高效液相色谱-串联质谱法同时测定人血浆中瑞格列奈和二甲双胍及其在人体药动学中的应用

发布时间：2018-04-26 12:15

  本文选题：瑞格列奈 + 二甲双胍　； 参考：《中国医院药学杂志》2015年11期

【摘要】：目的:建立高效液相色谱-串联质谱法(HPLC-MS/MS)同时测定人血浆中瑞格列奈和二甲双胍浓度的方法,并进行人体药动学研究。方法:以乙腈沉淀蛋白处理血浆样品,替米沙坦做内标,采用Kromasil 60-5CN色谱柱(2.1 mm×100 mm,5μm),流动相为20 mmol·L-1醋酸铵水溶液(含0.2%甲酸)-乙腈(45∶55);质谱采用电喷雾离子化-多反应离子监测(ESIMRM)。并测定12名健康志愿者单剂量口服瑞格列奈盐酸二甲双胍复方片(2 mg∶500 mg)后瑞格列奈和二甲双胍的血浆浓度。结果:瑞格列奈和二甲双胍分别在0.05~50μg·L-1、2~2 000μg·L-1范围内线性良好,定量下限分别为0.05μg·L-1和2μg·L-1,日内日间精密度均小于8%,提取回收率分别为77.32%~80.65%和78.98%~82.46%。瑞格列奈和二甲双胍的主要药动学参数Cmax分别为(29.50±9.57),(1 167±197.77)μg·L-1;tmax分别为(0.83±0.39),(1.88±0.64)h;t1/2分别为(1.11±0.38),(4.31±0.86)h;AUC0→∞分别为(56.90±20.31),(7 407.32±1 653.25)μg·L-1·h-1。结论:建立的分析方法灵敏、准确可靠,样品处理快速、简便,适用于瑞格列奈/盐酸二甲双胍复方片人体药动学和生物等效性研究。
[Abstract]:Objective: to establish a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS / MS) method for simultaneous determination of reaglinide and metformin in human plasma and to study their pharmacokinetics. Methods: plasma samples were treated with acetonitrile precipitated protein and misartan was used as internal standard. The mobile phase was 20 mmol L-1 ammonium acetate aqueous solution (containing 0.2% formic acid-acetonitrile 45: 55) with Kromasil 60-5CN column of 2.1 mm 脳 100 mm ~ 5 渭 m ~ (-1). ESIMRM was monitored by electrospray ionization and multi-reaction ion. Plasma concentrations of repaglinide and metformin in 12 healthy volunteers were determined after oral administration of metformin hydrochloride compound tablets (2 mg:500 mg). Results: the linear range of reaglinide and metformin was 0.05 渭 g / L and 2 渭 g / L, respectively. The lower limit of quantification was 0.05 渭 g / L and 2 渭 g / L, respectively. The intra-day precision was less than 8 渭 g / L, and the recoveries were 77.32 ~ 80.65% and 78.98 ~ 82.46, respectively. The main pharmacokinetic parameters (Cmax) of repaglinide and metformin were 29.50 卤9.57, 1.167 卤197.77) 渭 g 路L ~ (-1) T _ (-1), respectively, were 0.83 卤0.39 ~ (-1) h ~ (-1) t ~ (-1), 1.88 卤0.64 h ~ (-1) h ~ (-1 / 2) were 1.11 卤0.384.31 卤0.86 h ~ (-1) AUC _ (0) 鈭，

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