Evaluation of preparative high performance liquid chromatography and cryoprobe-nuclear magnetic resonance spectroscopy for the early quantitative estimation of drug metabolites in human plasma

被引：43

作者：

Dear, G. J. ^{[1
]}

Roberts, A. D. ^{[1
]}

Beaumont, C. ^{[1
]}

North, S. E. ^{[1
]}

机构：

[1] GlaxoSmithKline, PCD DMPK Dept, Struct ID Grp, Toxicokinet & Biotransformat, Ware SG12 0DP, Herts, England

来源：

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2008年 / 876卷 / 02期

关键词：

Metabolites; Human plasma; Preparative HPLC; NMR; Quantification;

D O I：

10.1016/j.jchromb.2008.10.040

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Definitive information on the metabolism of a drug candidate in humans is achieved through dosing radiolabelled drug as part of a clinical study, and is typically conducted post-proof of concept in Phase III of the clinical development plan. Here we describe a novel approach, using preparative high performance liquid chromatography and cryoprobe-nuclear magnetic resonance spectroscopy, to determine the human systemic exposure to a drug and its metabolites using samples derived from Phase I clinical studies. Using the described methodology, novel human plasma metabolites, as low as 10 ng/ml can be detected and quantified. This provides an opportunity, early in the development process to understand the potential role of metabolites in the safety and efficacy of drugs in humans. (C) 2008 Elsevier B.V. All rights reserved.

引用

页码：182 / 190

页数：9

共 25 条

[1] Metabolic profile of XK469 (2(R)-[4-(7-chloro-2-quinoxalinyl)oxyphenoxy]-propionic acid; NSC698215) in patients and in vitro:: low potential for active or toxic metabolites or for drug-drug interactions [J].