title: UPLC MS/MS assay for routine quantification of dabigatran - a direct thrombin inhibitor - in human plasma.
abstract: This article described the development and full validation of rapid and accurate liquid chromatography method, coupled with tandem mass spectrometry detection, for quantification of dabigatran in human plasma with [(13)C(6)]-dabigatran as internal standard. Plasma pretreatment involved a single step protein precipitation with methanol. Separation was performed by ultra performance reversed-phase chromatography on an Acquity UPLC BEH C8 100 mm × 1 mm × 1.7 μm column using a gradient elution mode. The mobile phase was a mix of distilled water containing 0.1% formic acid and methanol containing 0.1% formic acid. Specific multiple reaction monitoring transitions were recorded in positive electrospray ionization. The method was linear over the concentration range of 2-500 μg/L. The intra- and inter-day precision values were below 11.3% and accuracy was within 93.8% and 108.8% for all QC levels (5, 75 and 400 μg/L). The lower limit of quantification was 2 μg/L. Total analysis time was to 10 min including sample preparation.
authors: Laboratory of Pharmacology and Toxicology, University Hospital, F-42055 Saint-Etienne, France. xavier.delavenne@chu-st-etienne.fr
authors: Xavier
authors: X
authors: Delavenne
authors: Julie
authors: J
authors: Moracchini
authors: Silvy
authors: S
authors: Laporte
authors: Patrick
authors: P
authors: Mismetti
authors: Thierry
authors: T
authors: Basset
mesh_terms: D000368:Aged; D000991:Antithrombins / Q000097:blood* / Q000737:chemistry; D001562:Benzimidazoles / Q000097:blood* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods; D000069604:Dabigatran; D004355:Drug Stability; D006801:Humans; D057230:Limit of Detection; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013923:Thromboembolism / Q000188:drug therapy; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry
chemical_list: D000991:Antithrombins; D001562:Benzimidazoles; D015091:beta-Alanine; D000069604:Dabigatran