Application of LC-NMR for characterization of rat urinary metabolites of zonampanel monohydrate (YM872).
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.
Sohda
Kin-ya
KY
Drug Metabolism Laboratories, Drug Development Division, Yamanouchi Pharmaceutical Co. Ltd., 1-1-8 Azusawa, Itabashi-ku, Tokyo 174-8511, Japan. souda@yamanouchi.co.jp
Minematsu
Tsuyoshi
T
Hashimoto
Tadashi
T
Suzumura
Ken-ichi
K
Funatsu
Masashi
M
Suzuki
Katsuhiro
K
Imai
Harumitsu
H
Usui
Takashi
T
Kamimura
Hidetaka
H
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism / Q000652:urine*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D011810:Quinoxalines / Q000737:chemistry / Q000378:metabolism / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007093:Imidazoles; D011810:Quinoxalines; C110629:YM 872