基于UHPLC-Orbitrap HRMS的盐酸二甲双胍及其片剂中N-亚硝基二甲胺的测定  

UHPLC-Orbitrap HRMS Method for Determination of NDMA in Metformin Hydrochloride and Its Tablets

作　　者：吴静芳[1] 李玮玲[1] WU Jing-fang;LI Wei-ling(Guangzhou Institute for Drug Control,Guangdong Guangzhou 510160,China)

机构地区：[1]广州市药品检验所,广东广州510160

出　　处：《广州化工》2024年第16期77-79,111,共4页GuangZhou Chemical Industry

基　　金：广州市市场监督管理局科技项目(2023KJ27)。

摘　　要：建立了测定盐酸二甲双胍及其片剂中N-亚硝基二甲胺(NDMA)的超高效液相色谱-静电场轨道阱高分辨质谱法(UHPLC-Orbitrap HRMS)。采用Waters XSelect CSH C18色谱柱(150 mm×3.0 mm,2.5μm),以0.1%甲酸水溶液-0.1%甲酸甲醇溶液为流动相,梯度洗脱;大气压化学电离源(APCI),正离子模式,产物离子扫描。结果显示NDMA在1~100 ng/mL范围内线性关系良好,检测限和定量限分别为0.3 ng/mL和0.9 ng/mL,原料药和片剂的平均加标回收率分别为101.4%和98.5%。本方法专属性好、灵敏度和准确度高,适用于盐酸二甲双胍及其片剂中痕量遗传毒性杂质NDMA的检查与控制。An UHPLC-Orbitrap HRMS method was established for determination of NDMA in metformin hydrochloride and its tablets.The separation was carried out on a Waters XSelect CSH C 18 column(150 mm×3.0 mm,2.5μm)by linear gradient elution using 0.1%formic acid and 0.1%formic acid methanol as mobile phase.The orbitrap mass spectrometer was coupled with the atmospheric pressure chemical ionization source(APCI).The positive ion product ion scan mode was adopted.Linear calibration was established for NDMA in the range of 1 to 100 ng/mL.The limit of quantification(LOQ)was 0.9 ng/mL and the limit of detection(LOD)was 0.3 ng/mL.The average recoveries were 101.4%and 98.5%of metformin hydrochloride and its tablets.The established UHPLC-Orbitrap HRMS method was proved to be suitable for the determination of NDMA in metformin hydrochloride and its tablets.

关 键 词：UHPLC-Orbitrap HRMS N-亚硝基二甲胺 遗传毒性杂质 盐酸二甲双胍 

分 类 号：R917[医药卫生—药物分析学]