LC-MS/MS法定量检测恩格列净原料药中杂质的含量  

Related substances in empagliflozin determined by LC-MS/MS

作　　者：周浩[1,2] 孟繁华[2] 孙磊[2] 乔善义[2] 张国刚[1] 

机构地区：[1]沈阳药科大学中药学院,沈阳110016 [2]军事医学科学院毒物药物研究所植物化学室,北京100850

出　　处：《国际药学研究杂志》2016年第4期753-756,共4页Journal of International Pharmaceutical Research

摘　　要：目的建立一种LC-MS/MS法用于定量检测恩格列净原料药中杂质X（简称EPLZ-X）的含量。方法采用Thermo BDS C18（4.6 mm×100 mm,2.4μm）色谱柱,以乙腈-水（75∶25,V/V）为流动相,流速0.7 ml/min。质谱扫描方式选用正离子模式,用于定量的多反应监测（MRM）离子对为m/z 785→m/z 475（CE为43 V）和m/z 785→m/z 418（CE为50 V）。结果在0.5~100.6 ng/ml范围内线性关系良好,低、中和高浓度质控样品的日内精密度分别为5.9%、5.4%和7.9%。日间精密度分别为6.3%、11.8%和10.7%,加样回收率分别为105.1%、109.8%、102.6%,最低定量下限为0.5 ng/ml。结论使用此法成功测定了3批原料药中该杂质的含量,均符合要求（不得超过60×10-6g）。本法专属性强,灵敏度高,可用于其他批次样品的分析。Objective To develop a LC-MS/MS method for the quantification of empagliflozin（EPLZ）impurity X（EPLZ-X）in EPLZ pharmaceutical product. Methods Isocratic chromatographic separation was performed on a Thermo BDS C18column（4.6 mm ×100 mm,2.4mm）. The mobile phase consisting of acetonitrile-water（75∶25,V/V）was eluted at a flow rate of 0.7 ml/min. ESI source was applied and operated in the positive ion mode. multiple reaction monitoring（MRM）mode with the transitions of m/z 785→ m/z 475 and m/z 785→ m/z 418 were used to quantify the EPLZ-X. Results The method was linar in the concentration range from 0.5 to 100.6ng/ml. The limit of quantification was 0.5 ng/ml. The intra-and inter-day precision values were both below 11.8%,and accuracy was within ±2.5% in all quality control samples. The average recovery was 105.1%、109.8% and 102.6%,respectively. Conclusion The method provides a sensitive and specific means for the determination of EPLZ-X in EPLZ pharmaceutical substances and completely meets the requirement of European Medicines Evaluation Agency（EMEA）（a limit of not more than 60×10-6g for the mutagenic impurity EPLZ-X）.

关 键 词：LC-MS/MS 恩格列净 杂质 含量 

分 类 号：R927.2[医药卫生—药学] O657.63[理学—分析化学]