Chiral separation of a basic drug with two chiral centers by electrokinetic chromatography for its pharmaceutical development
Identifiers
Permanent link (URI): http://hdl.handle.net/10017/48188DOI: 10.1016/j.chroma.2016.08.041
ISSN: 00219673
Date
2016-10-07Affiliation
Universidad de Alcalá. Departamento de Química Analítica, Química Física e Ingeniería QuímicaBibliographic citation
Journal of Chromatography A, 2016, v. 1467, p. 427-435
Keywords
Chiral drug
Enantiomeric purity
Chiral stability
Electrokinetic chromatography with cyclodextrins
Project
Ministerio de Ciencia e Innovación (CTQ2009-09022)
info:eu-repo/grantAgreement/MEC//CTQ2006-03849/ES/Nuevas Contribuciones para el Desarrollo de Metodologías Analíticas de Alta Sensibilidad y Resolución Mediante Técnicas Microseparativas/
info:eu-repo/grantAgreement/MINECO//CTQ2013-48740-P/ES/METODOLOGIAS AVANZADAS PARA ANALISIS QUIRAL MEDIANTE TECNICAS MICROSEPARATIVAS. BUSQUEDA DE BIOMARCADORES EN SISTEMAS ENANTIOSELECTIVOS/
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
© Elsevier
Access rights
info:eu-repo/semantics/openAccess
Abstract
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.
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