Metabolism of a New Neuroprotective Agent for Ischemia-Reperfusion Damage, KR-31543 in the Rats using Liquid Chromatography/Electrospray Mass Spectrometry

  • Kim, John (Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Department of Clinical Research, LG Life Sciences, Ltd) ;
  • Ji, Hye-Young (Medicinal Resources Research Center and Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University) ;
  • Lee, Seung-Seok (Medicinal Resources Research Center and Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University) ;
  • Yoo, Sung-Eun (Korea Research Institute of Chemical Technology) ;
  • Kim, Sun-Ok (AgroPharma Research Institute, Dongbu Hannong Chemical Company) ;
  • Lee, Dong-Ha (AgroPharma Research Institute, Dongbu Hannong Chemical Company) ;
  • Lim, Hong (AgroPharma Research Institute, Dongbu Hannong Chemical Company) ;
  • Lee, Hye-Suk (Medicinal Resources Research Center and Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University)
  • Published : 2002.10.01

Abstract

KR-31543,(2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran is a new neuroprotetive agent for ischemia-reperfusion damage. The in vitro and in vivo metabolism of KR-31543 in rats has been studied by LC-electrospray mass spectrometry. Rat liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of a metabolite M1. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC-MS/MS analysis with the synthesized authentic standard. Rat CYP3A1 and 3A2 are the major CYP isozymes involved in the formation of M1.

Keywords

References

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