直接耦合高效液相色谱 - 核磁共振 - 质谱联用技术及¹H核磁共振光谱研究在Sprague-Dawley大鼠2,3 - 苯并呋喃代谢研究中的应用

Application of directly coupled high performance liquid chromatography-NMR-mass spectometry and 1H NMR spectroscopic studies to the investigation of 2,3-benzofuran metabolism in Sprague-Dawley rats.

作者信息

Connelly John C, Connor Susan C, Monte Soria, Bailey Nigel J C, Borgeaud Nathan, Holmes Elaine, Troke Jeff, Nicholson Jeremy K, Gavaghan Claire L

机构信息

Department of Biological Chemistry, Faculty of Medicine, Imperial College of Science, Technology, and Medicine, London, United Kingdom.

出版信息

Drug Metab Dispos. 2002 Dec;30(12):1357-63. doi: 10.1124/dmd.30.12.1357.

DOI:10.1124/dmd.30.12.1357

PMID:12433803

Abstract

The urinary excretion of metabolites of 2,3-benzofuran was studied in Sprague-Dawley rats (n = 5) given a single dose of 150 mg/kg i.p. Urine samples were collected at defined intervals up to 7 days postdose and analyzed using (1). H NMR and directly coupled high performance liquid chromatography (HPLC)-NMR, HPLC-(mass spectrometry) MS and HPLC-MS-NMR methods. The principal metabolites were determined to be 2-hydroxyphenylacetic acid and 2-(2-hydroxyethyl)phenyl hydrogen sulfate, representing 24.3 +/- 6.0% and 19.6 +/- 6.4% of the dose, respectively. This indicates that metabolism of benzofuran to the polar species excreted in urine involves cleavage of the furan ring.

摘要

在给予150mg/kg腹腔注射单剂量的斯普拉格-道利大鼠（n = 5）中研究了2,3-苯并呋喃代谢物的尿排泄情况。在给药后长达7天的规定时间间隔收集尿液样本，并使用（1）¹H NMR以及直接联用高效液相色谱（HPLC）-NMR、HPLC-（质谱）MS和HPLC-MS-NMR方法进行分析。确定主要代谢物为2-羟基苯乙酸和2-（2-羟乙基）苯基硫酸氢酯，分别占给药剂量的24.3±6.0%和19.6±6.4%。这表明苯并呋喃代谢为尿液中排泄的极性物质涉及呋喃环的裂解。