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目的建立LC-MS/MS测定复方制剂中二甲双胍、吡格列酮及其活性代谢产物酮基吡格列酮(M-Ⅲ)、羟基吡格列酮(M-Ⅳ)的浓度。方法 吡格列酮样品以乙腈沉淀蛋白,美金刚为内标,采用Ultimate C18(2.1 mm×150 mm,5μm)色谱柱,以乙腈-5 mmol·L-1醋酸铵(55∶45)为流动相,流速为0.3 mL·min-1;二甲双胍样品以乙腈沉淀蛋白,卡马西平为内标,采用Ultimate XB-CN色谱柱(2.1 mm×150 mm,5μm),以乙腈-0.1%甲酸水溶液(内含10 mmol·L-1乙酸铵)(73∶27);流速为0.3mL·min-1,柱温:35℃。结果 吡格列酮、M-Ⅲ、M-Ⅳ线性范围分别为5.08～1 016.0μg·L-1,2.45～490.0μg·L-1,4.20～840.0μg·L-1,定量下限分别为5.08、2.45、4.20μg·L-1,线性良好。提取回收率均大于89.67%,日内日间RSD均小于15%。结论 本法测定准确、简便可靠,适用于复方二甲双胍吡格列酮片的人体药动学研究。
Objective To establish a LC-MS / MS method for the determination of metformin, pioglitazone and their active metabolites ketopaglitazone (M-Ⅲ) and hydroxy pioglitazone (M-Ⅳ) in compound preparations. Methods The samples of pioglitazone were precipitated with acetonitrile and memantine as internal standard. The mobile phase was acetonitrile (5 mmol·L -1) ammonium acetate (55:45) with the mobile phase of Ultimate C18 (2.1 mm × 150 mm, 5 μm) (0.3 mL · min-1). The metformin sample was precipitated with acetonitrile and carbamazepine as internal standard. The column was eluted with Ultimate XB-CN (2.1 mm × 150 mm, 5 μm) mmol·L -1 ammonium acetate) (73:27); the flow rate was 0.3 mL · min -1 and the column temperature was 35 ° C. Results The linear ranges of pioglitazone, M-Ⅲ and M-Ⅳ were 5.08-1 016.0μg · L-1 and 2.45-590.0μg · L-1 and 4.20-840.0μg · L-1 respectively. The lower limits of quantitation were 5.08 and 2.45 respectively. 4.20μg · L-1, good linearity. The extraction recovery rate was more than 89.67%, day RSD were less than 15%. Conclusion The method is accurate, simple and reliable and is suitable for the study of human pharmacokinetics of the compound metformin pioglitazone tablets.