Liquid chromatography-electrospray tandem mass spectrometry investigations of fragmentation pathways of biliary 4,4'-methylenedianiline conjugates produced in rats.
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: see text]
Chen
Kan
K
Department of Chemistry, University of New Orleans, 2000 Lakeshore Dr., New Orleans, LA 70148, USA.
Dugas
Tammy R
TR
Cole
Richard B
RB
D000814:Aniline Compounds / Q000032:analysis* / Q000737:chemistry; D000818:Animals; D001646:Bile / Q000737:chemistry* / Q000378:metabolism; D001711:Biotransformation; D002853:Chromatography, Liquid / Q000379:methods; D020723:Glucuronic Acid / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D005998:Glycine / Q000737:chemistry; D006900:Hydroxylation; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D001559:Benzhydryl Compounds
D000814:Aniline Compounds; D020723:Glucuronic Acid; D005978:Glutathione; D005998:Glycine; C009505:4,4'-diaminodiphenylmethane; D001559:Benzhydryl Compounds