title: Enantioselective separation of mirtazapine and its metabolites by capillary electrophoresis with acetonitrile field-amplified sample stacking and its application.
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.
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Shanghai Key Laboratory for Pharmaceutical Metabolite Research, Second Military Medical University, Shanghai, 200433, China. wenjunapple@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Wen
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Shanghai Key Laboratory for Pharmaceutical Metabolite Research, Second Military Medical University, Shanghai, 200433, China. zhangwt2011@163.com.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Shanghai Key Laboratory for Pharmaceutical Metabolite Research, Second Military Medical University, Shanghai, 200433, China. cao_weiqun@wuxiapptec.com.
authors.forename: Wei-Qun
authors.initials: WQ
authors.lastname: Cao
authors.affiliation: Department of Pharmacy, Kunming General Hospital of Chengdu Military Command, Kunming, 650032, China. gigiliji@163.com.
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Shanghai Key Laboratory for Pharmaceutical Metabolite Research, Second Military Medical University, Shanghai, 200433, China. gaofangyuan@outlook.com.
authors.forename: Fang-Yuan
authors.initials: FY
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Shanghai Key Laboratory for Pharmaceutical Metabolite Research, Second Military Medical University, Shanghai, 200433, China. luckyyangnan123@163.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Shanghai Key Laboratory for Pharmaceutical Metabolite Research, Second Military Medical University, Shanghai, 200433, China. guorfan@outlook.com.
authors.forename: Guo-Rong
authors.initials: GR
authors.lastname: Fan
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000284:Administration, Oral; D000929:Antidepressive Agents, Tricyclic / Q000097:blood* / Q000493:pharmacokinetics; D001711:Biotransformation; D002021:Buffers; D005591:Chemical Fractionation / Q000379:methods*; D003497:Cyclic N-Oxides / Q000097:blood; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000078785:Mirtazapine; D015203:Reproducibility of Results; D013237:Stereoisomerism; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D000097:Acetonitriles; D000929:Antidepressive Agents, Tricyclic; D002021:Buffers; D003497:Cyclic N-Oxides; D047392:beta-Cyclodextrins; C441457:carboxymethyl-beta-cyclodextrin; C517417:mirtazapine-N-oxide; D008803:Mianserin; D000078785:Mirtazapine; C415843:8-hydroxymirtazapine; C119256:demethylmirtazapine; C032159:acetonitrile
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