title: A rapid and sensitive HPLC-MS/MS method for determination of an aminopyridazine derived anti-neuroinflammatory agent (ZW14) in dog plasma: Application to a pharmacokinetic study.
abstract: 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.
authors.affiliation: School of Bioscience & Bioengineering, South China University of Technology, Guangzhou 510640, PR China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Cardiology, Zhujiang Hospital of Southern Medical University, Guangzhou 510280, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, PR China.
authors.forename: Bijun
authors.initials: B
authors.lastname: Lv
authors.affiliation: Zhongshan PharmaSS Corporation, Zhongshan 528437, PR China.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Guo
authors.affiliation: The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, PR China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Liang
authors.affiliation: Zhongshan PharmaSS Corporation, Zhongshan 528437, PR China.
authors.forename: Jiawen
authors.initials: J
authors.lastname: Tang
authors.affiliation: The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, PR China. Electronic address: brennan_huixie@126.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
mesh_terms: D000085:Acetates / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004285:Dogs; D006207:Half-Life; D059625:Liquid-Liquid Extraction / Q000379:methods; D010949:Plasma / Q000737:chemistry*; D011724:Pyridazines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000085:Acetates; D000893:Anti-Inflammatory Agents; D011724:Pyridazines; C513630:aminopyridazine; C007650:ethyl acetate
keywords: Alzheimer's disease; Aminopyridazine; Dog; HPLC–MS/MS; Pharmacokinetics