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Molecules 2014, 19(4), 4907-4923; doi:10.3390/molecules19044907
Article

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

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Received: 3 March 2014; in revised form: 10 April 2014 / Accepted: 14 April 2014 / Published: 17 April 2014
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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.
Keywords: chiral capillary zone electrophoresis; acetonitrile-field-amplified sample stacking; mirtazapine; N-demethylmirtazapine; 8-hydroxymirtazapine; liquid-liquid extraction chiral capillary zone electrophoresis; acetonitrile-field-amplified sample stacking; mirtazapine; N-demethylmirtazapine; 8-hydroxymirtazapine; liquid-liquid extraction
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Wen, J.; Zhang, W.-T.; Cao, W.-Q.; Li, J.; Gao, F.-Y.; Yang, N.; Fan, G.-R. Enantioselective Separation of Mirtazapine and Its Metabolites by Capillary Electrophoresis with Acetonitrile Field-Amplified Sample Stacking and Its Application. Molecules 2014, 19, 4907-4923.

AMA Style

Wen J, Zhang W-T, Cao W-Q, Li J, Gao F-Y, Yang N, Fan G-R. Enantioselective Separation of Mirtazapine and Its Metabolites by Capillary Electrophoresis with Acetonitrile Field-Amplified Sample Stacking and Its Application. Molecules. 2014; 19(4):4907-4923.

Chicago/Turabian Style

Wen, Jun; Zhang, Wen-Ting; Cao, Wei-Qun; Li, Ji; Gao, Fang-Yuan; Yang, Nan; Fan, Guo-Rong. 2014. "Enantioselective Separation of Mirtazapine and Its Metabolites by Capillary Electrophoresis with Acetonitrile Field-Amplified Sample Stacking and Its Application." Molecules 19, no. 4: 4907-4923.


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