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

• Published in: Biomedical chromatography Vol. 20; no. 12; pp. 1328 - 1335
• Main Authors: Kato, Kota, Noguchi, Kiyoshi, Aoki, Toshiko, Soeishi, Yoshiaki, Kamimura, Hidetaka
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.12.2006
• Subjects: AMPA receptor antagonist; Animals; Chromatography, High Pressure Liquid - methods; dog; Dogs; Drug Stability; Excitatory Amino Acid Antagonists - blood; Haplorhini; monkey; plasma; Pyridines - blood; Pyridines - pharmacokinetics; rat; Rats; Receptors, AMPA - antagonists & inhibitors; Reproducibility of Results; Sensitivity and Specificity; Thiazines - blood; Thiazines - pharmacokinetics; validation; YM928
• ISSN: 0269-3879; 1099-0801
• DOI: 10.1002/bmc.701

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. Copyright © 2006 John Wiley & Sons, Ltd.