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Enantioselective Separation of Mirtazapine and Its Metabolites by Capillary Electrophoresis with Acetonitrile Field-Amplified Sample Stacking and Its Application
A simple, rapid and sensitive chiral capillary zone electrophoresis coupled with acetonitrile-field-amplified sample stacking method was developed that allows the simultaneous enantioselective separation of the mirtazapine, N-demethylmirtazapine, 8-hydroxymirtazapine and mirtazapine-N-oxide. The sep...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270698/ https://www.ncbi.nlm.nih.gov/pubmed/24747648 http://dx.doi.org/10.3390/molecules19044907 |
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author | Wen, Jun Zhang, Wen-Ting Cao, Wei-Qun Li, Ji Gao, Fang-Yuan Yang, Nan Fan, Guo-Rong |
author_facet | Wen, Jun Zhang, Wen-Ting Cao, Wei-Qun Li, Ji Gao, Fang-Yuan Yang, Nan Fan, Guo-Rong |
author_sort | Wen, Jun |
collection | PubMed |
description | A simple, rapid and sensitive chiral capillary zone electrophoresis coupled with acetonitrile-field-amplified sample stacking method was developed that allows the simultaneous enantioselective separation of the mirtazapine, N-demethylmirtazapine, 8-hydroxymirtazapine and mirtazapine-N-oxide. The separation was achieved on an uncoated 40.2 cm × 75 μM fused silica capillary with an applied voltage of 16 kV. The electrophoretic analyses were carried out in 6.25 mM borate–25 mM phosphate solution at pH 2.8 containing 5.5 mg/mL carboxymethyl-β-cyclodextrin. The detection wavelength was 200 nm. Under these optimized conditions, satisfactory chiral separations of four pair enantiomers were achieved in less than 7 min in vitro. After one step clean-up liquid-liquid extraction using 96-well format, sample was introduced capillary zone electrophoresis with acetonitrile-field-amplified sample stacking to enhance the sensitivity of enantiomers. The method was validated with respect to specificity, linearity, lower limit of quantitation, accuracy, precision, extraction recovery and stability. The lower limit of quantification was 0.5 ng/mL with linear response over the 0.5–50 ng/mL concentration range for each mirtazapine, N-demethylmirtazapine and 8-hydroxymirtazapine enantiomer. The developed and validated method has been successfully applied to the enantioselective pharmacokinetic studies in 12 healthy volunteers after oral administration of rac- mirtazapine. |
format | Online Article Text |
id | pubmed-6270698 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62706982019-01-02 Enantioselective Separation of Mirtazapine and Its Metabolites by Capillary Electrophoresis with Acetonitrile Field-Amplified Sample Stacking and Its Application Wen, Jun Zhang, Wen-Ting Cao, Wei-Qun Li, Ji Gao, Fang-Yuan Yang, Nan Fan, Guo-Rong Molecules Article A simple, rapid and sensitive chiral capillary zone electrophoresis coupled with acetonitrile-field-amplified sample stacking method was developed that allows the simultaneous enantioselective separation of the mirtazapine, N-demethylmirtazapine, 8-hydroxymirtazapine and mirtazapine-N-oxide. The separation was achieved on an uncoated 40.2 cm × 75 μM fused silica capillary with an applied voltage of 16 kV. The electrophoretic analyses were carried out in 6.25 mM borate–25 mM phosphate solution at pH 2.8 containing 5.5 mg/mL carboxymethyl-β-cyclodextrin. The detection wavelength was 200 nm. Under these optimized conditions, satisfactory chiral separations of four pair enantiomers were achieved in less than 7 min in vitro. After one step clean-up liquid-liquid extraction using 96-well format, sample was introduced capillary zone electrophoresis with acetonitrile-field-amplified sample stacking to enhance the sensitivity of enantiomers. The method was validated with respect to specificity, linearity, lower limit of quantitation, accuracy, precision, extraction recovery and stability. The lower limit of quantification was 0.5 ng/mL with linear response over the 0.5–50 ng/mL concentration range for each mirtazapine, N-demethylmirtazapine and 8-hydroxymirtazapine enantiomer. The developed and validated method has been successfully applied to the enantioselective pharmacokinetic studies in 12 healthy volunteers after oral administration of rac- mirtazapine. MDPI 2014-04-17 /pmc/articles/PMC6270698/ /pubmed/24747648 http://dx.doi.org/10.3390/molecules19044907 Text en © 2014 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Wen, Jun Zhang, Wen-Ting Cao, Wei-Qun Li, Ji Gao, Fang-Yuan Yang, Nan Fan, Guo-Rong Enantioselective Separation of Mirtazapine and Its Metabolites by Capillary Electrophoresis with Acetonitrile Field-Amplified Sample Stacking and Its Application |
title | Enantioselective Separation of Mirtazapine and Its Metabolites by Capillary Electrophoresis with Acetonitrile Field-Amplified Sample Stacking and Its Application |
title_full | Enantioselective Separation of Mirtazapine and Its Metabolites by Capillary Electrophoresis with Acetonitrile Field-Amplified Sample Stacking and Its Application |
title_fullStr | Enantioselective Separation of Mirtazapine and Its Metabolites by Capillary Electrophoresis with Acetonitrile Field-Amplified Sample Stacking and Its Application |
title_full_unstemmed | Enantioselective Separation of Mirtazapine and Its Metabolites by Capillary Electrophoresis with Acetonitrile Field-Amplified Sample Stacking and Its Application |
title_short | Enantioselective Separation of Mirtazapine and Its Metabolites by Capillary Electrophoresis with Acetonitrile Field-Amplified Sample Stacking and Its Application |
title_sort | enantioselective separation of mirtazapine and its metabolites by capillary electrophoresis with acetonitrile field-amplified sample stacking and its application |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270698/ https://www.ncbi.nlm.nih.gov/pubmed/24747648 http://dx.doi.org/10.3390/molecules19044907 |
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