UPLC-MS/MS法测定盐酸二甲双胍原料药及缓释片中的二甲胺

Determination of dimethylamine in Metformin hydrochloride raw materials and sustained-release tablets by UPLC-MS/MS

目的采用柱前衍生化超高效液相色谱-串联质谱法检测盐酸二甲双胍原料及缓释片中的痕量二甲胺。方法以2,4-二硝基氟苯为衍生化试剂,采用Agilent ZORBAX SB-C18色谱柱(50 mm×2.1 mm,1.8μm),以0.1%甲酸水溶液-乙腈为流动相,梯度洗脱,正离子(ESI+)模式下平行反应监测(PRM)方式检测。结果2.70~270.53 ng·mL^(-1)二甲胺与峰面积线性关系良好(r=0.9990);原料、缓释片的平均回收率分别为115.1%、111.2%,RSD分别为5.30%、4.90%(n=9);二甲胺的检测限为5.3×10^(-4)ng。9批原料和6批缓释片均检出二甲胺。结论所用方法灵敏度高,准确性好,可用于盐酸二甲双胍原料和制剂中二甲胺的痕量检查。

OBJECTIVE To establish a pre-column derivatization-UPLC-MS for the determination of trace amounts of dimethylamine in Metformin hydrochloride raw materials and sustained-release tablets.METHODS The separation was performed on an Agilent Zorbax SB-C18(50 mm×2.1 mm,1.8μm)column,with mobile phase consisting of 0.1%formic acid solution and acetonitrile by gradient elution;the detection was accomplished by ESI in the positive mode using multiple-reaction monitoring.RESULTS A good linear relationship was obtained between the peak areas and the concentrations of dimethylamine in the range from 2.70 to 270.53 ng·mL^(-1)(r=0.9990).The average recovery of raw materials was 115.1%with the RSD of 5.30%(n=9),and the average recovery of sustained-release tablets was 111.2%with the RSD of 4.90%(n=9).The detection limit of dimethylamine was 5.3×10^(-4)ng.Dimethylamine was detected in 9 batches of raw materials and 6 batches of sustained-release tablets.CONCLUSION The method is sensitive and accurate,and can be used for the determination of trace dimethylamine in metformin hydrochloride raw materials and preparations.