Identification of major urinary metabolites of the catechol-O-methyltransferase inhibitor entacapone in the dog

Eur J Drug Metab Pharmacokinet. Oct-Dec 1993;18(4):359-67. doi: 10.1007/BF03190186.

Abstract

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.

MeSH terms

  • Animals
  • Biotransformation
  • Catechol O-Methyltransferase Inhibitors*
  • Catechols / chemistry
  • Catechols / pharmacokinetics
  • Catechols / urine*
  • Chromatography, High Pressure Liquid
  • Dogs
  • Female
  • Glucuronates / urine
  • Hydrolysis
  • Isomerism
  • Male
  • Mass Spectrometry
  • Nitriles
  • Spectrophotometry, Infrared
  • Spectrophotometry, Ultraviolet
  • Sulfates / urine

Substances

  • Catechol O-Methyltransferase Inhibitors
  • Catechols
  • Glucuronates
  • Nitriles
  • Sulfates
  • entacapone