Chiral Discrimination of Mexiletine Enantiomers by Capillary Electrophoresis Using Cyclodextrins as Chiral Selectors and Experimental Design Method Optimization
Mexiletine (MXL) is a class IB antiarrhythmic agent, acting as a non-selective voltage-gated sodium channel blocker, used in therapy as a racemic mixture <i>R</i>,<i>S</i>-MXL hydrochloride. The aim of the current study was the development of a new, fast, and efficient method...
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| Format: | Article |
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MDPI AG
2022-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/17/5603 |
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| author | Melania Cârcu-Dobrin Gabriel Hancu Lajos Attila Papp Ibolya Fülöp |
| author_facet | Melania Cârcu-Dobrin Gabriel Hancu Lajos Attila Papp Ibolya Fülöp |
| author_sort | Melania Cârcu-Dobrin |
| collection | DOAJ |
| description | Mexiletine (MXL) is a class IB antiarrhythmic agent, acting as a non-selective voltage-gated sodium channel blocker, used in therapy as a racemic mixture <i>R</i>,<i>S</i>-MXL hydrochloride. The aim of the current study was the development of a new, fast, and efficient method for the chiral separation of MXL enantiomers using capillary electrophoresis (CE) and cyclodextrins (CDs) as chiral selectors (CSs). After an initial CS screening, using several neutral and charged CDs, at four pH levels, heptakis-2,3,6-tri-O-methyl-β-CD (TM-β-CD), a neutral derivatized CD, was chosen as the optimum CS for the enantioseparation. For method optimization, an initial screening fractional factorial design was applied to identify the most significant parameters, followed by a face-centered central composite design to establish the optimal separation conditions. The best results were obtained by applying the following optimized electrophoretic conditions: 60 mM phosphate buffer, pH 5.0, 50 mM TM-β-CD, temperature 20 °C, applied voltage 30 kV, hydrodynamic injection 50 mbar/s. MXL enantiomers were baseline separated with a resolution of 1.52 during a migration time of under 5 min; <i>S</i>-MXL was the first migrating enantiomer. The method’s analytical performance was verified in terms of precision, linearity, accuracy, and robustness (applying a Plackett–Burman design). The developed method was applied for the determination of MXL enantiomers in pharmaceuticals. A computer modeling of the MXL-CD complexes was applied to characterize host–guest chiral recognition. |
| first_indexed | 2024-03-10T01:29:26Z |
| format | Article |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T01:29:26Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-2444dc0d428945b69f2b998ecd9275a42023-11-23T13:44:56ZengMDPI AGMolecules1420-30492022-08-012717560310.3390/molecules27175603Chiral Discrimination of Mexiletine Enantiomers by Capillary Electrophoresis Using Cyclodextrins as Chiral Selectors and Experimental Design Method OptimizationMelania Cârcu-Dobrin0Gabriel Hancu1Lajos Attila Papp2Ibolya Fülöp3Department of Pharmaceutical and Therapeutic Chemistry, Faculty of Pharmacy, University of Medicine, Pharmacy, Science and Technology “George Emil Palade” of Târgu Mureș, 540142 Târgu Mureș, RomaniaDepartment of Pharmaceutical and Therapeutic Chemistry, Faculty of Pharmacy, University of Medicine, Pharmacy, Science and Technology “George Emil Palade” of Târgu Mureș, 540142 Târgu Mureș, RomaniaDepartment of Pharmaceutical and Therapeutic Chemistry, Faculty of Pharmacy, University of Medicine, Pharmacy, Science and Technology “George Emil Palade” of Târgu Mureș, 540142 Târgu Mureș, RomaniaDepartment of Toxicology and Biopharmacy, Faculty of Pharmacy, University of Medicine, Pharmacy, Science and Technology “George Emil Palade” of Târgu Mureș, 540142 Târgu Mureș, RomaniaMexiletine (MXL) is a class IB antiarrhythmic agent, acting as a non-selective voltage-gated sodium channel blocker, used in therapy as a racemic mixture <i>R</i>,<i>S</i>-MXL hydrochloride. The aim of the current study was the development of a new, fast, and efficient method for the chiral separation of MXL enantiomers using capillary electrophoresis (CE) and cyclodextrins (CDs) as chiral selectors (CSs). After an initial CS screening, using several neutral and charged CDs, at four pH levels, heptakis-2,3,6-tri-O-methyl-β-CD (TM-β-CD), a neutral derivatized CD, was chosen as the optimum CS for the enantioseparation. For method optimization, an initial screening fractional factorial design was applied to identify the most significant parameters, followed by a face-centered central composite design to establish the optimal separation conditions. The best results were obtained by applying the following optimized electrophoretic conditions: 60 mM phosphate buffer, pH 5.0, 50 mM TM-β-CD, temperature 20 °C, applied voltage 30 kV, hydrodynamic injection 50 mbar/s. MXL enantiomers were baseline separated with a resolution of 1.52 during a migration time of under 5 min; <i>S</i>-MXL was the first migrating enantiomer. The method’s analytical performance was verified in terms of precision, linearity, accuracy, and robustness (applying a Plackett–Burman design). The developed method was applied for the determination of MXL enantiomers in pharmaceuticals. A computer modeling of the MXL-CD complexes was applied to characterize host–guest chiral recognition.https://www.mdpi.com/1420-3049/27/17/5603mexiletinecapillary electrophoresiscyclodextrinschiral separationexperimental designmolecular modeling |
| spellingShingle | Melania Cârcu-Dobrin Gabriel Hancu Lajos Attila Papp Ibolya Fülöp Chiral Discrimination of Mexiletine Enantiomers by Capillary Electrophoresis Using Cyclodextrins as Chiral Selectors and Experimental Design Method Optimization Molecules mexiletine capillary electrophoresis cyclodextrins chiral separation experimental design molecular modeling |
| title | Chiral Discrimination of Mexiletine Enantiomers by Capillary Electrophoresis Using Cyclodextrins as Chiral Selectors and Experimental Design Method Optimization |
| title_full | Chiral Discrimination of Mexiletine Enantiomers by Capillary Electrophoresis Using Cyclodextrins as Chiral Selectors and Experimental Design Method Optimization |
| title_fullStr | Chiral Discrimination of Mexiletine Enantiomers by Capillary Electrophoresis Using Cyclodextrins as Chiral Selectors and Experimental Design Method Optimization |
| title_full_unstemmed | Chiral Discrimination of Mexiletine Enantiomers by Capillary Electrophoresis Using Cyclodextrins as Chiral Selectors and Experimental Design Method Optimization |
| title_short | Chiral Discrimination of Mexiletine Enantiomers by Capillary Electrophoresis Using Cyclodextrins as Chiral Selectors and Experimental Design Method Optimization |
| title_sort | chiral discrimination of mexiletine enantiomers by capillary electrophoresis using cyclodextrins as chiral selectors and experimental design method optimization |
| topic | mexiletine capillary electrophoresis cyclodextrins chiral separation experimental design molecular modeling |
| url | https://www.mdpi.com/1420-3049/27/17/5603 |
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