Silver nanoparticles‐tragacanth gel as a green membrane for effective extraction and determination of capecitabine

A novel eco‐friendly and effective electromembrane extraction method combining high‐performance liquid chromatography with UV detection was developed for the enrichment and determination of capecitabine. Tragacanth‐silver nanoparticles conjugated gel was prepared by dissolving the tragacanth powder in synthesized silver nanoparticles solution and was used as a green membrane in electromembrane extraction. The porosity and presence of silver nanoparticles in the gel were characterized by field emission scanning electron microscopy. This new electromembrane extraction approach uses neither organic solvent nor carrier agents to extract the target analyte. The best electromembrane extraction efficiency was obtained by using 4.0 mm membrane gel thickness containing 2.5% w/v of tragacanth gum, donor phase pH = 5.0, acceptor phase pH = 3.0, applied voltage 50 V, extraction time 20 min, and agitation rate 500 rpm. During method validation under the optimized conditions, good linearity dynamic range between 1 and 500 ng/mL with the coefficient of determination (R²) = 0.998 was obtained. Limit of detection and Limit of quantitation were estimated to be 0.84 and 1.0 ng/mL, respectively. Finally, the applicability of this method in real samples was confirmed by an acceptable performance in extraction and determination of capecitabine in human plasma samples.     

Electromembrane extraction in microfluidic formats

Electromembrane extraction is a microextraction technique where charged analytes are extracted across a supported liquid membrane and selectively isolated from the sample based on an electrical field. Since the introduction in 2006, there has been continuously increasing interest in electromembrane extraction, and currently close to 50 new articles are published per year. Electromembrane extraction can be performed in different technical configurations, based on standard laboratory glass vials or 96-well plate systems, and applications are typically related to pharmaceutical, environmental, and food and beverages analysis. In addition to this, conceptual research has developed electromembrane extraction into different milli- and microfluidic formats. These are much more early-stage activities, but applications among others related to organ-on-chip systems and smartphone detection indicate unique perspectives. To stimulate more research in this direction, the current article reviews the scientific literature on electromembrane extraction in milli- and microfluidic formats. About 20 original research articles have been published on this subject so far, and these are discussed critically in the following. Based on this and the authors own experiences with the topic, we discuss perspectives, challenges, and future research.     

One-way and two-way pulsed electromembrane extraction for trace analysis of amino acids in foods and biological samples

In the present work, pulsed electromembrane extraction (PEME) was performed for the first time, as a new concept of electrically enhanced microextraction method, for extraction and quantification of histidine, phenylalanine and tryptophan in different matrices. PEME offers an alternative to conventional electromembrane extraction (EME), which faces problems such as serious instabilities in the analysis of real samples with high concentration levels of ions. In these samples, increasing of the ion transportation across the liquid membrane results in Joule heating during the extraction process which may follow by punctuation of the organic membrane, increasing of the current level and bubble formation due to electrolysis reactions. A mixture of 2-nitrophenyl octyl ether (NPOE), di-(2-ethylhexyl) phosphate (DEHP) and tris-(2-ethylhexyl) phosphate (TEHP) was immobilized in the pores of hollow fiber as the organic liquid membrane. Other effective parameters such as extraction time, ion balance and pulse frequency were optimized using the experimental design. Extraction recoveries in the range of 7.1–21.6% and satisfactory repeatability (2.1 < CV% < 4.5) were obtained. Limits of detection were 5, 10 and 30 ng mL⁻¹ for tryptophan, phenylalanine and histidine, respectively. The method offers acceptable linearity with correlation coefficients higher than 0.9979. Furthermore, the figures of merit of PEME are compared with the results from conventional electromembrane extraction (EME), which proves the advantages of the proposed technique. The method was applied to the determination and quantification of amino acids in foods and biological samples. Also, two-way PEME was employed as a novel approach for highly selective extraction of tryptophan as a model analyte to introduce an interesting ability of the proposed technique.     

Development and application of SBA‐15 assisted electromembrane extraction followed by corona discharge ion mobility spectrometry for the determination of Thiabendazole in fruit juice samples

A new sample preparation method based on SBA‐15 assisted electromembrane extraction coupled with corona discharge ion mobility spectrometer was developed for the determination of Thiabendazole as a model basic pesticide in fruit juice samples. The addition of SBA‐15 in the supported liquid membrane in electromembrane extraction system not only can lead to enhancement of the effective surface area, but also introducing the negatively charged silanol groups into supported liquid membrane might improve migration of positively charged analytes toward the supported liquid membrane and finally into the acceptor solution. To investigate the effect of the presence of SBA‐15 in the supported liquid membrane on the extraction efficiency, a comparative study was carried out between the conventional electromembrane extraction and SBA‐15/electromembrane extraction methods. Under the optimized conditions, SBA‐15/electromembrane extraction method showed higher extraction efficiencies in comparison with conventional electromembrane extraction method. SBA‐15/electromembrane extraction method exhibited a low limit of detection (0.9 ng/mL), high preconcentration factor (167) and high recovery (83%). Finally, the applicability of SBA‐15/electromembrane extraction method was studied by the extraction and determination of Thiabendazole as a model basic pesticide in fruit juice samples.     

Investigation of the continuous flow of the sample solution on the performance of electromembrane extraction: Comparison with conventional procedure

In this study, electromembrane extraction from a flowing sample solution, termed as continuous‐flow electromembrane extraction, was developed and compared with conventional procedures for the determination of four basic drugs in real samples. Experimental parameters affecting the extraction efficiency were further studied and optimized. Under optimum conditions, linearity of continuous‐flow procedure was within 8.0–500 ng/mL, while it was wider for conventional procedures (2.0–500 ng/mL). Moreover, repeatability (percentage relative standard deviation) was found to range between 5.6 and 10.4% (n  = 3) for the continuous‐flow procedure, with a better repeatability than that of conventional procedures (2.3–5.5% (n  = 3)). Also, for the continuous‐flow procedure, the estimated detection limit (signal‐to‐noise ratio = 3) was less than 2.4 ng/mL and extraction recoveries were within 8–10%, while the corresponding figures for conventional procedures were less than 0.6 ng/mL and 42–60%, respectively. Thus, the results showed that both continuous flow and conventional procedures were applicable for the extraction of model compounds. However, the conventional procedure was more convenient to use, and thus it was applied to determine sample drugs in real urine and wastewater samples.     

Surfactant‐assisted electromembrane extraction combined with cyclodextrin‐modified capillary electrophoresis for the separation and quantification of Tranylcypromine enantiomers in biological samples

Surfactant‐assisted electromembrane extraction coupled with cyclodextrin‐modified capillary electrophoresis was developed for the separation and determination of Tranylcypromine enantiomers in biological samples. This combination would provide a new strategy for selective and sensitive determination of target analytes. The addition of surfactant in the donor solution improved the analyte transport into the lumen of hollow fiber that resulted in an enhancement in the analytes migration into acceptor solution. Optimization of the variables, affecting proposed method, was carried out and best results were achieved with a 175 V potential as driving force of the electromembrane extraction, 2‐nitrophenyloctylether as the supported liquid membrane, donor solution containing 0.2 mM Triton X‐100 with pH 3 and 0.1 M HCl for acceptor solution. Then, the extract was analyzed using cyclodextrin‐modified capillary electrophoresis method for separation of Tranylcypromine enantiomers. The best results were obtained with a phosphate running buffer (100 mM, pH 2.0) containing 7% w/v hydroxypropyl‐α‐cyclodextrin. Under the optimum conditions, a low limit of detection (3.03 ng/mL), good linearity (R² > 0.9953), and relative standard deviations below 4.0% (n = 5) were obtained. Finally, this procedure was applied to determine the concentration of Tranylcypromine enantiomers in urine samples with satisfactory results.     

Electromembrane extraction of verapamil and riluzole from urine and wastewater samples using a mixture of organic solvents as a supported liquid membrane: Study on electric current variations

In this study, the application of a mixture of organic solvents as a supported liquid membrane for improving the efficiency of the electromembrane extraction procedure was investigated. The extraction process was followed by high‐performance liquid chromatography analysis of two model drugs (verapamil and riluzole). In this research, four organic solvents, including 1‐heptanol, 1‐octanol, 2‐nitrophenyl octyl ether, and 2‐ethyl hexanol, were selected as model solvents and different binary mixtures (v/v 2:1, 1:1 and 1:2) were used as the supported liquid membrane. The mixture of 2‐ethyl hexanol and 1‐otanol (v/v, 2:1) improved the extraction efficiency of model drugs by 1.5 to 12 times. It was found that extraction efficiency is greatly influenced by the level of electric current. In this study, for various mixtures of organic solvents, the electric current fluctuated between 50 and 2500 μA, and the highest extraction efficiencies were obtained with low and stable electric currents. Finally, the optimized extraction condition was validated and applied for the determination of model drugs in urine and wastewater samples.     

Two-step voltage dual electromembrane extraction: A new approach to simultaneous extraction of acidic and basic drugs

In the present work, acidic and basic drugs were simultaneously extracted by a novel method of high efficiency herein referred to as two-step voltage dual electromembrane extraction (TSV-DEME). Optimizing effective parameters such as composition of organic liquid membrane, pH values of donor and acceptor solutions, voltage and duration of each step, the method had its figures of merit investigated in pure water, human plasma, wastewater, and breast milk samples. Simultaneous extraction of acidic and basic drugs was done by applying potentials of 150 V and 400 V for 6 min and 19 min as the first and second steps, respectively. The model compounds were extracted from 4 mL of sample solution (pH = 6) into 20 μL of each acceptor solution (32 mM NaOH for acidic drugs and 32 mM HCL for basic drugs). 1-Octanol was immobilized within the pores of a porous hollow fiber of polypropylene, as the supported liquid membrane (SLM) for acidic drugs, and 2-ethyle hexanol, as the SLM for basic drugs. The proposed TSV-DEME technique provided good linearity with the resulting correlation coefficients ranging from 0.993 to 0.998 over a concentration range of 1–1000 ng mL⁻¹. The limit of detections of the drugs were found to range within 0.3–1.5 ng mL⁻¹, while the corresponding repeatability ranged from 7.7 to 15.5% (n = 4). The proposed method was further compared to simple dual electromembrane extraction (DEME), indicating significantly higher recoveries for TSV-DEME procedure (38.1–68%), as compared to those of simple DEME procedure (17.7–46%). Finally, the optimized TSV-DEME was applied to extract and quantify model compounds in breast milk, wastewater, and plasma samples.     

Parallel electromembrane extraction in the 96-well format

The repeatability and extraction recoveries of parallel electromembrane extraction (Pa-EME) was thoroughly investigated in the present project. Amitriptyline, fluoxetine, and haloperidol were isolated from eight samples of pure water, undiluted human plasma, and undiluted human urine, respectively; in total 24 samples were processed in parallel. The repeatability was found to be independent of the different sample matrices (pure water samples, human plasma, and water) processed in parallel, although the respective samples contained different matrix components. In another experiment seven of the 24 wells were perforated. Even though the perforation caused the total current level in the Pa-EME setup to increase, the intact circuits were unaffected by the collapse in seven of the circuits. In another approach, exhaustive extraction of amitriptyline, fluoxetine, and haloperidol was demonstrated from pure water samples. Amitriptyline and haloperidol were also isolated exhaustively from undiluted human plasma samples; the extraction recovery of fluoxetine from undiluted human plasma was 81%. Finally, the sample throughput was increased with the Pa-EME configuration. The extraction recoveries were investigated by processing 1, 8, 68, or 96 samples in parallel in 10 min; neither the extraction recoveries nor the repeatability was affected by the total numbers of samples. Eventually, the Pa-EME was combined with ultra performance liquid chromatography (UPLC) to combine high-throughput sample preparation with high-throughput analytical instrumentation. The aim of the present investigation was to demonstrate the potential of electromembrane extraction as a high throughput sample preparation platform; and hopefully to increase the interest for EME in the bioanalytical field to solve exisiting and novel analytical challenges.     

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.     

Isolation of Chromium(VI) from Aqueous Solution by Electromembrane Extraction

Electromembrane extraction (EME) is a powerful extraction and preconcentration technique for ionizable species. However, the ionic contents in the sample can influence the extraction efficiency and system stability due to electrolysis. In this work, the electromembrane extraction of chromium(VI) was developed using various levels of ionic samples. 2-Nitrophenyl octyl ether was the most suitable supported liquid membrane that delayed the electrolytic occurrence of air bubbles at the electrodes due to its high viscosity and high dielectric constant properties. The electromembrane extraction method was optimized using 5?mM NaCl (630?µS?cm^?1); the applied potential was 100?V and the extraction time was 15?min. The enrichment factor of 80 was obtained over a linear working range of 10.0–80.0?µg?L^?1. The method performance was tested using mineral water, drinking water, tap water, and surface water. The method recoveries based on matrix-matched calibration were 95–125% with standard deviations within 15%.     

A selective electromembrane extraction of uranium (VI) prior to its fluorometric determination in water

A novel method for the selective electromembrane extraction (EME) of U⁶⁺ prior to fluorometric determination has been proposed. The effect of extraction conditions including supported liquid membrane (SLM) composition, extraction time and extraction voltage were investigated. An SLM composition of 1% di-2-ethyl hexyl phosphonic acid in nitrophenyl octyl ether (NPOE) showed good selectivity, recovery and enrichment factor. The best performance was achieved at an extraction potential of 80 volts and an extraction time of 14 minutes Under the optimized conditions, a linear range from 1 to 1000 ng mL⁻¹ and LOD of 0.1 ng mL⁻¹ were obtained for the determination of U⁶⁺. The EME method showed good performance in sample cleanup and the reduction of the interfering effects of Mn²⁺, Zn²⁺, Cd²⁺, Ni²⁺, Fe³⁺, Co²⁺, Cu²⁺, Cl⁻ and PO₄³⁻ ions during fluorometric determination of uranium in real water samples. The recoveries above 54% and enrichment factors above 64.7 were obtained by the proposed method for real sample analysis.     

Determination of gold in water samples using electromembrane extraction

In this work, an electromembrane extraction (EME) technique was used for the extraction and determination of gold from water samples prior to UV-Vis spectrophotometry. An artificial neural network (ANN) combined with imperialist competitive algorithm (ICA) has been applied to optimize the EME. The effective parameters including pH of acceptor phase, extraction time (t), volume of sample solution (V), stirring rate (S), and voltage (E) were chosen as input variables and the extraction recovery of gold was considered as output variable. The mean of squared error (i.e., 0.0009) and determination coefficient (i.e., 0.9821) were applied to estimate the performance of the ANN model. The limit of detection was 4.5?µg L^?1 (S/N?=?3) on the optimized variables. The intra- and interday precisions (%) were found to be 6.7% and 2.6%, respectively. This technique was then applied for analysis of gold from environment water samples.     

Simultaneous extraction of acidic and basic drugs via on-chip electromembrane extraction

In the present work, a on-chip electromembrane extraction (CEME) was designed and employed for simultaneous extraction of mefenamic acid (MEF) and diclofenac (DIC), as acidic model analytes, and betaxolol (BET), as a basic model analyte, followed by HPLC-UV. The CEME consists of two polymethyl methacrylate (PMMA) parts which each part consists of two separated microfluidic channels. A polypropylene sheet membrane impregnated with an organic solvent was sandwiched between the parts. One of the parts was used as the flow path for the sample solution and the other one as holder for the acceptor phases. The separated microfluidic channels of the sample solution part were connected to each other using a small piece of a capillary tube and the sample solution was pumped through them by means of a micro-syringe pump. However, the acceptor phases of the acidic and basic analytes were separately kept stagnant in the two microfluidic channels during the extraction process. A d.c. potential was applied for migration of the analytes from sample solution through the organic membrane into the acceptor phases. All effective variables on the extraction efficiency of the analytes were optimized. Under the optimized conditions, preconcentration factors higher than 15 were achieved and the calibration curves were linear in the range of 10–500 μg L⁻¹ (r² > 0.9982). RSD% values (n = 4) and LODs were less than 7.1% and 5.0 μg L⁻¹. The results demonstrated that CEME could efficiently be used for the simultaneous analysis of acidic and basic analytes in biological samples.     

Speciation of chromium in environmental samples by dual electromembrane extraction system followed by high performance liquid chromatography

This study proposes the dual electromembrane extraction followed by high performance liquid chromatography for selective separation-preconcentration of Cr(VI) and Cr(III) in different environmental samples. The method was based on the electrokinetic migration of chromium species toward the electrodes with opposite charge into the two different hollow fibers. The extractant was then complexed with ammonium pyrrolidinedithiocarbamate for HPLC analysis. The effects of analytical parameters including pH, type of organic solvent, sample volume, stirring rate, time of extraction and applied voltage were investigated. The results showed that Cr(III) and Cr(VI) could be simultaneously extracted into the two different hollow fibers. Under optimized conditions, the analytes were quantified by HPLC instrument, with acceptable linearity ranging from 20 to 500 μg L⁻¹ (R² values ≥ 0.9979), and repeatability (RSD) ranging between 9.8% and 13.7% (n = 5). Also, preconcentration factors of 21.8–33 that corresponded to recoveries ranging from 31.1% to 47.2% were achieved for Cr(III) and Cr(VI), respectively. The estimated detection limits (S/N ratio of 3:1) were less than 5.4 μg L⁻¹. Finally, the proposed method was successfully applied to determine Cr(III) and Cr(VI) species in some real water samples.     

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.     

A novel approach for electromembrane extraction based on the use of silver nanometallic-decorated hollow fibers

A novel approach based on the use of nanometallic-decorated hollow fibers to assist electromembrane extraction is proposed. Microporous polypropylene hollow fibers, on which nanometallic silver was deposited, have been used for the first time as liquid membrane support in electromembrane extraction (EME). Different methods for the generation/deposition of silver nanoparticles (AgNPs) were studied. The best results were obtained with chemical reduction of silver nitrate using NaBH₄ in aqueous solution followed by direct deposition on the hollow fibers. The extraction performance of the new supports was compared with a previously developed EME procedure used for the extraction of selected non-steroidal anti-inflammatory drugs (NSAIDs), resulting in an increase in the extraction ratio by a factor of 1.2–2 with a 30% reduction in the extraction time. The new nanometallic-decorated supports open new possibilities for EME due to the singular properties of nanometallic particles, including chemical fiber functionalization.     

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%.     

Diffusion Boundary Layers in Transport of Aliphatic Acids in Electromembrane Systems

The regularities of the formation of diffusion boundary layers during the transport of aliphatic acids in electromembrane systems are studied and their characteristics obtained experimentally are analyzed. It is shown that their concentration profiles in solutions of the electrodialyzer sections are asymmetric near membranes of different polarity. Experimental values of diffusion layer thicknesses are compared with those following from the known theoretical relations. The equation, which is proposed for the surface concentration, permits the prediction of the operation mode of apparatus during electrodialysis of solutions of aliphatic acids and other weak electrolytes. Specific features characterizing the emergence of a limiting state and the character of the distribution of limiting current densities over the height of the membrane channel are revealed.     

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 (r² = 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.