aminopyridazine and ethyl-acetate

The unclear etiology of Alzheimer's disease leaves a large space for drug exploration. A novel anti-neuroinflammation agent (ZW14) was previously determined to have comparable efficacy to the marketed drug (donepezil) in the Aβ-induced model mice. Herein, a sensitive and rapid HPLC-MS/MS quantitative method was developed and validated for the further evaluation of ZW14 in dogs. Plasma samples were processed by liquid-liquid extraction with ethyl acetate and separated on Luna C18 column (2.1 mm × 50 mm, 1.7 μm) at room temperature with a flow rate of 0.2 mL/min. The analyte and IS were all detected by monitoring the precursor → product ion transition at unit resolution using multiple reaction monitoring (MRM) scan mode with positive ionization mode. No endogenous interference was observed and the linear range was 0.05-1500 ng/mL with the lower limit of quantification of 0.05 ng/mL. The intra- and inter-day precisions were within 10.9%, while the accuracy was all between 96.0% and 110%. The developed method was successfully applied to the pharmacokinetic study of ZW14 in beagle dogs after oral and intravenous administration of 2 mg/kg. The oral bioavailability of ZW14 was 26.3% with half-life of 2.6h.

Topics: Acetates; Animals; Anti-Inflammatory Agents; Biological Availability; Chromatography, High Pressure Liquid; Dogs; Half-Life; Liquid-Liquid Extraction; Plasma; Pyridazines; Tandem Mass Spectrometry