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.
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.
Skordi
E
E
Biological Chemistry, Sir Alexander Fleming Building, Imperial College London, South Kensington, London SW7 2AZ, UK.
Wilson
I D
ID
Lindon
J C
JC
Nicholson
J K
JK
D000284:Administration, Oral; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D005260:Female; D020719:Glucuronides / Q000652:urine*; D006801:Humans; D007660:Ketoprofen / Q000008:administration & dosage* / Q000652:urine*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011522:Protons
D020719:Glucuronides; D011522:Protons; D007660:Ketoprofen