Main Degradation Products of Dabigatran Etexilate Evaluated by LC-UV and LC-ESI-MS, Degradation Kinetics and in vitro Cytotoxicity Studies

• Published in: Journal of the Brazilian Chemical Society 2015-04, Vol.26 (4), p.660-666
• Main Authors: Bernardi, Raquel M., D'Avila, Felipe B., Todeschini, Vítor, Andrade, Juliana M. M., Fröehlich, Pedro E., Bergold, Ana M.
• Format: Article
• Language: English
• Subjects: CHEMISTRY, MULTIDISCIPLINARY
• ISSN: 0103-5053; 1678-4790
• DOI: 10.5935/0103-5053.20150023

The present study reports the stability profile of an antithrombotic drug: dabigatran etexilate (DAB). The drug was subjected to thermal degradation at 60 ºC and products formed were investigated by liquid chromatography-UV (LC-UV) and liquid chromatography-mass spectrometry (LC-ESI-MS). Chromatographic separation of the degradation products was performed on a GL Sciences Inc. Inertsil ODS-2 column (250 mm × 4.6 mm i.d., with a particle size of 5 µm and pore size of 110 Å) with mobile phase consisting of acetonitrile and ammonium acetate buffer (pH 5.5; 10 mmol L−1) (65:35, v/v) pumped at 1.0 mL min−1 flow rate. Column temperature was set at 30 ºC and detection at 225 nm using a UV detector. LC-UV method previously validated was extended to LC-ESI-MS for the characterization of the degradation products (DP-01 and DP-02) formed, without complicated isolation or purification processes, based on retention times and confirmation of molecular weight. Degradation kinetics of DAB was also evaluated and could be described as a first-order process (R2= 0.9900). Furthermore, no evidence of cytotoxicity in human mononuclear cells was observed for DAB degraded samples.