液相色谱-串联质谱法测定人血浆中罗格列酮  

Determination of rosiglitazone in human plasma by liquid chromatography-tandem mass spectrometry

作　　者：杨洪梅[1] 陈笑艳[2] 孙玉明[1] 张逸凡 钟大放[1] 

机构地区：[1]沈阳药科大学药物代谢与药物动力学实验室,辽宁沈阳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：《中国新药与临床杂志》2006年第3期179-183,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家863基金项目(2003AA2Z347C)

摘　　要：目的:建立测定人血浆中罗格列酮的液相色谱-质谱-质谱联用法,并用于临床药动学研究。方法: 血浆样品经液-液萃取后,以乙腈-水-甲酸(90:10:0．5)为流动相,采用Zorbax SB—C18柱分离,通过电喷雾离子化四极杆串联质谱,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／z 358→ 135(罗格列酮)和m／z 256→167(内标苯海拉明)。结果:标准曲线线性范围为0．50～1 000μg·L-1,定量下限为0．50μg·L-1,日内、日间精密度(RSD)均小于7．4％。应用此法测试了20名男性健康受试者口服酒石酸罗格列酮片(相当于罗格列酮4 mg)后血浆中罗格列酮的浓度。结论:该法灵敏、快速、准确,操作简便、线性范围宽,适用于罗格列酮的临床药动学研究。AIM： To develop a sensitive and specific LC/MS/MS method for determination of rosiglitazone in human plasma and provide climical research for pharmacokinetics. METHODS： Rosiglitazone and internal standard diphenhydramine were extracted from plasma using liquid-liquid extraction, then chromatographed by using a Zorbax SB-C18 column. The mobile phase consisted of acetonitrile-water-formic acid （90：10：0.5）. A tandem mass spectrometer equipped with electrospray 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 358→135 （rosiglitazone） and m/z 256→167 （internal standard diphenhydramine） was performed. RESULTS： The linear calibration curve was obtained in the concentration range of 0.50 -1 000 μg· L^-1.The lower limit of quantification was 0.50 μg· L^-1. The intra- and inter-day precision （RSD）across three validation runs over the entire concentration range was less than 7.4 %.The method was successfully applied to a clinical pharmacokinetic study for 20 healthy male volunteers given orally 4 mg rosiglitazone, and then the plasma concentration were determined. CONCLUTION： The method is proved to be sensitive,rapid and robust,and suitable for clinical pharmacokinetic investigations of rosiglitazone.

关 键 词：罗格列酮 色谱法 高压液相 药动学 光谱法 质量 电喷雾电离 液相色谱-质谱-质谱联用法 

分 类 号：R917[医药卫生—药物分析学] R977.15[医药卫生—药学]