Electro membrane extraction of biological anions with ion chromatographic analysis

A simple and sensitive single step electro membrane extraction (EME) procedure was demonstrated for biological organic anions with determination by ion chromatography (IC). Nitrite, adipate, oxalate, iodide, fumarate, thiocyanate and perchlorate were extracted from aqueous donor solutions, across a supported liquid membrane (SLM) consisting of methanol impregnated in the walls of a porous polypropylene membrane bag and into an alkaline aqueous acceptor solution in the lumen of the propylene envelope by the application of potential of 12 V applied across the SLM. The acceptor solution was analyzed by IC. Parameters affecting the extraction performance such as type of SLM, extraction time, pH of the donor and acceptor solution, and extraction voltage were studied. The most favorable EME conditions were methanol as the SLM, extraction time of 5 min, pH of acceptor and sample solutions of 12 and 4, respectively, and a voltage of 12 V. Portable 12 V batteries were used in the study. Under these optimized conditions, all anions had enrichment factors ranging from 3.6 to 36.2 with relative standard deviations (n = 3) of between 6.6 and 17.5%. Good linearity ranging from 0.1 to 10 μg mL⁻¹ with coefficients of correlation (r) of between 0.9981 and 0.9996 were obtained. The limits of detection of the EME-IC method were from 0.01 to 0.14 μg mL⁻¹. The developed methodology was applied to amniotic fluid samples to evaluate the feasibility of the method for real applications.     

Effects of selected operational parameters on efficacy and selectivity of electromembrane extraction. Chlorophenols as model analytes

Effects of organic solvent type, pH value, and composition of donor/acceptor solution on the efficacy of electromembrane extraction (EME) were examined. For the first time, a comprehensive quantitative study, based also on measurements of electric charge passed through the EME system, was carried out, which demonstrates that apart from the pH value, also the nature of counter‐ions in donor and acceptor solution plays a significant role in the electrically induced transfer of charged analytes across supported liquid membranes (SLMs). The EME transfer of model analytes correlated well with electrophoretic mobilities of inorganic cations, which were added to acceptor solutions during their alkalization with alkali metal hydroxides, and were highest for counter‐cations with highest mobilities. Up to a 53‐fold improvement of extraction efficiency was achieved for EMEs using optimized composition of donor (alkalized with KOH to pH 7) and acceptor (10 mM CsOH, pH 12) solutions. Six chlorophenols (CPs) were selected as model analytes due to the wide range of pH values that are required for their ionization and due to their high environmental relevance; quantitative measurements were carried out by CE with UV detection. Extraction recoveries of the six CPs ranged between 14 and 25% for 5 min EMEs at 150 V and 750 rpm across SLMs impregnated with 1‐ethyl‐2‐nitrobenzene. Calibration curves were strictly linear (r² ≥ 0.999) in 0.01–10 μg/mL range, repeatability values of peak areas were between 0.7 and 5.6% and LODs for standard solutions and environmental samples were better than 5 ng/mL.     

Optimization of some experimental parameters in the electro membrane extraction of chlorophenols from seawater

An electro membrane extraction (EME) methodology was utilized to study the isolation of some environmentally important pollutants, such as chlorophenols, from aquatic media based upon the electrokinetic migration process. The analytes were transported by application of an electrical potential difference over a supported liquid membrane (SLM). A driving force of 10 V was applied to extract the analytes through 1-octanol, used as the SLM, into a strongly alkaline solution. The alkaline acceptor solution was subsequently analyzed by high performance liquid chromatography-ultraviolet (HPLC-UV) detection. The parameters influencing electromigration, including volumes and pH of the donor and acceptor phases, the organic solvent used as the SLM, and the applied voltage and its duration, were investigated to find the most suitable extraction conditions. Since the developed method showed a rather high degree of selectivity towards pentachlorophenol (PCP), validation of the method was performed using this compound. An enrichment factor of 23 along with acceptable sample clean-up was obtained for PCP. The calibration curve showed linearity in the range of 0.5–1000 ng/mL with a coefficient of estimation corresponding to 0.999. Limits of detection and quantification, based on signal-to-noise ratios of 3 and 10, were 0.1 and 0.4 ng/mL, respectively. The relative standard deviation of the analysis at a PCP concentration of 0.5 ng/mL was found to be 6.8% (n = 6). The method was also applied to the extraction of this contaminant from seawater and an acceptable relative recovery of 74% was achieved at a concentration level of 1.0 ng/mL.     

An electromembrane extraction–HPLC‐UV analysis for the determination of valproic acid in human plasma

In this study, an electromembrane extraction (EME) method combined with a simple HPLC‐UV analysis was developed and validated for the determination of valproic acid in human plasma samples. The major parameters influencing EME procedure, namely the solvent composition, voltage, pH of acceptor and donor solutions, salt effect, and time of extraction, were evaluated and optimized. The drug was extracted from the donor aqueous sample solution (pH 5) to the acceptor aqueous solution (pH 13). The donor and acceptor phases were separated by a hollow fiber dipped in 1‐octanol as a supported liquid membrane. A voltage of 60 V during 25 min was applied as the driving force. The drug concentration enrichment factor obtained was >125, which enhanced the sensitivity of the method. The limit of detection and the limit of quantitation were 0.2 and 0.5 μg/mL, respectively. The proposed method was successfully applied to a human plasma sample, with a relative recovery of 75%. The method was linear over the range 0.5–10 μg/mL for valproic acid (R² > 0.9996) with a repeatability (%RSD) between 0.9 and 3.3% (n = 3). Valproic acid is an anticonvulsant drug with poor UV absorption, and EME can improve the sensitivity of HPLC‐UV for the determination of valproic acid in plasma samples.     

Exhaustive extraction of peptides by electromembrane extraction

This fundamental work illustrates for the first time the possibility of exhaustive extraction of peptides using electromembrane extraction (EME) under low system-current conditions (<50 μA). Bradykinin acetate, angiotensin II antipeptide, angiotensin II acetate, neurotensin, angiotensin I trifluoroacetate, and leu-enkephalin were extracted from 600 μL of 25 mM phosphate buffer (pH 3.5), through a supported liquid membrane (SLM) containing di-(2-ethylhexyl)-phosphate (DEHP) dissolved in an organic solvent, and into 600 μL of an acidified aqueous acceptor solution using a thin flat membrane-based EME device. Mass transfer of peptides across the SLM was enhanced by complex formation with the negatively charged DEHP. The composition of the SLM and the extraction voltage were important factors influencing recoveries and current with the EME system. 1-nonanol diluted with 2-decanone (1:1 v/v) containing 15% (v/v) DEHP was selected as a suitable SLM for exhaustive extraction of peptides under low system-current conditions. Interestingly, increasing the SLM volume from 5 to 10 μL was found to be beneficial for stable and efficient EME. The pH of the sample strongly affected the EME process, and pH 3.5 was found to be optimal. The EME efficiency was also dependent on the acceptor solution composition, and the extraction time was found to be an important element for exhaustive extraction. When EME was carried out for 25 min with an extraction voltage of 15 V, the system-current across the SLM was less than 50 μA, and extraction recoveries for the model peptides were in the range of 77–94%, with RSD values less than 10%.     

Electromembrane extraction of zwitterionic compounds as acid or base: Comparison of extraction behavior at acidic and basic pHs

This study has performed on electromembrane extraction (EME) of some zwitterionic compounds based on their acidic and basic properties. High performance liquid chromatography (HPLC) equipped with UV detection was used for determination of model compounds. Cetirizine (CTZ) and mesalazine (MS) were chosen as model compounds, and each of them was extracted from acidic (as a cation) and basic (as an anion) sample solutions, separately. 1-Octanol and 2-nitrophenyl octylether (NPOE) were used as the common supported liquid membrane (SLM) solvents. EME parameters, such as extraction time, extraction voltage and pH of donor and acceptor solutions were studied in details for cationic and anionic forms of each model compound and obtained results for two ionic forms (cationic and anionic) of each compound were compared together. Results showed that zwitterionic compounds could be extracted in both cationic and anionic forms. Moreover, it was found that the extraction of anionic form of each model compound could be done in low voltages when 1-octanol was used as the SLM solvent. Results showed that charge type was not highly effective on the extraction efficiency of model compounds whereas the position of charge within the molecule was the key parameter. In optimized conditions, enrichment factors (EF) of 27–60 that corresponded to recoveries ranging from 39 to 86% were achieved.     

Electromembrane extraction combined with gas chromatography for quantification of tricyclic antidepressants in human body fluids

Recent advances in electromembrane extraction (EME) methodology calls for effective and accessible detection methods. Using imipramine and clomipramine as model therapeutics, this proof-of-principle work combines EME with gas chromatography analysis employing a flame ionization detector (FID). The drugs were extracted from acidic aqueous sample solutions, through a supported liquid membrane (SLM) consisting of 2-nitrophenyl octyl ether (NPOE) impregnated on the walls of the hollow fiber. EME parameters, such as SLM composition, type of ion carrier, pH and the composition of donor and acceptor solutions, agitation speed, extraction voltage, and extraction time were studied in detail. Under optimized conditions, the therapeutics were effectively extracted from different matrices with recoveries ranging from 90 to 95%. The samples were preconcentrated 270–280 times prior to GC analysis. Reliable linearity was also achieved for calibration curves with a regression coefficient of at least 0.995. Detection limits and intra-day precision (n = 3) were less than 0.7 ng mL⁻¹ and 8.5%, respectively. Finally, method was applied to determination and quantification of drugs in human plasma and urine samples and satisfactory results were achieved.     

Drop-to-drop microextraction across a supported liquid membrane by an electrical field under stagnant conditions

Electromembrane extraction (EME) of basic drugs from 10 μL sample volumes was performed through an organic solvent (2-nitrophenyl octyl ether) immobilized as a supported liquid membrane (SLM) in the pores of a flat polypropylene membrane (25 μm thickness), and into 10 μL 10 mM HCl as the acceptor solution. The driving force for the extractions was 3–20 V d.c. potential sustained over the SLM. The influence of the membrane thickness, extraction time, and voltage was investigated, and a theory for the extraction kinetics is proposed. Pethidine, nortriptyline, methadone, haloperidol, and loperamide were extracted from pure water samples with recoveries ranging between 33% and 47% after only 5 min of operation under totally stagnant conditions. The extraction system was compatible with human urine and plasma samples and provided very efficient sample pretreatment, as acidic, neutral, and polar substances with no distribution into the organic SLM were not extracted across the membrane. Evaluation was performed for human urine, providing linearity in the range 1–20 μg/mL, and repeatability (RSD) in average within 12%.     

Electro membrane extraction of sodium diclofenac as an acidic compound from wastewater,urine, bovine milk,and plasma samples and quantification by high-performance liquid chromatography

Electro membrane extraction (EME) as a new microextraction method was applied for extraction of sodium diclofenac (SDF) as an acidic compound from wastewater, urine, bovine milk and plasma samples. Under applied potential of 20 V during the extraction, SDF migrated from a 2.1 mL of sample solution (1 mM NaOH), through a supported liquid membrane (SLM), into a 30 μL acceptor solution (10 mM NaOH), exist inside the lumen of the hollow fiber. The negative electrode was placed in the donor solution, and the positive electrode was placed in the acceptor solution. 1-octanol was immobilized in the pores of a porous hollow fiber of polypropylene as SLM. Then the extract was analyzed by means of high-performance liquid chromatography (HPLC) with UV-detection for quantification of SDF. Best results were obtained using a phosphate running electrolyte (10 mM, pH 2.5). The ranges of quantitation for different samples were 8–500 ng mL⁻¹. Intra- and inter-day RSDs were less than 14.5%. Under the optimized conditions, the preconcentration factors were between 31 and 66 and also the limit of detections (LODs) ranged from 2.7 ng mL⁻¹ to 5 ng mL⁻¹ in different samples. This procedure was applied to determine SDF in wastewater, bovine milk, urine and plasma samples (spiked and real samples). Extraction recoveries for different samples were between 44–95% after 5 min of extraction.     

Determination of inorganic anions in ethyl acetate by ion chromatography with an electromembrane extraction method

In this work, the determination of inorganic anions in slightly water-soluble organic solvents (ethyl acetate) was realized by ion chromatography (IC) with a novel-efficient electromembrane extraction method. From an 8 mL ethyl acetate sample, three inorganic anions migrated through the pores of a polypropylene hollow fiber membrane, and into deionized water inside the lumen of the hollow fiber by the application of 600 V. The transport was forced by an electrical potential difference sustained over the liquid membrane, resulting in electrokinetic migration of inorganic anions from the donor compartment to the acceptor solution. After the electromembrane extraction, the acceptor solution was analyzed by IC with a sodium carbonate-sodium bicarbonate eluent. The applied voltage, stirring speed, and extraction time for controlling the extraction efficiency were optimized. Within 10 min of operation at 600 V, chloride, bromide, and sulfate were extracted with recoveries in the range 76-110%, which corresponded to a linear range of 0.01-1 mg/L. The procedure was applied to the analysis of inorganic anions in a real ethyl acetate sample and expands onto other slightly water-soluble organic solvents.     

Kinetic aspects of hollow fiber liquid-phase microextraction and electromembrane extraction

In this paper, extraction kinetics was investigated experimentally and theoretically in hollow fiber liquid-phase microextraction (HF-LPME) and electromembrane extraction (EME) with the basic drugs droperidol, haloperidol, nortriptyline, clomipramine, and clemastine as model analytes. In HF-LPME, the analytes were extracted by passive diffusion from an alkaline sample, through a (organic) supported liquid membrane (SLM) and into an acidic acceptor solution. In EME, the analytes were extracted by electrokinetic migration from an acidic sample, through the SLM, and into an acidic acceptor solution by application of an electrical potential across the SLM. In both HF-LPME and EME, the sample (donor solution) was found to be rapidly depleted for analyte. In HF-LPME, the mass transfer across the SLM was slow, and this was found to be the rate limiting step of HF-LPME. This finding is in contrast to earlier discussions in the literature suggesting that mass transfer across the boundary layer at the donor–SLM interface is the rate limiting step of HF-LPME. In EME, mass transfer across the SLM was much more rapid due to electrokinetic migration. Nevertheless, mass transfer across the SLM was rate limiting even in EME. Theoretical models were developed to describe the kinetics in HF-LPME, in agreement with the experimental findings. In HF-LPME, the extraction efficiency was found to be maintained even if pH in the donor solution was lowered from 10 to 7–8, which was below the pK_a-value for several of the analytes. Similarly, in EME, the extraction efficiency was found to be maintained even if pH in the donor solution increased from 4 to 11, which was above the pK_a-value for several of the analytes. The two latter experiments suggested that both techniques may be used to effectively extract analytes from samples in a broader pH range as compared to the pH range recommended in the literature.     

Electromembrane extraction of amino acids from body fluids followed by capillary electrophoresis with capacitively coupled contactless conductivity detection

Electromembrane extraction (EME) proved to be a simple and rapid pretreatment method for analysis of amino acids and related compounds in body fluid samples. Body fluids were acidified to the final concentration of 2.5 M acetic acid and served as donor solutions. Amino acids, present as cations in the donor solutions, migrated through a supported liquid membrane (SLM) composed of 1-ethyl-2-nitrobenzene/bis-(2-ethylhexyl)phosphonic acid (85:15 (v/v)) into the lumen of a porous polypropylene hollow fiber (HF) on application of electric field. The HF was filled with 2.5 M acetic acid serving as the acceptor solution. Matrix components in body fluids were efficiently retained on the SLM and did not interfere with subsequent analysis. Capillary electrophoresis with capacitively coupled contactless conductivity detection was used for determination of 17 underivatized amino acids in background electrolyte solution consisting of 2.5 M acetic acid. Parameters of EME, such as composition of SLM, pH and composition of donor and acceptor solution, agitation speed, extraction voltage, and extraction time were studied in detail. At optimized conditions, repeatability of migration times and peak areas of 17 amino acids was better than 0.3% and 13%, respectively, calibration curves were linear in a range of two orders of magnitude (r(2)=0.9968-0.9993) and limits of detection ranged from 0.15 to 10 μM. Endogenous concentrations of 12 amino acids were determined in EME treated human serum, plasma, and whole blood. The method was also suitable for simple and rapid pretreatment and determination of elevated concentrations of selected amino acids, which are markers of severe inborn metabolic disorders.     

Parameters affecting electro membrane extraction of basic drugs

Thirty-five different basic drugs were extracted by electro membrane extraction (EME), from acidified samples containing HCl as the BGE, through an organic solvent immobilized in the pores in the wall of a porous hollow fiber (supported liquid membrane, SLM), and into an acidified acceptor solution (HCl) in the lumen of the hollow fiber by the application of an electrical potential difference of 50 V. With 2-nitrophenyl pentyl ether (NPPE) as the SLM, and with 10 mM HCl as BGE in the sample and acceptor solution, singly charged basic drugs with log P >2 were extracted with recoveries in the range 30-81% within 5 min. For doubly charged basic drugs, extraction was effectively enhanced by decreasing the concentration of HCl in the sample from 10 to 0.1 mM, reducing the ionization of the analytes. For medium polar analytes (1 < log P < 2), an ion balance of 0.01 was combined with addition of tris-(2-ethylhexyl) phosphate (TEHP) to the SLM, and this provided recoveries in the range 36-70%. The ion balance was defined as the concentration ratio of BGE between the sample and the acceptor solution. For the most polar drugs (log P <1), EME was accomplished with an ion balance of 0.01 and with di-(2-ethylhexyl) phosphate (DEHP) added to the SLM, but in spite of this, recoveries were in the range of only 4-17%.     

Determination of thebaine in water samples, biological fluids, poppy capsule, and narcotic drugs, using electromembrane extraction followed by high-performance liquid chromatography analysis

Opium determination is of great importance from toxicological and pharmaceutical standpoints. In present work, electromembrane extraction (EME) coupled with high-performance liquid chromatography (HPLC) and ultraviolet (UV) detection was developed for determination of thebaine as a natural alkaloid, in different matrices containing water, urine, poppy capsule, street heroine, and codeine tablet. Thebaine migrated from 3 mL of sample solutions, through a thin layer of 2-nitrophenyl octyl ether (NPOE) immobilized in the pores of a porous hollow fiber, and into a 15 μL acidic aqueous acceptor solution present inside the lumen of the fiber. The variables of interest, such as chemical composition of the organic liquid membrane, stirring speed, extraction time and voltage, pH of donor and acceptor phases and salt effect in the EME process were optimized. Under optimal conditions, thebaine was effectively extracted from different matrices with recoveries in the range of 45–55%, which corresponded to preconcentration factors in the range of 90–110. Good linearity was achieved for calibration curves with a coefficient of estimation higher than 0.997. Detection limits and intra-day precision (n = 3) were less than 15 μg L⁻¹ and 8.9%, respectively.     

Electro membrane isolation of nerve agent degradation products across a supported liquid membrane followed by capillary electrophoresis with contactless conductivity detection

In the present study, electro membrane isolation (EMI) of four nerve agent degradation products has been successfully explored. In the procedure, a polypropylene sheet membrane folded into an envelope with an open end with its wall pores impregnated with 1-octanol was employed as the artificial supported liquid membrane (SLM). The envelope containing the extractant or aqueous acceptor phase (at pH 6.8) was immersed in the sample or donor phase (also aqueous at a pH of 6.8) for extraction. This ensured that the target analytes were fully ionized. A voltage was then applied, with the negative electrode placed in the donor phase with agitation, and the positive electrode in the acceptor phase. The ionized analytes were thus driven to migrate from the donor phase across the SLM to the acceptor phase. The factors influential to extraction: type of organic solvent, voltage, agitation speed, extraction time, pH of the donor and acceptor phase and concentration of humic acids were investigated in detail. After extraction, the acceptor phase was collected and directly injected for capillary electrophoretic (CE) analysis. Combined with capacitively coupled contactless conductivity detection (C(4)D), the direct detection of these compounds could be achieved. Moreover, large-volume sample injection was employed to further enhance the sensitivity of this method. Limits of detection (LODs) as low as ng/mL were reached for the studied analytes, with overall LOD enhancements of four orders of magnitude.     

The effect of electric field geometry on the performance of electromembrane extraction systems: Footprints of a third driving force along with migration and diffusion

The distribution of electric field vectors was first calculated for electromembrane extraction (EME) systems in classical and cylindrical electrode geometries. The results showed that supported liquid membrane (SLM) has a general field amplifying effect due to its lower dielectric constant in comparison with aqueous donor/acceptor solutions. The calculated norms of the electric field vector showed that a DC voltage of 50 V can create huge electric field strengths up to 64 kV m⁻¹ and 111 kV m⁻¹ in classical and cylindrical geometries respectively. In both cases, the electric field strength reached its peak value on the inner wall of the SLM. In the case of classical geometry, the field strength was a function of the polar position of the SLM whereas the field strength in cylindrical geometry was angularly uniform. In order to investigate the effect of the electrode geometry on the performance of real EME systems, the analysis was carried out in three different geometries including classical, helical and cylindrical arrangements using naproxen and sodium diclofenac as the model analytes. Despite higher field strength and extended cross sectional area, the helical and cylindrical geometries gave lower recoveries with respect to the classical EME. The observed decline of the signal was proved to be against the relations governing migration and diffusion processes, which means that a third driving force is involved in EME. The third driving force is the interaction between the radially inhomogeneous electric field and the analyte in its neutral form.     

Electromembrane extraction using two separate cells: A new design for simultaneous extraction of acidic and basic compounds

Simultaneous extraction of acidic and basic analytes from a sample is seen to be a challenging task. In this work, a novel and efficient electromembrane extraction (EME) method based on two separate cells was applied to simultaneously extract and preconcentrate two acidic drugs (naproxen and ibuprofen) along with a basic drug (ketamine). Once both cells were filled with the sample solution, basic drug was extracted from one cell with the other cell used to extract acidic drugs. The employed supported liquid membranes for the extraction of acidic and basic drugs were 2‐ethyl hexanol and 1‐octanol, respectively. Under an applied potential of 250 V in the course of the extraction process, acidic, and basic drugs were extracted from a 3.0 mL aqueous sample solution into 25 μL acceptor solutions. The pH values of the donor and acceptor solutions in the cathodic cell were 5.0 and 1.5, respectively, the corresponding values in the anodic cell were, however, 8.0 and 12.5, respectively. The rates of recovery obtained within 20 min of extraction time at a stirring rate of 750 rpm ranged from 45 to 54%. With correlation coefficients ranging from 0.990 to 0.996, the proposed EME technique provided good linearity over a concentration range of 20–1000 ng/mL. The LOD for all drugs was found to be 6.7 ng/mL, while reproducibility ranged from 7 to 12% (n = 5). Finally, applying the proposed method to determine and quantify the drugs in urine and wastewater samples, satisfactory results were achieved.     

Stability and efficiency of supported liquid membranes in electromembrane extraction—a link to solvent properties

The current work presents a large systematic screening of 61 possible organic solvents used as supported liquid membranes (SLM) in electromembrane extraction (EME). For each organic solvent, recovery, current across the SLM, and stability considerations have been investigated and correlated to relevant solvent properties through partial least square regression analysis. The five unpolar basic drugs pethidine, haloperidol, methadone, nortriptyline, and loperamide were used as model analytes. Efficient EME solvents were found to have a low water solubility (<0.5 g L^?1) and belonged to cluster 2 of a Kamlet–and–Taft-based solvent classification system (high dipole moments and proton acceptor properties). These parameters were especially found in nitroaromatic compounds and ketones. Small molecules with low log P value and high water solubility were unsuitable, as they tended to give unstable extractions, caused by a high current across the SLM. This was often combined with substantial solvent-related interferences and the generation of an electroosmotic flow across the SLM, with resulting acceptor solution expansion. Large molecules with a high log P value were classified as inefficient. For these solvents, no current was measured across the SLM and no analytes were extracted. This is the first time systematic knowledge on the SLM in EME has been gathered and investigated, and the presented results could be highly beneficial for future development and optimization of EME.     

Hollow fiber‐based liquid membrane microextraction combined with high‐performance liquid chromatography for extraction and determination of trimetazidine in human plasma

A hollow fiber‐based liquid phase microextraction strategy combined with high‐performance liquid chromatography was evaluated for the quantitative determination of trimetazidine in human plasma. Trimetazidine was extracted from a 2.1 mL basified plasma sample (donor phase) into the organic solvent (n‐octanol) impregnated in the pores of a hollow fiber and then extracted into an acidic solution (acceptor phase) inside the lumen of the hollow fiber. The result showed that transport of drugs from alkaline sample solution into 0.5 m HCl occurred efficiently when 25 μL of 250 mm sodium 1‐octanesulfonate was added into the donor phase. Several parameters influencing the efficiency of the method, such as the nature of organic solvent used to impregnate the membrane, compositions of donor phase and acceptor phase, type and concentration of carrier, extraction time, stirring rate and salt concentration, were investigated and optimized. Under the optimal conditions, the calibration curves were obtained in the range of 5–200 ng/mL with reasonable linearity (r > 0.9980). The method was successfully applied to determine the concentration of trimetazidine in human plasma. Copyright © 2012 John Wiley & Sons, Ltd.     

Kinetic electro membrane extraction under stagnant conditions—Fast isolation of drugs from untreated human plasma

Amitriptyline, citalopram, fluoxetine, and fluvoxamine were isolated by electro membrane extraction (EME) from 70 μl of untreated plasma (pH 7.4), through a supported liquid membrane (SLM) of 1-ethyl-2-nitrobenzene immobilized in the pores of a porous polypropylene hollow fiber, and into 30 μl of 10 mM HCOOH as acceptor solution inside the lumen of the hollow fiber. The driving force of the extraction was a 9 V potential sustained over the SLM with a common battery, with the positive electrode placed in the plasma sample and the negative electrode placed in the acceptor solution. Extractions were performed under totally stagnant conditions with a very simple device for 1 min (kinetic regime), and subsequently the acceptor solution was analyzed directly by liquid chromatography–mass spectrometry (LC–MS). Recoveries were 12, 13, 22, and 17% for fluoxetine, amitriptyline, citalopram, and fluvoxamine, respectively. Sample clean-up was comparable to reversed-phase solid-phase extraction (SPE), but EME required substantially less time than SPE. The time advantage of EME was further improved by parallel extraction of three samples (for 1 min) with the same 9 V battery. EME from plasma combined with LC–MS provided limits of quantification (S/N = 10) in the range 0.4–2.3 ng/ml, linearity in the range 1–1000 ng/ml with r²-values of 0.998–0.999, and repeatability in the range 3.2–8.9% RSD in the mid-therapeutic window (100 ng/ml).