Urinary metabolites of DX-8951, a novel camptothecin analog, in rats and humans

Arzneimittelforschung. 2001;51(3):253-7. doi: 10.1055/s-0031-1300032.

Abstract

Urinary metabolites of DX-8951 ((1S,9S)-1-amino-9-ethyl-5-fluoro- 1,2,3,9,12,15-hexahydro-9-hydroxy-4-methyl-10H,13H- benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13-dione, CAS 171335-80-1, exatecan) in rats and humans were identified. Rats were dosed with the drug, and two major metabolites (UM-1 and UM-2) in the urine were isolated and purified by using ion-exchange column and HPLC. From NMR and mass spectra, they are suggested to be 4-hydroxymethyl metabolite (UM-1) and 3-hydroxy metabolite (UM-2) of the drug. Their chemical structures were confirmed by comparing their NMR spectra with those of chemically synthesized metabolites. Two major metabolites were found in human urine obtained in phase I trial. They were also confirmed to be UM-1 and UM-2 by LC/MS/MS by comparing their mass fragment patterns with those of synthetic metabolites.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / urine*
  • Biotransformation
  • Camptothecin / urine*
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Female
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Middle Aged
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antineoplastic Agents, Phytogenic
  • Camptothecin