通过液相色谱法改进对映体选择性测定人血浆中氟西汀和去甲氟西汀对映体的方法。

Improved enantioselective assay for the determination of fluoxetine and norfluoxetine enantiomers in human plasma by liquid chromatography.

作者信息

Gatti Giuliana, Bonomi Ilaria, Marchiselli Roberto, Fattore Cinzia, Spina Edoardo, Scordo Gabriella, Pacifici Roberta, Perucca Emilio

机构信息

Clinical Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia, Piazza Botta 10, 27100, Pavia, Italy.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Feb 5;784(2):375-83. doi: 10.1016/s1570-0232(02)00820-6.

DOI:10.1016/s1570-0232(02)00820-6

PMID:12505785

Abstract

A simple and innovative assay is described which allows the chiral separation of the four enantiomers of fluoxetine and norfluoxetine, with performance characteristics adequate for therapeutic drug monitoring. The assay requires liquid-liquid extraction into acetonitrile/n-hexane/isopropylic alcohol and re-extraction into phosphoric acid for clean-up. The acidic layer is injected onto the HPLC system after filtering. Separation of the analytes is achieved with a Chiralcel ODR column and a mobile phase consisting of potassium hexafluorophosphate/acetonitrile. Detection is made by ultraviolet absorbance at 227 nm. Standard curves are linear for each enantiomer (r(2)>/=0.992) over the range of 10-1000 ng/ml with a limit of quantification of 10 ng/ml for each enantiomer. Within-day and between-day CV% are </=10% for each enantiomer.

摘要

本文描述了一种简单且创新的分析方法，该方法可实现氟西汀和去甲氟西汀四种对映体的手性分离，其性能特征适用于治疗药物监测。该分析方法需要将样品液液萃取至乙腈/正己烷/异丙醇中，然后再萃取至磷酸中进行净化处理。过滤后，将酸性层注入高效液相色谱系统。使用Chiralcel ODR柱和由六氟磷酸钾/乙腈组成的流动相实现分析物的分离。通过在227nm处的紫外吸光度进行检测。每种对映体在10 - 1000 ng/ml范围内的标准曲线呈线性（r(2)≥0.992），每种对映体的定量限为10 ng/ml。每种对映体的日内和日间变异系数（CV%）≤10%。