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

✍ Scribed by Kota Kato; Kiyoshi Noguchi; Toshiko Aoki; Yoshiaki Soeishi; Hidetaka Kamimura

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 285 KB
• Volume: 20
• Category: Article
• ISSN: 0269-3879
• DOI: 10.1002/bmc.701

✦ Synopsis

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.