TITLE

Liquid chromatography–electrospray tandem mass spectrometry investigations of fragmentation pathways of biliary 4,4′-methylenedianiline conjugates produced in rats

AUTHOR(S)
Kan Chen; Dugas, Tammy R.; Cole, Richard B.
PUB. DATE
May 2008
SOURCE
Analytical & Bioanalytical Chemistry;May2008, Vol. 391 Issue 1, p271
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
4,4′-methylenedianiline (DAPM) is the main building block for production of 4,4′-methylenediphenyldiisocyanate that has been widely used in the manufacturing of polyurethane materials including medical devices. Although it was revealed that damage to biliary epithelial cells of the liver and common bile duct occurred upon acute exposure to DAPM, the exact mechanism of DAPM toxicity is not fully understood. Both phase I and II biotransformations of DAPM, some of which generate reactive intermediates, are characterized in detail by liquid chromatography electrospray tandem mass spectrometry. The two most prominent metabolites found in rat bile (M2 and M7) implicated glutathione, glucuronic acid, and glycine conjugations (phase II) following hydroxylation, and N-oxidation (phase I). Their decomposition pathways, as evidenced by MS n experiments, have been elucidated in detail. [Figure not available: see fulltext.]
ACCESSION #
31722417

 

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