Gel Electromembrane Extraction Research Articles

Ultra-sensitive detection of cadmium and lead in water using crown ether gel electromembrane extraction coupled with miniaturized electrochemical system

This study presents the development of an electrochemical technique combined with gel electromembrane extraction (G-EME) for the simultaneous detection of cadmium and lead in environmental water samples. Crown ether (18C6) was added to the gel as a complexing agent and cationic carrier. The electrochemical responses were evaluated using differential pulse anodic stripping voltammetry (DPASV) across various pH levels and deposition times. The most sensitive response (acetate buffer pH 4, deposition time 90 s) was selected for the development of the G-EME process. By applying a 30 V electrical potential across the gel membrane containing 1 % (w/v) of 18C6 for 10 min, positively charged Cd2+ and Pb2+ ions migrated from the donor phase (pH 5.0) through the 18C6@gel membrane (pH 5.0) into the acceptor phase (pH 5.0). This resulted in a linear range from 0.3 to 5 µg/L for Cd2+ and 0.5 to 5 µg/L for Pb2+, with detection limits of 0.10 µg/L and 0.19 µg/L, respectively— up to 120 times more sensitive than direct electrochemical measurements. Furthermore, the proposed technique maintained selectivity for cadmium and lead, despite the presence of other potential heavy metal ions in the environment.

Confined Gel-Electromembrane Extraction of Oligonucleotides.

Gel-electromembrane extraction (G-EME) is an increasingly popular green variant of electromembrane extraction (EME). However, the electroendosmosis (EEO) flow associated with G-EME greatly limits the development of this technology. To address this challenge, the current study proposed the concept of confined G-EME (CG-EME), and a three-dimensional-printed modular device was elaborately designed to realize this concept. The device blocked the EEO flow by limiting the volume of the sample compartment. Moreover, the mesh structure at the bottom of the extraction module helps to prepare thin and stable gel films, which enhance the electromigration driving force and shorten the migration path. In addition, polar oligonucleotides, a nucleic acid analyte, were extracted for the first time to prove the concept of CG-EME. After optimization, 62% of the oligonucleotides were extracted at 50 V voltage for 15 min using a 3 mm thick agarose (3%) gel film. Finally, the application capability of CG-EME was further demonstrated by recovering DNA primers and isolating disease biomarkers (miRNA-181b) from real samples. In combination with CG-EME and quantitative polymerase chain reaction (qPCR) analysis, the upregulation of miRNA-181b expression in the peripheral blood of patients with schizophrenia was observed. In conclusion, this study proposes CG-EME to diminish EEO and push EME into the clinical field to isolate nucleic acid biomarkers, which will greatly expand the application scenarios of this emerging technology.

Simultaneous extraction and preconcentration of two dyes with the same color from food samples by dual gel electro-membrane and determination by spectrophotometric method

In this study, the dual gel electromembrane extraction (G-EME) method coupled with UV–Vis spectrophotometry was developed to monitor the trace amount of Tartrazine (Tt) and auramine O (AO) in food samples. These dyes have different acidic and basic properties, but their colors are the same. The main driving forces of the dual G-EME are electro-migration and electroendosmosis (EEO). Tt as acidic and AO as basic analyte from 10 mL aqueous sample solution (pH 5.27) with a voltage of 65 V and a time of 29 min were extracted into 600 µL acidic (pH 9) and basic (pH 4) acceptor solution after passing through the agar membrane. The parameters, including the agar gel concentration (% w/v), the thickness of the agar gel, the pH of the gel, and the acceptor phases were optimized by one factor at a time also the design of the Experiment program was used to analyze and optimize the parameters such as the pH of the donor phase, voltage, time and stirring rate. Under the optimal conditions, the linear range for both dyes Tt and AO was 0.05–2.0 μg mL−1 with R2 > 0.99, the detection limits were 0.0256 and 0.0310 μg mL−1 and % recovery 85.0–111 and 91.7–112 respectively. Finally, the proposed method was successfully applied to the determination of Tt and AO in food samples. This novel approach offers a sensitive and accurate way to monitor the presence of these dyes in food products, which can be crucial for ensuring food safety and quality control.

Dextrin-assisted gel electromembrane extraction of chiral drugs: Improving the extraction efficiency and investigation of enantioselectivity of extraction

The present study investigates the use of dextrins (maltodextrin, β-cyclodextrin, and hydroxypropyl-β-cyclodextrin) to improve the efficiency of the agarose-based gel electromembrane extraction technique for extracting chiral basic drugs (citalopram, hydroxyzine, and cetirizine). Additionally, it examines the enantioselectivity of the extraction process for these drugs. To achieve these, dextrins were incorporated into either the sample solution, the membrane, or the acceptor solution, and then the extraction procedure was performed. Enantiomers were separated and analyzed using a capillary electrophoresis device equipped with a UV detector. The results obtained under the optimal extraction conditions (sample solution pH: 4.0, acceptor solution pH: 2.0, gel membrane pH: 3.0, agarose concentration: 3 % w/v, stirring rate: 1000 rpm, gel thickness: 4.4 mm, extraction voltage: 62.3 V, and extraction time: 32.1 min) indicated that incorporating dextrins into either the sample solution, membrane or the acceptor solution enhances extraction efficiency by 17.3–23.1 %. The most significant increase was observed when hydroxypropyl-β-cyclodextrin was added to the acceptor solution. The findings indicated that the inclusion of hydroxypropyl-β-cyclodextrin in the sample solution resulted in an enantioselective extraction, yielding an enantiomeric excess of 6.42–7.14 %. The proposed method showed a linear range of 5.0–2000 ng/mL for enantiomers of model drugs. The limit of detection and limit of quantification for all enantiomers were found to be < 4.5 ng/mL and <15.0 ng/mL, respectively. Intra- and inter-day RSDs (n = 4) were less than 10.8 %, and the relative errors were less than 3.2 % for all the enantiomers. Finally, the developed method was successfully applied to determine concentrations of enantiomers in a urine sample with relative recoveries of 96.8–99.2 %, indicating good reliability of the developed method.

Graphene-based gel electromembrane extraction coupled with modified screen-printed carbon electrode for detecting streptomycin in honey samples: Greener strategy for food analysis

This paper presents a greener methodology for the first time to determine streptomycin in honey based on the modification of gel in the gel electromembrane extraction (G-EME) technique using exfoliated graphene (EG). Differential pulse voltammetry (DPV) with a modified screen-printed carbon electrode was used as a detection technique. The EG was prepared by applying an electrochemical exfoliation of pencil graphite as an environmentally friendly and simple method. EG has conductivity properties, large specific surface areas, and the possibility of noncovalent π–π stacking. The addition of EG to G-EME could enhance the extraction efficiency by increasing the transfer rate of streptomycin, resulting in better LOQ.Out of several materials tested (AuNPs, AgNPs, graphene oxide, graphite, EG of pencil graphite 6B), EG powder of 6B was the best nanomaterial for carrying out G-EME. Furthermore, the problem associated with increasing electric current and electroendosmosis due to addition of graphene-based nanomaterial has been totally solved by tuning the acceptor phase’s volume.Under the optimal conditions to perform EG@G-EME and DPV in the honey matrix, a good linearity was obtained between 20 and 580 μg kg−1 (R2 > 0.9964) with LOD and LOQ equal to 4.9 and 16.4 μg kg−1, respectively, in the honey matrix. Inter- and intra-assay results showed relative standard deviations of about 5 %. Compare to the conventional G-EME, our developed method showed better sensitivity.

Application of oxygen scavengers in gel electromembrane extraction: A green methodology for simultaneous determination of nitrate and nitrite in sausage samples.

The generation of oxygen from electrolysis in gel electromembrane extraction (G-EME) causes a negative error when applied to the analysis of easily oxidized species such as nitrite. Nitrite in G-EME is oxidized by oxygen to nitrate, leading to the negative error and the impossibility of simultaneous analysis. In this work, the application of oxygen scavengers to the acceptor phase of the G-EME system was attempted to minimize the oxidation effect. Several oxygen scavengers were selected and examined according to their compatibility with ion chromatography. The mixture of sulfite and bisulfite (14mg L-1) showed the highest efficiency in preventing the oxidation of nitrite to nitrate. Under the optimized conditions, a good linear range was obtained (10-200μg L-1; R2>0.998) with a detection limit of 8µg L-1 for both nitrite and nitrate. This method was applied to the simultaneous determination of nitrite and nitrate in sausage samples.

Solar energy-based electromembrane extraction using agarose gel for the determination of nonsteroidal anti-inflammatory drugs from biological samples: An environmentally friendly strategy

This paper presents the application of solar energy as a renewable resource in gel electromembrane extraction (G-EME). The extraction driving force (electrical field) generated from solar energy is stored through photovoltaic panels and significantly contributes to reducing the emission of greenhouse gasses. Moreover, the replacement of the polypropylene membrane and organic extracting solvents with biodegradable agarose membrane and the aqueous extracting solutions makes the presented approach compatible with the principles of green chemistry. Naproxen (NAP) and ibuprofen (IBF) were extracted from urine samples to the aqueous acceptor phase containing an anode electrode situated on the other side of the agarose gel membrane. Acceptable linearity was obtained in the concentration ranges of 6–100 and 9–100 μg. L − 1 with detection limits of 2 and 3 μg. L − 1 for NAP and IBF, respectively.

In-tube gel electromembrane extraction: A green strategy for the extraction of narcotic drugs from biological samples

The development of green and miniature extraction methods is always a major and controversial challenge in the field of sample preparation. In this work, in-tube gel electromembrane extraction (IT-G-EME) was developed as a miniaturized extraction device for the extraction of six narcotic drugs (codeine, oxycodone, hydrocodone, tramadol, thebaine, and noscapine) from biological samples. A transparent capillary tube (∼6 cm) was used as a microextraction unit. The middle part of the tube was filled with a narrow plug (∼3 mm) of the agarose gel (3.0% w/v) as a membrane and the other sides were filled with aqueous extractant solution (pH 2.0, 20 µL) and sample solution (pH 5.0, 200 µL). By applying electrical potential (400 V), the target drugs with positive charge were migrated from sample solution toward the extractant solution through gel membrane during short extraction time (5 min). Then, the enriched analytes in extractant solution was analyzed by HPLC-UV. Under the optimized conditions, the calibration curves were linear within the permissible range of 10.0–1500 ng/mL (r2 ≥ 0.991). Limits of detection and extraction recoveries were in the range of 3.0–4.5 ng/mL and 61.9–86.9%, respectively. On the basis of four replications, the repeatability of the method was also evaluated in terms of intra- and inter-day RSDs (%), which did not exceed from 6.6 and 7.9%, respectively in aqueous media. The figures of merit were also assessed in biological samples. Eventually, the developed method was profitably used for simultaneous determination of narcotic drugs in the real urine and plasma samples.

Electromembrane extraction using biodegradable deep eutectic solvents and agarose gel as green and organic solvent-free strategies for the determination of polar and non-polar bases drugs from biological samples: A comparative study

Two modes of electromembrane extraction (EME) were evaluated in this work, one using deep eutectic solvents (DESs) as liquid membrane, and another was gel electromembrane extraction (G-EME) based on solid agarose membrane. Both EME modes have eliminated organic solvents and are recognized as green strategies. Unlike classic EME in which polypropylene membrane and organic extracting solvents play an essential role in the extraction process, new modes of EME are based on biodegradable membranes and aqueous extracting solutions. Approaches of EME based on the new designs follow the green chemistry principles. Each mode of EME was evaluated for the determination of polar and non-polar bases drugs from human urine samples using high-performance liquid chromatography (HPLC) equipped with a diode array detector (DAD). EME using DES A was suitable for determining polar and non-polar bases drugs in a large polarity window. While extraction recoveries for all six drugs studied by G-EME were lower than EME using DES A. Comparing the two EME modes shows similar results in the analytical figures of merit. However, differences in extraction recoveries of the drugs by two EME modes were observed which is related to the difference in membranes structure. Our findings indicate that the differences between membranes properties used in two EME modes, including the permeability, hydrophilicity, hydrophobicity, and variety of interactions, are influencer factors on extraction efficiency. The two EME modes provided good linearity in the ranges of 16–100 and 19–100 μg. L−1 for G-EME and EME using DES A, respectively with (r2 > 0.993). Also, the detection limits (LODs) were 19–32 and 19–29 μg. L−1 for G-EME and EME using DES A, respectively.

Evaluation of complexing agents in the gel electro-membrane extraction: An efficient approach for the quantification of zinc (II) ions in water samples

In this work, gel electro-membrane extraction (G-EME) combined with flame atomic absorption spectrometry (FAAS) was used for the determination of zinc ions (Zn2+) in water samples. For the first time, the effect of the presence of three types of complexing agents such as phenanthroline (Phen), crown ethers (12C4, 15C5, 18C6), and ethylene-diamine-tetra-acetic acid (EDTA) on the extraction efficiency of zinc ions was studied. In addition, the electroendosmosis (EEO) flow as an unwanted actuator was monitored in the presence and absence of complexing agents. By applying 50 V electrical potential across the membrane, the positive charged Zn2+ ions were migrated from a donor phase (pH 5.0) through the agarose gel membrane (pH 5.0, containing a complexing agent) into the acceptor phase (pH 3.0). The obtained results showed that the highest extraction recoveries were obtained when crown ethers, especially 1% (w/v) 18C6 was added to the gel membrane. In addition, EEO flow was decreased in the presence of all complexing agents (except EDTA), probably due to the increase in electrical resistance. Using the optimum conditions, the limit of detection (LOD), the limit of quantification (LOQ), and extraction recovery% (ER%) were 5.0 μg L−1, 15.0 μg L−1, and 92.5%, respectively. In the end, the applicability of the developed approach was successfully evaluated to determine Zn2+ in tap, mineral, and river water samples.

Enrichment of psychotropic drugs using rhamnolipid bioaggregates after electromembrane extraction based on an agarose gel using a rotating electrode as a green and organic solvent-free strategy

We here present an efficient approach for the tandem extraction of psychotropic drugs using biodegradable materials. In this regard, gel electromembrane extraction (G-EME) was combined with the emulsification-based microextraction (ME) technique by rhamnolipid bioaggregates as a green extraction approach. The tandem extraction technique consists of two stages: (i) extraction of psychotropic drugs from human urine samples to the acceptor phase situated on the other side of the agarose gel membrane, and (ii) transfer of analytes from the acceptor phase into a colloidal phase of rhamnolipid biosurfactants. The colloidal phase was formed by adding rhamnolipid biosurfactants to the extracted phase of the first step. The colloidal phase was finally injected into a liquid chromatographic system for quantitative analysis. G-EME mechanism is based on electrokinetic migration of charged species toward oppositely charged electrode located in the acceptor solution under the influence of the electric field. After extraction, the analytes were trapped in an emulsion phase floating on the surface of the solution and at the end were injected into the liquid chromatographic system. The method provided good linearity in the ranges of 5-100 and 10-100 μg. L−1 for methamphetamine and amphetamine, respectively with (r2 > 0.992). Also, the detection limits (LODs) were 1 and 5 μg. L−1 for methamphetamine and amphetamine, respectively. The mean extraction recoveries by G-EME-ME for real samples at three spiked concentrations were in the range 95.9-101.1% and complete analytical workflow within only 18 min.

Simultaneous separation and quantification of acidic and basic dye specimens via a dual gel electro-membrane extraction from real environmental samples

In this work, an environmentally friendly and easy-in-performance dual gel electro-membrane extraction approach (dual G-EME) was combined with high performance liquid chromatography. Method was arranged for parallel isolation, enrichment and determination of brilliant green (BG) and reactive red (RR), serving as model basic and acidic dyes, respectively. A DIY (do-it-yourself) agarose-based gel membrane was fabricated, and served as green and highly selective filtering item. The extractions were hazards-free (i.e., there was no need for organic solvents or toxic regents) and membrane assembly is highly degradable as being of fully natural character. Thereby, setup has met the requirements of being a green analytical chemistry technique. By using an electric potential of 50 V during 20 min extraction time, the positively charged BG and negatively charged RR migrated selectively from a 7.0 mL aqueous sample (pH 7.0) to the 500 μL cathodic (pH 4.0) and 500 μL anodic (pH 9.0) aqueous acceptor phases, respectively. Under the optimal conditions, limits of detection were 0.020 and 0.025 ng mL−1, and extraction recoveries were of 75–78% and 67–71% for BG and RR, respectively. The linearity was in the range of 0.06–1.0 μg mL−1 with correlation coefficient higher than 0.996, obtained for both model analytes. Finally, the methodology was successfully applied for parallel quantification of BG and RR in complex environmental samples.

Two-phase agarose gel-electromembrane extraction: Effect of organic solvent as an acceptor phase in electroendosmosis flow phenomenon

In this study, a new mode of gel electromembrane extraction (G-EME) namely as "Two-phase G-EME", is suggested for the sensitive quantification of five basic drugs (desipramine, clomipramine, trimipramine, citalopram and clozapine) in biological samples. Compared to classical G-EME which is based on aqueous-gel-aqueous layout, herein, the aqueous acceptor phase (AP) was replaced with organic solvent. Briefly, negative electrode was immersed into the organic AP (with low conductivity) and positive electrode into the aqueous donor phase (DP). Based on our results, this simple adjustment significantly reduced electroendosmosis (EEO) flow phenomenon which is considered as the main issue in G-EME. In the workflow, target analytes were extracted from the 7.0 mL sample, across the fabricated agarose gel membrane, to the 100 μL of the AP under the optimized extraction conditions (organic solvent type: acetonitrile; pH of gel membrane: 5.0, pH of sample solution: 4.0, voltage: 45 V and extraction time: 22 min). Then, the organic AP with analytes was analyzed by gas chromatography (GC) instrument with flame-ionization detector (FID). The methodology offered limits of detection (LODs) and recoveries in the range of 1.0–1.5 ng mL−1 and 48.5–89.0 %, respectively. Finally, we note that two-phase G-EME assembly was able to extract analytes-of-interest in the convenient and safe manner from the hazardous and difficult-to-process biological specimens such as human serum and urine.

Electromembrane extraction based on agarose gel for the extraction of phenolic acids from fruit juices

Extraction of polar acidic compounds is a challenging task in electromembrane extraction. In this study, gel-electromembrane extraction was employed for the extraction of phenolic acids as the polar acidic compounds from fruit juices. For this aim, the extraction of phenolic acids from the juice samples (4 mL, pH = 6.0) was carried out across the agarose gel membrane (concentration of agarose; 3% (w/v), pH of gel; 10.0, and thickness of membrane: 3 mm) into the acceptor solution (100 μL, pH = 12.0). Also, this extraction process was conducted by applying the optimum potential (25 V) for 15 min to the extraction system. Under the optimized condition, acceptable linearity (R2 ≥ 0.993) over a concentration range of 10.0–2500 ng mL−1 was achieved. The limits of detection were between 3.0 and 15.2 ng mL−1, while the corresponding repeatabilities ranged from 5.3 to 11.4% (n = 4). The recoveries achieved for the extraction of target compounds were ranged from 26.8 to 74.4%. The proposed method was used for the extraction of phenolic acids from orange, apple and kiwi juices, and the obtained relative recoveries in the range of 78.0–104.2% and RSDs in the range of 6.3 to 11.3% indicated successful extraction of phenolic acids.

Gel electro-membrane extraction of propranolol and atenolol from blood serum samples: Effect of graphene-based nanomaterials on extraction efficiency of gel membrane

In this work, gel electro-membrane extraction (G-EME) method is suggested for extraction and determination of propranolol and atenolol in complex biological samples. An in-house membrane based on agarose was used as green and biodegradable gel membrane. Essential chemical parameters that influence on extraction efficiency were tested, optimized and evaluated via a central composite design (CCD) and response surface methodology (RSM). Optimal conditions for extraction of drugs from the 7.0 mL sample were as follows: 3% (w/v) agarose with 0.1% (v/v) acetic acid functioning as membrane, voltage: 50 V; pH of the donor phase (DP): 8.1; pH of the AP: 3.3; extraction time: 35.9 min. Under these conditions, the acceptable normalized extraction recoveries were obtained such as 71.9 ± 5.4% that were in good agreement with the predicted values (i.e., 73.1 ± 0.9%). Limits of detection (LODs) for propranolol and atenolol were 5.0 ng mL˗1 and 7.5 ng mL˗1, respectively. Moreover, for the first time, the effect of presence of four graphene-based nanomaterials such as graphene (G), graphene oxide (GO), three-dimensional nitrogen doped graphene oxide (3D-ND-GO) and high nitrogen doped graphene oxide (HND-GO) in agarose gel membrane on extraction efficiency, was investigated. The results showed that in presence of these nanomaterials, the normalized recovery depressed significantly due to increasing of electric current and electroendosmosis (EEO) phenomenon. Eventually, the proposed method was applied to quantify basic drugs in real plasma samples with relative recoveries in the range of 85.7–97.5%, indicating good reliability of the assay.

Gel electromembrane extraction using rotating electrode: A new strategy for mass transfer enhancement of basic drugs from real human urine samples

This study proposed a new method of EME based on agarose gel named rotating electrode gel electromembrane extraction (RE-G-EME) for extraction and determination of naloxone, naltrexone, and nalbuphine as basic drugs from real human urine samples. In this new method, a rotating electrode connected to the armature was used to agitate the acceptor phase (AP). With this new development, the extraction efficiency enhanced due to increasing analytes mass transfer from gel membrane interface toward the AP. The effective parameters on the extraction efficiency were optimized and the maximum recoveries of the analytes were obtained under the optimal extraction conditions (3.0% (w/v) agarose with pH 5.0 as gel membrane; voltage: 25 V; pH of the donor phase (DP): 6.0; pH of the AP: 4.0; stirring rate of the DP: 750 rpm; electrode rotation speed within AP: 125 rpm; extraction time: 25 min). The method offered limits of detection (LODs) and extraction recoveries in the range of 0.3–1.5 ng mL−1, and 74.3% − 87.0%, respectively. Also, the repeatability of the proposed method was measured for four repeated experiments and was in the acceptable range of 4.3% − 8.1%. To understand the influence of agitation of the AP on the extraction efficiency, a comparative study was carried out between conventional G-EME and RE-G-EME methods. The results showed that, for short the extraction times (t ≤ 10 min), extraction efficiency of G-EME was almost the same as that of RE-G-EME. However, at longer extraction times (25 min), the extraction efficiency of RE-G-EME was significantly higher than that of G-EME. Finally, the proposed method was successfully applied to determine concentrations of model drugs in real urine samples with relative recoveries of 81.1–96.1% indicating good reliability of the proposed method.

Gel-electromembrane extraction of peptides: Determination of five hypothalamic agents in human plasma samples

Agarose gel as a green membrane has been proposed for use in electromembrane extraction of five hypothalamic-related peptides without an ionic carrier. Octreotide, goserelin, triptorelin, cetrorelix, and somatostatin were extracted from 5.0 mL of sample solution (adjusted to pH 5.0) into a microvolume acceptor solution (HCl, 100 mM) under the applied voltage of 30 V in 15 min. The pH of the agarose gel 3.0% (w/v) was adjusted to 4.0 to facilitate the movement of peptides through the membrane. Quantification was performed using an HPLC-UV system on a C18 column. Quantification and detection limits were found to be in the range of 15.0–20.0 ng mL−1 and 4.5–6.0 ng mL−1, respectively. Dynamic linear ranges were found to be in the range of 15.0–1000 ng mL−1 (R2 > 0.995) and recoveries were in the range of 62.3–77.6%. The optimized method was applied to spiked human plasma samples. The method showed relative recoveries in the range of 44.8–66.0%. Finally, the proposed method was compared with and shown to have higher recoveries than, the conventional electromembrane extraction method for the peptides under study.

Combination of gel-electromembrane extraction with switchable hydrophilicity solvent-based homogeneous liquid-liquid microextraction followed by gas chromatography for the extraction and determination of antidepressants in human serum, breast milk and wastewater

The current study presents for the first time a combination of the gel electromembrane extraction (GEL-EME) and switchable hydrophilicity solvent-based homogeneous liquid-liquid microextraction (SHS-HLLME) methods which can be used as an efficient hyphenated extraction procedure. This coupled method, which was followed by GC-FID, was applied for quantification of antidepressants (desipramine, clozapine, and citalopram) in biological and wastewater samples. The effective parameters of both GEL-EME and SHS-HLLME procedures were optimized. Using an agarose gel membrane, analytes were extracted from 7.0 mL of the sample solution to 500 µL of the aqueous acceptor solution. The maximum extraction of analytes of interest was obtained under the optimized conditions (pH of acceptor solution, 5.0; pH of gel membrane, 5.0; pH of sample solution, 7.0, voltage value, 30 V; and extraction time, 30 min). Then, the acceptor solution was transferred to the extraction cell and the SHS-HLLME procedure was conducted again under the optimized conditions. Dipropylamine (50 µL) was selected as an extraction solvent. The introduced technique exhibited good linearities with coefficients of determinatin (R2) higher than 0.983 and an acceptable linear range of 5.0–1000 ng/mL. Accordingly, the limit of detection was ≤ 1.0 ng/mL (S/N = 3) for all analytes, and the high enrichment factors were obtained in the range of 178.7–194.8. Moreover, the corresponding repeatability was from 4.0 to 8.7% (n = 3). The proposed method was successfully utilized to determine trace levels of the drugs in human serum, wastewater, and breast milk samples.

Inside gel electromembrane extraction: A novel green methodology for the extraction of morphine and codeine from human biological fluids

In this work, a new mode of gel-electromembrane extraction (G-EME), called “inside” gel-EME (IG-EME) is proposed for the extraction of morphine and codeine as model basic drugs from complex biological samples. Here, an aqueous media that was captured inside the agarose gel membrane, acted as both gel membrane and the acceptor phase (AP) at the same time. In this regard, the membrane served as the separation filter (membrane) and supported liquid acceptor phase (SLAP) as well. With this new development, unwanted changes of the AP volume during the extraction, which is a common issue in the G-EME (due to electroendosmosis (EEO) phenomenon), was addressed properly. Briefly, the setup involved insertion of negative electrode inside the gel membrane and positive electrode into the donor phase (DP). Following that, the IG-EME was easily performed using optimal conditions (pH of the DP: 6.0; membrane composition (agarose concentration: 1% (w/v) in aqueous media with pH 3.0, and 15 mm thickness); voltage: 25 V; and extraction time: 30 min). After extraction, the agarose gel was withdrawn and centrifuged for 5 min with 12000 rpm, to disrupt its framework to release the “trapped aqueous AP” apart from the gel structure. The separated AP was finally injected into the HPLC-UV for the analysis. The limits of detection (LODs) and recoveries in this proposed method were obtained 1.5 ng mL−1 and 67.7 %–73.8 %, respectively. The system feasibility was examined by the quantification of model drugs in the real plasma and urine samples.

Gel electromembrane extraction: Study of various gel types and compositions toward diminishing the electroendosmosis flow

For the first time, the effect of electroendosmosis (EEO) flow phenomenon was investigated in detail, on the gel electromembrane extraction (G-EME). When electric field is used as an actuator of ion transport in G-EME, the EEO flow phenomenon can occur within the agarose gel membrane interface and is generally considered the dominant issue. In this regard, various agarose-based gel membrane types with low-, medium- and high-EEO were fabricated and tested. To further diminish the EEO effect, the different gel membrane additives such as dextrin, chitosan and xylan with different concentrations i.e., 5%, 10% and 15% were also examined. The positively charged Cr(III) and negatively charged Cr(VI) were chosen as model analytes. The Cr(III) and Cr(VI) were simultaneously extracted from an aqueous sample (pH 3.0) via the cathodic and anodic gel membranes (pH 3.0 for both membranes), into the cathodic and anodic aqueous acceptors (200 µL each, pH 2.0), respectively. After extraction at the optimal conditions (i.e., voltage: 32 V, extraction time: 22 min), the both compounds were quantified by a cheap and easy-to-perform reader platform termed as microfluidic paper-based analytical device (μPAD). The results showed that high extraction recoveries such as 87% for Cr(III) and 75% for Cr(VI), were acquired when the low-EEO agarose gel membrane with 5% (w/v) dextrin was used. On the other hand, using the high-EEO agarose gel membrane with no additive lead to the high EEO flow and the increase of cathodic acceptor volume (equal to 350 µL) while the recovery depressed to about 50% due to the dilution effect. Simultaneously, the volume of anodic acceptor became almost vacant (~50 µL). Ultimately, by means of such simple gel membrane adjusting (i.e., low-EEO agarose with 5% dextrin), the both target compounds were quantitatively extracted at a single step achieving limits of detection (LODs) of 0.5 and 0.7 ng mL−1 for Cr(III) and Cr(VI), respectively.