Liquid chromatographic determination of a new catechol-O-methyltransferase inhibitor, entacapone, and its Z-isomer in human plasma and urine.
Assay procedures for analysis of entacapone, (E)-2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)-propenamide++ +, and its Z-isomer in human plasma and urine are described. The methods were based on reversed-phase liquid chromatography with amperometric detection. Entacapone and its Z-isomer were extracted with n-hexane-ethyl acetate mixtures after acidification with hydrochloric acid. From urine extracts the analytes were back-extracted into phosphate buffer (pH 7.2). During sample treatment 1-2% of entacapone was changed to the Z-isomer. With recoveries exceeding 75% the relative standard deviations for within-day precision were less than 11% for plasma and less than 6% for urine at the quantitation limit (10 ng ml-1) and less than 6% for both methods at higher concentrations (20-2000 ng ml-1). The assays were specific with respect to all known metabolites and selective, sensitive and precise enough for determination of entacapone and its Z-isomer in plasma and urine down to 10 ng ml-1. The methods are thus suitable for the kind of pharmacokinetic studies exemplified in this paper.
Karlsson
M
M
Orion Corporation, Orion Research Center, Espoo, Finland.
Wikberg
T
T
D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000097:blood* / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D009570:Nitriles; D013237:Stereoisomerism
D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D009570:Nitriles; C071192:entacapone