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

Symmetry ◽  
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.

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

Symmetry ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2186
Author(s):  
Melania Cârcu-Dobrin ◽  
Gabriel Hancu ◽  
Lajos Attila Papp ◽  
Ibolya Fülöp ◽  
Hajnal Kelemen
Keyword(s):  
Capillary Electrophoresis ◽  
Experimental Design ◽  
Chiral Separation ◽  
Computer Modelling ◽  
Vascular Diseases ◽  
Chiral Selectors ◽  
Optimal Separation ◽  
Method Optimization ◽  
Electrophoresis Method ◽  
Cardio Vascular

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.

scholarly journals Study of interaction between polyphenolic compounds and protein using computational and capillary electrophoresis techniques

2013 ◽  
Author(s):  
◽  
Myalowenkosi Innocent Sabela
Keyword(s):  
Capillary Electrophoresis ◽  
Molecular Docking ◽  
Protein Interactions ◽  
Method Development ◽  
Docking Studies ◽  
Chiral Selector ◽  
Chiral Compounds ◽  
Multiple Binding Sites ◽  
Important Regulator ◽  
Inorganic Molecules

The present work involves the interaction studies of chiral compounds with the Human Serum Albumin (HSA) protein using computational and experimental methods. The HSA protein has multiple binding sites that forms the basis for its exceptional ability to interact with many organic and inorganic molecules, which makes this protein an important regulator of intercellular fluxes and the pharmacokinetic behaviour of many drugs. This study was undertaken to evaluate the related pharmacokinetic and enantioselective binding parameters of the racemic catechin enantiomers with the HSA. Accordingly, this work involved a method development for the chiral separation of a racemic compound, by capillary electrophoresis-electrokinetic chromatography (CE-EKC) with a highly sulphated beta-cyclodextrin (HS--CD) as a chiral selector. The experimental work was supported by two molecular docking studies. The first included the mimicking of the host-guest interactions between a chiral selector and an enantiomeric compound. The second study included the estimation of the pseudo enantioselective (ES) binding of catechin to HSA. Overall, it was found that CE-EKC is the preferred method for the(±)-catechin binding to HSA protein evaluation. Moreover, the technique used in this work is not restricted to HSA or polyphenols, but can also be applied to other proteins and ligands that possess chirality. Furthermore, the molecular docking approaches also proved to be very useful for the evaluation of chiral recognition systems and for elucidation of the ligand-protein interactions.

scholarly journals Enantioseparation and Determination of Mephedrone and Its Metabolites by Capillary Electrophoresis Using Cyclodextrins as Chiral Selectors

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2879
Author(s):  
Pavel Řezanka ◽  
Denisa Macková ◽  
Radek Jurok ◽  
Michal Himl ◽  
Martin Kuchař
Keyword(s):  
Capillary Electrophoresis ◽  
Chiral Separation ◽  
Simplex Method ◽  
Background Electrolyte ◽  
Detection Limits ◽  
Chiral Selector ◽  
Designer Drug ◽  
Optimal Composition ◽  
Linear Calibration

Mephedrone, a psychoactive compound derived from cathinone, is widely used as a designer drug. The determination of mephedrone and its metabolites is important for understanding its possible use in medicine. In this work, a method of capillary electrophoresis for the chiral separation of mephedrone and its metabolites was developed. Carboxymethylated β-cyclodextrin was selected as the most effective chiral selector from seven tested cyclodextrin derivates. Based on the simplex method, the optimal composition of the background electrolyte was determined: at pH 2.75 and 7.5 mmol·L−1 carboxymethylated β-cyclodextrin the highest total resolution of a mixture of analytes was achieved. For mephedrone and its metabolites, calibration curves were constructed in a calibration range from 0.2 to 5 mmol·L−1; limits of detection, limits of quantification, precision, and repeatability were calculated, and according to Mandel’s fitting test, the linear calibration ranges were determined.

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