Simultaneous determination of YM928, a novel noncompetitive AMPA receptor antagonist, and its demethylated metabolite in rat, dog and monkey plasma by high-performance liquid chromatography with ultraviolet detection |
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Authors: | Kato Kota Noguchi Kiyoshi Aoki Toshiko Soeishi Yoshiaki Kamimura Hidetaka |
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Affiliation: | Drug Metabolism Research Laboratories, Astellas Pharma Inc., 1-8, Azusawa 1-chome, Itabashi-ku, Tokyo 174-8511, Japan. kota.kato@jp.astellas.com |
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Abstract: | A specific HPLC method for the simultaneous determination of YM928, a novel noncompetitive AMPA receptor antagonist, and its demethylated metabolite (YM-58875) in rat, dog and monkey plasma was developed and validated. The method utilized multiple-step liquid-liquid extraction followed by a reversed-phase HPLC with UV detection at 275 nm. No interfering peaks were observed at the retention times of YM928, YM-58875 or internal standard. The validated quantitation range was 5-5000 ng/mL for both YM928 and YM-58875 when 1 mL of the plasma sample was used. The intra- and inter-day precision was less than 5.3 and 2.5% for YM928, and 3.7 and 2.3% for YM-58875, respectively. The intra- and inter-day accuracies were -8.7-5.3% and 0.7-1.9% for YM928, and -10.0-6.1% and 1.3-3.4% for YM-58875, respectively. The mean recoveries in the extraction process were 52.7-62.8%. The utility of this analytical method was demonstrated by the investigation of the pharmacokinetics of the unchanged drug and its metabolite in preclinical studies. |
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Keywords: | AMPA receptor antagonist YM928 rat dog monkey plasma validation PK |
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