RT Journal Article
SR Electronic
T1 Electrochemistry-Mass Spectrometry Unveils the Formation of Reactive Triclocarban Metabolites
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 2130
OP 2138
DO 10.1124/dmd.110.034546
VO 38
IS 12
A1 Baumann, A.
A1 Lohmann, W.
A1 Rose, T.
A1 Ahn, K. C.
A1 Hammock, B. D.
A1 Karst, U.
A1 Schebb, N. H.
YR 2010
UL http://dmd.aspetjournals.org/content/38/12/2130.abstract
AB Triclocarban (3,4,4′-trichlorocarbanilide, TCC) is a widely used antibacterial agent in personal care products and is frequently detected as an environmental pollutant in waste waters and surface waters. In this study, we report novel reactive metabolites potentially formed during biotransformation of TCC. The oxidative metabolism of TCC has been predicted using an electrochemical cell coupled online to liquid chromatography and electrospray ionization mass spectrometry. The electrochemical oxidation unveils the fact that hydroxylated metabolites of TCC may form reactive quinone imines. Moreover, a so-far unknown dechlorinated and hydroxylated TCC metabolite has been identified. The results were confirmed by in vitro studies with human and rat liver microsomes. The reactivity of the newly discovered quinone imines was demonstrated by their covalent binding to glutathione and macromolecules, using β-lactoglobulin A as a model protein. The results regarding the capability of the electrochemical cell to mimic the oxidative metabolism of TCC are discussed. Moreover, the occurrence of reactive metabolites is compared with findings from earlier in vivo studies and their relevance in vivo is argued.