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 1H 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.
Footnotes
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↵1 Present address: Metabometrix Limited, RSM Prince Consort Road, London, SW7 2BP, UK
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↵2 Present address: Department of Safety Assessment, GlaxoSmithKline Pharmaceuticals, Ware, Herts, SG12 0DP, UK.
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↵3 Present address: Department of Analytical Sciences, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.
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This study was supported by GlaxoSmithKline Pharmaceuticals.
- Abbreviations used are::
- BF
- 2,3-benzofuran
- HPLC
- high performance liquid chromatography
- MS
- mass spectrometry
- LC
- liquid chromatography
- SD
- Sprague-Dawley
- SPEC
- solid phase extraction chromatography
- xD
- 1 or 2 dimension(s)
- FID
- free induction decays
- COSY
- correlation spectroscopy
- MS-MS
- tandem mass spectrometry
- metabolite A
- 2-(2-hydroxyphenyl) acetic acid
- metabolite B
- 2-(2-hydroxyethyl)phenyl hydrogen sulfate
- 2-HEP
- 2-(2-hydroxyethyl)phenol
- p.d.
- postdose
- Received May 17, 2002.
- Accepted August 26, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
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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
