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

被引:39
作者
Abdel-Hamid, M [1 ]
Novotny, L [1 ]
Hamza, H [1 ]
机构
[1] Kuwait Univ, Fac Pharm, Dept Pharmaceut Chem, Safat 13110, Kuwait
来源
JOURNAL OF CHROMATOGRAPHY B | 2001年 / 753卷 / 02期
关键词
celecoxib;
D O I
10.1016/S0378-4347(00)00574-0
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Celecoxib is a cyclooxygenase-2 specific inhibitor, that has been recently and intensively prescribed as an antiinflammatory drug in rheumatic osteoarthiritis. A robust, highly reliable and reproducible liquid chromatographic-mass spectrometric assay is developed for the determination of celecoxib in human plasma using sulindac as an internal standard. The run cycle-time is <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. The reconstituted solution of the residue was injected onto a Shim Pad; GLC-CN, C-18 column and chromatographed with a mobile phase comprised of acetonitrile-1% acetic acid solution (4:1) at a flow-rate of 1 ml/min. The mass spectrometer (LCQ Finnigan Mat) was programmed in the positive single-ion monitoring 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 ng/ml of celecoxib. Within- and between-day precision are within 1.58-4.0% relative standard deviation and the accuracy is 99.4-107.3% deviation of the nominal concentrations. The relative recoveries of celecoxib from human plasma ranged from 102.4 to 103.3% indicating the suitability of the method for the extraction of celecoxib and I.S. from plasma samples. The validated LC-MS method has been utilized to establish various pharmacokinetic parameters of celecoxib following a single oral dose administration of celecoxib capsules in two selected volunteers. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:401 / 408
页数:8
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