Identification of a novel glutathione conjugate of diclofenac by LTQ-Orbitrap.
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.
Teffera
Yohannes
Y
Pharmacokinetics and Drug Metabolism, Amgen, Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA. yteffera@amgen.com
Waldon
Daniel J
DJ
Colletti
Adria E
AE
Albrecht
Brian K
BK
Zhao
Zhiyang
Z
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods; D003653:Decarboxylation; D004008:Diclofenac / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
C540520:2-(2,6-dichlorophenylamino)benzoic acid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D005978:Glutathione