Aqueous Acceptor Solution Research Articles

Ionic liquid based three-phase liquid–liquid–liquid solvent bar microextraction for the determination of phenols in seawater samples

For the first time, an ionic liquid based three-phase liquid–liquid–liquid solvent bar microextraction (IL-LLL-SBME) was developed for the analysis of phenols in seawater samples. The ionic liquid, 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF 6]), was used as the intermediary solvent for LLL-SBME, enhancing the extraction efficiency for polar analytes. In the procedure, the analytes were extracted from the aqueous sample into the ionic liquid intermediary and finally, back-extracted into an aqueous acceptor solution in the lumen of the hollow fiber. The porous polypropylene membrane acted as a filter to prevent potential interfering materials from being extracted, and no additional cleanup was required. After extraction, the acceptor solution could be directly injected into a high-performance liquid chromatographic system for analysis. Six phenols, 2-nitrophenol, 4-chlorophenol, 2,3-dichlorophenol, 2,4-dichlorophenol, 2,4,6-trichlorophenol and pentachlorophenol were selected here as model compounds for developing and evaluating the method. The most influential extraction parameters were evaluated, including the ionic liquid, the composition of donor solution and acceptor solution, the extraction time and the extraction temperature, the effect of ionic strength, and the agitation speed. Under the most favorable extraction parameters, the method showed good linearity (from 0.05–50 to 0.5–50 μg/L, depending on the analytes) and repeatability of extractions (RSD below 8.3%, n = 5). The proposed method was compared to conventional three-phase LLL-SBME and ionic liquid supported hollow fiber protected three-phase liquid–liquid–liquid microextraction, and showed higher extraction efficiency. The proposed method was demonstrated to be a simple, fast, and efficient method for the analysis of phenols from environmental water samples.

Electrokinetic extraction on artificial liquid membranes of amphetamine-type stimulants from urine samples followed by high performance liquid chromatography analysis

Electromembrane extraction (EME) coupled with high performance liquid chromatography and ultraviolet detection was developed for determination of amphetamine-type stimulants in human urine samples. Amphetamines migrated from 3 mL of different human urine matrices, through a thin layer of 2-nitrophenyl octyl ether (NPOE) containing 15% tris-(2-ethylhexyl) phosphate (TEHP) 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. Equilibrium extraction conditions were obtained after 7 min of operation. Experimental design and response surface methodology (RSM) were used for optimization of EME parameters. Under optimal conditions, amphetamines were effectively extracted with recoveries in the range of 54–70%, which corresponded to preconcentration factors in the range of 108–140. The calibration curves were investigated in the range of 0–7 μg mL −1 and good linearity was achieved with a coefficient of estimation better than 0.991. Detection limits and inter-day precision ( n = 3) were less than 0.01 μg mL −1 and 11.2%, respectively.

Electromembrane extraction (EME) and HPLC determination of non-steroidal anti-inflammatory drugs (NSAIDs) in wastewater samples

In this paper, an electromembrane extraction (EME) combined with a HPLC procedure using diode array (DAD) and fluorescence detection (FLD) has been developed for the determination of six widely used non-steroidal anti-inflammatory drugs (NSAIDs): salicylic acid (SAC), ketorolac (KTR), ketoprofen (KTP), naproxen (NAX), diclofenac (DIC) and ibuprofen (IBU). The drugs were extracted from basic aqueous sample solutions, through a supported liquid membrane (SLM) consisting of 1-octanol impregnated in the walls of a S6/2 Accurel® polypropylene hollow fiber, and into a basic aqueous acceptor solution resent inside the lumen of the hollow fiber with a potential difference of 10V applied over the SLM. Extractions that were carried out in 10min using a potential of 10V from pH 12 NaOH aqueous solutions shown concentration enrichments factors of 28–49 in a pH 12 NaOH aqueous acceptor solution. The proposed method was successfully applied to urban wastewaters. Excellent selectivity was demonstrated as no interfering peaks were detected. The procedure allows very low detection and quantitation limits of 0.0009–9.0 and 0.003–11.1μgL−1, respectively.

Electromembrane Extraction: A New Technique for Accelerating Bioanalytical Sample Preparation

The recent societal requirements to explore more environmentaly friendly solutions in the field of sample preparation have gained increasing focus during recent years. A reduction in the consumption of hazardous organic solvent owing to environmental and cost perspectives, small amounts of sample available and time reduction, have been major incentives for scientists to miniaturize existing sample preparation methods. Some of these challenges were addressed by the introduction of electromembrane extraction (EME), a totally new extraction principle where a potential difference is applied across a thin organic membrane immobilized in the pores in the wall of a porous polypropylene membrane. The potential difference is utilized to extract charged analytes of interest from the sample, across the organic membrane, and into an aqueous acceptor solution present inside the lumen of the hollow fiber. This article focuses on the potential of EME in bioanalysis, including discussions of EME performance.

Electromembrane extraction of levamisole from human biological fluids

Electromembrane extraction coupled with high-performance liquid chromatography (HPLC) and ultraviolet (UV) detection was developed for the determination of levamisole in some human biological fluids. Levamisole migrated from 4 mL of different acidized biological matrices, through a thin layer of 2-nitrophenyl octyl ether containing 5% tris-(2-ethylhexyl) phosphate immobilized in the pores of a porous hollow fiber, into a 20-μL acidic aqueous acceptor solution present inside the lumen of the fiber. The parameters influencing electromigration were investigated and optimized. Within 15 min of operation at 200 V, levamisole was extracted from different biological fluid samples with recoveries in the range of 59-65%, which corresponded to preconcentration factors in the range of 118-130. The calibration curves showed linearity in the range of 0.5-10, 0.2-10 and 0.1-10 μg/mL for plasma, urine and saliva, respectively. Limits of detection of 0.1, 0.07 and 0.05 μg/mL and limits of quantification of 0.5, 0.2 and 0.1 μg/mL were obtained for plasma, urine and saliva, respectively. The relative standard deviations of the analysis were found to be in the range of 5.6-9.7% (n = 3). Electromembrane extraction was successfully processed for determination of levamisole in plasma, urine and saliva samples.

Fundamental studies on the electrokinetic transfer of net cationic peptides across supported liquid membranes

By the application of an electrical potential difference (25 V), 37 different peptides were extracted from 500 μL aqueous sample (10 mM formic acid, positive electrode), through a supported liquid membrane (SLM) impregnated in the walls of a porous hollow fiber, and into 25 μL aqueous acceptor solution (100 mM formic acid, negative electrode) present inside the lumen of the fiber. Most of the peptides were obtained by tryptic digestion of cytochrome c and bovine serum albumin, which yielded complex samples for extraction. Three different SLMs were utilized to correlate the peptides extractability with the highly variable physical-chemical properties of the peptides. The first SLM (pure eugenol) provided an electromembrane extraction system for hydrophobic and intermediate peptides (hydrophilicity values below 0.2), where the extraction of peptides into the SLM was mainly based on solvent interactions. The second SLM (1-octanol/di-isobutylketone/di-(2-ethylhexyl) phosphate) extracted both hydrophobic and hydrophilic peptides (hydrophilicity values in the range from -2 to+1) successfully, and the transfer of peptides was principally based on ionic interactions with di-(2-ethylhexyl) phosphate. The third SLM (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.

Potential‐driven peptide extractions across supported liquid membranes: Investigation of principal operational parameters

Fundamental experiments on electromembrane extraction were performed to increase the basic knowledge about the current and the mass transfer of target peptides and background electrolyte ions. Three peptides (angiotensin 2, bradykinin, and enkephalin) were extracted from 500 microL aqueous donor solution (1 mM HCl, positive electrode), through a 200 microm supported liquid membrane (SLM) of 1-octanol/di-isobutylketon/di-(2-ethylhexyl) phosphate (55:35:10 w/w/w) sustained in the pores of a porous hollow fiber, and into 25 microL aqueous acceptor solution (50 mM HCl, negative electrode) present inside the lumen of the fiber by the application of an electrical potential (50 V) and agitation (1050 rpm). Recoveries were typically in the range of 55-65% after 5 min of extraction and were principally determined by the chemical composition of the SLM and by the applied voltage. The electrical current in the system was measured during the extraction and was close to 350 microA. The current arose to some extent from mass transfer of the target peptides, but the major contribution was due to a background current from di-(2-ethylhexyl) phosphate in the SLM and from mass transfer of background electrolytes. Operation at relatively low background current was important to maintain a stable system.

Rapid isolation of angiotensin peptides from plasma by electromembrane extraction

The present study has for the first time demonstrated the isolation of peptides from human plasma by electromembrane extraction (EME). Angiotensin 1, angiotensin 2, and angiotensin 3 migrated from 500 μL of diluted plasma, through a thin layer of 1-octanol and 8% di-(2-ethylhexyl) phosphate immobilized as a supported liquid membrane (SLM) in the pores of a porous hollow fiber, and into a 25 μL aqueous acceptor solution present inside the lumen of the fiber. The driving force for the extraction was a 15 V potential difference applied across the SLM. After only 10 min of EME, the peptides were isolated from diluted plasma (pH 3) with extraction recoveries between 25 and 43%. After optimization, the extraction system was evaluated using spiked plasma samples of angiotensin 2. The evaluation was performed by liquid chromatography electrospray mass spectrometry, showing linearity of angiotensin 2 in the range 2.5–125.0 ng/mL ( r 2 = 0.989), and repeatability (RSD) between 5.6 and 11.6% ( n = 6). The results demonstrate the possibility of isolating angiotensin peptides from plasma in only 10 min, using electromembrane extraction. The experimental findings are therefore promising with regard to future peptide extractions.

Ion-pair liquid–liquid–liquid microextraction of nerve agent degradation products followed by capillary electrophoresis with contactless conductivity detection

The four nerve agent degradation products methylphosphonic acid (MPA), ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA) and cyclohexyl methylphosphonic acid (CMPA) have been successfully extracted from aqueous sample solution by ion-pair liquid–liquid–liquid microextraction. In this procedure, the target analytes in the sample solution were converted into their ion-pair complexes with tri- n-butyl amine and then extracted by an organic solvent (1-octanol) layer on top of the sample solution. Simultaneously, the analytes were back-extracted into a drop of an aqueous acceptor solution which was suspended in the organic phase at a microsyringe needle tip. The factors influential to extraction: type of organic solvent, type of ion-pair reagent and its concentration, pH values of sample solution and acceptor aqueous phase, stirring rate and extraction time were investigated in detail. After extraction, the drop of the acceptor solution was withdrawn into the syringe and injected into a capillary electrophoresis system for analysis. Using contactless conductivity detection, direct quantification of these compounds is possible. Moreover, large-volume sample injection was employed for further preconcentration. Improvements in the limits of detection between 2.5 and 4 orders of magnitude could be achieved and concentrations at the ng/mL level can be determined. This newly established approach was successfully applied to a spiked river water sample.

Low-voltage electromembrane extraction of basic drugs from biological samples

The present work has for the first time demonstrated electromembrane extraction (EME) at voltages obtainable by common batteries. Five basic drugs were extracted from acidified aqueous sample solutions, across a supported liquid membrane (SLM) consisting of 1-isopropyl-4-nitrobenzene impregnated in the walls of a hollow fiber, and into an acidified aqueous acceptor solution present inside the lumen of the hollow fiber with potential differences of 1–10 V applied over the SLM. Extractions from 1 ml standard solutions prepared in 10 mM HCl for 5 min and with a potential of 10 V demonstrated analyte recoveries of 50–93% in 25 μl of 10 mM HCl as acceptor solution. This corresponds to enrichment factors of 20–37. Similar results were obtained with a common 9 V battery as power supply. Recoveries from low-voltage EME on human plasma, urine, and breast milk diluted with acetate buffer (pH 4) demonstrated recoveries in the range of 37–55% after 5 min of extraction. Excellent selectivity was demonstrated as no interfering peaks were detected. Standard curves in the range of 0.0625–0.625 μg/ml demonstrated correlation coefficients of 0.994–0.999. Extraction recoveries from human plasma, urine or breast milk were not found to be sensitive towards individual variations. The results show that low-voltage EME has a future potential as a simple, selective, and time-efficient sample preparation technique of biological fluids.

Bulk Liquid Membrane Transport of Hg(II) by a Crown Ether Derivative

A kinetic study of Hg(II) transport from an aqueous donor solution into an aqueous acceptor solution through a liquid membrane containing 4′‐nitrobenzo [15‐cown‐5] 1 as a carrier was studied. The kinetic parameters (k1, k2, Rm max, tmax , Jd max, Ja max) for the transport were investigated in terms of the effect of temperature, stirring rate, and carrier concentration. The kinetics of transport was analyzed in the formalism of two consecutive irreversible first‐order reactions. The membrane entrance rate, and exit rate constants were increased with increasing the temperature stirring rate, and carrier concentration. The activation energy values are calculated as 20.33±2.10 and 115.90±10.5 kj mol−1 for extraction and reextraction, respectively. The values of calculated activation energy indicate that the process is diffusionally controlled by species.

Development and application of microporous hollow fiber protected liquid-phase microextraction via gaseous diffusion to the determination of phenols in water

A new organic solvent-free microextraction technique termed liquid–gas–liquid microextraction (LGLME) was developed. In this technique, a small amount (6 μl) of aqueous acceptor solution (0.5 M NaOH) is introduced into the channel of a 2.65 cm polypropylene hollow fiber. The hollow fiber is then immersed in an aqueous sample donor solution. The aqueous acceptor phase in the channel of the hollow fiber is separated from the sample solution by the hydrophobic microporous hollow fiber wall with air inside its pores. The analytes (phenols) passed through the microporous hollow fiber membrane by gas diffusion and were then trapped by the basic acceptor solution. After extraction, the acceptor solution was withdrawn into a microsyringe and injected into a capillary electrophoresis sample vial for subsequent analysis. Limits of detection of between 0.5 and 10 μg/l for eight phenols could be achieved. The relative standard deviations ( n = 6) of this technique between 2.7 and 7.6%. The technique also provides good enrichment factors for all the eight analytes.

Electrokinetic migration across artificial liquid membranes: Tuning the membrane chemistry to different types of drug substances

Twenty different basic drugs were electrokinetically extracted across a thin artificial organic liquid membrane with a 300 V d.c. electrical potential difference as the driving force. From a 300 μl aqueous sample (acidified corresponding to 10 mM HCl), the drugs were extracted for 5 min through a 200 μm artificial liquid membrane of a water immiscible organic solvent immobilized in the pores of a polypropylene hollow fiber, and into a 30 μl aqueous acceptor solution of 10 mM HCl inside the lumen of the hollow fiber. Hydrophobic basic drugs (log P > 1.7) were effectively isolated utilizing 2-nitrophenyl octyl ether (NPOE) as the artificial liquid membrane, with recoveries up to 83%. For more hydrophilic basic drugs (log P < 1.0), a mixture of NPOE and 25% (w/w) di-(2-ethylhexyl) phosphate (DEHP) was required to ensure efficient extraction, resulting in recoveries up to 75%. DEHP was expected to act as an ion-pair reagent ion-pairing the protonated hydrophilic drugs at the interface between the sample and the membrane, resulting in permeation of the interface.

Liquid Membrane Transport of Hg(II) by an Azocalix[4]arene Derivative

A kinetic study of Hg(II) transport from an aqueous donor solution into an aqueous acceptor solution through a liquid membrane containing 25,26,27–tribenzoyloxy‐28‐hydroxy‐5,11,17,23‐tetra‐(4‐n‐butylphenylazo)calix[4]arene 1 as a carrier was studied. The kinetic parameters (k 1, k 2, R m max, t max, J d max, J a max) for the transport were investigated in terms of the effect of temperature, the stirring rate, the carrier concentration, and the type of solvent. The kinetics of transport was analyzed in the formalism of two consecutive irreversible first‐order reactions. The membrane entrance rate, and exit rate constants were increased with increasing of temperature stirring rate, and carrier concentration. The membrane entrance rate and exit rate constants depended on the type of solvent and was found to be in order of CH2Cl2> CHCl3> CCl4. The activation energy values are calculated as 30.67±2.64 and 57.33±4.90 kj mol−1 for extraction and reextraction, respectively. The values of calculated activation energy indicate that the process is diffusionally controlled by species.

Electrokinetic migration across artificial liquid membranes: New concept for rapid sample preparation of biological fluids

Basic drug substances were transported across a thin artificial organic liquid membrane by the application of 300 V d.c. From a 300 μl aqueous donor compartment (containing 10 mM HCl), the drugs migrated through a 200 μm artificial liquid membrane of 2-nitrophenyl octyl ether immobilized in the pores of a polypropylene hollow fiber, and into a 30 μl aqueous acceptor solution of 10 mM HCl inside the lumen of the hollow fiber. The transport was forced by an electrical potential difference sustained over the liquid membrane, resulting in electrokinetic migration of drug substances from the donor compartment to the acceptor solution. Within 5 min of operation at 300 V, pethidine, nortriptyline, methadone, haloperidol, and loperamide were extracted with recoveries in the range 70–79%, which corresponded to enrichments in the range 7.0–7.9. The chemical composition of the organic liquid membrane strongly affected the permeability, and may serve as an efficient tool for controlling the transport selectivity. Water samples, human plasma, and human urine were successfully processed, and in light of the present report, electrokinetic migration across thin artificial liquid membranes may be an interesting tool for future isolation within chemical analysis.

Kinetic Study of Hg(II) Transport Through a Bulk Liquid Membrane Containing Ester Derivative of bis‐Calix[4]arene

A kinetic study of Hg(II) transport from an aqueous donor solution into an aqueous acceptor solution through a bulk liquid membrane containing N,N′‐bis[carbonylmethoxy(5,11,17,23‐tetra‐tert‐butyl‐25,26,27‐tris‐(ethoxycarbonyl‐methoxy)calix(4)arenyl)]‐1,2‐diaminoethane as a carrier was studied. The kinetic parameters (k 1d, k 2m, k 2a, t max, R m max, J d max, J a max) for the transport were investigated in terms of the effect of temperature, the stirring rate, the carrier concentration, and the type of solvent. In this study, the pseudo‐first‐order apparent rate constant of the interfacial transport of the Hg(II) is determined by using the spectrophotometric method. The kinetics of the transport was analyzed in the formalism of two consecutive irreversible first‐order reactions. The membrane entrance and exit rate constants were increased with increasing of temperature, stirring rate, and carrier concentration. The membrane entrance and exit rate constants depended on the type of solvent and was found to be in the order of CH2Cl2 > CHCl3 > CCl4. The activation energy values are calculated as 25.50 ± 2.20 and 45.62 ± 4.38 kJ mol−1 for extraction and reextraction, respectively. The values of the calculated activation energy indicate that the process is diffusionally controlled by species.

Liquid-phase microextraction based on carrier mediated transport combined with liquid chromatography–mass spectrometry: New concept for the determination of polar drugs in a single drop of human plasma

Recently, we demonstrated for the first time liquid-phase microextraction (LPME) of polar drugs based on carrier mediated transport. In this new extraction technique, selected analytes were extracted as ion-pairs from small volumes of biological samples, through a thin layer of a water immiscible organic solvent immobilised in the pores of a porous hollow fibre (liquid membrane), and into a μl volume of an acidic aqueous acceptor solution placed inside the lumen of the hollow fibre. In the current paper, this new extraction technique was combined with liquid chromatography–mass spectrometry (LC–MS) for the first time. Carrier mediated LPME was evaluated for several new model drugs (0.01 < log P < 1.76), the sample clean-up aspects were investigated in detail, and this new extraction technique was fully validated for the first time. Extractions were performed from 50 μl of human plasma samples, which provided sufficient material in combination with LC–MS. Sodium octanoate (50 mM) was added to the sample as carrier, 1-octanol (≈15 μl) was used as the liquid membrane in the wall of the hollow fibre, and 50 mM HCl was utilized as acceptor solution in the lumen of the hollow fibre. The addition of carrier to the samples was found to significantly improve extraction recoveries for the polar drugs tested, providing recoveries in the range 16–78%. Validation was accomplished for atenolol and cimetidine. Limits of quantification (S/N = 5) from 50 μl of plasma were 25 and 50 ng/ml for atenolol and cimetidine, respectively. The intra-day precision (R.S.D.) ranged from 7.8 to 17.2% and from 9.5 to 14.1% for atenolol and cimetidine, respectively, and corresponding inter-day precisions (R.S.D.) were within 6.7–1.4% and 7.7–20.3%. The method was linear in the range 25–1500 ng/ml for atenolol ( r = 0.992), and 50–3500 ng/ml for cimetidine ( r = 0.976). The accuracy of the method was found to be in range 89.1–99.6% and 83.4–86% for atenolol and cimetidine, respectively. The sample clean-up obtained by carrier mediated LPME was excellent, providing a significantly lower back-ground level in total ion current chromatograms by LC–MS as compared to protein precipitation.

Recovery, enrichment and selectivity in liquid-phase microextraction: Comparison with conventional liquid–liquid extraction

Mathematical descriptions for extraction recovery and enrichment were applied for liquid-phase microextraction (LPME) and comparison with conventional two- and three-phase liquid–liquid extraction techniques (LLE) was made. The LPME theoretical calculations were verified by experimental determination of actual partition coefficients and by data obtained with LPME in a robust hollow fibre formate. With hollow fibre LPME operated in the two-phase mode, analytes were extracted from 1 to 4 ml aqueous samples into 25–50 μl of an organic solvent present in the pores and in the lumen of the porous hollow fibres. Compared with conventional two-phase LLE, two-phase LPME provided substantially higher enrichments for compounds with relatively large partition coefficients ( K org/d>500). In contrast, because of the large volume of organic solvent relative to the sample volume, LLE provided high recovery and moderate enrichment even for compounds with relatively low partition coefficients ( K org/d>5). Thus, two-phase LPME may be used for substantially enhanced extraction selectivity and enrichment of relatively hydrophobic analytes as compared with LLE whereas conventional two-phase LLE is superior for more hydrophilic analytes. Similar results were found for three-phase LPME where analytes where extracted from 1 to 4 ml aqueous samples through approximately 20 μl organic solvent immobilized within the pores of the hollow fibre and into 25 μl of an aqueous acceptor solution inside the lumen of the hollow fibre. The fundamental differences of LPME and LLE were further demonstrated with practical experiments on extraction of the basic drugs promethazine, methadone, and haloperidol from human plasma and urine.

Development of a simple in-vial liquid-phase microextraction device for drug analysis compatible with capillary gas chromatography, capillary electrophoresis and high-performance liquid chromatography

A simple, inexpensive and disposable device for liquid-phase microextraction (LPME) is presented for use in combination with capillary gas chromatography (GC), capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC). 1–4 ml samples of human urine or plasma were filled into conventional 4-ml vials, whereafter 15–25 μl of the extraction medium (acceptor solution) was filled into a short piece of a porous hollow fiber and placed into the sample vial. The drugs of interest were extracted from the sample solutions and into the small volumes of acceptor solution based on high partition coefficients and were preconcentrated by a factor of 30–125. For LPME in combination with GC, the porous hollow fiber was filled with 15 μl n-octanol as the acceptor solution. Following 30 min of extraction, the organic acceptor solution was injected directly into the GC system. For LPME in combination with CE and HPLC, n-octanol was immobilized within the pores of the hollow fiber, while the internal volume of the fiber was filled with either 25 μl of 0.1 M HCl (for extraction of basic compounds) or 25 μl 0.02 M NaOH (for acidic compounds). Following 45 min extraction, the aqueous acceptor solution was injected directly into the CE or HPLC system. Owing to the low cost, the extraction devices were disposed after a single extraction which eliminated the possibility of carry over effects. In addition, because no expensive instrumentation was required for LPME, 10–30 samples were extracted in parallel to provide a high number of samples per unit time capacity.