Characterization and in silico Mutagenic Assessment of a New Betahistine Degradation Impurity
Autor(a) principal: | |
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Data de Publicação: | 2019 |
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=S0103-50532019000701415 |
Resumo: | Currently, the pharmaceutical industry devotes great attention to drug degradation products because these compounds can offer risks to patients. A previous degradation study of betahistine (N-α-methyl-2-pyridylethylamine) conducted under different stress conditions detected three main impurities named A, B and C. Degradation products were analyzed by high-resolution mass spectrometry in electrospray source and time of flight analyzer (ESI-TOF) and nuclear magnetic resonance (NMR). Impurity mutagenicity was evaluated by Derek Nexus and Sarah Nexus softwares. Liquid chromatography hyphenate with tandem mass spectrometry (LC-MS/MS) analysis of the betahistine forced degradation sample indicated the presence of a new impurity, which was named impurity C1. 2D NMR experiments allowed the complete structural characterization of the new entity. The active pharmaceutical ingredient and degradation impurities were classified as inactive in the in silico mutagenic studies. Systematic investigation of a forced degradation sample led to the characterization of a new betahistine impurity. The in silico mutagenicity study of the betahistine degradation impurities may be useful in the risk assessment of the drug products. |
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Characterization and in silico Mutagenic Assessment of a New Betahistine Degradation Impuritybetahistinedrug stabilitydrug impuritiesforced-degradation studiesCurrently, the pharmaceutical industry devotes great attention to drug degradation products because these compounds can offer risks to patients. A previous degradation study of betahistine (N-α-methyl-2-pyridylethylamine) conducted under different stress conditions detected three main impurities named A, B and C. Degradation products were analyzed by high-resolution mass spectrometry in electrospray source and time of flight analyzer (ESI-TOF) and nuclear magnetic resonance (NMR). Impurity mutagenicity was evaluated by Derek Nexus and Sarah Nexus softwares. Liquid chromatography hyphenate with tandem mass spectrometry (LC-MS/MS) analysis of the betahistine forced degradation sample indicated the presence of a new impurity, which was named impurity C1. 2D NMR experiments allowed the complete structural characterization of the new entity. The active pharmaceutical ingredient and degradation impurities were classified as inactive in the in silico mutagenic studies. Systematic investigation of a forced degradation sample led to the characterization of a new betahistine impurity. The in silico mutagenicity study of the betahistine degradation impurities may be useful in the risk assessment of the drug products.Sociedade Brasileira de Química2019-07-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532019000701415Journal of the Brazilian Chemical Society v.30 n.7 2019reponame:Journal of the Brazilian Chemical Society (Online)instname:Sociedade Brasileira de Química (SBQ)instacron:SBQ10.21577/0103-5053.20190037info:eu-repo/semantics/openAccessMello,Murilo B. M. deOliveira,Antonio A. F. deOliveira,Caroline L. deUltramari,Mariah A.Gama,Fernando H. S.Mascarello,AlessandraGuimarães,Cristiano R. W.Freitas,Miller N. deCunha,Carlos E.Lourenço,Tiago C.Ferreira,Fernanda P.Lopes,João L. C.Clososki,Giuliano C.eng2019-07-01T00:00:00Zoai:scielo:S0103-50532019000701415Revistahttp://jbcs.sbq.org.brONGhttps://old.scielo.br/oai/scielo-oai.php||office@jbcs.sbq.org.br1678-47900103-5053opendoar:2019-07-01T00:00Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)false |
dc.title.none.fl_str_mv |
Characterization and in silico Mutagenic Assessment of a New Betahistine Degradation Impurity |
title |
Characterization and in silico Mutagenic Assessment of a New Betahistine Degradation Impurity |
spellingShingle |
Characterization and in silico Mutagenic Assessment of a New Betahistine Degradation Impurity Mello,Murilo B. M. de betahistine drug stability drug impurities forced-degradation studies |
title_short |
Characterization and in silico Mutagenic Assessment of a New Betahistine Degradation Impurity |
title_full |
Characterization and in silico Mutagenic Assessment of a New Betahistine Degradation Impurity |
title_fullStr |
Characterization and in silico Mutagenic Assessment of a New Betahistine Degradation Impurity |
title_full_unstemmed |
Characterization and in silico Mutagenic Assessment of a New Betahistine Degradation Impurity |
title_sort |
Characterization and in silico Mutagenic Assessment of a New Betahistine Degradation Impurity |
author |
Mello,Murilo B. M. de |
author_facet |
Mello,Murilo B. M. de Oliveira,Antonio A. F. de Oliveira,Caroline L. de Ultramari,Mariah A. Gama,Fernando H. S. Mascarello,Alessandra Guimarães,Cristiano R. W. Freitas,Miller N. de Cunha,Carlos E. Lourenço,Tiago C. Ferreira,Fernanda P. Lopes,João L. C. Clososki,Giuliano C. |
author_role |
author |
author2 |
Oliveira,Antonio A. F. de Oliveira,Caroline L. de Ultramari,Mariah A. Gama,Fernando H. S. Mascarello,Alessandra Guimarães,Cristiano R. W. Freitas,Miller N. de Cunha,Carlos E. Lourenço,Tiago C. Ferreira,Fernanda P. Lopes,João L. C. Clososki,Giuliano C. |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Mello,Murilo B. M. de Oliveira,Antonio A. F. de Oliveira,Caroline L. de Ultramari,Mariah A. Gama,Fernando H. S. Mascarello,Alessandra Guimarães,Cristiano R. W. Freitas,Miller N. de Cunha,Carlos E. Lourenço,Tiago C. Ferreira,Fernanda P. Lopes,João L. C. Clososki,Giuliano C. |
dc.subject.por.fl_str_mv |
betahistine drug stability drug impurities forced-degradation studies |
topic |
betahistine drug stability drug impurities forced-degradation studies |
description |
Currently, the pharmaceutical industry devotes great attention to drug degradation products because these compounds can offer risks to patients. A previous degradation study of betahistine (N-α-methyl-2-pyridylethylamine) conducted under different stress conditions detected three main impurities named A, B and C. Degradation products were analyzed by high-resolution mass spectrometry in electrospray source and time of flight analyzer (ESI-TOF) and nuclear magnetic resonance (NMR). Impurity mutagenicity was evaluated by Derek Nexus and Sarah Nexus softwares. Liquid chromatography hyphenate with tandem mass spectrometry (LC-MS/MS) analysis of the betahistine forced degradation sample indicated the presence of a new impurity, which was named impurity C1. 2D NMR experiments allowed the complete structural characterization of the new entity. The active pharmaceutical ingredient and degradation impurities were classified as inactive in the in silico mutagenic studies. Systematic investigation of a forced degradation sample led to the characterization of a new betahistine impurity. The in silico mutagenicity study of the betahistine degradation impurities may be useful in the risk assessment of the drug products. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-07-01 |
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=S0103-50532019000701415 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532019000701415 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.21577/0103-5053.20190037 |
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.30 n.7 2019 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_ |
1750318182047940608 |