Bioanalytical method development for polmacoxib in rat plasma using LC-MS/MS and Its preclinical pharmacokinetic...

Area of Science:

• Analytical Chemistry
• Pharmacokinetics
• Bioanalysis

Background:

• Polmacoxib (POL) is a novel drug requiring robust quantification methods.
• Preclinical pharmacokinetic evaluation is essential for drug development.

Purpose of the Study:

• To develop and validate a sensitive and selective LC-MS/MS method for quantifying polmacoxib in rat plasma.
• To integrate this method for preclinical pharmacokinetic assessment of polmacoxib.

Main Methods:

• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for polmacoxib quantification.
• The method utilized a Varian C8 column with a methanol and ammonium acetate mobile phase.
• Validation was performed according to USFDA guidelines, with sample analysis in Sprague-Dawley rats.

Main Results:

• The LC-MS/MS method demonstrated excellent linearity (1.56-800 ng/mL, r² = 0.9994) and a low limit of quantification (LLOQ) of 1.56 ng/mL.
• Pharmacokinetic parameters determined included Cmax of 643 ± 32 ng/mL, Tmax of 4 h, and T1/2 of 10.4 ± 0.8 h.
• The assay exhibited acceptable accuracy, precision, recovery, and matrix effects.

Conclusions:

• The validated LC-MS/MS assay is robust, sensitive, and selective for polmacoxib quantification.
• This method is suitable for preclinical pharmacokinetic, bioequivalence, and drug-drug interaction studies of polmacoxib.