Validated HPLC-UV Method for the Quantification of a Novel BCr-Abl 1 Inhibitor, Vodobatinib, in Rat Plasma: Application to a Pharmacokinetic Study

Vodobatinib is a Bcr-Abl 1 inhibitor, currently entering into Phase 2 clinical trials as a potential drug to treat glioblastoma patients. In the present work, a validated high-performance liquid chromatography (HPLC) detection method for the quantification of vodobatinib in rat plasma was established. Sample preparation involved liquid-liquid extraction method. The chromatographic separation of vodobatinib and the IS was accomplished on an XBridge C₁₈ column using 10 mM ammonium acetate and acetonitrile in gradient condition. The flow-rate and injection volume were 0.8 mL/min and 20 μL, respectively. The eluent was detected at 310 nm. Vodobatinib and the IS eluted at 7.5 and 5.9 min, respectively, with a total run time of 10 min. Validation tests were performed according to FDA requirements. The established method showed good linearity in the range of 50.5-6534 ng/mL. Interday and intraday coefficients of variations were < 5.11%. Stability studies, dilution integrity, and incurred sample reanalysis met the acceptance criteria. Subsequently, the validated HPLC method was used to study the disposition kinetics of vodobatinib in rats.

HPLC; method validation; pharmacokinetics; rat plasma; vodobatinib.