Development of a Chiral Capillary Electrophoresis Method for the Enantioseparation of Verapamil Using Cyclodextrins as Chiral Selectors and Experimental Design Optimization

Chirality is a property of asymmetry which determines the pharmacokinetic and pharmacological profiles of optically active pharmaceuticals. Verapamil (VER), a calcium channel blocker phenylalkylamine derivative used in the treatment of cardio-vascular diseases, is a chiral compound, marketed as a ra...

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Autores principales:	Melania Cârcu-Dobrin, Gabriel Hancu, Lajos Attila Papp, Ibolya Fülöp, Hajnal Kelemen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	verapamil chiral separation capillary electrophoresis cyclodextrin experimental design molecular modelling Mathematics QA1-939
Acceso en línea:	https://doaj.org/article/df69a0c708d14f3b9fef2dc0f7f54a08
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spelling	oai:doaj.org-article:df69a0c708d14f3b9fef2dc0f7f54a082021-11-25T19:07:25ZDevelopment of a Chiral Capillary Electrophoresis Method for the Enantioseparation of Verapamil Using Cyclodextrins as Chiral Selectors and Experimental Design Optimization10.3390/sym131121862073-8994https://doaj.org/article/df69a0c708d14f3b9fef2dc0f7f54a082021-11-01T00:00:00Zhttps://www.mdpi.com/2073-8994/13/11/2186https://doaj.org/toc/2073-8994Chirality is a property of asymmetry which determines the pharmacokinetic and pharmacological profiles of optically active pharmaceuticals. Verapamil (VER), a calcium channel blocker phenylalkylamine derivative used in the treatment of cardio-vascular diseases, is a chiral compound, marketed as a racemate, although differences between the pharmacokinetic and pharmacological attributes of the enantiomers have been reported. The aim of our study was to develop a new chiral separation method for VER enantiomers by capillary electrophoresis (CE) using cyclodextrins (CDs) as chiral selectors (CSs). After an initial screening, using different native and derivatized CDs, at four pH levels, heptakis 2,3,6-tri-O-methyl-β-CD (TM-β-CD), a neutral derivatized CD, was identified as the optimum CS. For method optimization, a preliminary univariate approach was applied to characterize the influence of analytical parameters on the separation followed by a Box–Behnken experimental design to establish the optimal separation conditions. Chiral separation of enantiomers was achieved with a resolution of 1.58 in approximately 4 min; the migration order was <i>R</i>-VER followed by <i>S</i>-VER. The method analytical performance was evaluated in terms of precision, linearity, accuracy, and robustness (applying a Plackett–Burnam experimental design). The developed method was applied for the determination of VER enantiomers in pharmaceuticals. Finally, a computer modelling of VER–CD complexes was used to describe host–guest chiral recognition.Melania Cârcu-DobrinGabriel HancuLajos Attila PappIbolya FülöpHajnal KelemenMDPI AGarticleverapamilchiral separationcapillary electrophoresiscyclodextrinexperimental designmolecular modellingMathematicsQA1-939ENSymmetry, Vol 13, Iss 2186, p 2186 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	verapamil chiral separation capillary electrophoresis cyclodextrin experimental design molecular modelling Mathematics QA1-939
spellingShingle	verapamil chiral separation capillary electrophoresis cyclodextrin experimental design molecular modelling Mathematics QA1-939 Melania Cârcu-Dobrin Gabriel Hancu Lajos Attila Papp Ibolya Fülöp Hajnal Kelemen Development of a Chiral Capillary Electrophoresis Method for the Enantioseparation of Verapamil Using Cyclodextrins as Chiral Selectors and Experimental Design Optimization
description	Chirality is a property of asymmetry which determines the pharmacokinetic and pharmacological profiles of optically active pharmaceuticals. Verapamil (VER), a calcium channel blocker phenylalkylamine derivative used in the treatment of cardio-vascular diseases, is a chiral compound, marketed as a racemate, although differences between the pharmacokinetic and pharmacological attributes of the enantiomers have been reported. The aim of our study was to develop a new chiral separation method for VER enantiomers by capillary electrophoresis (CE) using cyclodextrins (CDs) as chiral selectors (CSs). After an initial screening, using different native and derivatized CDs, at four pH levels, heptakis 2,3,6-tri-O-methyl-β-CD (TM-β-CD), a neutral derivatized CD, was identified as the optimum CS. For method optimization, a preliminary univariate approach was applied to characterize the influence of analytical parameters on the separation followed by a Box–Behnken experimental design to establish the optimal separation conditions. Chiral separation of enantiomers was achieved with a resolution of 1.58 in approximately 4 min; the migration order was <i>R</i>-VER followed by <i>S</i>-VER. The method analytical performance was evaluated in terms of precision, linearity, accuracy, and robustness (applying a Plackett–Burnam experimental design). The developed method was applied for the determination of VER enantiomers in pharmaceuticals. Finally, a computer modelling of VER–CD complexes was used to describe host–guest chiral recognition.
format	article
author	Melania Cârcu-Dobrin Gabriel Hancu Lajos Attila Papp Ibolya Fülöp Hajnal Kelemen
author_facet	Melania Cârcu-Dobrin Gabriel Hancu Lajos Attila Papp Ibolya Fülöp Hajnal Kelemen
author_sort	Melania Cârcu-Dobrin
title	Development of a Chiral Capillary Electrophoresis Method for the Enantioseparation of Verapamil Using Cyclodextrins as Chiral Selectors and Experimental Design Optimization
title_short	Development of a Chiral Capillary Electrophoresis Method for the Enantioseparation of Verapamil Using Cyclodextrins as Chiral Selectors and Experimental Design Optimization
title_full	Development of a Chiral Capillary Electrophoresis Method for the Enantioseparation of Verapamil Using Cyclodextrins as Chiral Selectors and Experimental Design Optimization
title_fullStr	Development of a Chiral Capillary Electrophoresis Method for the Enantioseparation of Verapamil Using Cyclodextrins as Chiral Selectors and Experimental Design Optimization
title_full_unstemmed	Development of a Chiral Capillary Electrophoresis Method for the Enantioseparation of Verapamil Using Cyclodextrins as Chiral Selectors and Experimental Design Optimization
title_sort	development of a chiral capillary electrophoresis method for the enantioseparation of verapamil using cyclodextrins as chiral selectors and experimental design optimization
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/df69a0c708d14f3b9fef2dc0f7f54a08
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Development of a Chiral Capillary Electrophoresis Method for the Enantioseparation of Verapamil Using Cyclodextrins as Chiral Selectors and Experimental Design Optimization

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