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

被引:13
作者
Connelly, JC [1 ]
Connor, SC [1 ]
Monte, S [1 ]
Bailey, NJC [1 ]
Borgeaud, N [1 ]
Holmes, E [1 ]
Troke, J [1 ]
Nicholson, JK [1 ]
Gavaghan, CL [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biol Sci, Dept Biol Chem, London, England
关键词
D O I
10.1124/dmd.30.12.1357
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
(T)he 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 H-1 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.
引用
收藏
页码:1357 / 1363
页数:7
相关论文
共 22 条
[1]   Characterization of metabolites in intact Streptomyces citricolor culture supernatants using high-resolution nuclear magnetic resonance and directly coupled high-pressure liquid chromatography-nuclear magnetic resonance spectroscopy [J].
Abel, CBL ;
Lindon, JC ;
Noble, D ;
Rudd, BAM ;
Sidebottom, PJ ;
Nicholson, JK .
ANALYTICAL BIOCHEMISTRY, 1999, 270 (02) :220-230
[2]   ONLINE USE OF NMR DETECTION IN SEPARATION CHEMISTRY [J].
ALBERT, K .
JOURNAL OF CHROMATOGRAPHY A, 1995, 703 (1-2) :123-147
[3]  
Bailey NJC, 2000, RAPID COMMUN MASS SP, V14, P679, DOI 10.1002/(SICI)1097-0231(20000430)14:8<679::AID-RCM936>3.0.CO
[4]  
2-V
[5]   INVESTIGATION OF COMPLEX NETWORKS OF SPIN-SPIN COUPLING BY TWO-DIMENSIONAL NMR [J].
BAX, A ;
FREEMAN, R .
JOURNAL OF MAGNETIC RESONANCE, 1981, 44 (03) :542-561
[6]  
BUDAVARI S, 1989, MERCK INDEX ENCY CHE, P169
[7]  
CONNELLY JC, 1983, THESIS U SURREY SURR
[8]   HYDROCARBON GASES EMITTED FROM VEHICLES ON THE ROAD .1. A QUALITATIVE GAS-CHROMATOGRAPHY MASS-SPECTROMETRY SURVEY [J].
HAMPTON, CV ;
PIERSON, WR ;
HARVEY, TM ;
UPDEGROVE, WS ;
MARANO, RS .
ENVIRONMENTAL SCIENCE & TECHNOLOGY, 1982, 16 (05) :287-298
[9]  
*IARC, 1995, MON EV CARC RISK CHE, V63, P434
[10]   INVESTIGATION OF EXCHANGE PROCESSES BY 2-DIMENSIONAL NMR-SPECTROSCOPY [J].
JEENER, J ;
MEIER, BH ;
BACHMANN, P ;
ERNST, RR .
JOURNAL OF CHEMICAL PHYSICS, 1979, 71 (11) :4546-4553