Abstract
High resolution accurate MS with an LTQ-Orbitrap identified two novel metabolites of diclofenac in rat bile and rat and human hepatocyte incubations: a benzyl-S-glutathione conjugate and 2-(2,6-dichlorophenylamino) benzoic acid. A mechanism for the bioactivation of diclofenac involving decarboxylation is proposed.
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
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Chromatography, Liquid / methods
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Decarboxylation
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Diclofenac / analogs & derivatives
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Diclofenac / metabolism
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Diclofenac / pharmacokinetics*
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Glutathione / metabolism
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Hepatocytes / metabolism
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Humans
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Male
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Mass Spectrometry / methods*
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Microsomes, Liver / metabolism
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Rats
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Rats, Sprague-Dawley
Substances
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2-(2,6-dichlorophenylamino)benzoic acid
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Anti-Inflammatory Agents, Non-Steroidal
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Diclofenac
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Glutathione