Identification of a novel glutathione adduct of diclofenac, 4'-hydroxy-2'-glutathion-deschloro-diclofenac, upon incubation with human liver microsomes.

Studies on cytochrome P-450-mediated bioactivation of diclofenac in rats and in human hepatocytes: identification of glutathione conjugated metabolites.

The nonsteroidal anti-inflammatory drug diclofenac causes a rare but potentially fatal hepatotoxicity that may be associated with the formation of reactive metabolites. In this study, three glutathione (GSH) adducts, namely 5-hydroxy-4-(glutathion-S-yl)diclofenac (M1), 4'-hydroxy-3'-(glutathion-S-yl)diclofenac (M2), and 5-hydroxy-6-(glutathion-S-yl)diclofenac (M3), were identified by liquid chr...

Detection of a novel reactive metabolite of diclofenac: evidence for CYP2C9-mediated bioactivation via arene oxides.

A new glutathione adduct (M4) was tentatively identified, likely as 2'-hydroxy-3'-(glutathione-S-yl)-monoclofenac, using liquid chromatography-tandem mass spectrometry analysis of incubations of diclofenac with human liver microsomes. The same conjugate was not detected in incubations with either rat or monkey liver microsomes. Formation of M4 was mediated specifically by CYP2C9 in human liver ...

Short Communication IDENTIFICATION OF A NOVEL GLUTATHIONE ADDUCT OF DICLOFENAC, 4 -HYDROXY-2 -GLUTATHION-DESCHLORO-DICLOFENAC, UPON INCUBATION WITH HUMAN LIVER MICROSOMES

Clinical use of the nonsteroidal anti-inflammatory drug diclofenac (DF) is associated with an incidence of idiosyncratic hepatoxicity. The formation of reactive metabolites of DF in vivo has been proposed to be responsible for such toxicity. One type of reactive metabolite, a benzoquinone imine of DF formed through oxidation by cytochromes P450, can be trapped by glutathione in vitro in liver m...

One-electron oxidation of diclofenac by human cytochrome P450s as a [potential] bioactivation mechanism for formation of 2’-(glutathion-S-yl)-deschloro-diclofenac Adapted from: One-electron oxidation of diclofenac by human cytochrome P450s as a [potential] bioactivation mechanism for formation of 2’-(glutathion-S-yl)-deschloro-diclofenac

Detection of novel reactive metabolites of trazodone: evidence for CYP2D6-mediated bioactivation of m-chlorophenylpiperazine.

Several new glutathione adducts (M3-M7) of trazodone were tentatively identified in human liver microsomal incubations using liquid chromatography-tandem mass spectrometry (LC/MS/MS). Following incubations with trazodone in the presence of glutathione, 1-(3'-chlorophenyl)piperazine (m-CPP), a major circulating and pharmacologically active metabolite of several antidepressants including trazodon...