Novel LC-MS/MS Method for CJ-023423 (Grapiprant) Determination in Rabbit Plasma

Abstract: Grapiprant is a new anti-inflammatory drug that pref erentially targets the EP4 receptor of prostaglandin E2 limitin g the wide range of adverse effects caused by the classical non steroid eal anti-inflammatory drugs. The aim of this study was to develop and val idate a new, simple, sensitive and rapid Liquid Chromatography tandem Ma ss Spectrometry method (LC-MS/MS) in order to quantify this novel dr ug in plasma. The method involved a simple liquid extraction followed by a gradient elution with formic acid 0.2% in water and acetonitrile in rev erse phase chromatography. The method was validated according t o international guidelines determining selectivity, linearity, sensiti vity, recovery, matrix effect and precision. Linearity was obtained over a range of 5-1000 ng mL − 1 . The obtained Limit of Quantitation (LOQ) and of Determ ination (LOD) were of 5 and 1.5 ng mL − 1 respectively. Extraction recovery was >73% for all th e tested concentrations. Matrix effect, expressed as ion suppression, was ≤9%. The intraday and inter-day precision results showed go od RSD values. All the validation parameters were satisfactory making this new method an interesting tool for scientists to further investiga tions on pharmacokinetics parameters. This validated method was applied to asse ss the pharmacokinetic of grapiprant in one rabbit administered with 0.5 mg kg−1