LC-MS/MS测定复方二甲双胍、吡格列酮和吡格列酮活性代谢产物的浓度  

Determination of Metformin,Pioglitazone and Active Metabolites of Pioglitazone in Human Plasma by HPLC-MS/MS

作　　者：李颖慧[1] 彭克垄[1] 杨春[1] 尹春萍[1] 吕永宁[2] 刘亚妮[2] 翟学佳[2] 郑恒[3] 

机构地区：[1]华中科技大学同济医学院药学院,武汉430030 [2]华中科技大学同济医学院附属协和医院药剂科,武汉430030 [3]华中科技大学同济医学院附属同济医院药剂科,武汉430030

出　　处：《中国药学杂志》2013年第13期1103-1108,共6页Chinese Pharmaceutical Journal

摘　　要：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 an LC-MS method to determine the concentrations of metformin, pioglitazone and the active metabolites of pioglitazone（ketopioglitazone M-III and hydroxylpioglitazone M-IV） in plasma after administration of compound metformin and pioglitazone tablets. Methods Pioglitazone and the internal standard carbamazepine were extracted from plasma with acetonitrile. The concentrations of pioglitazone and its active metabolites were analyzed on Ultimate C18 column（2.1 mm×150 mm,5 μm） with mobile phase consisting of acetonitrile-5 mmol·L-1 ammonium acetate（55∶45） at a flow rate of 0.3 mL·min-1.The column temperature was 35 ℃. Metformin and the internal standard memantine were extracted from plasma with acetonitrile and analyzed on Ultimate XB-CN column（2.1 mm×150 mm,5 μm） with mobile phase consisting of acetonitrile-0.1% formic acid（containing 10 mmol·L-1 ammonium acetate）（73∶27） at a flow rate of 0.3 mL·min-1. Results The liner ranges were 5.08-1016.0 μg·L-1,2.45-490.0 μg·L-1,and 4.20-840.0 μg·L-1 for metformin, pioglitazone, ketopioglitazone（M-III）and hydroxylpioglitazone（M-IV）respectively. The limits of quantitation were 6.0, 5.08, 2.45, and 4.2 μg·L-1, respectively. The extraction recoveries were more that 89.67%, while the intra- and inter-day precisions（RSD） were less that 15%. Conclusion This assay is accurate, reliable and suitable for pharmacokinetic studies of metformin, pioglitazone and its active metabolites in human plasma.

关 键 词：复方二甲双胍吡格列酮 药动学 液相色谱-串联质谱 

分 类 号：R969.11[医药卫生—药理学]