用于右芬氟拉明药代动力学评估的新型手性高效液相色谱方法。

New chiral high-performance liquid chromatographic methodology used for the pharmacokinetic evaluation of dexfenfluramine.

作者信息

Zeng J N, Dou L, Duda M, Stuting H H

机构信息

Analytical Chemistry Department, Roche Biomedical Laboratories, Raritan, NJ 08869.

出版信息

J Chromatogr B Biomed Appl. 1994 Apr 1;654(2):231-48. doi: 10.1016/0378-4347(94)00004-2.

DOI:10.1016/0378-4347(94)00004-2

PMID:8044284

Abstract

A new chiral high-performance liquid chromatographic (HPLC) method utilizing ultraviolet (UV) detection has been developed for determining plasma and urinary concentrations of d-fenfluramine and its major metabolite d-norfenfluramine, while being able to determine the possible presence of l-fenfluramine after oral administration of enantiopure d-fenfluramine hydrochloride. Sensitivity, stability, and specificity were enhanced by derivatizing the extracted analytes with 3,5-dinitrophenylisocyanate while utilizing a Pirkle-type chiral recognition approach. In vitro and in vivo statistical data are analogous. Overall plasma inter-assay precision was less than 7% with a minimum quantitation limit of 10 ng/ml. Overall urine inter-assay precision was also less than 7% with a minimum quantitation limit of 25 ng/ml.

摘要

已开发出一种利用紫外（UV）检测的新型手性高效液相色谱（HPLC）方法，用于测定右芬氟拉明及其主要代谢物去甲右芬氟拉明的血浆和尿液浓度，同时能够在口服对映体纯的盐酸右芬氟拉明后测定左芬氟拉明的可能存在情况。通过用3,5 - 二硝基苯基异氰酸酯衍生化提取的分析物，同时采用Pirkle型手性识别方法，提高了灵敏度、稳定性和特异性。体外和体内统计数据相似。血浆分析间总体精密度小于7%，最低定量限为10 ng/ml。尿液分析间总体精密度也小于7%，最低定量限为25 ng/ml。