title: Simultaneous quantitative determination of celecoxib and its two metabolites using liquid chromatography-tandem mass spectrometry in alternating polarity switching mode.
abstract: A simple and rapid quantitative analytical method for the simultaneous detection of celecoxib and its two main metabolites, hydroxycelecoxib (celecoxib-OH) and celecoxib carboxylic acid (celecoxib-COOH), in rat plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. The plasma sample was prepared through simple protein precipitation, and the reconstitution solution (0.1% formic acid in 50% methanol) was optimized to achieve the best peak shape and recovery. The analytes were separated using an Atlantis T3 column (2.1 mm × 100 mm, 3 μm), and the mobile phase was composed of 10 mM ammonium formate in either 5% acetonitrile or 95% acetonitrile. The detection of the analytes was performed in alternating polarity switching mode using electrospray ionization. As celecoxib-OH and celecoxib-COOH were slightly unstable following freeze-thaw cycles and long-term storage at -80°C in stability tests, every analysis was carefully conducted with one-freeze thaw cycle and a short storage duration (<1 week). Acceptable accuracy (<15%) and precision (<15%) were obtained in intra- and inter-day validations. The method was successfully applied to the pharmacokinetic study of celecoxib, celecoxib-OH and celecoxib-COOH following the oral administration of celecoxib in rats at a dose of 10mg/kg. Comparing the related pharmacokinetic parameters of celecoxib and its metabolites, celecoxib was quickly metabolized into celecoxib-OH and subsequently converted to celecoxib-COOH in short intervals. The AUCs for the two metabolites were less than 10% of that for celecoxib, indicating that the rate of celecoxib metabolism was low.
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; Department of Biological Sciences, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Hyun-A
authors.initials: HA
authors.lastname: Oh
authors.affiliation: Department of Biological Sciences, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Donghak
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Medical Records and Health Information Management, College of Nursing and Health, Kongju National University, Kongju 314-701, Republic of Korea. Electronic address: lsh5027@kongju.ac.kr.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea; University of Science and Technology (UST), Daejeon 305-600, Republic of Korea. Electronic address: jbhluck@kist.re.kr.
authors.forename: Byung Hwa
authors.initials: BH
authors.lastname: Jung
mesh_terms: D000818:Animals; D000068579:Celecoxib; D002853:Chromatography, Liquid / Q000379:methods; D008297:Male; D011720:Pyrazoles / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib
keywords: Alternating polarity switching; Celecoxib; Celecoxib metabolites; Liquid chromatography–tandem mass spectrometry; Quantitation