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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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).
Compliance with ethical standards
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).
Conflict of interest
The authors declare that they have no conflicts of interest.
Ghambarian M, Yamini Y, Esrafili A. Developments in hollow fiber based liquid-phase microextraction: principles and applications. Microchim Acta. 2012;177:271–94.CrossRefGoogle Scholar
Huang C, Jensen H, Seip KF, Gjelstad A, Pedersen-Bjergaard S. Mass transfer in electromembrane extraction—the link between theory and experiments. J Sep Sci. 2016;39:188–97.CrossRefGoogle Scholar
Fernández E, Vidal L. Liquid-phase microextraction techniques. In: Pena-Pereira F, editor. Miniaturization sample preparation. Warsaw: De Gruyter Open; 2014. p. 191–252.Google Scholar
Gjelstad A, Pedersen-Bjergaard S. Recent developments in electromembrane extraction. Anal Methods. 2013;5:4549–57.CrossRefGoogle Scholar
Marothu VK, Gorrepati M, Vusa R. Electromembrane extraction—a novel extraction technique for pharmaceutical, chemical, clinical and environmental analysis. J Chromatogr Sci. 2013;51:619–31.CrossRefGoogle Scholar
Gjelstad A, Rasmussen KE, Pedersen-Bjergaard S. Electrokinetic migration across artificial liquid membranes tuning the membrane chemistry to different types of drug substances. J Chromatogr A. 2006;1124:29–34.CrossRefGoogle Scholar
Nojavan S, Fakhari AR. Electro membrane extraction combined with capillary electrophoresis for the determination of amlodipine enantiomers in biological samples. J Sep Sci. 2010;33:3231–8.CrossRefGoogle Scholar
Fakhari AR, Tabani H, Nojavan S, Abedi H. Electromembrane extraction combined with cyclodextrin-modified capillary electrophoresis for the quantification of trimipramine enantiomers. Electrophoresis. 2012;33:506–15.CrossRefGoogle Scholar
Davarani SSH, Najarian AM, Nojavan S, Tabatabaei M-A. Electromembrane extraction combined with gas chromatography for quantification of tricyclic antidepressants in human body fluids. Anal Chim Acta. 2012;725:51–6.CrossRefGoogle Scholar
Hasheminasab KS, Fakhari AR. Development and application of carbon nanotubes assisted electromembrane extraction (CNTs/EME) for the determination of buprenorphine as a model of basic drugs from urine samples. Anal Chim Acta. 2013;767:75–80.CrossRefGoogle Scholar
Ahmar H, Fakhari AR, Tabani H, Shahsavani A. Optimization of electromembrane extraction combined with differential pulse voltammetry using modified screen-printed electrode for the determination of sufentanil. Electrochim Acta. 2013;96:117–23.CrossRefGoogle Scholar
Huang C, Eibak LEE, Gjelstad A, Shen X, Trones R, Jensen H, Pedersen-Bjergaard S. Development of a flat membrane based device for electromembrane extraction: a new approach for exhaustive extraction of basic drugs from human plasma. J Chromatogr A. 2014;1326:7–12.CrossRefGoogle Scholar
Asl YA, Yamini Y, Seidi S, Amanzadeh H. Dynamic electromembrane extraction: automated movement of donor and acceptor phases to improve extraction efficiency. J Chromatogr A. 2015;1419:10–8.CrossRefGoogle Scholar
Rouhollahi A, Kouchaki M, Seidi S. Electrically stimulated liquid phase microextraction combined with differential pulse voltammetry: a new and efficient design for in situ determination of clozapine from complicated matrices. RSC Adv. 2016;6:12943–52.CrossRefGoogle Scholar
Gjelstad A, Rasmussen KE, Pedersen-Bjergaard S. Electromembrane extraction of basic drugs from untreated human plasma and whole blood under physiological pH conditions. Anal Bioanal Chem. 2009;393:921–8.CrossRefGoogle Scholar
Eibak LEE, Gjelstad A, Rasmussen KE, Pedersen-Bjergaard S. Kinetic electro membrane extraction under stagnant conditions—fast isolation of drugs from untreated human plasma. J Chromatogr A. 2010;1217:5050–6.CrossRefGoogle Scholar
Jamt REG, Gjelstad A, Eibak LEE, Øiestad EL, Christophersen AS, Rasmussen KE, Pedersen-Bjergaard S. Electromembrane extraction of stimulating drugs from undiluted whole blood. J Chromatogr A. 2012;1232:27–36.CrossRefGoogle Scholar
Šlampová A, Kubáň P, Boček P. Electromembrane extraction using stabilized constant d.c. electric current—a simple tool for improvement of extraction performance. J Chromatogr A. 2012;1234:32–7.CrossRefGoogle Scholar
Kjelsen IJØ, Gjelstad A, Rasmussen KE, Pedersen-Bjergaard S. Low-voltage electromembrane extraction of basic drugs from biological samples. J Chromatogr A. 2008;1180:1–9.CrossRefGoogle Scholar
Seip KF, Faizi M, Vergel C, Gjelstad A, Pedersen-Bjergaard S. Stability and efficiency of supported liquid membranes in electromembrane extraction-a link to solvent properties. Anal Bioanal Chem. 2014;406:2151–61.CrossRefGoogle Scholar
Huang C, Seip KF, Gjelstad A, Pedersen-Bjergaard S. Electromembrane extraction for pharmaceutical and biomedical analysis—quo vadis. J Pharm Biomed Anal. 2015;113:97–107.CrossRefGoogle Scholar
Huang C, Seip KF, Gjelstad A, Pedersen-Bjergaard S. Electromembrane extraction of polar basic drugs from plasma with pure bis(2-ethylhexyl) phosphite as supported liquid membrane. Anal Chim Acta. 2016;934:80–7.CrossRefGoogle Scholar
Bicker J, Fortuna A, Alves G, Falcão A. Liquid chromatographic methods for the quantification of catecholamines and their metabolites in several biological samples—a review. Anal Chim Acta. 2013;768:12–34.CrossRefGoogle Scholar
Paugam M-F, Valencia LS, Boggess B, Smith BD. Selective dopamine transport using a crown boronic acid. J Am Chem Soc. 1994;116:11203–4.CrossRefGoogle Scholar
Takeuchi M, Koumoto K, Goto M, Shinkai S. Efficient glucoside extraction mediated by a boronic acid with an intramolecular quaternary ammonium ion. Tetrahedron. 1996;52:12931–40.CrossRefGoogle Scholar
Di Luccio M, Smith BD, Kida T, Borges CP, Alves TLM. Separation of fructose from a mixture of sugars using supported liquid membranes. J Memb Sci. 2000;174:217–24.CrossRefGoogle Scholar
Kanamori T, Funatsu T, Tsunoda M. Determination of catecholamines and related compounds in mouse urine using column-switching HPLC. Analyst. 2016;141:2568–73.CrossRefGoogle Scholar
Kubán P, Boček P. The effects of electrolysis on operational solutions in electromembrane extraction: the role of acceptor solution. J Chromatogr A. 2015;1398:11–9.CrossRefGoogle Scholar
Miller JN, Miller JC. Statistics and chemometrics for analytical chemistry. fifth ed. London: Pearson Prentice Hall; 2005.Google Scholar