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验证的高效液相色谱法测定人血浆中氯吡格雷羧酸代谢物及其在药代动力学研究中的应用。

Validated HPLC method for determination of carboxylic acid metabolite of clopidogrel in human plasma and its application to a pharmacokinetic study.

作者信息

Souri Effat, Jalalizadeh Hassan, Kebriaee-Zadeh Abbas, Shekarchi Maral, Dalvandi Afshin

机构信息

Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (14155-6451), Iran.

出版信息

Biomed Chromatogr. 2006 Dec;20(12):1309-14. doi: 10.1002/bmc.697.

DOI:10.1002/bmc.697
PMID:16977589
Abstract

A new, simple, and reproducible method for determination of carboxylic acid metabolite of clopidogrel in human plasma has been developed. After liquid-liquid extraction in acidic medium with chloroform, samples were quantified on a Nova-pak C(8), 5 microm column using a mixture of 30 mM K(2)HPO(4)-THF-acetonitrile (pH = 3, 79:2:19, v/v/v) as mobile phase with UV detection at 220 nm. The flow rate was set at 0.9 mL/min. Ticlopidine was used as internal standard and the total run time of analysis was about 12 min. The method was linear over the range of 0.2-10 microg/mL of clopidogrel metabolite in plasma (r(2) > 0.999). The within-day and between-day precision values were in the range 1.0-4.8%. The limit of quantification of the method was 0.2 microg/mL. The method was successfully used to study the pharmacokinetics of clopidogrel in healthy volunteers.

摘要

已开发出一种用于测定人血浆中氯吡格雷羧酸代谢物的新的、简单且可重复的方法。在酸性介质中用氯仿进行液液萃取后,样品在Nova-pak C(8)、5微米柱上进行定量分析,使用30 mM K(2)HPO(4)-四氢呋喃-乙腈(pH = 3,79:2:19,v/v/v)的混合物作为流动相,在220 nm处进行紫外检测。流速设定为0.9 mL/min。噻氯匹定用作内标,分析的总运行时间约为12分钟。该方法在血浆中氯吡格雷代谢物浓度为0.2 - 10微克/毫升范围内呈线性(r(2) > 0.999)。日内和日间精密度值在1.0 - 4.8%范围内。该方法的定量限为0.2微克/毫升。该方法已成功用于研究健康志愿者体内氯吡格雷的药代动力学。

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