UPLC-MS/MS法测定维格列汀中4-二甲氨基吡啶  

Detection of 4-dimethylaminopyridine in vildagliptin by the UPLC-MS/MS method

作　　者：王玉如 刘晓敏 卢忠秋 兰公剑 WANG Yuru;LIU Xiaomin;LU Zhongqiu;LAN Gongjian(Nanjing Chia-Tai Tianqing Pharmaceutical Company,Jiangsu,Nanjing 210046,China)

机构地区：[1]南京正大天晴制药有限公司,江苏南京210046

出　　处：《中国医药科学》2023年第3期79-82,共4页China Medicine And Pharmacy

摘　　要：目的建立超高效液相色谱串联质谱法(UPLC-MS/MS)测定维格列汀中基因毒性杂质4-二甲氨基吡啶。方法采用Waters ACQUITY BEH HILIC(50 mm×2.1 mm,1.7μm)色谱柱;流动相为乙酸盐缓冲溶液(10 mmol/L乙酸铵溶液,乙酸调至pH 4.0)-乙腈(体积比10∶90);流速0.3 ml/min,柱温30℃;采用电喷雾离子源(ESI)正离子扫描,以监测模式为多反应监测模式(MRM),定量离子对为123.2→107.1(m/z)进行检测。结果4-二甲氨基吡啶浓度在0.55~10.98 ng/ml范围内与峰面积呈良好线性关系(r=0.9993);定量限为0.02 ng/ml;检出限为0.005 ng/ml;平均加样回收率为91.06%,RSD为1.25%(n=9)。结论本方法专属性强、灵敏度高、准确度好,可用于维格列汀原料药中4-二甲氨基吡啶的测定。Objective To detect 4-dimethylaminopyridin,a genotoxic impurity in vildagliptin,by the ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method.Methods Waters ACQUITY BEH HILIC(50 mm×2.1 mm,1.7μm)chromatographic column was used.The mobile phase was acetate buffer solution(10 mmol/L ammonium acetate solution,acetic acid adjusted to pH 4.0)-acetonitrile(volume ratio was 10∶90).The flow speed was 0.3 ml/min,and the column temperature was 30℃.Electron Spray Ionization(ESI)was used for positive ion scanning,and the monitoring mode was multi-reaction monitoring(MRM)mode,and the quantitative ion pair was 123.2→107.1(m/z)for detection.Results The concentration of 4-dimethylaminopyridine showed a good linear relationship with the peak area in the range of 0.55~10.98 ng/ml(r=0.9993).The quantitative limit was 0.02 ng/ml,and the detection limit was 0.005 ng/ml.The average recovery rate was 91.06%and the RSD was 1.25%(n=9).Conclusion The method is highly specific,sensitive and accurate,which can be used for the detection of 4-dimethylaminopyridine in the vildagliptin API.

关 键 词：维格列汀 基因毒性杂质 4-二甲氨基吡啶 超高效液相色谱-质谱联用 

分 类 号：R969[医药卫生—药理学]