Identification of a novel glutathione conjugate of diclofenac by LTQ-Orbitrap

Drug Metab Lett. 2008 Jan;2(1):35-40. doi: 10.2174/187231208783478506.

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

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Chromatography, Liquid / methods
  • Decarboxylation
  • Diclofenac / analogs & derivatives
  • Diclofenac / metabolism
  • Diclofenac / pharmacokinetics*
  • Glutathione / metabolism
  • Hepatocytes / metabolism
  • Humans
  • Male
  • Mass Spectrometry / methods*
  • Microsomes, Liver / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • 2-(2,6-dichlorophenylamino)benzoic acid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Diclofenac
  • Glutathione