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Ultrasound-assisted dispersive liquid–liquid microextraction coupled with field-amplified capillary electrophoresis for sensitive and quantitative determination of fluoxetine and norfluoxetine enantiomers in biological fluids

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Abstract

A rapid, simple, and sensitive technique for the quantitative detection of fluoxetine and norfluoxetine enantiomers in biological fluids was developed based on the combination of field-amplified sample stacking (FASS)–related capillary electrophoresis (CE) with ultrasound-assisted dispersive liquid–liquid microextraction (UA-DLLME). The extraction efficiency of UA-DLLME was strongly related to extraction time, salt concentration, type of extraction and dispersion solvents, and volume of extraction and dispersion solvents. The extracted fluoxetine and norfluoxetine enantiomers in a mixture of 50% methanol and 50% deionized water were efficiently stacked using FASS and then separated using cyclodextrin-modified CE. Under optimal conditions of FASS (chiral selector, 3 mM trimethyl-β-cyclodextrin; and background electrolyte, 100 mM phosphate buffer) and UA-DLLME (extraction solvent, 200 μL of acetone; and dispersed solvent, 50 μL of C2H2Cl4 in 1 mL of the sample solution), the obtained enrichment factors of fluoxetine and norfluoxetine enantiomers reached approximately 2000. The linear ranges for the quantification of fluoxetine and norfluoxetine enantiomers were 0.3–150 and 0.6–150 nM, respectively. The relative standard deviations in peak areas and migration time for four analytes were less than 3.3% and 6.3%, respectively. The proposed system provided limits of detection (signal-to-noise ratio of 3) for four analytes corresponding to 0.1 nM. The precision and accuracy for urine and serum samples were less than 6.8 and 8.3%, respectively. These findings suggested that the proposed system exhibited a high potential for the reliable determination of fluoxetine and norfluoxetine enantiomers in clinical samples.

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Abbreviations

DLLME:

Dispersive liquid–liquid microextraction

FASS:

Field-amplified sample stacking

Flx:

Fluoxetine

Nflx:

Norfluoxetine

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Funding

This work was financially supported by the Ministry of Science and Technology of Taiwan under contract number MOST 108-2113-M-017-003.

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Authors and Affiliations

  1. Department of Chemistry, National Kaohsiung Normal University, No.62 Shenjhong Rd., Yanchao District, Kaohsiung City, 82446, Taiwan

    Zheng Ren Wang & Ming Mu Hsieh

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  1. Zheng Ren Wang
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  2. Ming Mu Hsieh
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Correspondence to Ming Mu Hsieh.

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The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki, as reflected in a priori approval by the Institutional Review Board (IRB) of Human Research Ethics Committee at National Cheng University (NCKU HREC-F-107-044-2). The urine and serum samples in this work were collected from three healthy volunteers. Written, informed consent was obtained from all participants.

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The authors declare that they have no conflict of interest.

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Published in the topical collection Euroanalysis XX with guest editor Sibel A. Ozkan

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Wang, Z.R., Hsieh, M.M. Ultrasound-assisted dispersive liquid–liquid microextraction coupled with field-amplified capillary electrophoresis for sensitive and quantitative determination of fluoxetine and norfluoxetine enantiomers in biological fluids. Anal Bioanal Chem 412, 5113–5123 (2020). https://doi.org/10.1007/s00216-020-02441-x

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