A method for the simultaneous determination of etoricoxib and its carbon-13 analog ( 13 C 6 -etoricoxib) from human plasma has been developed and used to support bioavailability studies. Plasma samples (0.5 mL) were extracted by using a 3M Empore TM 96-well plate (C 8 ) and the resulting extracts were analyzed by using a PE-Sciex API-3000 HPLC±MS/MS with a heated nebulizer interface (5008C). The method was validated with two different calibration curve ranges, one for etoricoxib (5 to 2500 ng/mL) determined in the presence of lower concentrations of 13 C 6 -etoricoxib (0.5 to 250 ng/mL), and a second curve for the quantitation of similar concentrations of both etoricoxib and 13 C 6 -etoricoxib (0.5 to 250 ng/mL). Extraction recoveries of etoricoxib, 13 C 6 -etoricoxib, and a methylated internal standard were >70% over the range of concentrations included in both calibration curves. Intraday precision and accuracy for the quantitation of etoricoxib were 7.8% relative standard deviation (RSD) or less and within 3.4% respectively over the range of 5 to 2500 ng/mL, and 10.8% RSD or less and within 4 % respectively over the range of 0.5 to 250 ng/mL. Within-batch precision and accuracy for the quantitation of 13 C 6 -etoricoxib over the range of 0.5 to 250 ng/mL were 8.3% RSD or less and within 2.3%, respectively. The validated assay was used in support of human clinical trials.