IDENTIFICATION OF MAJOR URINARY METABOLITES OF THE CATECHOL-O-METHYLTRANSFERASE INHIBITOR ENTACAPONE IN THE DOG

Metabolites of entacapone, -cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitro phenyl) propenamide, a potent inhibitor of catechol-O-methyltransferas e, were isolated from dog urine. After hydrolysis of glucuronides and sulfates, 5 metabolites were identified in addition to unchanged entac apone by HPLC with diode-array UV detection, electron ionization mass spectrometry and IR spectroscopy. The (Z)-isomer of entacapone was the most abundant phase I metabolite while less abundant metabolites were formed through cleavage or reduction of the side chain carbon-carbon double bond, hydrolysis of the amide bond or through hydration of the nitrile group. The most abundant urinary metabolites were glucuronides . The glucuronidation site of these ortho-nitrocatechols was shown to be the hydroxyl meta to the nitro group.