摘要
目的建立测定人血浆中格列齐特的液相色谱-质谱/质谱联用法,并应用于人体药代动力学研究.方法 0.25mL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 C8柱分离,通过大气压化学电离四极杆串联质谱,以选择离子反应监测（SRM）方式进行检测.用于定量分析的离子反应分别为m/z 324～m/z 127（格列齐特）和m/z 494（m/z369（内标格列本脲）.结果格列齐特血浆质量浓度线性范围为1.0～4 000μg·L^-1,定量下限为1.0μg·L^-1.日内和日间精密度（RSD）均小于4%,准确度（RE）在±5.1%内.每个样品色谱分析仅为2.8 min,应用此法每天可以测试150个样品.结论该法操作简便、快速、灵敏,适用于格列齐特的临床药动学研究及制剂的生物等效性评价.
OBJECTIVE To develop a LC-MS/MS method for the quantification of gliclazide in human plasma and to evaluate the pharmacokineties of gliclazide in healthy volunteers.METHODS After a simple liquid-liquid extraction, gliclazide anti the internal standard glibenclamide were separated on a Zorbax SB C8 column and detected by tandem mass spectrometry. The mobile phase consisted of acetonitrilewater-formic acid （90： 10：0.5）. An atmospherie pressure chemical ionization interface was applied and operated in the positive ion mode, Selected reaction monitoring （SRM） mode was usod with the trasitions of m/z 324 - m/z 127 tot gliclazlde and m/z 494 - m/z 369 tot the internal standard,respectively. RESULTS The linear calibration curve was obtained in the coneentration range of 1.0 - 4 000μg·L^-1. The limit of quantification was 1.0μg·L^-1.The inte- and intra-day precision （RSD） were less than 4%, and aecuracy （ relative error） were within± 5.1%, Each plasma sample was chromatographod within 2.8min. More than 150 plasma samples were assayed within each day. The method was successfully applied in a pharmacokinetic study of glicalzide, CONCLUSION The method is proved to be suitable tot the clinical investigation of glielazide pharmaeokineties, which offers the advantages of specificity, speed and greater sensitivity compared with the reported methods.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2006年第11期864-867,共4页
Chinese Pharmaceutical Journal
基金
国家863计划资助项目(2003AA2Z347C)
关键词
格列齐特
液相色谱-串联质谱法
药动学
gliclazide
liquid chromatography-tandem mass spectrometry
phannacokinetics
