Liquid chromatographic-mass spectrometric determination of celecoxib in plasma using single-ion monitoring and its use in clinical pharmacokinetics

Celecoxib is a cyclooxygenase-2 specific inhibitor, that has been recently and intensively prescribed as an antiinflammatory drug in rheumatic osteoar thiritis. A robust, highly reliable and reproducible liquid chromatographic -mass spectrometric assay is developed for the determination of celecoxib i n human plasma using sulindac as an internal standard. The run cycle-time i s <4 min. The assay method involved extraction of the analytes from plasma samples at pH 5 with ethyl acetate and evaporation of the organic layer. Th e reconstituted solution of the residue was injected onto a Shim Pad; GLC-C N, C-18 column and chromatographed with a mobile phase comprised of acetoni trile-1% acetic acid solution (4:1) at a flow-rate of 1 ml/min. The mass sp ectrometer (LCQ Finnigan Mat) was programmed in the positive single-ion mon itoring mode to permit the detection and quantitation of the molecular ions of celecoxib and sulindac at m/z 382 and 357, respectively, The peak area ratio of celecoxib/sulindac and concentration are linear (r(2)>0.994) over the concentration range 50-1000 ng/ml with a lowest detection limit of 20 n g/ml of celecoxib. Within- and between-day precision are within 1.58-4.0% r elative standard deviation and the accuracy is 99.4-107.3% deviation of the nominal concentrations. The relative recoveries of celecoxib from human pl asma ranged from 102.4 to 103.3% indicating the suitability of the method f or the extraction of celecoxib and I.S. from plasma samples. The validated LC-MS method has been utilized to establish various pharmacokinetic paramet ers of celecoxib following a single oral dose administration of celecoxib c apsules in two selected volunteers. (C) 2001 Elsevier Science B.V. All righ ts reserved.