Detection and quantification of the selective EP4 receptor antagonist CJ-023423 (grapiprant) in canine plasma by HPLC with spectrofluorimetric detection

De Vito, Virginia, Saba, Alessandro, Lee, Hong-Ki, Owen, Helen, Poapolathep, Amnari and Giorgi, Mario (2016) Detection and quantification of the selective EP4 receptor antagonist CJ-023423 (grapiprant) in canine plasma by HPLC with spectrofluorimetric detection. Journal of Pharmaceutical and Biomedical Analysis, 118 251-258. doi:10.1016/j.jpba.2015.11.004


Author De Vito, Virginia
Saba, Alessandro
Lee, Hong-Ki
Owen, Helen
Poapolathep, Amnari
Giorgi, Mario
Title Detection and quantification of the selective EP4 receptor antagonist CJ-023423 (grapiprant) in canine plasma by HPLC with spectrofluorimetric detection
Journal name Journal of Pharmaceutical and Biomedical Analysis   Check publisher's open access policy
ISSN 0731-7085
1873-264X
Publication date 2016-01-25
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.jpba.2015.11.004
Open Access Status Not Open Access
Volume 118
Start page 251
End page 258
Total pages 8
Place of publication Amsterdam, The Netherlands
Publisher Elsevier
Collection year 2017
Language eng
Formatted abstract
Grapiprant, a novel pharmacologically active ingredient, acts as a selective EP4 receptor antagonist whose physiological ligand is prostaglandin E2 (PGE2). It is currently under development for use in humans and dogs for the control of pain and inflammation associated with osteoarthritis. The aim of the present study was to develop an easy and sensitive method to quantify grapiprant in canine plasma and to apply the method in a canine patient. Several parameters, both in the extraction and detection method were evaluated. The final mobile phase consisted of ACN:AcONH4 (20 mM) solution, pH 4 (70:30, v/v) at a flow rate of 1 mL/min. The elution of grapiprant and IS (metoclopramide) was carried out in isocratic mode through a Synergi Polar-RP 80A analytical column (150 mm × 4.6 mm). The best excitation and emission wavelengths were 320 and 365 nm, respectively. Grapiprant was extracted from the plasma using CHCl3, which gave a recovery of 88.1 ± 10.22% and a lower limit of quantification (LLOQ) of 10 ng/mL. The method was validated in terms of linearity, limit of detection (LOD), LLOQ, selectivity, accuracy and precision, extraction recovery, stability, and inter-laboratory cross validation, according to international guidelines. The chromatographic runs were specific with no interfering peaks at the retention times of the analyte and IS, as confirmed by HPLC-MS experiments. In conclusion, this was a simple and effective method using HPLC-FL to detect grapiprant in plasma, which may be useful for future pharmacokinetic studies.
Keyword Dog
Fluorescence
Grapiprant
HPLC
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: eSpace Followup
School of Veterinary Science Publications
 
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