Identification of major urinary metabolites of the catechol-O-methyltransferase inhibitor entacapone in the dog.
Metabolites of entacapone, (E)-2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl) propenamide, a potent inhibitor of catechol-O-methyltransferase, were isolated from dog urine. After hydrolysis of glucuronides and sulfates, 5 metabolites were identified in addition to unchanged entacapone 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.
Wikberg
T
T
Orion-Farmos Pharmaceuticals, Orion Research Center, Espoo, Finland.
Ottoila
P
P
Taskinen
J
J
D000818:Animals; D001711:Biotransformation; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005260:Female; D005965:Glucuronates / Q000652:urine; D006868:Hydrolysis; D007536:Isomerism; D008297:Male; D013058:Mass Spectrometry; D009570:Nitriles; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013431:Sulfates / Q000652:urine
D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D005965:Glucuronates; D009570:Nitriles; D013431:Sulfates; C071192:entacapone