标题：Rapid quantitative analysis of etoricoxib in human plasma by UPLC-MS/MS and application to a pharmacokinetic study in Chinese healthy volunteers
作者：Zhang, Xiaoran; Guo, Nan; Ji, Wei; Wen, Qing
作者机构：[Zhang, Xiaoran; Ji, Wei; Wen, Qing] Shandong Univ, Jinan Cent Hosp, Jinan, Shandong, Peoples R China.; [Guo, Nan] Shandong Univ, Inst Clin Pharmaco 更多
通讯作者地址：[Wen, Q]Shandong Univ, Jinan Cent Hosp, Jinan, Shandong, Peoples R China.
关键词：etoricoxib; UPLC-MS/MS; pharmacokinetic; Chinese healthy volunteers;; food effect
摘要：A selective and sensitive liquid chromatography-tandem mass spectrometry method was developed for simultaneous determination of etoricoxib in human plasma. Chromatography was performed on an Acquity UPLC HSS T3 column (1.8 mu m, 50 x 2.1 mm), with a flow rate of 0.600 mL/min, using a gradient elution with acetonitrile and water which contained 2 mm ammonium acetate as the mobile phase. Detection was carried out on Triple QuadTM 5500 mass spectrometer under positive-ion multiple reaction monitoring mode. The respective mass transitions used for quantification of etoricoxib and etoricoxib-d3 were m/z 359.0 -> 280.1 and m/z 362.0 -> 280.2. Calibration curves were linear over the concentration range of 5-5000 ng/mL. The validated method was applied in the pharmacokinetic study of etoricoxib in Chinese healthy volunteers under fed and fasted conditions. After a single oral dose of 120 mg, the main pharmacokinetic parameters of etoricoxib in fasted and fed groups were respectively as follows: peak concentration, 2364.78 +/- 538.01 and 1874.55 +/- 367.90 ng/mL; area under the concentration-time curve from 0 to 120 h, 44,605.53 +/- 15,266.66 and 43,516.33 +/- 12,425.91 ng h/mL; time to peak concentration, 2.00 and 2.50 h; and half-life, 24.08 +/- 10.06 and 23.64 +/- 6.72 h. High-fat food significantly reduced the peak concentration of etoricoxib (p = 0.001) but had no effect on the area under the concentration-time curve.