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Complexation-mediated electromembrane extraction of highly polar basic drugs—a fundamental study with catecholamines in urine as model system

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Abstract

Complexation-mediated electromembrane extraction (EME) of highly polar basic drugs (log P < −1) was investigated for the first time with the catecholamines epinephrine, norepinephrine, and dopamine as model analytes. The model analytes were extracted as cationic species from urine samples (pH 4), through a supported liquid membrane (SLM) comprising 25 mM 4-(trifluoromethyl)phenylboronic acid (TFPBA) in bis(2-ethylhexyl) phosphite (DEHPi), and into 20 mM formic acid as acceptor solution. EME was performed for 15 min, and 50 V was used as extraction voltage across the SLM. TFPBA served as complexation reagent, and selectively formed boronate esters by reversible covalent binding with the model analytes at the sample/SLM interface. This enhanced the mass transfer of the highly polar model analytes across the SLM, and EME of basic drugs with log P in the range −1 to −2 was shown for the first time. Meanwhile, most matrix components in urine were unable to pass the SLM. Thus, the proposed concept provided highly efficient sample clean-up and the system current across the SLM was kept below 50 μA. Finally, the complexation-mediated EME concept was combined with ultra-high performance liquid chromatography coupled to tandem mass spectrometry and evaluated for quantification of epinephrine and dopamine. Standard addition calibration was applied to a pooled human urine sample. Calibration curves using standards between 25 and 125 μg L−1 gave a high level of linearity with a correlation coefficient of 0.990 for epinephrine and 0.996 for dopamine (N = 5). The limit of detection, calculated as three times signal-to-noise ratio, was 5.0 μg L−1 for epinephrine and 1.8 μg L−1 for dopamine. The repeatability of the method, expressed as coefficient of variation, was 13% (n = 5). The proposed method was finally applied for the analysis of spiked pooled human urine sample, obtaining relative recoveries of 91 and 117% for epinephrine and dopamine, respectively.

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Acknowledgements

The authors would like to thank the Spanish Ministry of Science and Innovation (project n. CTQ2011-23968) and Generalitat Valenciana (Spain) (projects n. GVA/2014/096 and PROMETEO/2013/038) for the financial support. E. Fernández thanks Spanish Ministry of Education for her FPU grant (FPU13/03125) and mobility grant (EST15/00074).

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Authors and Affiliations

  1. Department of Analytical Chemistry, Nutrition and Food Sciences and University Institute of Materials, University of Alicante, P.O. Box 99, 03080, Alicante, Spain

    Elena Fernández, Lorena Vidal & Antonio Canals

  2. School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, 0316, Oslo, Norway

    Linda Vårdal, Astrid Gjelstad & Stig Pedersen-Bjergaard

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  1. Elena Fernández
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  2. Linda Vårdal
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  3. Lorena Vidal
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  4. Antonio Canals
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  5. Astrid Gjelstad
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  6. Stig Pedersen-Bjergaard
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Corresponding authors

Correspondence to Lorena Vidal or Stig Pedersen-Bjergaard.

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Informed consent was obtained from all individual participants included in the study. Urine samples were collected from healthy volunteers and randomized. Collection was performed in accordance with ethical standards and approved by the Director of School of Pharmacy (University of Oslo, Norway).

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The authors declare that they have no conflicts of interest.

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Fernández, E., Vårdal, L., Vidal, L. et al. Complexation-mediated electromembrane extraction of highly polar basic drugs—a fundamental study with catecholamines in urine as model system. Anal Bioanal Chem 409, 4215–4223 (2017). https://doi.org/10.1007/s00216-017-0370-2

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