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Enantioselective Separation of Mirtazapine and Its Metabolites by Capillary Electrophoresis with Acetonitrile Field-Amplified Sample Stacking and Its Application

Authors :
Jun Wen
Wen-Ting Zhang
Wei-Qun Cao
Ji Li
Fang-Yuan Gao
Nan Yang
Guo-Rong Fan
Source :
Molecules, Vol 19, Iss 4, Pp 4907-4923 (2014)
Publication Year :
2014
Publisher :
MDPI AG, 2014.

Abstract

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.

Details

Language :
English
ISSN :
14203049
Volume :
19
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.9a31ceac27a04d0db1d6018feac416c3
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules19044907