Preparative separation of nadolol racemates by fixed-bed and SMB liquid chromatography using C18 columns

Arafah, Rami; Ribeiro, António E.; Rodrigues, Alírio; Pais, Luís S.

Publication

Preparative separation of nadolol racemates by fixed-bed and SMB liquid chromatography using C18 columns

2017Conference object

dc.contributor.author	Arafah, Rami
dc.contributor.author	Ribeiro, António E.
dc.contributor.author	Rodrigues, Alírio
dc.contributor.author	Pais, Luís S.
dc.date.accessioned	2020-02-26T16:10:49Z
dc.date.available	2020-02-26T16:10:49Z
dc.date.issued	2017
dc.description.abstract	Nadolol is one representative beta-blocker pharmaceutical drug prescribed worldwide for relieve of several diseases mainly related with the cardiovascular system. However, like other pharmaceutical drugs, it is also related with some severe risks, such as depression, insomnia and cardiovascular failure, among others. Some authors refer that this problem is related, or could be related, to the fact that nadolol drug is still marketed as a mixture of equal amounts of its four stereoisomers. In the pharmaceutical industry and in terms of preparative scale, there are two main strategies to obtain pure enantiomer drugs. The first strategy is based on traditional methods of selective organic synthesis that allows the attainment of large amounts of a single product but with the disadvantage of being large time consuming. The other preparative strategy makes use of continuous separation processes based on multicolumn and cyclic adsorptive liquid chromatographic techniques to achieve the resolution of a racemic mixture. The use of such technologies allows, in a short period of time, the obtaining of enough amounts of pure enantiomers needed to perform the main pharmacological studies in the first steps of drug development. Lately, our research group reported the pseudo-binary separation of RSR-nadolol stereoisomer, referred in the literature as being the one responsible of the nadolol drug therapeutic action, by means of simulated moving bed (SMB) chromatography using both coated Chiralpak AD and Chiralpak IA immobilized chiral stationary phases (CSP).1,2 This technology is generally based on the use of chiral adsorbents which must have enough recognition for all the chiral species. In this work it is proposed an alternative strategy, implementing a first achiral separation step, to be followed by two subsequent parallel chiral separation steps.3-5 In this first achiral step, C18 columns are used to perform the separation of the two pairs of nadolol enantiomers (“racemate A” from “racemate B”) under reversed-phase mode. The C18 achiral adsorbent allows the separation of the two pairs of nadolol diastereomers, i.e., the first racemate (composed by the nadolol compounds 2 and 3) co-eluting in the raffinate, and the second racemate (composed by the nadolol compounds 1 and 4) to be obtained in the extract SMB stream. After this preliminary achiral separation step, two parallel SMB runs must be carried out using a chiral stationary phase to achieve the complete separation of all the four nadolol stereoisomers. Extensive experimental and simulation results will be presented including solvent screening, measurement of equilibrium adsorption isotherms, breakthrough measurements, and both fixed-bed (Azura prep LC unit) and SMB (FlexSMB-LSRE unit) preparative separations using C18 columns.	pt_PT
dc.description.sponsorship	This work was financially supported by: Project POCI-01-0145-FEDER-006984- Associate Laboratory LSRE-LCM funded by FEDER through COMPETE2020- Programa Operational Competitividade e lnternacionalização (POCI) -and by national funds through FCT- Fundação para a Ciência ea Tecnologia	pt_PT
dc.description.version	info:eu-repo/semantics/publishedVersion	pt_PT
dc.identifier.citation	Arafah, Rami; Ribeiro, António E.; Rodrigues, A.E.; Pais, L.S. (2017). Preparative separation of nadolol racemates by fixed-bed and SMB liquid chromatography using C18 columns. In XXIII Encontro Galego Portugués de Química. Ferrol. ISBN 978-84-697-7356-7	pt_PT
dc.identifier.issn	978-84-697-7356-7
dc.identifier.uri	http://hdl.handle.net/10198/20698
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by-nc/4.0/	pt_PT
dc.subject	SMB	pt_PT
dc.subject	Fixed-bed	pt_PT
dc.subject	Preparative liquid chromatography	pt_PT
dc.subject	Nadolol racemates	pt_PT
dc.title	Preparative separation of nadolol racemates by fixed-bed and SMB liquid chromatography using C18 columns	pt_PT
dc.type	conference object
dspace.entity.type	Publication
oaire.citation.conferencePlace	Ferrol, Espanha	pt_PT
oaire.citation.title	XXIII Encontro Galego Portugués de Química	pt_PT
person.familyName	Arafah
person.familyName	Ribeiro
person.familyName	Pais
person.givenName	Rami
person.givenName	António E.
person.givenName	Luís S.
person.identifier.ciencia-id	AB16-ECBF-B886
person.identifier.ciencia-id	3211-D5B0-870D
person.identifier.ciencia-id	421E-0CCD-A84F
person.identifier.orcid	0000-0002-7743-4988
person.identifier.orcid	0000-0003-4569-7887
person.identifier.orcid	0000-0002-3000-2862
person.identifier.scopus-author-id	57151342900
person.identifier.scopus-author-id	23390701300
person.identifier.scopus-author-id	6603930478
rcaap.rights	openAccess	pt_PT
rcaap.type	conferenceObject	pt_PT
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