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Metabolism of a novel antiangiogenic agent KR‐31831 in rats using liquid chromatography‐electrospray mass spectrometry
Author(s) -
Kim HuiHyun,
Paek In Bok,
Ji Hye Young,
Lee Sunkyung,
Yi Kyu Yang,
Lee Hye Suk
Publication year - 2005
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.200500159
Subject(s) - chemistry , chromatography , metabolism , in vivo , hydroxymethyl , amino acid , mass spectrometry , electrospray ionization , metabolite , stereochemistry , biochemistry , microbiology and biotechnology , biology
Abstract KR‐31831 ((2 S ,3 R ,4 S )‐4‐(((1H‐imidazol‐2‐yl)methyl)(4‐chlorophenyl)amino)‐6‐amino‐2‐(dimethoxymethyl)‐2‐methyl‐3,4‐dihydro‐2H‐chromen‐3‐ol) is a novel antiangiogenic agent. In vitro and in vivo metabolism of KR‐31831 in rats has been investigated using LC‐MS and LC‐MS/MS analysis. Incubation of rat liver microsomes and hepatocytes with KR‐31831 produced three metabolites (M1–M3). M1, M2, and M3 were identified as N ‐((1H‐imidazol‐2‐yl)methyl)‐4‐chlorobenzenamine, (2 R ,3 R ,4 S )‐4‐(((1H‐imidazol‐2‐yl)methyl)(4‐chlorophenyl) amino)‐6‐amino‐2‐(hydroxymethyl)‐2‐methyl‐3,4‐dihydro‐2H‐chromen‐3‐ol, and N ‐((2 S ,3 R ,4 S )‐4‐(((1H‐imidazol‐2‐yl)methyl)(4‐chlorophenyl)amino)‐2‐(dimethoxymethyl)‐3‐hydroxy‐2‐methyl‐3,4‐dihydro‐2H‐chromen‐6‐yl)acetamide, respectively, by co‐chromatography with the authentic standards and by comparison with product ion spectra of the authentic standards. Those in vitro metabolites were also detected in bile, plasma, or urine samples after an intravenous administration of KR‐31831 to rats. The metabolic routes for KR‐31381 included the metabolism of acetal group to hydroxymethyl group (M2), N ‐dealkylation to M1, and N ‐acetylation at the 6‐amino group (M3).