Chiral separation of a basic drug with two chiral centers by electrokinetic chromatography for its pharmaceutical development

A chiral method using capillary electrophoresis was developed for the separation of the four stereoisomers of a new chiral substance currently undergoing drug development as single enantiomer. After the selection of highly sulfated beta-CD as chiral selector, an exhaustive study on the influence of...

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Detalles Bibliográficos
Autores: Martínez Girón, Ana Belén, Marina Alegre, María Luisa|||0000-0002-5583-1624, Crego Navazo, Antonio Luis|||0000-0002-4083-5294
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universidad de Alcalá (UAH)
Repositorio:e_Buah Biblioteca Digital Universidad de Alcalá
Idioma:inglés
OAI Identifier:oai:ebuah.uah.es:10017/48188
Acceso en línea:http://hdl.handle.net/10017/48188
https://dx.doi.org/10.1016/j.chroma.2016.08.041
Access Level:acceso abierto
Palabra clave:Chiral drug
Enantiomeric purity
Chiral stability
Electrokinetic chromatography with cyclodextrins
Química
Chemistry
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spelling Chiral separation of a basic drug with two chiral centers by electrokinetic chromatography for its pharmaceutical developmentMartínez Girón, Ana BelénMarina Alegre, María Luisa|||0000-0002-5583-1624Crego Navazo, Antonio Luis|||0000-0002-4083-5294Chiral drugEnantiomeric purityChiral stabilityElectrokinetic chromatography with cyclodextrinsQuímicaChemistryA chiral method using capillary electrophoresis was developed for the separation of the four stereoisomers of a new chiral substance currently undergoing drug development as single enantiomer. After the selection of highly sulfated beta-CD as chiral selector, an exhaustive study on the influence of several experimental variables on the resolution was performed, being the substitution degree of the CD a very decisive factor. Run time and resolutions were about 20 min and higher than 2.0, respectively. The method was validated in terms of selectivity, linearity, accuracy, precision, and limits of detection and quantitation according to the requirements of the International Conference on Harmonisation for the determination of the chiral purity of a drug substance. The usefulness of the method was demonstrated in the control of stereoisomeric impurities in raw material as well as in the determination of the chiral stability of the drug in the solid state and in dosage forms used in safety assessment. Finally, the chiral method was used to investigate the possible in vivo inversion in biological samples. (C) 2016 Elsevier B.V. All rights reserved.Ministerio de Educación y CienciaMinisterio de Ciencia e InnovaciónMinisterio de Economía y Competitividad20162016-10-07journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10017/48188https://dx.doi.org/10.1016/j.chroma.2016.08.041reponame:e_Buah Biblioteca Digital Universidad de Alcaláinstname:Universidad de Alcalá (UAH)InglésengMinisterio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Not available CTQ2009-09022 ESMinisterio de Educación y Ciencia Not available CTQ2006-03849 Nuevas Contribuciones para el Desarrollo de Metodologías Analíticas de Alta Sensibilidad y Resolución Mediante Técnicas MicroseparativasMinisterio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 Not available CTQ2013-48740-P Metodolgoías avanzadas para análisis quiral mediante técnicas microseparativas. Búsqueda de biomarcadores en sistemas enantioselectivosopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-ShareAlike 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:ebuah.uah.es:10017/481882026-06-18T11:13:07Z
dc.title.none.fl_str_mv Chiral separation of a basic drug with two chiral centers by electrokinetic chromatography for its pharmaceutical development
title Chiral separation of a basic drug with two chiral centers by electrokinetic chromatography for its pharmaceutical development
spellingShingle Chiral separation of a basic drug with two chiral centers by electrokinetic chromatography for its pharmaceutical development
Martínez Girón, Ana Belén
Chiral drug
Enantiomeric purity
Chiral stability
Electrokinetic chromatography with cyclodextrins
Química
Chemistry
title_short Chiral separation of a basic drug with two chiral centers by electrokinetic chromatography for its pharmaceutical development
title_full Chiral separation of a basic drug with two chiral centers by electrokinetic chromatography for its pharmaceutical development
title_fullStr Chiral separation of a basic drug with two chiral centers by electrokinetic chromatography for its pharmaceutical development
title_full_unstemmed Chiral separation of a basic drug with two chiral centers by electrokinetic chromatography for its pharmaceutical development
title_sort Chiral separation of a basic drug with two chiral centers by electrokinetic chromatography for its pharmaceutical development
dc.creator.none.fl_str_mv Martínez Girón, Ana Belén
Marina Alegre, María Luisa|||0000-0002-5583-1624
Crego Navazo, Antonio Luis|||0000-0002-4083-5294
author Martínez Girón, Ana Belén
author_facet Martínez Girón, Ana Belén
Marina Alegre, María Luisa|||0000-0002-5583-1624
Crego Navazo, Antonio Luis|||0000-0002-4083-5294
author_role author
author2 Marina Alegre, María Luisa|||0000-0002-5583-1624
Crego Navazo, Antonio Luis|||0000-0002-4083-5294
author2_role author
author
dc.subject.none.fl_str_mv Chiral drug
Enantiomeric purity
Chiral stability
Electrokinetic chromatography with cyclodextrins
Química
Chemistry
topic Chiral drug
Enantiomeric purity
Chiral stability
Electrokinetic chromatography with cyclodextrins
Química
Chemistry
description A chiral method using capillary electrophoresis was developed for the separation of the four stereoisomers of a new chiral substance currently undergoing drug development as single enantiomer. After the selection of highly sulfated beta-CD as chiral selector, an exhaustive study on the influence of several experimental variables on the resolution was performed, being the substitution degree of the CD a very decisive factor. Run time and resolutions were about 20 min and higher than 2.0, respectively. The method was validated in terms of selectivity, linearity, accuracy, precision, and limits of detection and quantitation according to the requirements of the International Conference on Harmonisation for the determination of the chiral purity of a drug substance. The usefulness of the method was demonstrated in the control of stereoisomeric impurities in raw material as well as in the determination of the chiral stability of the drug in the solid state and in dosage forms used in safety assessment. Finally, the chiral method was used to investigate the possible in vivo inversion in biological samples. (C) 2016 Elsevier B.V. All rights reserved.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-10-07
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10017/48188
https://dx.doi.org/10.1016/j.chroma.2016.08.041
url http://hdl.handle.net/10017/48188
https://dx.doi.org/10.1016/j.chroma.2016.08.041
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Ciencia e Innovación http://dx.doi.org/10.13039/501100004837 Not available CTQ2009-09022 ES
Ministerio de Educación y Ciencia Not available CTQ2006-03849 Nuevas Contribuciones para el Desarrollo de Metodologías Analíticas de Alta Sensibilidad y Resolución Mediante Técnicas Microseparativas
Ministerio de Economía y Competitividad http://dx.doi.org/10.13039/501100003329 Not available CTQ2013-48740-P Metodolgoías avanzadas para análisis quiral mediante técnicas microseparativas. Búsqueda de biomarcadores en sistemas enantioselectivos
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:e_Buah Biblioteca Digital Universidad de Alcalá
instname:Universidad de Alcalá (UAH)
instname_str Universidad de Alcalá (UAH)
reponame_str e_Buah Biblioteca Digital Universidad de Alcalá
collection e_Buah Biblioteca Digital Universidad de Alcalá
repository.name.fl_str_mv
repository.mail.fl_str_mv
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