Experimental and theoretical study on chiral recognition mechanism of ketoconazole enantiomers using heptakis (2,3,6-tri-o-methyl)-β-Cyclodextrin
Capillary electrokinetic chromatography (EKC) has been established as a versatile and robust capillary electrophoresis (CE) method for the separation of enantiomers. One of the most attractive advantages of EKC for the separation of enantiomers is its ease of change of separation media in method dev...
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| Format: | Article |
| Language: | English |
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Penerbit UTM Press
2014
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| Online Access: | http://eprints.utm.my/59739/1/SitiRosilah2014_ExperimentalandTheoreticalStudyonChiral.pdf |
| _version_ | 1796860771091611648 |
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| author | Wan Ibrahim, Wan Aini Arsad, Siti Rosilah Maarof, Hasmerya Sanagi, Mohd. Marsin |
| author_facet | Wan Ibrahim, Wan Aini Arsad, Siti Rosilah Maarof, Hasmerya Sanagi, Mohd. Marsin |
| author_sort | Wan Ibrahim, Wan Aini |
| collection | ePrints |
| description | Capillary electrokinetic chromatography (EKC) has been established as a versatile and robust capillary electrophoresis (CE) method for the separation of enantiomers. One of the most attractive advantages of EKC for the separation of enantiomers is its ease of change of separation media in method development. The separation solution can easily be altered to find the optimum separation media and one can also use an expensive chiral selector because small amounts of it are required. This work aims to develop experimental and theoretical analysis of the chiral separation of ketoconazole using EKC and molecular modelling study, respectively. In the first part of the study, several cyclodextrins (CD) as the chiral selectors (CS) namely α-cyclodextrin, sulfated β-cyclodextrin, (2-hydroxylpropyl)-β-cyclodextrin, heptakis(2,6-di-O-methyl)-β-cyclodextrin, and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin were screened. CDs were initially chosen as they are easily available and cheap. Heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin (TMβCD) exhibited a higher enantioselectivity power compared with other tested CDs. The influence of TMβCD concentration, buffer pH, buffer concentration, separation temperature and applied voltage were investigated. The optimum conditions for chiral separation of ketoconazole was achieved using 10 mM phosphate buffer at pH 3.0 containing 20 mM TMβCD with an applied voltage of 30 kV at 35°C with 5 s injection time (hydrodynamic injection). The ketoconazole enantiomers were resolved in less than 10 min (Rs 1.79). In order to understand possible chiral recognition mechanisms of ketoconazole with TMβCD, host-guest binding procedures of TMβCD and ketoconazole were studied using the semi-empirical PM3 calculations. |
| first_indexed | 2024-03-05T19:46:16Z |
| format | Article |
| id | utm.eprints-59739 |
| institution | Universiti Teknologi Malaysia - ePrints |
| language | English |
| last_indexed | 2024-03-05T19:46:16Z |
| publishDate | 2014 |
| publisher | Penerbit UTM Press |
| record_format | dspace |
| spelling | utm.eprints-597392022-04-14T04:24:34Z http://eprints.utm.my/59739/ Experimental and theoretical study on chiral recognition mechanism of ketoconazole enantiomers using heptakis (2,3,6-tri-o-methyl)-β-Cyclodextrin Wan Ibrahim, Wan Aini Arsad, Siti Rosilah Maarof, Hasmerya Sanagi, Mohd. Marsin QD Chemistry Capillary electrokinetic chromatography (EKC) has been established as a versatile and robust capillary electrophoresis (CE) method for the separation of enantiomers. One of the most attractive advantages of EKC for the separation of enantiomers is its ease of change of separation media in method development. The separation solution can easily be altered to find the optimum separation media and one can also use an expensive chiral selector because small amounts of it are required. This work aims to develop experimental and theoretical analysis of the chiral separation of ketoconazole using EKC and molecular modelling study, respectively. In the first part of the study, several cyclodextrins (CD) as the chiral selectors (CS) namely α-cyclodextrin, sulfated β-cyclodextrin, (2-hydroxylpropyl)-β-cyclodextrin, heptakis(2,6-di-O-methyl)-β-cyclodextrin, and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin were screened. CDs were initially chosen as they are easily available and cheap. Heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin (TMβCD) exhibited a higher enantioselectivity power compared with other tested CDs. The influence of TMβCD concentration, buffer pH, buffer concentration, separation temperature and applied voltage were investigated. The optimum conditions for chiral separation of ketoconazole was achieved using 10 mM phosphate buffer at pH 3.0 containing 20 mM TMβCD with an applied voltage of 30 kV at 35°C with 5 s injection time (hydrodynamic injection). The ketoconazole enantiomers were resolved in less than 10 min (Rs 1.79). In order to understand possible chiral recognition mechanisms of ketoconazole with TMβCD, host-guest binding procedures of TMβCD and ketoconazole were studied using the semi-empirical PM3 calculations. Penerbit UTM Press 2014-07 Article PeerReviewed application/pdf en http://eprints.utm.my/59739/1/SitiRosilah2014_ExperimentalandTheoreticalStudyonChiral.pdf Wan Ibrahim, Wan Aini and Arsad, Siti Rosilah and Maarof, Hasmerya and Sanagi, Mohd. Marsin (2014) Experimental and theoretical study on chiral recognition mechanism of ketoconazole enantiomers using heptakis (2,3,6-tri-o-methyl)-β-Cyclodextrin. Malaysian Journal of Fundamental and Applied Sciences, 10 (2). pp. 105-110. ISSN 2289-5981 http://dx.doi.org/10.11113/mjfas.v10n2.262 DOI:10.11113/mjfas.v10n2.262 |
| spellingShingle | QD Chemistry Wan Ibrahim, Wan Aini Arsad, Siti Rosilah Maarof, Hasmerya Sanagi, Mohd. Marsin Experimental and theoretical study on chiral recognition mechanism of ketoconazole enantiomers using heptakis (2,3,6-tri-o-methyl)-β-Cyclodextrin |
| title | Experimental and theoretical study on chiral recognition mechanism of ketoconazole enantiomers using heptakis (2,3,6-tri-o-methyl)-β-Cyclodextrin |
| title_full | Experimental and theoretical study on chiral recognition mechanism of ketoconazole enantiomers using heptakis (2,3,6-tri-o-methyl)-β-Cyclodextrin |
| title_fullStr | Experimental and theoretical study on chiral recognition mechanism of ketoconazole enantiomers using heptakis (2,3,6-tri-o-methyl)-β-Cyclodextrin |
| title_full_unstemmed | Experimental and theoretical study on chiral recognition mechanism of ketoconazole enantiomers using heptakis (2,3,6-tri-o-methyl)-β-Cyclodextrin |
| title_short | Experimental and theoretical study on chiral recognition mechanism of ketoconazole enantiomers using heptakis (2,3,6-tri-o-methyl)-β-Cyclodextrin |
| title_sort | experimental and theoretical study on chiral recognition mechanism of ketoconazole enantiomers using heptakis 2 3 6 tri o methyl β cyclodextrin |
| topic | QD Chemistry |
| url | http://eprints.utm.my/59739/1/SitiRosilah2014_ExperimentalandTheoreticalStudyonChiral.pdf |
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