title: Selective and rapid liquid chromatography-mass spectrometry method for the quantification of rofecoxib in pharmacokinetic studies with humans.
abstract: An easy, rapid and selective method for the determination of rofecoxib in human plasma is presented. The analytical technique is based on reversed-phase high-performance liquid chromatography coupled to atmospheric pressure chemical ionisation mass spectrometry (Finnigan Mat LCQ ion trap). The retention time of rofecoxib was 1.2 min. The method has been validated over a linear range from 1 to 500 microg/l using celecoxib as internal standard. After validation, the method was used to study the pharmacokinetic profile of rofecoxib in 12 healthy volunteers after administration of a single oral dose (12.5 mg). The presented method was sufficient to cover more than 95% of the area under the curve. The pharmacokinetic characteristics (mean+/-SD) were tmax: 2.4+/-1.0 h, Cmax: 147+/-34 microg/l, AUCinfinity: 2038+/-581 microg h/l and t 1/2: 11.3+/-2.1 h.
authors.affiliation: Department of Experimental and Clinical Pharmacology and Toxicology, Friedrich Alexander University Erlangen-Nuremberg, Germany. ulrike.werner@pharmakologie.uni-erlangen.de
authors.forename: U
authors.initials: U
authors.lastname: Werner
authors.forename: D
authors.initials: D
authors.lastname: Werner
authors.forename: R
authors.initials: R
authors.lastname: Mundkowski
authors.forename: M
authors.initials: M
authors.lastname: Gillich
authors.forename: K
authors.initials: K
authors.lastname: Brune
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001274:Atmospheric Pressure; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects; D007783:Lactones / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013450:Sulfones
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases