Main Degradation Products of Dabigatran Etexilate Evaluated by LC-UV and LC-ESI-MS, Degradation Kinetics and in vitro Cytotoxicity Studies
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Journal of the Brazilian Chemical Society (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532015000400660 |
Resumo: | 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. |
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Main Degradation Products of Dabigatran Etexilate Evaluated by LC-UV and LC-ESI-MS, Degradation Kinetics and in vitro Cytotoxicity Studiescytotoxitydabigatran etexilatedegradation kineticsdegradation productsLC-ESI-MSThe 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.Sociedade Brasileira de Química2015-04-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532015000400660Journal of the Brazilian Chemical Society v.26 n.4 2015reponame:Journal of the Brazilian Chemical Society (Online)instname:Sociedade Brasileira de Química (SBQ)instacron:SBQ10.5935/0103-5053.20150023info:eu-repo/semantics/openAccessBernardi,Raquel M.D’Avila,Felipe B.Todeschini,VítorAndrade,Juliana M. M.Fröehlich,Pedro E.Bergold,Ana M.eng2015-05-11T00:00:00Zoai:scielo:S0103-50532015000400660Revistahttp://jbcs.sbq.org.brONGhttps://old.scielo.br/oai/scielo-oai.php||office@jbcs.sbq.org.br1678-47900103-5053opendoar:2015-05-11T00:00Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)false |
dc.title.none.fl_str_mv |
Main Degradation Products of Dabigatran Etexilate Evaluated by LC-UV and LC-ESI-MS, Degradation Kinetics and in vitro Cytotoxicity Studies |
title |
Main Degradation Products of Dabigatran Etexilate Evaluated by LC-UV and LC-ESI-MS, Degradation Kinetics and in vitro Cytotoxicity Studies |
spellingShingle |
Main Degradation Products of Dabigatran Etexilate Evaluated by LC-UV and LC-ESI-MS, Degradation Kinetics and in vitro Cytotoxicity Studies Bernardi,Raquel M. cytotoxity dabigatran etexilate degradation kinetics degradation products LC-ESI-MS |
title_short |
Main Degradation Products of Dabigatran Etexilate Evaluated by LC-UV and LC-ESI-MS, Degradation Kinetics and in vitro Cytotoxicity Studies |
title_full |
Main Degradation Products of Dabigatran Etexilate Evaluated by LC-UV and LC-ESI-MS, Degradation Kinetics and in vitro Cytotoxicity Studies |
title_fullStr |
Main Degradation Products of Dabigatran Etexilate Evaluated by LC-UV and LC-ESI-MS, Degradation Kinetics and in vitro Cytotoxicity Studies |
title_full_unstemmed |
Main Degradation Products of Dabigatran Etexilate Evaluated by LC-UV and LC-ESI-MS, Degradation Kinetics and in vitro Cytotoxicity Studies |
title_sort |
Main Degradation Products of Dabigatran Etexilate Evaluated by LC-UV and LC-ESI-MS, Degradation Kinetics and in vitro Cytotoxicity Studies |
author |
Bernardi,Raquel M. |
author_facet |
Bernardi,Raquel M. D’Avila,Felipe B. Todeschini,Vítor Andrade,Juliana M. M. Fröehlich,Pedro E. Bergold,Ana M. |
author_role |
author |
author2 |
D’Avila,Felipe B. Todeschini,Vítor Andrade,Juliana M. M. Fröehlich,Pedro E. Bergold,Ana M. |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Bernardi,Raquel M. D’Avila,Felipe B. Todeschini,Vítor Andrade,Juliana M. M. Fröehlich,Pedro E. Bergold,Ana M. |
dc.subject.por.fl_str_mv |
cytotoxity dabigatran etexilate degradation kinetics degradation products LC-ESI-MS |
topic |
cytotoxity dabigatran etexilate degradation kinetics degradation products LC-ESI-MS |
description |
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. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-04-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532015000400660 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532015000400660 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.5935/0103-5053.20150023 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Química |
publisher.none.fl_str_mv |
Sociedade Brasileira de Química |
dc.source.none.fl_str_mv |
Journal of the Brazilian Chemical Society v.26 n.4 2015 reponame:Journal of the Brazilian Chemical Society (Online) instname:Sociedade Brasileira de Química (SBQ) instacron:SBQ |
instname_str |
Sociedade Brasileira de Química (SBQ) |
instacron_str |
SBQ |
institution |
SBQ |
reponame_str |
Journal of the Brazilian Chemical Society (Online) |
collection |
Journal of the Brazilian Chemical Society (Online) |
repository.name.fl_str_mv |
Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ) |
repository.mail.fl_str_mv |
||office@jbcs.sbq.org.br |
_version_ |
1750318177025261568 |