液相色谱-串联质谱法测定人血浆中格列本脲  

LC-MS/MS determination of glyburide in human plasma

作　　者：杨洪梅[1] 陈笑艳[2] 段小涛[1] 张逸凡 孔璋[1] 钟大放[2] 

机构地区：[1]沈阳药科大学药物代谢与药物动力学实验室,沈阳110016 [2]中国科学院上海药物研究所药物代谢研究中心,上海201203

出　　处：《药物分析杂志》2007年第6期796-799,共4页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立测定人血浆中格列本脲的液相色谱-串联质谱法,并用于临床药代动力学研究。方法:血浆样品经液-液萃取后,以乙腈-水-甲酸(90:10:0.2)为流动相,采用 Zorbax SB-C_8 柱(150mm×4.6mm,5μm)分离,通过大气压化学电离源四极杆串联质谱,以选择反应监测(SRM)方式进行检测。用于定量分析的离子反应分别为 m/z494→369(格列本脲)和m/z 324→127(内标格列齐特)。结果:LC-MS/MS 法测定人血浆中格列本脲的线性范围为0.50～500 ng·mL^(-1),定量下限为0.50 ng·mL^(-1)。以3个浓度水平的质量控制样品求得各浓度水平日内、日间精密度(RSD)均小于5.4%,相对偏差(RE)在±2.3%以内。在临床药代动力学研究中,应用此法测试了20名受试者口服盐酸二甲双胍格列本脲胶囊后血浆中格列本脲的浓度。结论:该法灵敏、快速、准确,操作简便,线性范围宽,适用于临床药代动力学研究。Objective：To develop a sensitive and specific liquid chromatographic -tandem mass spectrometric （LC - MS/MS） method for determination of glyburide in human plasma. Methods： Glyburide and internal standard gliclazide were extracted from plasma using liquid - liquid extraction, then chromatographed by a Zorbax SB - Cs column （ 150 mm ×4. 6 mm,5 μm）. The mobile phase consisted of acetonitrile - water - formic acid （90： 10： 0. 2）. A tandem mass spectrometer equipped with atmospheric pressure chemical ionization source was used as detector and operated in the positive ion mode. Selected reaction monitoring （SRM） using the precursor → product ion combinations of m/z 494→369 and m/z 324→127 were used to quantify glyburide and the internal standard, respectively. Results： The linear calibration curve was obtained in the concentration range of 0. 50 - 500 ng · mL^- 1. The lower limit of quantification was 0. 50 ng · mL^- 1. The intra - and inter - day precision （RSD） across three validation runs over the entire concentration range was less than 5.4% , and the accuracy （relative error, RE） was within ± 2. 3%. The method was successfully applied in a pharmacokinetic study of glyburide in human. Conclusion： The method is proved to be sensitive, rapid, and suitable for clinical pharmacokinetics investigation of glyburide.

关 键 词：格列本脲 液相色谱-串联质谱法 血浆药物浓度 

分 类 号：R917[医药卫生—药物分析学]