Structural characterization of methyl-β-cyclodextrins by high-performance liquid chromatography and nuclear magnetic resonance spectroscopy and effect of their isomeric composition on the capillary electrophoresis enantioseparation of daclatasvir.

Autor: Krait S; Department of Pharmaceutical/Medicinal Chemistry, Friedrich-Schiller-University Jena, Philosophenweg 14, Jena 07743, Germany., Salgado A; NMR Spectroscopy Center (CERMN), CAI Químicas, Faculty of Pharmacy, University of Alcalá, Madrid, Alcalá de Henares 28805, Spain., Malanga M; CycloLab Ltd., Illatos út 7, Budapest 1097, Hungary., Sohajda T; CycloLab Ltd., Illatos út 7, Budapest 1097, Hungary., Benkovics G; CycloLab Ltd., Illatos út 7, Budapest 1097, Hungary., Szakály PS; CycloLab Ltd., Illatos út 7, Budapest 1097, Hungary., Chankvetadze B; Institute of Physical and Analytical Chemistry, School of Exact and Natural Sciences, Tbilisi State University, Tbilisi 0179, Georgia., Scriba GKE; Department of Pharmaceutical/Medicinal Chemistry, Friedrich-Schiller-University Jena, Philosophenweg 14, Jena 07743, Germany. Electronic address: gerhard.scriba@uni-jena.de.
Jazyk: angličtina
Zdroj: Journal of chromatography. A [J Chromatogr A] 2022 Jan 04; Vol. 1661, pp. 462675. Date of Electronic Publication: 2021 Nov 09.
DOI: 10.1016/j.chroma.2021.462675
Abstrakt: The separation of daclatasvir and its R,R,R,R-enantiomer was studied by capillary electrophoresis using various randomly methylated β-CDs and the single isomer heptakis(2,6-di-O-methyl)-β-CD (2,6-DM-β-CD) as chiral selectors in an acidic background electrolyte. Opposite enantiomer migration order was observed for randomly substituted CDs compared to 2,6-DM-β-CD as well as methylated β-CDs with different composition according to the specifications of the manufacturers. HPLC and NMR analyses confirmed that the presence of a high 2,6-DM-β-CD content in the CDs enables to achieve the migration order R,R,R,R-enantiomer > daclatasvir. In contrast, products with low 2,6-DM-β-CD isomer content and/or the presence of a large amount of methylated CD isomers, in which d-glucopyranose moieties are not substituted in either position 2 or 6, displayed the opposite enantiomer migration order daclatasvir > R,R,R,R-enantiomer. The study indicated the importance of the type and composition of derivatized CDs on chiral separations in capillary electrophoresis as well as the importance of proper quality control for cyclodextrin manufacturers. Moreover, the observed migration order could be rationalized based on the composition and substitution pattern of the CDs.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021. Published by Elsevier B.V.)
Databáze: MEDLINE
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