LC-MS/MS法测定人血浆中西格列汀浓度及其药物动力学研究  

Determination of sitagliptin in human plasma by liquid chromatography tandem mass spectrometry and its pharmacokinetics application

作　　者：李贺[1] 陈国耘[1] 沈琦[1] 黄越[1] 朱逢佳[1] 刘炜[1] 李力[1] LI He CHEN Guoyun SHEN Qi HUANG Yue ZHU Fengjia LIU Wei LI Li(Department of Pharmacy ,Zhejiang Hospital, Hangzhou 310013, Zhejiang , China)

机构地区：[1]浙江医院药剂科

出　　处：《中国临床药理学与治疗学》2016年第10期1144-1148,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家科技重大专项项目-老年病新药临床技术平台(2013ZX09303005);浙江省自然科学基金(LQ15H310003)

摘　　要：目的：建立LC-MS/MS法测定人血浆中西格列汀的浓度并进行药动学研究。方法：人血浆样品用乙酸乙酯提取后,选用ZORBAX Eclipse XDB C18（2.1 mm×100 mm,3.5μm）色谱柱,以乙腈-10 mmol/L醋酸铵溶液（80∶20,含0.1%甲酸）为流动相,流速为0.30 m L/min,采用电喷雾离子化源,正离子方式,多反应监测（MRM）扫描方式进行监测,用于定量分析的离子反应分别为m/z 408.1→m/z 235.1（西格列汀）和m/z 303.2→m/z 152.9（内标橙皮素）。结果：血浆中西格列汀的线性范围为0.20~1 000 ng/m L（r=0.998 0）,定量下限为0.20 ng/m L;方法回收率在93.2%~105.5%;日内、日间RSD均小于15%;提取回收率81.6%~86.5%,无明显基质效应。结论：该方法快速、灵敏、准确,专属性强,重复性好,适用于人血浆中西格列汀浓度的测定,可应用于西格列汀的血药浓度检测和药物动力学研究。AIM： To develop an LC-MS / MS method for determination of sitagliptin in human plasma and applied to the pharmacokinetics study.METHODS： The plasma samples were processed with ethyl acetate extraction and separated on ZORBAX Eclipse XDB column（ 2. 1 mm × 100 mm,3. 5μm） and eluted with acetonitrile-10 mmol /L ammonium acetate,（ 80∶ 20,V / V,containing 0. 1% formic acid）. Detection of the analyte was achieved using positive ion electrospray ionization（ ESI） in the multiple reaction monitoring（ MRM） mode. The MS / MS ion transitions monitored were m / z 408. 1→m / z 235. 1 and m / z 303. 2→m / z 152. 9 for sitagliptin and internal standard,respectively. RESULTS：The linear calibration curve of sitagliptin was obtained concentration range of 0. 20- 1000 ng / m L（ r= 0. 998 0）,with the lower limit of quantitation（ LLOQ） of 0. 20 ng /m L. The relative recovery was93. 2%- 105. 5%,Intra-day and inter-day relative standard deviations were both below 15%. The absolute recovery in plasma was 81. 6%- 86. 5%,and no significant matrix effect was found. CONCLUSION： The established method is rapid,sensitive,accurate,specific and reliable,and suitable for the determination of sitagliptin in human plasma and pharmacokinetic study.

关 键 词：西格列汀 液质联用法 血药浓度 药物动力学 

分 类 号：R917[医药卫生—药物分析学]