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

Abstract

Grapiprant is a new anti-inflammatory drug that preferentially targets the EP4 receptor of prostaglandin E2 limiting the wide range of adverse effects caused by the classical non steroideal anti-inflammatory drugs. The aim of this study was to develop and validate a new, simple, sensitive and rapid Liquid Chromatography tandem Mass Spectrometry method (LC-MS/MS) in order to quantify this novel drug in plasma. The method involved a simple liquid extraction followed by a gradient elution with formic acid 0.2% in water and acetonitrile in reverse phase chromatography. The method was validated according to international guidelines determining selectivity, linearity, sensitivity, 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 Determination (LOD) were of 5 and 1.5 ng mL^-1 respectively. Extraction recovery was >73% for all the tested concentrations. Matrix effect, expressed as ion suppression, was ≤9%. The intraday and inter-day precision results showed good RSD values. All the validation parameters were satisfactory making this new method an interesting tool for scientists to further investigations on pharmacokinetics parameters. This validated method was applied to assess the pharmacokinetic of grapiprant in one rabbit administered with 0.5 mg kg^-1.