Short communicationDetection and quantification of cimicoxib, a novel COX-2 inhibitor, in canine plasma by HPLC with spectrofluorimetric detection: Development and validation of a new methodology
Graphical abstract
Introduction
Cimicoxib (CX), a novel imidazole derivative, is a second generation, highly selective COX-2 inhibitor that exhibits promising anti-inflammatory and analgesic activity. After a tentative clinical development as an anti-inflammatory and analgesic agent in humans, recently CX has been launched on the market for veterinary use [1], [2]. The selective COX-2 inhibitor class of drug has a critical role in veterinary medicine because most animal species are more susceptible than human to the gastrointestinal side effects triggered by non steroidal anti-inflammatory drugs (NSAIDs) [3]. To the best of authors’ knowledge, no analytical method to detect CX in the biological samples has been published. Hence, the aim of this study was to develop and validate an HPLC method to detect CX in canine plasma.
Section snippets
Chemical and reagents
Pure CX and parecoxib (PX) powders (both >99.0% purity) were donated by Vetoquinol (Bertinoro, Italy) and Pfizer (Groton, CT, USA), respectively. HPLC grade acetonitrile (ACN), methanol (MeOH), dichloromethane (CH2Cl2), diethyl ether (Et2O) and n-hexane (C6H14) were purchased from Merck (Darmstadt, Germany). Analytical grade trifluoroacetic acid (CF3COOH) was obtained from BDH (Poole, UK). Potassium chloride (KCl) and ammonium acetate (AcONH4) were purchased from Carlo Erba (Milano, Italy).
Detection method development
Derivation of the mobile phase was achieved using the data from a previously published method pertaining to other coxibs [6]. The optimal ratio between the organic phase and phase 10 mM AcONH4 buffer was found to be 35/65 (v/v). A range of buffer pH (3.0, 4.0, 4.5, 5.0, 6.0) were assayed to optimize the chromatographic separation. The retention time of CX was insensitive to pH giving negligible variations. However, pH 3 and 6 triggered asymmetries (tailing) in CX's peak shape. This behavior
Conclusion
In summary, this is the first time an analytical technique for detection of CX has been reported. This method (extraction, separation and applied techniques) is simple and efficacious for the determination of both analytes in canine plasma.
Conflict of interest statement
None of the authors of this paper does have a financial or personal relationship with other people or organizations that could inappropriately influence or bias the content of the paper.
Acknowledgements
None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper. Authors wish to thank Pfizer (Groton, CT, USA) and Vetoquinol (Bertinoro, Italy) for supplying pure analytical standards of PX and CX, respectively. The manufacturers of the agents under review were offered an opportunity to comment on this article. Some comments were received concerning editorial merit of the manuscript. This work was supported by athenaeum
References (8)
- et al.
An overview of the recent developments in analytical methodologies for determination of COX-2 inhibitors in bulk drugs, pharmaceuticals and biological matrices
J. Pharm. Biomed. Anal.
(2005) New drugs for small animals in 2011
Tierarztl. Prax. Ausg. K. Kleintiere Heimtiere
(2012)Veterinary pharmacology: is it still pharmacology's cinderella?
Clin. Exp. Pharmacol.
(2012)- et al.
The coxib NSAIDs: potential clinical and pharmacologic importance in veterinary medicine
J. Vet. Intern. Med.
(2005)
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