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 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 R-VER followed by S-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.

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Chiral separation of tramadol enantiomers by capillary electrophoresis using cyclodextrins as chiral selectors and experimental design method optimization

Chemical Papers ◽

10.1007/s11696-019-00789-8 ◽

2019 ◽

Vol 73 (9) ◽

pp. 2363-2370 ◽

Cited By ~ 4

Author(s):

Anita Sarkany ◽

Gabriel Hancu ◽

Anca Cârje ◽

Claudiu Drăguț ◽

Lajos Attila Papp

Keyword(s):

Capillary Electrophoresis ◽

Experimental Design ◽

Chiral Separation ◽

Design Method ◽

Chiral Selectors ◽

Experimental Design Method ◽

Method Optimization

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Venlafaxine Chiral Separation by Capillary Electrophoresis Using Cyclodextrin Derivatives as Chiral Selector and Experimental Design Method Optimization

Symmetry ◽

10.3390/sym12050849 ◽

2020 ◽

Vol 12 (5) ◽

pp. 849

Author(s):

Andreea Milan ◽

Gabriel Hancu ◽

Daniela Lupu ◽

Monica Budău ◽

Vladimir Garaj ◽

...

Keyword(s):

Capillary Electrophoresis ◽

Chiral Separation ◽

Method Development ◽

Computer Modelling ◽

Design Method ◽

Screening Strategy ◽

Chiral Selector ◽

Norepinephrine Reuptake Inhibitor ◽

Method Optimization ◽

Face Centered

Venlafaxine (VFX) is a modern antidepressant from the serotonin and norepinephrine reuptake inhibitor (SNRI) class. It is a chiral substance used in therapy as a racemate, but differences between the pharmacological properties of the two enantiomers have been reported. The current article presents the development of a simple capillary electrophoresis (CE) method for the rapid chiral separation of VFX enantiomers. A complex cyclodextrin (CD) screening at four different pH levels was carried out to establish the optimum chiral selector; carboxymethyl-β-CD (CM-β-CD) at pH 2.5 was selected for further method development. An initial “one factor at time” (OFAT) screening strategy was used to establish the influence of analytical parameters on the separation, followed by a face centered central composite design (FCCD) for the optimization process. The analytical performances of the newly developed method were verified in terms of accuracy, linearity, precision, repeatability, and sensitivity. The method was used for the determination of VFX enantiomer ratio in pharmaceutical forms. Finally, computer modelling of VFX-CD complexes was undertaken to characterize host–guest chiral recognition.

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Chiral Selectors in Capillary Electrophoresis: Trends During 2017–2018

Molecules ◽

10.3390/molecules24061135 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1135 ◽

Cited By ~ 22

Author(s):

Raymond B. Yu ◽

Joselito P. Quirino

Keyword(s):

Capillary Electrophoresis ◽

Molecular Mass ◽

Chiral Separation ◽

Chiral Separations ◽

Water Soluble ◽

Resonance Spectroscopy ◽

Electrokinetic Chromatography ◽

Chiral Selectors ◽

Analytical Technique ◽

Pharmaceutical Industries

Chiral separation is an important process in the chemical and pharmaceutical industries. From the analytical chemistry perspective, chiral separation is required for assessing the fit-for-purpose and the safety of chemical products. Capillary electrophoresis, in the electrokinetic chromatography mode is an established analytical technique for chiral separations. A water-soluble chiral selector is typically used. This review therefore examines the use of various chiral selectors in electrokinetic chromatography during 2017–2018. The chiral selectors were both low and high (macromolecules) molecular mass molecules as well as molecular aggregates (supramolecules). There were 58 papers found by search in Scopus, indicating continuous and active activity in this research area. The macromolecules were sugar-, amino acid-, and nucleic acid-based polymers. The supramolecules were bile salt micelles. The low molecular mass selectors were mainly ionic liquids and complexes with a central ion. A majority of the papers were on the use or preparation of sugar-based macromolecules, e.g., native or derivatised cyclodextrins. Studies to explain chiral recognition of macromolecular and supramolecular chiral selectors were mainly done by molecular modelling and nuclear magnetic resonance spectroscopy. Demonstrations were predominantly on drug analysis for the separation of racemates.

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