 75.0→58.0 were determined as quantitative and qualitative ions respectively.Results:The linearity range of NDMA was 1^(-1)00 ng·mL^(-1)and the detection limit was 0.25 ng·mL^(-1).The contents of NDMA in 30 batches were 0-0.46μg·g^(-1).Conclusion:This method can be used for the quantitation of NDMA in metformin hydrochloride drug substance and its products.

关 键 词：基因毒杂质 N-亚硝基二甲胺(NDMA) 盐酸二甲双胍 抗高血糖药物 液质联用 杂质测定 定量分析 

分 类 号：R917[医药卫生—药物分析学]