Document Detail


Characterization and quantification of metabolites of racemic ketoprofen excreted in urine following oral administration to man by 1H-NMR spectroscopy, directly coupled HPLC-MS and HPLC-NMR, and circular dichroism.
MedLine Citation:
PMID:  15801549     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The identity of the human metabolites of ketoprofen (2-(3-benzoylphenyl)-propanoic acid) excreted via urine was investigated after a single oral dose of the racemic drug. Drug metabolites were concentrated and partially purified from urine using solid-phase extraction chromatography before separation and identification by directly coupled HPLC-MS and HPLC-NMR. The metabolites identified were the ester glucuronides of the parent drug and its phase I metabolites, 2-[3-(3-hydroxybenzoyl)phenyl]-propanoic acid, 2-[3-(4-hydroxybenzoyl)phenyl]-propanoic acid and 2-[3-(hydroxy(phenyl)methyl)phenyl]-propanoic acid, the latter formed by reduction of the ketone group of ketoprofen. In addition, two novel minor metabolites were identified as the ether glucuronides of 2-[3-(3-hydroxybenzoyl)phenyl]-propanoic acid and 2-[3-(4-hydroxybenzoyl)phenyl]-propanoic acid. These conjugates were all observed as diastereoisomeric pairs of unequal proportions. Purification of these metabolites by preparative chromatography allowed stereochemistry assignments. Metabolites were quantified by 1H-NMR spectroscopy after spectral simplification achieved by hydrolysis of the conjugates.
Authors:
E Skordi; I D Wilson; J C Lindon; J K Nicholson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Xenobiotica; the fate of foreign compounds in biological systems     Volume:  34     ISSN:  0049-8254     ISO Abbreviation:  Xenobiotica     Publication Date:    2004 Nov-Dec
Date Detail:
Created Date:  2005-04-01     Completed Date:  2005-07-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1306665     Medline TA:  Xenobiotica     Country:  England    
Other Details:
Languages:  eng     Pagination:  1075-89     Citation Subset:  IM    
Affiliation:
Biological Chemistry, Sir Alexander Fleming Building, Imperial College London, South Kensington, London SW7 2AZ, UK.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Adult
Chromatography, High Pressure Liquid
Circular Dichroism
Female
Glucuronides / urine*
Humans
Ketoprofen / administration & dosage*,  urine*
Magnetic Resonance Spectroscopy
Mass Spectrometry
Protons
Chemical
Reg. No./Substance:
0/Glucuronides; 0/Protons; 22071-15-4/Ketoprofen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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