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

Detalhes bibliográficos
Autor(a) principal: Bernardi,Raquel M.
Data de Publicação: 2015
Outros Autores: D’Avila,Felipe B., Todeschini,Vítor, Andrade,Juliana M. M., Fröehlich,Pedro E., Bergold,Ana M.
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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spelling 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
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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
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