Journal of Chromatography A, 1248 (2012) 48–54 Contents lists available at SciVerse ScienceDirect Journal of Chromatography A j our na l ho me p ag e: www.elsevier.com/locate/chroma Selective electromembrane extraction at low voltages based on analyte polarity and charge Noelia Cabaleiro Domínguez a , Astrid Gjelstad b,∗ , Andrea Molina Nadal c , Henrik Jensen d , Nickolaj Jacob Petersen d , Steen Honoré Hansen d , Knut Einar Rasmussen b , Stig Pedersen-Bjergaard b,d a Departamento de Química Analítica y Alimentaria, Área de Química Analítica, Facultad de Química, Universidad de Vigo, Campus As Lagoas-Marcosende s/n, 36310 Vigo, Spain b School of Pharmacy, The Faculty of Mathematics and Natural Sciences, University of Oslo, P.O. Box 1068 Blindern, N-0316 Oslo, Norway c School of Pharmacy, University of Barcelona, Joan XXIII s/n, 08028 Barcelona, Spain d School of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark a r t i c l e i n f o Article history: Received 7 February 2012 Received in revised form 30 April 2012 Accepted 26 May 2012 Available online 5 June 2012 Keywords: Electromembrane extraction Basic drugs Extraction selectivity Supported liquid membrane a b s t r a c t Electromembrane extraction (EME) at low voltage (0–15 V) of 29 different basic model drug substances was investigated. The drug substances with log P < 2.3 were not extracted at voltages less than 15 V. Extraction of drug substances with log P ≥ 2.3 and with two basic groups were also effectively suppressed by the SLM at voltages less than 15 V. Drug substances with log P ≥ 2.3 and with one basic group were all extracted at low voltages and with a strong compound selectivity which appeared to have some influence from the polar surface area of the compound. For this group of substances, recoveries varied between 0 and 23% at 5 V, whereas, recoveries varied between 5.5 and 51% at 15 V. Based on mass transfer differences related to charge, polarity, and polar surface, highly selective extractions of drug substances were demonstrated from human plasma, urine, and breast milk. An initial evaluation at low voltage (5 V) was compared with similar extractions at a more normal voltage level (50 V), and this supported that reliable data can be obtained under these low-voltage (mild) conditions by EME. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Prior to chromatography, capillary electrophoresis, or mass spectrometry of biological fluids, like human plasma, urine, or saliva, some type of sample preparation is required. The main pur- pose of a sample preparation is (1) to transfer the analytes of interest to a medium compatible with the analytical instrument, (2) to clean-up the sample and remove interfering matrix com- ponents, and (3) to enrich the analytes of interest. Traditionally, sample preparation in this context is performed by solid-phase extraction (SPE), protein precipitation (PP), or liquid–liquid extrac- tion (LLE) [1]. However, several alternative techniques have been developed, among others solid-phase microextraction (SPME) [2], stir-bar sorptive extraction (SBSE) [3], microextraction in a packed syringe (MEPS) [4], and different types of liquid-phase microex- traction (LPME) [5–7]. Another recent technique for sample preparation of biological fluids is electromembrane extraction (EME) [8]. In EME, charged analytes are extracted from the biological fluid, through a sup- ported liquid membrane (SLM) sustained in the pores in the ∗ Corresponding author. Tel.: +47 22 85 75 58; fax: +47 22 85 44 02. E-mail address: astrid.gjelstad@farmasi.uio.no (A. Gjelstad). wall of a porous hollow fiber, and into an acceptor solution present inside the lumen of the hollow fiber. The driving force for the extraction is an electrical potential difference sustained over the SLM. For extraction of basic substances, both the sam- ple and the acceptor solution is acidified to ensure protonation of the analytes of interest, the positive electrode (anode) is located in the sample, and the negative electrode (cathode) is located in the acceptor solution. By application of voltage to the elec- trodes, the positively charged analytes are transferred into the acceptor solution based on electrokinetic migration across the SLM. For extraction of acidic analytes, the electrical potential is reversed, and both the sample and the acceptor solution are made alkaline. EME has been shown to give very clean extracts from biologi- cal fluids like human plasma [8], whole blood [9], urine [8], saliva [10], and breast milk [11]. Since acceptor solutions are aqueous, they are directly injectable after extraction into high-performance liquid chromatography (HPLC) [12], liquid chromatography–mass spectrometry (LC–MS) [13], and capillary electrophoresis (CE) [8]. EME is performed with a very low consumption of organic solvent per extraction to establish the SLM (<25 l). EME provides recover- ies typically in the range 25–75% after 5 min of extraction [14], and enrichments of target analytes up to 190 times have been reported [15]. Several applications of EME have been reported, including 0021-9673/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.chroma.2012.05.092