Main degradation products of dabigatran etexilate evaluated by LC-UV and LC-ESI-MS, degradation kinetics and in vitro cytotoxicity studies

• Autor(a) principal: Bernardi, Raquel Martini
• Data de Publicação: 2015
• Outros Autores: D'Avila, Felipe Bianchini, Todeschini, Vítor, Fasolo, Juliana Maria de Mello Andrade, Froehlich, Pedro Eduardo, Bergold, Ana Maria
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/230149
• topic: Citotoxicidade; Cinética de degradação; Produtos de degradação; Cytotoxity; Dabigatran etexilate; Degradation kinetics; Degradation products; LC-ESI-MS

The present study reports the stability profile of an antithrombotic drug: dabigatran etexilate (DAB). The drug was subjected to thermal degradation at 60 °C 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 °C 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.