Determination of the catechol-O-methyltransferase inhibitor tolcapone and three of its metabolites in animal and human plasma and urine by reversed-phase high-performance liquid chromatography with ultraviolet detection

J Chromatogr B Biomed Sci Appl. 1999 Jul 9;730(2):153-60. doi: 10.1016/s0378-4347(99)00146-2.

Abstract

Reversed-phase HPLC procedures were developed for the determination of tolcapone (Ro 40-7592) and its metabolites Ro 40-7591, Ro 61-1448, and Ro 47-1669 in plasma and in urine samples. One of the procedures for plasma involved the determination of tolcapone and its metabolite Ro 40-7591 and the other, the determination of the two other metabolites. The urine assay enabled the simultaneous determination of tolcapone and all metabolites in one run. Sample preparation in plasma involved protein precipitation with acetonitrile. Urine was simply diluted. The compounds of interest were monitored in the UV at 270 nm. The limits of quantification were 0.05 microg/ml for each compound (plasma assay) and 0.2 microg/ml for the urine assay. The mean inter-assay precisions (C.V.) were < or = 6% (plasma assay) and < or = 8% (urine assay). The procedures were successfully applied to the sample analysis of animal pharmacokinetic (rat, dog, mouse, rabbit and cynomolgus monkey) and clinical pharmacology studies.

MeSH terms

  • Animals
  • Benzophenones / blood
  • Benzophenones / pharmacokinetics*
  • Benzophenones / urine
  • Catechol O-Methyltransferase Inhibitors*
  • Chromatography, High Pressure Liquid / methods*
  • Dogs
  • Enzyme Inhibitors / blood
  • Enzyme Inhibitors / pharmacokinetics*
  • Enzyme Inhibitors / urine
  • Humans
  • Macaca fascicularis
  • Mice
  • Nitrophenols
  • Rabbits
  • Rats
  • Sensitivity and Specificity
  • Species Specificity
  • Spectrophotometry, Ultraviolet
  • Tolcapone

Substances

  • Benzophenones
  • Catechol O-Methyltransferase Inhibitors
  • Enzyme Inhibitors
  • Nitrophenols
  • Tolcapone