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Journal of Chinese Pharmaceutical Sciences ›› 2017, Vol. 26 ›› Issue (8): 589-594.DOI: 10.5246/jcps.2017.08.066

• Original articles • Previous Articles     Next Articles

Determination of dabigatran in dog plasma by LC-MS/MS and its application to a pharmacokinetic study of dabigatran etexilate nanosuspension

Shuangchen Cong, Yuanyuan Zhang, Jiongxi Lei, Maoyuan Song, Wenxi Zhang, Guanghua Peng, Mengya Yin, Jiajia Li, Jiaxing Wang, Xinru Li*   

  1. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System; School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

  • Received:2017-04-18 Revised:2017-05-20 Online:2017-08-31 Published:2017-06-15
  • Contact: Tel.: +86-010-82801508, E-mail: ll@bjmu.edu.cn
  • Supported by:
    The National Basic Research Program of China (Grant No. 2015CB932100).

Abstract:

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 carried 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 ofDABE-NS. The maximum concentration and the areas under curves of dabigatranfor DABE-NS were significantly higher than those of control formulation, indicating improved oral absorption.

Key words: Dabigatran, Dabigatran etexilate, LC-MS/MS, Nanosuspension, Pharmacokinetics

CLC Number: 

Supporting: