title: Rapid determination of apixaban concentration in human plasma by liquid chromatography/tandem mass spectrometry: application to pharmacokinetic study.
abstract: We described the development and full validation of a rapid, high throughput sensible and accurate LC method using tandem mass spectrometry detection for determining apixaban concentration with [(¹³C, ²H₇]-apixaban as internal standard in human plasma. Plasma pretreatment involved a one-step protein precipitation with methanol. The separation was performed by reverse-phase chromatography on a Luna MercuryMS C18 column (20 mm × 4 mm × 3 μm) column. The multiple reaction monitoring transitions used for quantification were m/z 460.20→443.27 and 460.20→198.99 for apixaban, 468.22→451.30 for [(¹³C, ²H₇]-apixaban in the electrospray positive ionization mode. The method was linear over the concentration range of 5-500 μg/L. The intra- and inter-day precision values were below 14% and accuracy was from 90.0 to 105.8% at all quality control levels. Sample analysis time was less than 10 min including sample preparation. The present method was successfully applied to a pharmacokinetic study following oral administration of apixaban.
authors.affiliation: Laboratory of Pharmacology and Toxicology, University Hospital, F-42055 Saint-Etienne, France. xavier.delavenne@chu-st-etienne.fr
authors.forename: Xavier
authors.initials: X
authors.lastname: Delavenne
authors.forename: Patrick
authors.initials: P
authors.lastname: Mismetti
authors.forename: Thierry
authors.initials: T
authors.lastname: Basset
mesh_terms: D000991:Antithrombins / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D011720:Pyrazoles / Q000097:blood*; D011728:Pyridones / Q000097:blood*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000991:Antithrombins; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban