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

Aim To develop and validate a rapid, sensitive, and selective LC – MS/MS method for quantifying polmacoxib (POL) in rat plasma and integrating for preclinical pharmacokinetic evaluation.Materials and methods POL was quantified using LC – MS/MS on a Varian C8 column with an isocratic mobile phase of methanol and 2 mM ammonium acetate (90:10, v/v; 0.4 mL/min) with run time of 6 min. Detection employed negative ion electrospray and MRM (m/z 360 → 296 for POL; m/z 313 → 257 for rofecoxib as IS). The method was validated as per USFDA guidelines. Male Sprague – Dawley rats received a single oral dose of 10 mg/kg POL, and plasma samples were collected up to 72 h.Results The method showed linearity (1.56–800 ng/mL, r2 = 0.9994), LLOQ 1.56 ng/mL, and acceptable accuracy, precision, recovery, and matrix effects. Pharmacokinetics: Cmax 643 ± 32 ng/mL, Tmax 4 h, T1/2 10.4 ± 0.8 h, AUC0–∞ 5326 ± 106 ng*h/mL.Conclusions The validated assay is robust, sensitive, and suitable for pharmacokinetic, bioequivalence, and drug – drug interaction studies of POL.