UPLC-APCI-MS/MS法测定二甲双胍格列吡嗪片中N-亚硝基二甲胺  

Determination of N-nitrosodimethylamine in metformin hydrochloride and glipizide tablets by UPLC-APCI-MS/MS

作　　者：章为 王晓菲 易必新 陈鸿玉 刘雁鸣 李晓燕 ZHANG Wei;WANG Xiao-fei;YI Bi-xin;CHEN Hong-yu;LIU Yan-ming;LI Xiao-yan(Hunan Institute for Drug Control(Hunan Pharmaceutical Excipients Testing and Inspection Center),Changsha 410001;Hunan Pharmaceutical Quality Evaluation Engineering and Technology Research Center,Changsha 410001;Xiangya School of Pharmaceutical Sciences,Centrol South University,Changsha 410013)

机构地区：[1]湖南省药品检验研究院(湖南药用辅料检验检测中心),长沙410001 [2]湖南省药品质量评价工程技术研究中心,长沙410001 [3]中南大学湘雅药学院,长沙410013

出　　处：《中南药学》2020年第9期1568-1571,共4页Central South Pharmacy

基　　金：湖南省自然科学基金项目(No.2020JJ9003)。

摘　　要：目的建立超高效液相色谱-大气压化学离子源-三重四极杆质谱联用法(UPLC-APCI-MS/MS)测定二甲双胍格列吡嗪片中N-亚硝基二甲胺(NDMA)含量。方法色谱柱为ACE EXCEL 3 C18-AR(4.6 mm×150 mm,3μm),以0.1%甲酸的水溶液为流动相A,以0.1%甲酸的甲醇溶液为流动相B,梯度洗脱,正离子多反应监测模式。结果NDMA在1.0699~106.99 ng·mL^-1与峰面积线性关系良好,低、中、高浓度平均回收率在87.95%~90.3%。检测限为0.27 ng·mL^-1,定量限为0.89 ng·mL^-1。共检测62批二甲双胍格列吡嗪片样品,15批次样品未检出NDMA;47批次检出NDMA(6.8~41.9 ng·g^-1),均在NDMA的限度规定内。结论本方法操作简便,灵敏度高,准确度好,可用于二甲双胍格列吡嗪片中NDMA的测定。Objective To determine N-nitrosodimethylame (NDMA) in metformin hydrochloride and glipizide tablets by UPLC-APCI-MS/MS.Methods ACE EXCEL 3 C18-AR (4.6 mm×150 mm,3 μm) column was used,with gradient elution of water (0.1% formic acid) as mobile A and methanol (0.1% formic acid) as mobile B,monitored by positive MRM mode.Results The linear calibration curve of NDMA was obtained over 1.0699~106.99 ng·mL-1.The low,middel,and high concentration recoveries were 87.95%~90.3%.The LOD was 0.27 ng·mL-1 and LOQ was 0.89 ng·mL-1.Totally 62 of batches samples were detected:NDMA was not detected in 15 samples,but was detected in the rest samples with content ranging 6.8~41.9 ng·g-1,none exceeding the limit of NDMA.Conclusion The method is simple,sensitive and accurate,and can be used for the determination of NDMA in metformin hydrochloride and glipizide tablets.

关 键 词：N-亚硝基二甲胺 UPLC-APCI-MS/MS 二甲双胍格列吡嗪片 遗传毒性杂质 

分 类 号：R927[医药卫生—药学]