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氟比洛芬的立体特异性高效液相色谱分析:在药代动力学研究中的应用

Stereospecific high-performance liquid chromatographic analysis of flurbiprofen: application to pharmacokinetic studies.

作者信息

Teng Xiao Wei, Wang Stephen W J, Davies Neal M

机构信息

Department of Pharmaceutical Sciences and Pharmacology, College of Pharmacy, Washington State University, P.O. Box 646534, Pullman, WA 99164-6534, USA.

出版信息

J Pharm Biomed Anal. 2003 Sep 15;33(1):95-100. doi: 10.1016/s0731-7085(03)00340-6.

Abstract

A method of analysis of flurbiprofen (+/- 2-(2-fluoro-4-biphenyl)-propionic acid) in biological fluids is necessary to study the kinetics of in vitro and in vivo metabolism and tissue distribution. A simple high-performance liquid chromatographic method was developed for simultaneous determination of flurbiprofen enantiomers in rat serum. Serum (0.1 ml) was extracted with 2,2,4-trimethylpentane-isopropanol (95:5, v/v) after addition of the internal standard (IS), S-naproxen and acidification with H(2)SO(4). Separation was achieved on a Chiralpak AD-RH column with UV detection at 247 nm. The calibration curve was linear ranging from 0.05 to 50 microg/ml for each enantiomer. The mean extraction efficiency was >95%. Precision of the assay was <11% (CV), and was within 12.6% at the limit of quantitation (LOQ) (0.05 microg/ml). Bias of the assay was lower than 13.1%, and was within 12.8% at the LOQ. The assay was applied successfully to the in vivo kinetic study of flurbiprofen in rats.

摘要

为研究氟比洛芬(±2-(2-氟-4-联苯基)-丙酸)在体外和体内的代谢动力学及组织分布,需要一种生物流体中氟比洛芬的分析方法。已开发出一种简单的高效液相色谱法,用于同时测定大鼠血清中氟比洛芬对映体。加入内标(IS)S-萘普生并用硫酸酸化后,用2,2,4-三甲基戊烷-异丙醇(95:5,v/v)提取血清(0.1 ml)。在Chiralpak AD-RH柱上进行分离,于247 nm处进行紫外检测。每种对映体的校准曲线在0.05至50 μg/ml范围内呈线性。平均提取效率>95%。该测定法的精密度<11%(CV),在定量限(LOQ)(0.05 μg/ml)处为12.6%以内。该测定法的偏差低于13.1%,在LOQ处为12.8%以内。该测定法已成功应用于大鼠体内氟比洛芬的动力学研究。

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