Abstract

Electromembrane extraction (EME) is a novel sample preparation technique in pharmaceutical, chemical, clinical and environmental analysis. This technique uses electromigration across artificial liquid membranes for selective extraction of analytes and sample enrichment from complex matrices. This review focuses on the setup, general procedure and parameters affecting the extraction efficiency of EME. An overview of innovations in EME (on-chip EME, low voltage EME, drop-to-drop EME, pulsed EME and EME followed by low-density solvent based ultrasound-assisted emulsification microextraction) is also presented in this article and attention is focused on the use of EME for pharmaceutical, chemical, clinical and environmental analysis.

Introduction

Pharmaceutical products, biological materials and environmental samples are very complex, often containing salts, acids, bases, metals, proteins and various organic compounds with chemical properties similar to those of analytes (1, 2). Thus, extraction is necessary to isolate the desired components from complex materials and to enrich the sample with respect to the analyte. This process enhances the sensitivity and ensures the compatibility of the injected sample with the analytical system. This is performed by liquid–liquid extraction (LLE), solid-phase extraction (SPE) or hollow fiber membrane liquid-phase microextraction (HF-LPME). LLE methods are more time consuming, tedious and require large amounts of organic solvents. SPE is relatively easy and consumption of organic solvents is low, but SPE cartridges are costly and evaporation of the eluent is required after extraction (2). Another sample preparation technique is HF-LPME, which was introduced in the mid-1990s. It is simple, fast and requires microliters of solvent. In HF-LPME, an organic solvent is immobilized in the pores of HFs (polymeric materials) and creates a thin supported liquid membrane (SLM). The SLM thickness and volume of the organic solvent in the SLM are given by thickness and by the porosity and pore size of the HF, respectively. The lumen of the HF is filled with a very small volume of acceptor solution (organic solvent means two-phase LPME; aqueous solvent means three-phase LPME) and the system is placed into a large volume of sample solution (donor) for extraction. During extraction, proper mixing of the sample solution is usually required. When the extraction is finished, the acceptor solution can be used for direct injection into analytical systems such as liquid chromatography (LC), gas chromatography (GC) and capillary electrophoresis (CE). The extraction principle in HF-LPME is based on the passive diffusion of analytes from the sample solution, through a water-immiscible organic solvent immobilized as an SLM into acceptor solution. The flux of analytes across the SLM depends upon distribution ratios between different aqueous and organic solvents. The disadvantage of this technique is longer equilibration times (3). To decrease equilibration times, a new extraction procedure was recently introduced by Pedersen-Bjergaard and Rasmussen (4), which has been called electromembrane extraction (EME). In this procedure, a potential difference was applied across the SLM that acts as the driving force (4–8). A platinum electrode is placed in the sample solution, and the other platinum electrode is located in the acceptor solution inside the lumen of the fiber. Charged analytes in the sample solution are migrated across the SLM toward the oppositely charged electrode in the acceptor solution. For basic analytes, a negative electrode is placed in the acceptor solution, whereas for acidic compounds, a positive electrode is placed in the acceptor solution. This procedure is simple, selective and rapid. EME has successfully been used to extract acidic, basic and zwitterionic drugs. It has also provided excellent sample cleanup and analyte enrichment from complex matrices (9, 10).

This review article presents the general setup of EME and parameters influencing the flux of analytes in EME. An overview of innovations in EME [on-chip EME, low voltage EME, drop-to-drop EME, pulsed EME and EME followed by low-density solvent based ultrasound-assisted emulsification microextraction (EME–LDS-USAEME)] is also presented and attention is focused on the use of EME for pharmaceutical, chemical, clinical and environmental analysis.

EME Setup and Procedure

The setup used for EME is shown in Figure 1. It consists of a glass vial with a screw cap used as a sample compartment, into which sample solution is filled. The HF (usually made up of polypropylene or other porous hydrophobic material) is cut into small pieces of required length and the lower end of the HF of required length is sealed by mechanical pressure, whereas the upper end is connected to a pipette tip as a guiding tube. The HF is dipped for few seconds into the organic solvent serving as the SLM. Excess of solvent in the SLM is gently removed with a medical wipe or by air-blowing with a medical syringe. Through the guiding tube, acceptor solution is filled into the lumen of the HF with a microsyringe. The filled HF and the guiding tube are inserted through the vial cap into the sample solution. One of the electrodes is set into the lumen of the fiber via the guiding tube, whereas the other electrode is led through the cap and directly into the sample solution. The electrodes are connected to the power supply with programmable voltage and the extraction unit is agitated on an agitator. Under the applied voltage, the target analytes migrate from the sample solution into the SLM and transported into the acceptor phase. After the extraction is completed, the acceptor solution is collected by a microsyringe and transferred to a vial for analysis in high-performance liquid chromatography (HPLC), GC, CE or any other technique.

Figure 1.

Schematic illustration of the setup for EME.

Figure 1.

Schematic illustration of the setup for EME.

Parameters influencing flux of analytes across SLM

Composition (organic solvent) of SLM, viscosity and thickness

The chemical nature of the SLM is highly critical to success in EME (11). The flux of the analyte is affected by difference in concentration of the analyte across the SLM, which is partially determined by the sample to SLM distribution ratio; this, in turn, is controlled by the type of solvent used as the SLM. In addition, the type of solvent also influences the diffusion coefficient of the analyte (12), which can also be tuned to increase the selectivity and to obtain good clean-up during extraction (13). There are specific requirements for a solvent to be used as an SLM in EME. The organic phase should have a certain dipole moment or electrical conductivity to support a relatively low current flow in the system, and it should have certain chemical properties to enable phase transfer and electrokinetic migration of the model analytes. Furthermore, the solvent should be immiscible in water to avoid losses from pores of the HF membrane wall and dissolution in the sample solution during stirring.

Extraction of basic drugs

Based upon literature reports (10, 12), nitro-aromatic solvents such as 2-nitrophenyl octylether (NPOE) and nitrophenyl pentyl ether (NPPE) are efficient organic solvents for the elctrokinetic migration of nonpolar (logP > 2) basic drugs through the SLM. It has also been reported that addition of hydrophobic alkylated phosphate reagents to SLM can improve the phase transfer and electrokinetic migration of basic analytes (12).

Polar (logP < 1) basic drugs were unable to penetrate through the interface between the donor phase and the SLM with pure NPOE. The high polarity of these analytes seemed to counteract the influence of the electric field. To facilitate the transport of polar drugs through SLM, an ion pair reagent such as di-(2-ethylhexyl) phosphate (DEHP) or tris-(2-ethylhexyl) phosphate (TEHP) was added to the organic solvent to form ion pairs with the analytes. An SLM consisting of 10% DEHP and 10% TEHP in NPOE was useful for the extraction of basic drugs with a large logP window (12).

Extraction of acidic drugs

Nitro-aromatic solvents are inefficient for the extraction of acidic drugs. Aliphatic alcohols like 1-octanol and 1-heptanol were found to be efficient for the extraction of acidic drugs (10). They are insoluble in water and easily impregnate the membrane. In addition, the alcohols showed an appropriate electrical resistance to the applied voltage (i.e., the current was low enough to avoid bubble formation and excessive electrolysis, but still sufficiently high for the system to maintain the properties of the closed circuit). The chemical nature of the organic solvent in combination with a proper potential difference can be used to design very selective extractions of different analyte classes (10).

The viscosity of the organic solvent is another parameter that significantly influences the diffusion of analytes through SLM: if viscosity is low, more diffusion is observed. The thickness of the SLM also influences the flux of analytes: a thicker membrane results in an increased diffusion path and theoretically reduces the extraction recovery (14).

Extraction voltage and time

In EME, the electrokinetic migration of the analytes across the SLM into the acceptor solution is greatly dependent upon the applied voltage (11). The flux of analytes (Ji) is affected by the magnitude of the applied voltage. Equation 1 describes how different parameters affect the flux of analytes through the SLM (15):  

(1)
formula
where Di is the diffusion coefficient for the analyte, h is the thickness of the membrane, ci is the analyte concentration at the SLM/sample interface and ci0 is the concentration of the analyte at the acceptor/SLM interface. Additionally, ν is a function of electrical potential and χ is the ratio of the total ionic concentration in the sample solution to that in the acceptor solution, which is defined as the ion balance.

Generally, the voltage is applied in the range of 5–600 V. At higher voltages, recovery values decrease because of bubble formation at the electrodes and instability of the system (4). Time is another parameter that can affect the flux of analytes in EME. Both time and voltage directly increase the flux of ions, and thus, increase extraction recovery, but there is an antagonist effect in which they are simultaneously considered; thus, an increase in extraction time limits the voltage and vice versa. Generally, at extraction times above 15 min, the recovery is decreased due to the instability of the electrical current in the system, back-diffusion of the analytes toward the donor phase due to changes in pH from electrolysis and a small loss of artificial liquid membrane (16).

pH of donor and acceptor phases (ion balance effect)

The pH values of donor and acceptor phases can determine the ion balance in the system. It has been shown that the total ionic concentration on the donor phase to that on the acceptor phase impresses the flux over the membrane (17). The flux may decrease by increasing this ratio. In EME, for the rapid extraction of basic analytes, pH in the sample and acceptor solutions is low to ionize the analytes, and the analytes are extracted across the SLM with a positive electrode placed in the sample and a negative electrode placed in the acceptor solution. For the extraction of acidic drugs (6), the extraction system is operated in reversed polarity and the pH of the donor and acceptor solutions was high (alkaline).

Agitation/stirring speed

Stirring speed plays an essential role in increasing the kinetics and efficiency of extraction by increasing the mass transfer and reducing the thickness of the double layer around the SLM. Generally, a stirring speed is used in the range of 0–1,250 rpm (18). At higher stirring rates, extraction recovery is decreased due to bubble formation in both the donor and acceptor phases and the leakage of the organic solvent from the SLM (18). This leads to incompatible analytical results.

Presence of salt/salt effect

The presence of ionic substances in the donor solution causes an increase in the value of the ion balance in the system, which decreases the flux of analytes across the SLM. Thus, the migration of analytes is more efficient in the absence of salt (11–13). However, some studies have shown that the addition of salt to the donor solution increased the extraction efficiency (19, 20). Basheer et al. (19) investigated the effect of the addition of salt (NaCl) on the EME of acidic and basic drugs. The optimum extraction was achieved with 30% (w/v) NaCl samples. Alhooshani et al. (20) investigated the influence of salt on the EME of haloacetic acids. Various amounts of NaCl were added to the donor solution, ranging from 3 to 15%. The addition of NaCl increased the extraction efficiency from ultrapure water to 5% NaCl; above 5%, a decrease in the extraction was observed due to an increase in viscosity and a change in the conductivity of the donor solution.

Temperature

The effect of temperature on extraction has also been reported. It was reported that high temperatures (up to 40°C) can speed up the extraction process and temperatures above 40°C cause partial degradation of the SLM (6).

Innovations in EME

On-chip EME

An interesting development in voltage controlled extraction is on-chip EME (21), which allows analyses to be performed with very small sample volumes, low consumption of chemicals and reagents, high extraction efficiency and rapid extraction because of a very short diffusion path. Online coupling to analytical instruments is also possible.

The device (Figure 2) is composed of porous polypropylene membrane bonded between two poly(methyl methacrylate) (PMMA) substrates, each with channel structures facing the membrane. The sample solution is pumped into the sample channel of the chip. From the channel, analytes are extracted through the SLM and into an acceptor reservoir in the chip located on the other side of the SLM. The acceptor solution is stagnant, and after each extraction, the acceptor solution is manually removed by a pipette and analyzed. The driving force for extraction is a direct current (DC) electrical potential.

Figure 2.

Schematic illustration of on-chip EME coupled to MS.

Figure 2.

Schematic illustration of on-chip EME coupled to MS.

Petersen et al. (21) first reported the on-chip EME of five basic model analytes (pethidine hydrochloride, nortriptyline HCl, methadone HCl, haloperidol and loperamide HCl) from human urine samples. In this study, NPOE was used as the SLM and 10 mM HCl was used as the sample and acceptor solution. A voltage of 15 V was applied across the membrane as the driving force. The flow rate was 2.5 µL/min and the extraction time was 10 min. Higher recovery values were obtained than with earlier EME systems. The advantage of this system is the continuous delivery of fresh sample to the electromembrane. The acceptor solution was stagnant, and after each extraction, the acceptor solution was removed manually by a pipette and analyzed offline.

Recently, Petersen's group (22, 23) developed a new approach by introducing a flow in the acceptor channel. With this system, the acceptor solution is continuously pumped into an ultraviolet (UV) detector or mass spectrometer (MS) for online analysis. They applied this system for the real time MS measurement of the metabolism of amitriptyline by rat liver microsomes.

Low voltage EME

In low voltage EME, extractions are conducted at voltages in the range of 0–15 V (24). Until now, voltages in the range of 50–1,000 V have been used for extractions. The investigation of EME at lower voltages is of interest because there is no concern about sample/analyte degradation, interelectrode distance is only few millimeters and extractions are driven by common batteries (24). This may be helpful for the development of portable sample preparation devices.

Kjelsen et al. (24) first reported the low voltage EME of five basic drugs from biological samples (human plasma, urine and breast milk). The SLM was composed of 1-isopropyl-4-nitrobenzene; 10 mM HCl was used as the donor and acceptor solution and a driving force of 10 V was applied across the SLM. The extraction time was 5 min and the extraction unit was agitated at a speed of 1,000 rpm. Extraction recovery values were in the range of 50–93%. Extractions using a common 9 V battery as the power supply were also examined and produced similar results.

Seidi et al. (25) reported the low voltage EME for the simultaneous extraction of acidic (diclofenac) and basic (nalmefene) drugs from urine samples. The extraction of these drugs was conducted at a voltage of 40 V for 14 min. The percentage recovery values obtained for diclofenac and nalmefene were between 90 and 98%. Dominguez et al. (26) reported the EME of 29 different basic model drug substances at low voltage. The drug substances with logP below 2.3 were not extracted at voltages less than 15 V. Drug substances with logP ≥ 2.3 and with two basic groups were also not extracted at voltages less than 15 V. Drug substances with one basic group were all extracted at low voltages and with strong compound selectivity. The selectivity was easily tuned by the electrical potential difference.

Drop-to-drop EME

Petersen et al. (27), for the first time, developed miniaturized EME by using flat membranes under stagnant conditions, called drop-to-drop EME. The equipment used for drop-to-drop EME is shown in Figure 3 (27). It consists of a platinum wire that is connected to the negative outlet of the DC power supply and serves as the electrode in the acceptor droplet. A small well is pressed into a piece of aluminum foil, which is used as the sample compartment. The aluminum foil is connected to the positive outlet of the power supply and the whole foil serves as the anode for the EME. EME is performed as follows. The sample solution is filled into a well formed in the aluminum foil by using a micropipette and the positive outlet of the power supply is connected to this foil. Organic solvent is delivered by a pipette into a membrane for rapid immobilization. Excess solvent is removed by a medical wipe. The membrane containing the SLM is placed on the top of sample; the membrane squeezes the sample to fill the whole well and they come into liquid contact with the sample. The acceptor solution is applied as a droplet on top of the membrane and is in direct liquid contact with the latter. The sample is sandwiched between the aluminum foil and the membrane. The negative electrode is inserted into the top of the acceptor droplet and a constant voltage is applied for a certain period of time to accomplish the extraction. After the extraction, the acceptor droplet is immediately transferred by a pipette to a vial for analysis. The advantage of this technique is the selective extraction of the target analytes from small sample volumes without preconcentration. The process is generally conducted at low voltages and with short reaction times. This precludes the electrochemical decomposition of the analytes. The system is very simple, the components cost little and are used only for a single extraction to avoid carryover, and the system is stagnant, with no requirements for agitation or pumping. Five basic drugs were extracted from human urine, plasma and pure water by using drop-to-drop EME. The SLM was composed of NPOE and the driving force for extraction was 15 V. HCl (10 mM) was used as the donor and acceptor solution; extraction time was 5 min. Recovery values were obtained in the ranges of 34 and 46% for pure water, 32 and 47% for urine and 19 and 33% for plasma.

Figure 3.

Equipment used for drop-to-drop EME.

Figure 3.

Equipment used for drop-to-drop EME.

Pulsed EME

In this technique, pulsed voltage in combination with common DC constant power is used. This provides a very stable system by decreasing the thickness of the double layer at the interfaces and improves the extractability by eliminating the mass transfer barrier. Potential difference is applied for a short time. The duration of the pulse is long enough for the analytes to extract, but it is so short that the thickness of the boundary layer is minimized. The voltage is turned off while the sample solution is still being stirred. Therefore, the ions accumulated on the interfaces are dispersed again throughout the solution and the double layer disappears. After the outage step, voltage is applied again for another period in a similar manner. A schematic diagram of the pulsed EME setup is shown in Figure 4 (28).

Figure 4.

Equipment used for the pulsed EME method (A); beginning of the pulse duration (B); end of the pulse duration (C); end of the outage period (D).

Figure 4.

Equipment used for the pulsed EME method (A); beginning of the pulse duration (B); end of the pulse duration (C); end of the outage period (D).

Rezazadeh et al. (28) presented the first pulsed EME (PEME) for the extraction of naltrexone and nalmefene from biological fluids. The results showed that PEME provides higher preconcentration factors (the preconcentration factor was defined as the ratio of the final analyte concentration in the acceptor phase to the initial concentration of the analyte in the sample solution) than conventional EME.

EME–LDS-USAEME

In this approach, the target analytes are first extracted by EME and further preconcentrated by LDS-USAEME (29). Thus, high extraction efficiency is obtained because of the combination of these techniques. Figure 5 shows a schematic of the EME–LDS-USAEME procedure.

Figure 5.

Schematic diagram of EME–LDS-USAEME: EME (first step) (A); LDS-USAEME (second step), including introduction of aqueous sample and extraction solvent (a); ultrasonication (b); phase separation after centrifugation (c); squeezing of the pipette bulb (d); collection of the extract (e) (B).

Figure 5.

Schematic diagram of EME–LDS-USAEME: EME (first step) (A); LDS-USAEME (second step), including introduction of aqueous sample and extraction solvent (a); ultrasonication (b); phase separation after centrifugation (c); squeezing of the pipette bulb (d); collection of the extract (e) (B).

In the first step, analytes are extracted by EME; the acceptor solution from the first step is employed as the sample solution for the second step, LDS-USAEME. In this approach, a soft plastic Pasteur pipette is employed as a convenient extraction device. The acceptor solution is transferred to pipette. If necessary, a suitable volume of ultrapure water is added to increase the amount of solution and extraction solvent of a lower density than water is injected into the sample solution held in the pipette. The pipette is immediately immersed in an ultrasound water bath to form an emulsion for facilitating the extraction. After extraction, the emulsion is separated into two phases by centrifugation. The pipette is held upside down and the bulb is squeezed gently to raise the upper layer (organic extract) into the narrow stem of the pipette. The organic extract is conveniently collected by using a microsyringe and transferred to a vial for injecting into the analytical system for analysis.

Guo and Lee (29) developed a highly efficient and fast two-step approach of EME combined with LDS-USAEME for the determination of six chlorophenols (2-chlorophenol, 4-chlorophenol, 2, 3-dichlorophenol, 2, 4-dichlorophenol, 2, 4, 6-trichlorophenol and pentachlorophenol) in drain water samples. The developed method had the advantages of EME and USAEME. The optimized conditions for the extraction were as follows: EME under 50 V voltage for 10 min with pH of 12 for both the sample and the acceptor solutions; 1-octanol as the SLM; 1,000 rpm agitation speed; toluene as the extraction solvent for LDS-USAEME for 2 min, followed by centrifugation at 4,000 rpm for 4 min. The relative recovery values (ratios of the peak areas of the analytes in drain water extracts to peak areas of the analytes in pure water extracts spiked at the same concentrations) of six analytes were in the range of 78 to 105%.

Applications of EME

Pharmaceutical/chemical/clinical applications

Extraction of drugs from standard solutions/biological fluids

Seidi et al. (11) described the EME of thebaine from water samples, biological fluids, poppy capsules and narcotic drugs. NPOE was used as the SLM; 1 and 100 mM of HCl were used as sample and acceptor solution, respectively, and a voltage of 300 V was used as driving force. The system was agitated at 1,250 rpm and the extraction time was 15 min. Preconcentration factors were obtained in the range of 90–110.

Middelthon-Bruer et al. (12) reported the EME of 35 basic drugs from the standard solutions with 10 mM HCl used as the sample and acceptor solution. NPPE was used as the SLM and a voltage of 50 V was applied for 5 min. Basic drugs with two basic groups (logP > 2) were efficiently extracted by decreasing the concentration of HCl from 10 mM (pH 2.0) to 0.1 mM (pH 4.0). Due to the increase in pH, the charge was reduced and the distribution into the SLM increased. Singly charged basic drugs with logP > 2 were extracted with NPPE as the SLM and 10 mM HCl as the sample and acceptor solution. Medium polar analytes (1 < logP < 2) were poorly extracted in the initial electromembrane system based on NPPE as the SLM. To improve the extractability of these drugs, 10% TEHP was added to NPPE as the SLM at an ion balance of 0.01. TEHP improved the distribution ratios of medium polar drugs by improving their solubility within the SLM through the hydrogen bonding between the model drug and TEHP. Basic drugs with logP < 1 (more polar) were not extracted with NPPE as the SLM. The addition of DEHP (50%) to the SLM significantly improved the distribution ratios because of ion pairing between DEHP and model drugs, which improved their solubility within the SLM.

Eibak et al. (14) reported the exhaustive EME of six basic drugs from human plasma by using three hollow fibers in the same sample. Exhaustive EME was accomplished by increasing the surface area of the SLM and the volume of acceptor phase by using three separate HFs in the same sample (Figure 6). Three cathodes were inserted, one in each of the three HFs. NPOE was used as the SLM and a voltage of 200 V was used as driving force. The system was agitated at 1,200 rpm and the extraction time was 10 min. Recovery values obtained from the undiluted human plasma were in the range of 56–102%.

Figure 6.

Exhaustive EME setup with three HFs.

Figure 6.

Exhaustive EME setup with three HFs.

Eskandari et al. (16) reported the EME of mebendazole from plasma and urine samples. NPOE was used as the SLM and 100 mM HCl was used as the sample and acceptor solution. The driving force for the extraction was 150 V and the extraction time was 15 min. Extraction was also performed by HF-LPME, but it required more time (60 min) than EME (15 min).

Rezazadeh et al. (17) reported the EME of naltrexone and nalmefene from human plasma and urine. SLM was composed of 85% NPOE and 15% DEHP; 10 and 100 mM HCl were used as the donor and acceptor solution, respectively. The driving force for the extraction was 100 V and the extraction time was 20 min. The unit was agitated at 1,250 rpm and preconcentration factors were obtained in the range of 109–149.

Seidi et al. (18) reported the selective EME of atenolol in the presence of betaxolol and propranolol from saliva samples with a preconcentration factor of 74. SLM was composed of NPOE containing 5% TEHP and 10% DEHP; 1 and 100 mM HCl were used as the donor and acceptor solution, respectively. A voltage of 250 V was used as the driving force, the system was agitated at 1,250 rpm and the extraction time was 15 min.

Gjelstad et al. (30) reported the EME of 20 different basic drugs from aqueous samples with 10 mM HCl used as the donor and acceptor solution. Hydrophobic basic drugs (logP > 1.7) were effectively extracted by using NPOE as the SLM and hydrophilic basic drugs (logP < 1.0) were extracted by using NPOE/25% DEHP as the SLM; the recovery values were up to 83% for hydrophobic drugs and up to 75% for hydrophilic drugs.

Gjelstad et al. (31) also investigated the kinetic aspects of HF-LPME and EME with basic drugs. In HF-LPME, the sample solution was alkaline and the acceptor solution was acidic, whereas in EME, both the acceptor and sample solutions were acidic. Mass transfer of the analyte across the SLM was lower in HF-LPME than EME. This is because of the passive diffusion of analytes in HF-LPME and the electrokinetic migration of analytes in EME.

Balchen et al. (32) reported the first electrokinetic migration of 11 acidic drugs (diclofenac, fenoprofen, flurbiprofen, gemfibrozil, ibuprofen, indomethacin, ketoprofen, probenecid, warfarin, naproxen and hexobarbital) across SLM. The optimal extraction conditions were as follows: 50 V voltage for 5 min with pH of 12 for both the sample and acceptor solutions; 1-heptanol as the SLM; agitation speed of 1,200 rpm. Eleven different acidic drugs were extracted with recovery values between 8 and 100%.

Nojavan et al. (33) performed the EME of zwitterionic compounds (cetirizine and mesalazine) in both acidic and basic pH levels and the results were compared. 1-Octanol and NPOE were used as the SLM solvents. The study showed that NPOE could not be used in basic pH levels because of its leakage into the acceptor and sample solutions. The results showed that the cationic form of cetirizine was extracted more than anionic form, where as the extraction efficiency values obtained for mesalazine were almost identical for both cationic and anionic forms.

Eibak et al. (34) reported the EME of citalopram, loperamide, methadone and sertraline from whole blood. In this, 10 µL of the blood sample was spotted on alginate and chitosan foams as the sampling media. HCl (1 mM) was used as the donor solution and 10 mM formic acid was used as acceptor solution. Commercial cards (Whatman FTA DMPK and Agilent Bond Elute DMS) were also used for sample preparation, but the recovery values were less than with the alginate and chitosan foam.

Kubáň and Boček (35) reported the EME of three basic drugs (nortriptyline, haloperidol and loperamide) from matrix components (inorganic cations, proteins, amino acids and bovine milk). SLMs impregnated with NPOE, 1-ethyl-2-nitrobenzene (ENB) or NPOE/DEHP were used to test the recovery and selectivity. Excellent selectivity and transfer of analytes were obtained by using NPOE. In the case of ENB, coextraction of interfering matrix components was observed and in the case of NPOE/DEHP, poor selectivity and recovery were observed.

Davarani et al. (36) reported the EME of tricyclic antidepressants from human plasma and urine samples. The SLM was composed of NPOE and the driving force for the extraction was 200 V. The pH of the donor solution was 4.0 and the acceptor solution was 2.0. The donor solution was agitated at 1,400 rpm and the extraction time was 20 min. Recovery values were obtained in the range of 90–95%.

Fakhari et al. (37) developed an EME procedure for the preconcentration of trimipramine enantiomers in biological samples. The SLM was composed of NPOE and the driving force was 51V. The extraction time was 34 min and the pH levels of the donor and acceptor solution were 4.5 and 1.0, respectively. Recovery values of the enantiomers obtained from the biological samples were in the range of 48–66%.

Slampová et al. (38) reported a new approach for the EME of basic drugs and amino acids by using stabilized constant DC electric current. They evaluated the performance of the two modes (constant DC. voltage versus constant DC electric current) of EME on the pretreatment process. The repeatability of the extraction process was significantly improved for EME at a constant electric current compared to EME at constant voltage. In addition, EME at constant electric current does not suffer from the SLM instability that is frequently reported in experiments with constant voltage (39, 40).

Gjelstad et al. (40) described the EME of six basic drugs (pethidine, nortriptyline, tramadol, methadone, haloperidol and loperamide) with protein binding in the range of 20–97% from untreated human plasma and whole blood. ENB was used as the SLM and 10 mM HCl was used as the acceptor solution. The driving force for the extraction was 10 V, which reduced the protein binding and facilitated the transport of the free drug through the SLM. The extraction time was 10 min and the donor solution was agitated at 1,050 rpm. Excellent recovery values in the range of 25–65% were obtained from biological matrices without any pretreatment.

Fotouhi et al. (41) compared HF-LPME and EME for the extraction of ephedrine from biological samples. Compared with HF-LPME, EME provides high extraction efficiency in very short time. Preconcentration factors of 120 and 35 for urine and 51 and 8 for human plasma were obtained by using EME and HF-LPME, respectively.

Jamt et al. (42) reported the EME of six basic drugs of abuse from undiluted whole blood and postmortem blood. The SLM consisted of ENB and the driving force for the extraction was 15 V. The extraction time was 5 min and was performed in a stagnant system without any convection of the extraction unit. Recovery values were achieved in the range of 10–30%.

Davarani et al. (43) reported the EME of sodium diclofenac as an acidic compound from wastewater, urine, bovine milk and plasma samples. The SLM was composed of 1-octanol and the driving force for the extraction was 20 V; 1 and 10 mM sodium hydroxide (NaOH) were used as donor and acceptor solution, respectively. The extraction time was 5 min and the recovery values obtained for different samples were between 44 and 95%.

Seidi et al. (44) reported the EME of amphetamine-type stimulants from human urine samples. The SLM was composed of NPOE containing 15% TEHP, the extraction time was 7 min and 1 and 10 mM HCl were used as donor and acceptor solution, respectively. The driving force for the extraction was 250 V and the unit was placed on a stirrer with a stirring speed of 1,000 rpm. Preconcentration factors were obtained between 108 and 140.

Seidi et al. (45) also reported the EME of levamisole from human biological fluids. The SLM was composed of NPOE with 5% TEHP and a potential difference of 200 V was applied across the SLM. The extraction time was 15 min and recovery values from biological fluids were in the range of 59–65%.

Nojavan and Fakhari (46) reported the EME of amlodipine enantiomers from plasma and urine samples. NPOE was used as the SLM and 10 mM HCl was used as the sample and acceptor solution. The driving force for the extraction was a voltage of 200 V and the extraction time was 15 min. A stirring speed of 100 rpm promoted the extraction efficiency and extraction recovery values obtained from the biological samples were in the range of 63–74%.

Eibak et al. (47) also reported the kinetic electromembrane extraction of amitriptyline, citalopram, fluoxetine and fluvoxamine from untreated human plasma under stagnant conditions. The SLM was composed of ENB and the driving force of the extraction was a 9 V potential applied over the SLM with a common battery. The extraction time was 1 min and the recovery values were 12, 13, 22 and 17% for fluoxetine, amitriptyline, citalopram and fluvoxamine, respectively.

Extraction of amino acids/peptides from standard solutions/biological fluids

Strieglerová et al. (39) reported the EME of 17 amino acids from body fluids (human serum, plasma and whole blood). The SLM was composed of ENB–DEHP (85:15, v/v) and 2.5M acetic acid was used as the donor and acceptor solution. The driving force for the extraction was 50 V and the extraction time was 10 min. The unit was stirred with a stirring speed of 500 rpm. The repeatability [relative standard deviation (RSD)] of the peak areas of 17 amino acids was better than 13%.

Balchen et al. (13) reported the EME of angiotensin peptides from plasma. The SLM was composed of 1-octanol and 8% DEHP. The driving force for the extraction was 15 V and the extraction time was 10 min. Extraction recovery values were obtained between 25 and 43%.

The EME of three biologically active peptides (angiotensin 2, endomorphin 1 and leu-enkephalin) from human plasma was also reported by Balchen's group (48). The SLM consisted of 1-octanol, diisobutyl ketone and DEHP (55:35:10, w/w/w). A potential of 20 V was applied across the SLM and the extraction time was 5 min. The pH of the donor solution was 3.2 and the acceptor solution was 1.3. HCl (50 mM) was used as the donor and acceptor solution. The donor solution was agitated at 900 rpm. The three peptides were quantified from spiked plasma samples with repeatability (RSD) ranging between 15 and 24% (n = 5).

Seip et al. (49) reported the EME of eight model peptides. In this study, SLMs with different organic solvents and carriers (2-octanone/DEHP, 2-octanone/tridecyl phosphate (TDP), 1-nonanol/DEHP, 1-nonanol/TDP and 1-octanol/DEHP/diisobutyl ketone) were tested. The SLM, composed of 2-octanone and TDP (90:10, w/w), provided high extraction recovery values with lower standard deviation (SD). The extraction time was 5 min. The driving force for the extraction was 10 V and the sample compartment was agitated at 900 rpm.

Balchen et al. (50) reported the EME of 37 peptides from aqueous samples In which 10 and 100 mM formic acid were used as donor and acceptor solution, respectively. In this study, three different SLMs were used to correlate the extractability of the peptides with the highly variable physical-chemical properties of the peptides. SLM-1 was composed of pure eugenol, which provided an EME system for hydrophobic and intermediate peptides (hydrophilicity values below 0.2), in which the extraction and dissolution of peptides into the SLM was primarily based on solvent interactions. SLM-2 (1-octanol/diisobutyl ketone/DEHP) provided efficient extraction of both hydrophobic and hydrophilic peptides (hydrophilicity values in the range from –2 to +1), and the transfer of peptides was based on ionic interactions with DEHP. SLM-3 (1-octanol/15-crown-5 ether) was selective for hydrophobic peptides (negative hydrophilicity values), and complexation of the peptides with the crown ether was important for the migration of peptides into the acceptor solution.

The EME of three peptides from aqueous solution was also reported by Balchen et al. (51). The SLM was composed of 1-octanol/diisobutyl ketone/DEHP (55:35:10, w/w/w) and the applied potential was 50 V; 1 and 50 mM HCl were used as acceptor and donor solution, respectively. The system was agitated at 1,050 rpm and the extraction time was 5 min. Extraction recovery values were in the range of 36–56%.

Balchen et al. (52) also reported the EME of eight peptides from aqueous solution. The SLM was composed of 1-octanol and 15% DEHP, the driving force potential was 50 V and 1 and 100 mM HCl were used as donor and acceptor solution, respectively. The sample solution was agitated at 1,050 rpm and sample enrichment up to 11 times was accomplished.

Extraction of metals

Strieglerová et al. (53) reported the EME of lithium from untreated human body fluids. The SLM was composed of 1-octanol. The donor solution was prepared in 0.5 mM Tris and the acceptor solution was 100 mM acetic acid. The donor solution was stirred at 750 rpm and a potential of 75 V was used as the driving force. The extraction time was 10 min. Lithium recovery values from blood serum, plasma, urine and whole blood were 98, 107, 92 and 90%, respectively.

Kubáň et al. (54) reported the EME of heavy metal cations from tap water and powdered milk samples. The SLM was composed of 1-octanol and 0.5% v/v bis(2-ethyl hexyl) phosphoric acid. The donor solution was water and the acceptor solution was 100 mM acetic acid. The extraction time was 5 min, the driving force was 75 V and the stirring rate was 750 rpm. Extraction recovery values were 15–42%.

Basheer et al. (55) reported the EME of lead ions from amniotic fluid, blood serum, lipstick and urine samples. The SLM was composed of toluene and a voltage of 300 V was applied across the SLM as a driving force. The extraction time was 15 min and the sample was agitated at 700 rpm. The recovery values were obtained in the ranges of 81.6 and 86.3% for amniotic fluid, 81.6 and 89.3 % for serum, 75.4 and 80.8% for lipstick and 58.0 and 69.6% for urine.

Extraction of ions

Hu et al. (56) reported the EME of inorganic anions (chloride, bromide and sulfate) from ethyl acetate. The driving force for the extraction was 600 V and deionized water was used as the acceptor solution. The extraction time was 10 min and the recovery values were in the range of 76–110%.

Tan et al. (57) demonstrated the EME of biological anions (nitrite, adipate, oxalate, iodide, fumarate, thiocyanate and perchlorate) from aqueous solutions and amniotic fluids. The SLM was composed of methanol and the driving force for the extraction was 12 V. The pH of the donor solution (10 mM NaOH) was 4.0 and the pH of the acceptor solution (10 mM NaOH) was 12.0. The extraction time was 5 min and the unit was agitated at 500 rpm. The enrichment factors obtained for all anions were in the range of 3.6 to 36.2.

See and Hauser (58) reported the electric field-driven extraction of lipophilic anions (propane sulfonate, octane sulfonate and decane sulfonate) across a carrier-mediated polymer inclusion membrane. The membrane was 20 µm thick and consisted of 60% cellulose triacetate as base polymer, 20% o-nitrophenyl octyl ether as plasticizer and 20% Aliquat 336 as cationic carrier in the perchlorate form. A potential of 700 V was applied across the membrane as a driving force and the extraction efficiency values of the analytes were > 90%. The developed method was applied for the extraction of the herbicide glycophosphate and its breakdown product aminomethylphosphonic acid from spiked river water.

Environmental applications

Basheer et al. (19) reported the simultaneous extraction of acidic and basic analytes from wastewater in a single step by using a compartmentalized membrane envelope. This was fabricated by combining four sheets of porous polypropylene membrane and heat-sealing at three edges (two sides and the bottom) using an electrical heat sealer to produce a three-compartment envelope. The outer compartments were filled with acidic and alkaline buffer solutions and the middle compartment was filled with acceptor solution (1-octanol). The outer skin of the membrane envelope was impregnated with toluene by dipping in the solvent for few seconds to form the SLM. This was placed in an extraction vial containing the sample solution for extraction. The positive and negative electrodes were placed into the acidic (pH 2) and basic (pH 12) buffer compartments, respectively. A DC potential difference of 300 V was applied for 10 min and the sample solution was agitated at 73 rad/s with a magnetic stirring bar. Under the application of voltage, the basic drugs migrated toward the negative electrode and became deionized. Similarly and concurrently, negatively charged acidic drugs migrated toward the positive electrode that was placed in the acidic buffer and became deionized. The deionized drugs were transported to a middle compartment containing the organic acceptor solvent, which is a better solvent for the deionized drugs than the buffer solutions. For this reason, both acidic and basic drugs were simultaneously extracted into the acceptor solvent. The experimental setup used for this purpose is shown in Figure 7 (19).

Figure 7.

Experimental setup of EME containing three compartment envelopes.

Figure 7.

Experimental setup of EME containing three compartment envelopes.

Alhooshani et al. (20) described the EME of haloacetic acids and aromatic acetic acids from wastewater. The SLM consisted of toluene and a potential of 200 V was used as driving force. The donor solution was 5% NaCl solution and the acceptor solution was phosphate buffer of pH 12. Sodium chloride solution increased the extraction efficiency more than ultrapure water. The sample solution was stirred at 450 rpm and the extraction time was 30 min. EME showed better recovery than SPE.

Rezazadeh et al. (59) reported the EME of β-receptor agonist drugs (salbutamol and terbutaline) from wastewater. The SLM was composed of 80% NPOE, 10% DEHP and 10% TEHP. The driving force was 200 V, the pH of the donor solution was 3.0 and the pH of the acceptor solution was 1.0. Preconcentration factors obtained for salbutamol and terbutaline were 89 and 72, respectively.

Kiplagat et al. (60) reported the EME of perchlorate from snow and drinking water. The SLM was composed of 1-heptanol and the driving force for extraction was 25 V. The extraction unit was stirred with a stirring rate of 750 rpm. The donor solution was deionized water and the acceptor solution was 1 mM Tris solution. The extraction time was 5 min and recovery values were between 95.9 and 106.7%.

Payán et al. (61) reported the EME of six non-steroidal anti-inflammatory drugs (NSAIDs) from wastewater samples. The SLM was composed of 1-octanol and a potential difference of 10 V was applied over the SLM. NaOH of pH 12 was used as the donor and acceptor solution and the extraction time was 10 min. The system was agitated at 600 rpm and recovery values were obtained between 60 and 100%.

Xu et al. (62) reported the electromembrane isolation of nerve agent degradation products (methylphosphonic acid, ethyl methylphosphonic acid, isopropyl methylphosphonic acid and cyclohexyl methylphosphonic acid) from spiked river water samples. The SLM was composed of 1-octanol and a voltage of 300 V was used as the driving force for extraction. The pH of the sample and acceptor solution was 6.8. The unit was agitated at 800 rpm and the extraction time was 30 min. Limit of detection values obtained for the analytes ranged from 0.022 to 0.11 ng/mL.

Lee et al. (63) reported the EME of chlorophenols (4-chlorophenol, 2,4-dichlorophenol, 2,4,6-trichlorophenol and pentachlorophenol), which are major environmental pollutants, from sea water. The SLM was composed of 1-octanol and the driving force for the extraction was 10 V. The pH of the donor and acceptor solution was 12. The system was agitated at 1,250 rpm and the extraction time was 10 min. This study revealed that the developed EME procedure exhibits particular selectivity toward pentachlorophenol.

Table I summarizes the applications of EME in pharmaceutical, chemical, clinical and environmental analyses.

Table I
Applications of EME*     
Analyte Matrix SLM composition Analytical method Reference 
Pharmaceutical/chemical/clinical applications   
Extraction of drugs from standard solutions/biological fluids   
Thebaine Water samples, biological fluids, poppy capsules and narcotic drugs NPOE HPLC–UV 11 
Thirty-five basic drugs Standard solutions NPPE, NPPE/TEHP, CE–UV 12 
NPPE/DEHP 
Basic drugs Human plasma NPOE LC–MS 14 
Citalopram 
Loperamide 
Methadone 
Paroxetine 
Pethidine 
Sertraline 
Mebendazole Plasma and urine NPOE HPLC–UV 16 
Nalmefene Human plasma and urine 85% NPOE and 15% DEHP HPLC–UV 17 
Naltrexone 
Three β-blocker drugs Saliva NPOE containing 5% TEHP and 10% DEHP HPLC 18 
Atenolol 
Betaxolol 
Propranolol 
Basic drugs Standard solutions NPOE HPLC–UV 31 
Clemastine     
Clomipramine     
Droperidol     
Haloperidol     
Nortriptyline     
Eleven acidic drugs Standard solutions 1-Heptanol CE–UV 32 
Zwitterionic compounds Standard solutions 1-Octanol and NPOE HPLC–UV 33 
Cetirizine     
Hydroxyzine     
Mesalazine     
Citalopram Whole blood NPOE LC–MS 34 
Loperamide     
Methadone     
Sertraline     
Three basic drugs Inorganic cations, NPOE, ENB, CE–C(4)D 35 
Haloperidol proteins, 1-octanol,   
Loperamide amino acids and NPOE/DEHP   
Nortriptyline bovine milk    
Clomipramine Human plasma and urine NPOE GC–FID 36 
Imipramine 
Trimipramine enantiomers Plasma and urine NPOE CD modified CE 37 
Basic drugs and amino acids Human urine and serum ENB, CE 38 
ENB/DEHP 
(85:15, v/v) 
Six basic drugs Untreated human plasma and whole ENB CE 40 
Haloperidol 
Loperamide blood    
Methadone     
Nortriptyline     
Pethidine     
Tramadol     
Ephedrine Human plasma and urine NPOE containing 10% (v/v) DEHP HPLC 41 
Six basic drugs Undiluted whole blood ENB UPLC–MS-MS 42 
Cathinone 
2,5-dimethoxy-4-iodo- 
amphetamine 
Methamphetamine 
3,4-methylene dioxy-amphetamine 
3,4-methylene dioxy-methamphetamine 
Ketamine 
Sodium diclofenac Wastewater, urine, 1-Octanol HPLC–UV 43 
 bovine milk and    
 plasma    
Amphetamine-type stimulants Human urine NPOE containing 15% TEHP HPLC–UV 44 
Levamisole Plasma, urine and saliva NPOE containing 5% TEHP HPLC–UV 45 
Amlodipine enantiomers Human plasma and urine NPOE CE–UV 46 
Amitriptyline Untreated human ENB LC–MS 47 
Citalopram plasma    
Fluoxetine     
Fluvoxamine     
Extraction of amino acids/peptides from standard solutions/biological fluids 
Seventeen amino acids Body fluids ENB/DEHP (85:15, v/v) CE–C(4)D 39 
Angiotensin-1 Human plasma 1-Octanol and 8 % DEHP LC–MS 13 
Angiotensin-2 
Angiotensin-3 
Three peptides Human plasma 1-octanol, LC–MS-MS 48 
Angiotensin 2 diisobutyl ketone 
Endomorphin 1 and DEHP 
Leu-enkephalin (55:35:10, w/w/w) 
Eight peptides — 2-Octanone and CE–HPLC 49 
TDP (90:10) 
Thirty-seven peptides — Eugenol, LC–MS-MS 50 
 1-octanol/diisobutyl ketone/DEHP, and CE–UV 
 1-octanol/15-crown-5 ether  
Three peptides — 1-Octanol/diisobutyl CE–UV 51 
Angiotensin 2 ketone/DEHP 
Bradykinin (55:35:10, w/w/w) 
Enkephalin  
Eight peptides — 1-Octanol and 15% DEHP HPLC 52 
Extraction of metals     
Lithium Human body fluids 1-Octanol CE–C(4)D 53 
Heavy metal cations Tap water and powdered milk samples 1-Octanol and 0.5% DEHP CE–C(4)D 54 
Lead Amniotic fluid, Toluene CE–UV 55 
blood serum, 
lip stick and 
urine samples 
Extraction of ions 
Inorganic anions Ethyl acetate — IC 56 
Biological anions Amniotic fluids Methanol IC 57 
Lipophilic anions — NPOE/Aliquat 336 CE–C(4)D 58 
Environmental applications:     
Acidic NSAIDs and basic β-blockers Wastewater samples Toluene GC–MS 19 
Haloacetic acids Wastewater Toluene HPLC–UV 20 
Salbutamol Wastewater 80% NPOE/10% DEHP/10% TEHP HPLC–UV 59 
Terbutaline 
Perchlorate Snow and drinking water 1-Heptanol CE–C(4)D 60 
Six NSAIDs Wastewater 1-Octanol HPLC–DAD-FLD 61 
Diclofenac 
Ibuprofen 
Ketoprofen 
Ketorolac 
Naproxen 
Salicylic acid 
Nerve agent degradation products River water 1-Octanol CE–C(4)D 62 
Chlorophenols Sea water 1-Octanol HPLC–UV 63 
Applications of EME*     
Analyte Matrix SLM composition Analytical method Reference 
Pharmaceutical/chemical/clinical applications   
Extraction of drugs from standard solutions/biological fluids   
Thebaine Water samples, biological fluids, poppy capsules and narcotic drugs NPOE HPLC–UV 11 
Thirty-five basic drugs Standard solutions NPPE, NPPE/TEHP, CE–UV 12 
NPPE/DEHP 
Basic drugs Human plasma NPOE LC–MS 14 
Citalopram 
Loperamide 
Methadone 
Paroxetine 
Pethidine 
Sertraline 
Mebendazole Plasma and urine NPOE HPLC–UV 16 
Nalmefene Human plasma and urine 85% NPOE and 15% DEHP HPLC–UV 17 
Naltrexone 
Three β-blocker drugs Saliva NPOE containing 5% TEHP and 10% DEHP HPLC 18 
Atenolol 
Betaxolol 
Propranolol 
Basic drugs Standard solutions NPOE HPLC–UV 31 
Clemastine     
Clomipramine     
Droperidol     
Haloperidol     
Nortriptyline     
Eleven acidic drugs Standard solutions 1-Heptanol CE–UV 32 
Zwitterionic compounds Standard solutions 1-Octanol and NPOE HPLC–UV 33 
Cetirizine     
Hydroxyzine     
Mesalazine     
Citalopram Whole blood NPOE LC–MS 34 
Loperamide     
Methadone     
Sertraline     
Three basic drugs Inorganic cations, NPOE, ENB, CE–C(4)D 35 
Haloperidol proteins, 1-octanol,   
Loperamide amino acids and NPOE/DEHP   
Nortriptyline bovine milk    
Clomipramine Human plasma and urine NPOE GC–FID 36 
Imipramine 
Trimipramine enantiomers Plasma and urine NPOE CD modified CE 37 
Basic drugs and amino acids Human urine and serum ENB, CE 38 
ENB/DEHP 
(85:15, v/v) 
Six basic drugs Untreated human plasma and whole ENB CE 40 
Haloperidol 
Loperamide blood    
Methadone     
Nortriptyline     
Pethidine     
Tramadol     
Ephedrine Human plasma and urine NPOE containing 10% (v/v) DEHP HPLC 41 
Six basic drugs Undiluted whole blood ENB UPLC–MS-MS 42 
Cathinone 
2,5-dimethoxy-4-iodo- 
amphetamine 
Methamphetamine 
3,4-methylene dioxy-amphetamine 
3,4-methylene dioxy-methamphetamine 
Ketamine 
Sodium diclofenac Wastewater, urine, 1-Octanol HPLC–UV 43 
 bovine milk and    
 plasma    
Amphetamine-type stimulants Human urine NPOE containing 15% TEHP HPLC–UV 44 
Levamisole Plasma, urine and saliva NPOE containing 5% TEHP HPLC–UV 45 
Amlodipine enantiomers Human plasma and urine NPOE CE–UV 46 
Amitriptyline Untreated human ENB LC–MS 47 
Citalopram plasma    
Fluoxetine     
Fluvoxamine     
Extraction of amino acids/peptides from standard solutions/biological fluids 
Seventeen amino acids Body fluids ENB/DEHP (85:15, v/v) CE–C(4)D 39 
Angiotensin-1 Human plasma 1-Octanol and 8 % DEHP LC–MS 13 
Angiotensin-2 
Angiotensin-3 
Three peptides Human plasma 1-octanol, LC–MS-MS 48 
Angiotensin 2 diisobutyl ketone 
Endomorphin 1 and DEHP 
Leu-enkephalin (55:35:10, w/w/w) 
Eight peptides — 2-Octanone and CE–HPLC 49 
TDP (90:10) 
Thirty-seven peptides — Eugenol, LC–MS-MS 50 
 1-octanol/diisobutyl ketone/DEHP, and CE–UV 
 1-octanol/15-crown-5 ether  
Three peptides — 1-Octanol/diisobutyl CE–UV 51 
Angiotensin 2 ketone/DEHP 
Bradykinin (55:35:10, w/w/w) 
Enkephalin  
Eight peptides — 1-Octanol and 15% DEHP HPLC 52 
Extraction of metals     
Lithium Human body fluids 1-Octanol CE–C(4)D 53 
Heavy metal cations Tap water and powdered milk samples 1-Octanol and 0.5% DEHP CE–C(4)D 54 
Lead Amniotic fluid, Toluene CE–UV 55 
blood serum, 
lip stick and 
urine samples 
Extraction of ions 
Inorganic anions Ethyl acetate — IC 56 
Biological anions Amniotic fluids Methanol IC 57 
Lipophilic anions — NPOE/Aliquat 336 CE–C(4)D 58 
Environmental applications:     
Acidic NSAIDs and basic β-blockers Wastewater samples Toluene GC–MS 19 
Haloacetic acids Wastewater Toluene HPLC–UV 20 
Salbutamol Wastewater 80% NPOE/10% DEHP/10% TEHP HPLC–UV 59 
Terbutaline 
Perchlorate Snow and drinking water 1-Heptanol CE–C(4)D 60 
Six NSAIDs Wastewater 1-Octanol HPLC–DAD-FLD 61 
Diclofenac 
Ibuprofen 
Ketoprofen 
Ketorolac 
Naproxen 
Salicylic acid 
Nerve agent degradation products River water 1-Octanol CE–C(4)D 62 
Chlorophenols Sea water 1-Octanol HPLC–UV 63 

*Note: Capillary electrophoresis with capacitively coupled contactless conductivity detection [CE–C(4)D]; diode array detection (DAD); electrospray ionization (ESI); fluorescence detection (FLD); flame ionization detection (FID); ion chromatography (IC); tandem mass spectrometry (MS-MS); ultra-performance liquid chromatography (UPLC).

Conclusions

EME is a selective, rapid, efficient and economic sample preparation technique in pharmaceutical, chemical, clinical and environmental analyses. On-chip EME allows continuous extraction and online coupling with analytical instruments. This helps to reduce the sample analysis time. Low voltage EME allows the extractions to be conducted at voltages obtainable by common batteries and there is no concern about sample/analyte degradation. This may be interesting for future developments of portable devices and for down-scaling the concept. Drop-to-drop EME requires small sample volumes and the components are only used for a single extraction, which precludes the carryover effect. Pulsed EME provides a very stable system in high voltages, which makes this system suitable for the rapid and effective extraction of analytes from complicated matrices. EME–LDS-USAEME provides a highly efficient extraction due to two-step extractions (EME followed by LDS-USAEME), which can directly be used for complex matrices. Finally, EME is well adapted for the trend toward miniaturization and is the technology for the future.

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