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