Application of LC-NMR for characterization of rat urinary metabolites of zonampanel monohydrate (YM872)

Chem Pharm Bull (Tokyo). 2004 Nov;52(11):1322-5. doi: 10.1248/cpb.52.1322.

Abstract

Zonampanel monohydrate (YM872) has a potent and selective antagonistic effect on the glutamate receptor subtype, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor. Metabolic fingerprinting in rat urine after a single intravenous administration of (14)C-labeled YM872 ((14)C-YM872) revealed the presence of two metabolites, R1 and R2. The two metabolites were semi-purified by preparative HPLC from rat urine after a single intravenous administration of non-labeled YM872, and their structures were elucidated by various instrumental analyses involving LC-NMR. The results showed that R1 and R2 have a hydroxyamino group and an amino group at the C-7 position of the quinoxalinedione skeleton, respectively. Therefore, the proposed metabolic pathway of YM872 in rats involves the reduction of the nitro group to a hydroxyamino group and then subsequent reduction to an amino group.

MeSH terms

  • Animals
  • Chromatography, Liquid / methods
  • Imidazoles / chemistry
  • Imidazoles / metabolism
  • Imidazoles / urine*
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Quinoxalines / chemistry
  • Quinoxalines / metabolism
  • Quinoxalines / urine*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Imidazoles
  • Quinoxalines
  • YM 872