Simultaneous detection and quantification of parecoxib and valdecoxib in canine plasma by HPLC with spectrofluorimetric detection: development and validation of a new methodology

Abstract

Parecoxib is the injectable prodrug of valdecoxib, a cicloxygenase-2 selective drug, currently used in human medicine. Recent studies have suggested both its excellent clinical effectiveness and wide safety profile. The aim of the present study was to develop and validate a new high-performance liquid chromatography (HPLC) with spectrofluorimetric detection method to quantify parecoxib and valdecoxib in canine plasma. Several parameters both in the extraction and the detection method were evaluated. The applicability of the method was determined by administering parecoxib to one dog: the protocol provided the expected pharmacokinetic results. The final mobile phase was acetonitrile: AcONH(4) (10 mM; pH 5.0) 55:45, v/v, with a flow rate of 0.4 mL min(-1), and excitation and emission wavelengths of 265 and 375 nm, respectively. The analytical column was a reverse-phase C18 ODS2 3-μm particle size. Protein precipitation in acidic medium followed by two successive liquid-liquid steps was carried out. The best extraction solvent was cyclohexane:Et(2)O (3:2, v/v) that gave recoveries ranging from 81.1% to 89.1% and from 94.8% to 103.6% for parecoxib and valdecoxib, respectively. The limits of quantification were 25 and 10 ng mL(-1) for parecoxib and valdecoxib, respectively. The chromatographic runs were specific with no interfering peaks at the retention times of the analytes, as confirmed by HPLC-mass spectrometry experiments. The other validation parameters were in agreement with the European Medicines Evaluation Agency and International Conference on Harmonisation guidelines. In conclusion, this method (extraction, separation and applied techniques) is simple and effective. This is the first time that use of a HPLC with spectrofluorimetric detection technique to simultaneously detect parecoxib and valdecoxib in plasma has been reported. This technique may have applications for pharmacokinetic studies.

Determination of parecoxib and valdecoxib in rat plasma by UPLC-MS/MS and its application to pharmacokinetics studies

“…To this end, the one-step protein precipitation method was employed in the current study. The traditional method often adopts high-performance liquid chromatography (HPLC) for the determination of PCX and VCX [22]. However, HPLC requires long-time sample running and exhibits low sensitivity.…”

The pharmacokinetics and in vitro/ex vivo cyclooxygenase selectivity of parecoxib and its active metabolite valdecoxib in cats

“…The HPLC analysis was carried out according to Saccomanni et al (2011) with some modifications. Briefly, plasma samples (100 μL) were added to 48 μL of DFU (0.5 μg/mL), then mixed with 10% CF3COOH (120 μL).…”

Effects of Dexmedetomidine on the Pharmacokinetics of Parecoxib and Its Metabolite Valdecoxib in Beagles by UPLC-MS/MS

“…Parecoxib ( Figure 1(a) ) is a water-soluble prodrug of a second-generation cycloxygenase-2- (COX-2-) specific inhibitor and the first of such agent to be developed for injectable use in human medicine. It is a kind of inactive ester amide prodrug, which is rapidly converted to valdecoxib ( Figure 1(b) ), a specific compound of COX-2, by enzymatic hydrolysis of the liver [ 7 ]. The elimination of valdecoxib is widely carried out in the liver in many ways, including cytochrome P450 3A4 (CYP3A4) and CYP2C9 isoenzyme metabolism and sulfaglucosylation (about 20%) [ 8 , 9 ].…”