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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.

journal_name

J Pharm Biomed Anal

journal_title

Journal of pharmaceutical and biomedical analysis

authors

Oh HA,Kim D,Lee SH,Jung BH

doi

10.1016/j.jpba.2014.12.004

subject

Has Abstract

pub_date

2015-03-25 00:00:00

pages

32-9

eissn

0731-7085

issn

1873-264X

pii

S0731-7085(14)00599-8

journal_volume

107

pub_type

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Simultaneous quantitative determination of celecoxib and its two metabolites using liquid chromatography-tandem mass spectrometry in alternating polarity switching mode.