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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)
Publication Information
Archives of Pharmacal Research / v.25, no.5, 2002 , pp. 664-668 More about this Journal
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
KR-31543; LC/MS/MS; Metabolism; CYP; Neuroprotective;
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