Simultaneous determination of unlabeled and carbon-13-labeled etoricoxib, a new cyclooxygenase-2 inhibitor, in human plasma using HPLC-MS/MS

• Published in: Journal of pharmaceutical sciences Vol. 91; no. 2; p. 405
• Main Authors: Rose, M J, Agrawal, N, Woolf, E J, Matuszewski, B K
• Format: Journal Article
• Language: English
• Published: United States 01-02-2002
• Subjects: Carbon Isotopes - blood; Chromatography, High Pressure Liquid - methods; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - blood; Drug Stability; Etoricoxib; Freezing; Humans; Isoenzymes - antagonists & inhibitors; Mass Spectrometry - methods; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Pyridines - blood; Sulfones - blood
• ISSN: 0022-3549
• DOI: 10.1002/jps.10038

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 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 (500 degrees C). 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.