Application of LC-NMR for Characterization of Rat Urinary Metabolites of Zonampanel Monohydrate (YM872)

Kin-ya Sohda; Tsuyoshi Minematsu; Tadashi Hashimoto; Ken-ichi Suzumura; Masashi Funatsu; Katsuhiro Suzuki; Harumitsu Imai; Takashi Usui; Hidetaka Kamimura

doi:10.1248/cpb.52.1322

Regular Articles

Application of LC-NMR for Characterization of Rat Urinary Metabolites of Zonampanel Monohydrate (YM872)

Kin-ya Sohda, Tsuyoshi Minematsu, Tadashi Hashimoto, Ken-ichi Suzumura, Masashi Funatsu, Katsuhiro Suzuki, Harumitsu Imai, Takashi Usui, Hidetaka Kamimura

Author information

Kin-ya Sohda
Drug Metabolism Laboratories, Drug Development Division, Yamanouchi Pharmaceutical Co., Ltd.
Tsuyoshi Minematsu
Drug Metabolism Laboratories, Drug Development Division, Yamanouchi Pharmaceutical Co., Ltd.
Tadashi Hashimoto
Drug Metabolism Laboratories, Drug Development Division, Yamanouchi Pharmaceutical Co., Ltd.
Ken-ichi Suzumura
Analysis Research, Analysis & Metabolism Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
Masashi Funatsu
Analysis Research, Analysis & Metabolism Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
Katsuhiro Suzuki
Drug Metabolism Laboratories, Drug Development Division, Yamanouchi Pharmaceutical Co., Ltd.
Harumitsu Imai
Drug Metabolism Laboratories, Drug Development Division, Yamanouchi Pharmaceutical Co., Ltd.
Takashi Usui
Drug Metabolism Laboratories, Drug Development Division, Yamanouchi Pharmaceutical Co., Ltd.
Hidetaka Kamimura
Drug Metabolism Laboratories, Drug Development Division, Yamanouchi Pharmaceutical Co., Ltd.

Keywords: LC-NMR, YM872, zonampanel monohydrate, urinary metabolite, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist

JOURNAL FREE ACCESS

2004 Volume 52 Issue 11 Pages 1322-1325

DOI https://doi.org/10.1248/cpb.52.1322

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Abstract

Zonampanel monohydrate (YM872) has a potent and selective antagonistic effect on the glutamate receptor subtype, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor. Metabolic fingerprinting in rat urine after a single intravenous administration of ¹⁴C-labeled YM872 (¹⁴C-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.

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