In this study, a sensitive and rapid LC-MS/MS method was developed and validated to determine dabigatran in plasma of beagle dogs after oral administration of dabigatran etexilate nanosuspension （DABE-NS）. The analy...In this study, a sensitive and rapid LC-MS/MS method was developed and validated to determine dabigatran in plasma of beagle dogs after oral administration of dabigatran etexilate nanosuspension （DABE-NS）. The analytes （dabigatran） and sertraline hydrochloride （internal standard, IS） were separated on a Kromasil C18 column using gradient elution consisting of methanol and formate buffer at a flow rate of 0.4 mL/min in 20 min. Detection and quantitation were carded out by multiple reaction monitoring following the transitions： m/z 472.17→289.07 and 305.98→275.00 for dabigatran and IS at positive ion mode, respectively. The calibration curves were linear from 1.0 to 500.0 ng/mL for dabigatran with r = 0.9995. The accuracy of each analyte ranged from 94.8% to 107.1%, and the precision was within 6%. Besides, this method was successfully applied in the investigation of the pharmacokinetic profile of dabigatran in beagle dogs after oral administration of DABE-NS. The maximum concentration and the areas under curves of dabigatran for DABE-NS were significantly higher than those of control formulation, indicating improved oral absorption.展开更多
基金The National Basic Research Program of China(Grant No.2015CB932100)
文摘In this study, a sensitive and rapid LC-MS/MS method was developed and validated to determine dabigatran in plasma of beagle dogs after oral administration of dabigatran etexilate nanosuspension （DABE-NS）. The analytes （dabigatran） and sertraline hydrochloride （internal standard, IS） were separated on a Kromasil C18 column using gradient elution consisting of methanol and formate buffer at a flow rate of 0.4 mL/min in 20 min. Detection and quantitation were carded out by multiple reaction monitoring following the transitions： m/z 472.17→289.07 and 305.98→275.00 for dabigatran and IS at positive ion mode, respectively. The calibration curves were linear from 1.0 to 500.0 ng/mL for dabigatran with r = 0.9995. The accuracy of each analyte ranged from 94.8% to 107.1%, and the precision was within 6%. Besides, this method was successfully applied in the investigation of the pharmacokinetic profile of dabigatran in beagle dogs after oral administration of DABE-NS. The maximum concentration and the areas under curves of dabigatran for DABE-NS were significantly higher than those of control formulation, indicating improved oral absorption.
