Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wen, Jun, Zhang, Wen-Ting, Cao, Wei-Qun, Li, Ji, Gao, Fang-Yuan, Yang, Nan, Fan, Guo-Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
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
_version_ 1783376758507044864
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
work_keys_str_mv AT wenjun enantioselectiveseparationofmirtazapineanditsmetabolitesbycapillaryelectrophoresiswithacetonitrilefieldamplifiedsamplestackinganditsapplication
AT zhangwenting enantioselectiveseparationofmirtazapineanditsmetabolitesbycapillaryelectrophoresiswithacetonitrilefieldamplifiedsamplestackinganditsapplication
AT caoweiqun enantioselectiveseparationofmirtazapineanditsmetabolitesbycapillaryelectrophoresiswithacetonitrilefieldamplifiedsamplestackinganditsapplication
AT liji enantioselectiveseparationofmirtazapineanditsmetabolitesbycapillaryelectrophoresiswithacetonitrilefieldamplifiedsamplestackinganditsapplication
AT gaofangyuan enantioselectiveseparationofmirtazapineanditsmetabolitesbycapillaryelectrophoresiswithacetonitrilefieldamplifiedsamplestackinganditsapplication
AT yangnan enantioselectiveseparationofmirtazapineanditsmetabolitesbycapillaryelectrophoresiswithacetonitrilefieldamplifiedsamplestackinganditsapplication
AT fanguorong enantioselectiveseparationofmirtazapineanditsmetabolitesbycapillaryelectrophoresiswithacetonitrilefieldamplifiedsamplestackinganditsapplication