Donor Solution Research Articles

Autonomous Temporal Control of Hydrogen Sulfide Delivery.

Hydrogen sulfide (H2S) is dichotomous in nature as it is lethal at higher concentrations, but at lower concentrations it shows a more cytoprotective nature. Due to its involvement in many physiological processes, it has recently risen to significance as a gasotransmitter alongside carbon monoxide (CO) and nitric oxide (NO). Experimentation using H2S is thus important to generate in vitro and in vivo models for this ubiquitous gasotransmitter. However, laboratory studies involving H2S are challenging due to the special handling conditions required to work with such a toxic gas. The use of chemical donors in the cell culture also show temporally varying release profiles, which are not optimal when trying to control H2S in cell cultures lasting several days. Previously we applied microfluidics to deliver stable concentrations of H2S, and in this work, we demonstrate a novel experimental method incorporating feedback control to precisely deliver H2S that accounts for donor solution concentration decay.

Headspace Passive Dosing of Volatile Hydrophobic Organic Chemicals from a Lipid Donor-Linking Their Toxicity to Well-Defined Exposure for an Improved Risk Assessment.

High hydrophobicity and volatility of chemicals often lead to substantial experimental challenges but were here utilized in headspace passive dosing (HS-PD) to establish and maintain exposure: the pure chemical served as a passive dosing donor for controlling exposure at saturation, whereas triglyceride oil containing the chemical was used to control lower exposure levels. These donor solutions were added to glass inserts placed in the closed test systems. Mass balance calculations confirmed a dominant donor capacity for all chemicals except isooctane. This HS-PD method was applied to algal growth inhibition and springtail lethality tests with terpenes, alkanes, and cyclic siloxanes. Headspace concentrations above the lipid donors were measured for three chemicals to determine their chemical activity, using saturated vapor as the analytical standard and thermodynamic reference. Toxicity was related to chemical activity and calculated concentrations in membranes at equilibrium with the lipid donor. For both tests and all chemicals, toxic effects were observed within or above the reported range for baseline toxicity, meaning that no excess toxicity was observed. The toxicity of siloxanes was markedly higher to the terrestrial springtail than the aquatic algae, which is consistent with a more efficient mass transfer of these volatile hydrophobic chemicals in air compared to water.

Selective determination of some beta-blockers in urine and plasma samples using continuous flow membrane microextraction coupled with high performance liquid chromatography

In this work, an efficient method termed as continuous flow membrane microextraction coupled with high performance liquid chromatography is introduced for a highly selective determination of metoprolol and propranolol in the biological samples. According to this method, an aqueous source phase of the analytes (donor phase, 10 mL) is circulated into an extraction cell, which is separated from an aqueous acceptor phase (100 μL) by a small piece of polypropylene membrane sheet whose pores are impregnated by an organic solvent (1-octanol, 15 μL). The analytes are extracted from the donor phase into the organic solvent. They are subsequently selectively back-extracted into the acceptor solution due to the pH gradient. The proposed method is very convenient and has the capability of being fully automated. It provides a good preconcentration and an excellent repeatability. The extractant is an aqueous phase, and by prevention of the extraction of macromolecules through the membrane, the developed method provides a high sample clean-up. In order to maximize the extraction efficiency, the influential parameters including the type of mediator solvent, pH values for the donor and acceptor solutions, extraction time, ionic strength, stirring rate, and volume of the acceptor solution are optimized. The calibration curves were obtained with a reasonable linearity (r2 = 0.999) in the range of 3–1000 ng mL−1. The limits of detection were 0.5 and 1.0 ng mL−1, and excellent relative standard deviations were obtained (between 3.2% and 4.0%). Finally, the reliability of the procedure is evaluated by determination of metoprolol and propranolol in the human urine and plasma samples, which indicates the suitability, sensitivity, and high sample clean-up of the proposed method.

Two-phase micro-electromembrane extraction with a floating drop free liquid membrane for the determination of basic drugs in complex samples

A two-phase micro-electromembrane extraction (μ-EME) using a floating drop of an organic solvent was presented for rapid and efficient pretreatment of complex biological samples. The μ-EME system consisted of a glass vial containing aqueous sample (donor solution) and a small drop of a water-immiscible organic solvent (4-nitrocumene), which was floating on the surface of the aqueous solution in form of a free liquid membrane (FLM). The vial geometry and the optimized volume ratios of the donor and the FLM ensured a stable position of the FLM in the center of the vial during μ-EME, and one electrode of a d.c. power supply was inserted directly into the FLM while the other electrode was placed into the aqueous sample. The active surface area of the floating drop FLM contacting the sample was considerably larger in comparison to formerly reported μ-EME formats employing FLMs and resulted in a faster and a more efficient transfer of target analytes from the sample to the FLM. Four basic drugs (nortriptyline, papaverine, loperamide, and haloperidol) were selected as model analytes and were extracted from physiological solution, human urine, and dried blood spot samples. At the optimized μ-EME conditions (250 V, 15 min, 300 rpm, acidic donor) and the optimized ratio of the sample to the FLM volume (500:14 μL), extraction recoveries between 49 and 100% and enrichment factors up to 35.7 were achieved. Quantitative analyses of the basic drugs in the resulting FLMs (diluted with methanol) were performed by capillary electrophoresis with ultraviolet detection and demonstrated excellent repeatability (RSD ≤ 4.9%) and linearity (r2 ≥ 0.9997), and low limits of detection (5–28 ng/mL) of the method.

Sugaring-out assisted electromembrane extraction of basic drugs from biological fluids: Improving the efficiency and stability of extraction system

In the current study, for the first time, the sugaring-out effect was assessed in a conventional electromembrane extraction (EME) system. Utilizing the sugars in the donor solution as green additives can result in production of a pioneering and influential EME mode. Sugaring-out assisted electromembrane extraction was combined with high-performance liquid chromatography (HPLC) to enhance the extraction of four basic model drugs (pseudoephedrine, lidocaine, propranolol, and ketoconazole). In this mode of EME, not only the transfer of analytes through the supported liquid membrane (SLM) was improved, but also the whole extraction system became more stable than the conventional one in the same voltage. The type and concentration of sugars were optimized in addition to the common experimental parameters influencing the EME, and figures of merit were also studied. Under the optimum conditions, repeatability (RSD%) was obtained in the range of 2.8–6.9% in the water, while RSD value was obtained in the range of 8.2–11.8% (n = 3) for conventional EME with the same state. The linearity range was also in the interval of 5.0–1000.0 ng mL-1 and limits of quantification and detection were in the ranges of 5.0–10.0 ng mL-1 and 1.5–3.0 ng mL-1, respectively, in the introduced EME. Extraction recoveries in the range of 41.2 and 80.8% were obtained resulting in enrichment factors in the range of 96–189. In light of such factor, new suggested EME mode was assessed in the real biological samples including human plasma and urine in order to prove the sugaring-out efficiency in EME systems.

Skin microbiome modulation induced by probiotic solutions

BackgroundThe skin is colonized by a large number of microorganisms, most of which are beneficial or harmless. However, disease states of skin have specific microbiome compositions that are different from those of healthy skin. Gut microbiome modulation through fecal transplant has been proven as a valid therapeutic strategy in diseases such as Clostridium difficile infections. Therefore, techniques to modulate the skin microbiome composition may become an interesting therapeutic option in diseases affecting the skin such as psoriasis or acne vulgaris.MethodsHere, we have used mixtures of different skin microbiome components to alter the composition of recipient skin microbiomes.ResultsWe show that after sequential applications of a donor microbiome, the recipient microbiome becomes more similar to the donor. After intervention, an initial week-long phase is characterized by the dominance of donor strains. The level of engraftment depends on the composition of the recipient and donor microbiomes, and the applied bacterial load. We observed higher engraftment using a multi-strain donor solution with recipient skin rich in Cutibacterium acnes subtype H1 and Leifsonia.ConclusionsWe have demonstrated the use of living bacteria to modulate skin microbiome composition.

Extraction and Preconcentration of Trace Malondialdehyde from Lipid-Rich Foods Using Ion Pair–Based Solvent Bar Liquid-Phase Microextraction

In this research, for the first time, a new strategy based on ion pair–based solvent bar liquid-phase microextraction (IP-SB-LPME) in combination with GC instrument was introduced for sensitive determination of malondialdehyde (MDA) in lipid-rich foods. In this three-phase process, a cationic surfactant was added initially into alkaline donor solution to form hydrophobic ion pair with the anionic analyte. Then, the ion pair formed was enriched into organic solvent immobilized in the pores of the HF and finally back extracted into an acidified acceptor phase in the lumen of the fiber. Significant parameters affecting the proposed method were optimized to obtain the maximum preconcentration factor. Under the optimized conditions, the method provided good linearity in the range of 3–600 μg L−1 in pure water, 65.0–6875.0 μg kg−1 in infant powder milk, and 52.5–6875.0 μg kg−1 in vegetable oils. Acceptable repeatability and reproducibility (CV < 4%) with preconcentration factors in the range of 82–100 times were obtained. Methodological validation was accomplished by using the conventional spectrophotometric TBA (2-thiobarbituric acid) test. Finally, this procedure was applied to monitor trace amounts of MDA in the lipid-rich foods with satisfactory results.

Effect of counter-ions on electromembrane extraction of non- steroidal antiinflammatory drugs

The paper describes a comprehensive study of the importance of cations to improve the efficiency and mass transfer in the electromembrane extraction for the determination of non-steroidal antiinflammatory. The procedure has been demonstrated to be adequate for the analysis of the selected non-steroidal anti-inflammatory drugs in human urine samples. Effects of donor and acceptor solution composition were examined studying the presence of different counter-ions in both aqueous solutions demonstrating to be an important parameter in the transference of the analytes across the membrane. Other parameters that are also critical for electromembrane, such as the organic solvent, the voltage, the extraction time and the donor solution volume were also optimized. The extracts were analyzed by high performance liquid chromatography with diode array and fluorescence detection. The highest enrichment factor was achieved using a pH7 donor composition adjusted with KOH and an acceptor composition at pH12 adjusted with NaOH. The enrichment factors were within the range of 85 and 133 for all compounds after 20min extraction, using a voltage of 60V, a stirring speed of 600rpm and 1-octanol as support liquid membrane. Detection and quantitation limits were within 0.1–1.5ngmL−1 and 0.3–3.0ngmL−1, respectively. The presence of K+ and Na+ as counter ions in the donor and the acceptor solution, respectively, demonstrated a higher enrichment compared to previous reported methods for the determination of non-steroidal antiinflammatory by electromembrane extraction using NaOH/NaOH as counter-ions.

The effect of membrane thickness on supported liquid membrane extractions in-line coupled to capillary electrophoresis for analyses of complex samples

The effect of membrane thickness on extraction performance was systematically examined in extractions through supported liquid membranes (SLM), which were in-line coupled to capillary electrophoresis (CE). Three porous polypropylene membranes with different thickness (25, 100 and 170 μm) were used as supports for SLM extractions of model basic drugs (nortriptyline, papaverine, haloperidol and loperamide) from complex samples. The analytes were transferred through the SLMs by a pH gradient and were in-line injected, separated and quantified using a commercial CE instrument with ultraviolet (UV) detection. Transfers of the model drugs through SLM decreased with the increased membrane thickness (in the order: 25 > 100 > 170 μm) and highest transfers were achieved for the thinnest membrane. Interferences from complex sample matrices were efficiently eliminated, moreover, impregnation of the 25 μm membrane required significantly reduced volume of organic solvent. Mechanical stability of the impregnated 25 μm membrane was excellent during in-line injections, which necessitated direct contact of CE separation capillary with the SLM. Repeatability of the hyphenated SLM-CE-UV method (using the 25 μm membrane) was lower than 11% (RSD values of peak areas) and calibration curves were strictly linear in 0.5–30 μg/mL concentration range (coefficients of determination ≥ 0.997). Transfers of the basic drugs from donor solutions (standard and undiluted human urine/plasma) through the SLMs ranged from 45 to 231% and limits of detection were between 0.02 and 0.15 μg/mL.

Efficient doping modulation of monolayer WS2 for optoelectronic applications**Project supported by the National Natural Science Foundation of China (Grant No. 21405109) and Seed Foundation of State Key Laboratory of Precision Measurement Technology and Instruments, China (Grant No. 1710).

Transition metal dichalcogenides (TMDCs) belong to a subgroup of two-dimensional (2D) materials which usually possess thickness-dependent band structures and semiconducting properties. Therefore, for TMDCs to be widely used in electronic and optoelectronic applications, two critical issues need to be addressed, which are thickness-controllable fabrication and doping modulation of TMDCs. In this work, we successfully obtained monolayer WS2 and achieved its efficient doping by chemical vapor deposition and chemical doping, respectively. The n- and p-type dopings of the monolayer WS2 were achieved by drop coating electron donor and acceptor solutions of triphenylphosphine (PPh3) and gold chloride (AuCl3), respectively, on the surface, which donates and captures electrons to/from the WS2 surface through charge transfer, respectively. Both doping effects were investigated in terms of the electrical properties of the fabricated field effect transistors. After chemical doping, the calculated mobility and density of electrons/holes are around 74.6/39.5 cm2·V−1·s−1 and 1.0 × 1012/4.2 × 1011 cm−2, respectively. Moreover, we fabricated a lateral WS2 p–n homojunction consisting of non-doped n-type and p-doped p-type regions, which showed great potential for photodetection with a response time of 1.5 s and responsivity of 5.8 A/W at VG = 0 V and VD = 1 V under 532 nm light illumination.

In-line coupling of supported liquid membrane extraction across nanofibrous membrane to capillary electrophoresis for analysis of basic drugs from undiluted body fluids.

Planar polyamide 6 nanofibrous membrane was for the first time used in direct coupling of supported liquid membrane (SLM) extraction to CE analysis. Disposable microextraction device with the nanofibrous membrane was preassembled and stored for immediate use. The membrane in the device was impregnated with 1 µL of 1-ethyl-2-nitrobenzene and the device was subsequently filled with 10 µL of acceptor solution (10 mM HCl) and 15 µL of donor solution (sample). The device was in-line coupled to CE system for selective extraction and direct injection, separation and quantification of model basic drugs (nortriptyline, haloperidol, loperamide and papaverine) from standard saline solutions (150mM NaCl) and from undiluted human body fluids (urine and blood plasma). Compared to standard polypropylene supporting material, the nanofibrous membrane demonstrated superior characteristics in terms of lower consumption of organic solvents, constant volumes of operational solutions, full transparency and possibility to preassemble the devices. Extraction parameters were better or comparable for the nanofibrous vs. the polypropylene membrane and the hyphenated SLM-CE method with the nanofibrous membrane was characterized by good repeatability (RSD ≤ 11.3%), linearity (r2 ≥ 0.9953; 0.5-20mg/L), sensitivity (LOD ≤ 0.4mg/L) and transfer (27-126%) of the basic drugs.

Impedometric investigation of salt effects on electromembrane extraction: Practical hints for pH adjustment

In the current work, an impedance system is developed to investigate the time variation of solution resistance, membrane resistance, and double layer capacitance during electromembrane extraction from salty solutions. For this purpose, the adverse effects of various salts such as NaCl, NaF, NaNO3, KNO3, KCl, LiCl, CH3COONa, Na2SO4, Na3PO4, MgCl2, LiClO4 and K2CO3 are studied. Two different model analytes are used including Naproxen and Verapamil as an acidic and basic drugs, respectively. In order to obtain a quantitative measure of the adverse effect of various salts, the recoveries were calculated along with those for the extraction from salt free donor phases. The decline of the recovery (called suppression throughout this work), due to the presence of the salt was taken as the quantitative measure of the adverse effect. In the case of the acidic drug, the percent suppression values had a wide range from 26.95 to 85.23%, except in the presence of LiClO4 which gave a suppression of 100%. The presence of salts during the extraction of the basic model analyte resulted in two different patterns. While NaNO3 and CH3COONa caused complete (100%) suppression, the rest of salts gave lower suppression values in the range of 16.99–38.32%. The impedance analysis results show that the free energy of transfer of accompanying ions has a significant effect on the time dependence of solution resistance and double layer capacitance. It is also shown that the suppression of recovery is significantly correlated with the rate and timescale of depletion of ionic species from the donor solution as well as the propagation of the double layer. In summary, it can be concluded that, when working with simple acids/bases for pH adjustment in EME, smaller counter ions are preferred.

Buccal delivery of small molecules – Impact of levulinic acid, oleic acid, sodium dodecyl sulfate and hypotonicity on ex vivo permeability and spatial distribution in mucosa

Studies of drug permeability rate and localization in buccal mucosa are essential to gain new knowledge of means such as chemical enhancers or osmolality to enhance buccal drug transport in the development of new buccal drug products. The transport of caffeine, diazepam and mannitol across porcine buccal mucosa was studied in modified Ussing chambers with a hypotonic donor solution, in the presence of levulinic acid (LA), oleic acid (OA), propylene glycol (PG) as well as sodium dodecyl sulfate (SDS). Subsequently, matrix-assisted laser desorption ionization – mass spectrometry imaging (MALDI-MSI) was applied to image the spatial distribution of caffeine, mannitol and SDS in cross-sections of porcine buccal mucosa. The results revealed that none of the permeation enhancing strategies improved the permeability of caffeine or diazepam, despite impact on the tissue integrity by OA and SDS, as seen by an increased permeability of mannitol. Further studies are needed with OA since PG solvent may have concealed the possible impact of OA. SDS decreased the permeability of caffeine and diazepam, a decrease which can be explained by micellar lipid extraction and encapsulation in micelles. MALDI-MSI showed that SDS permeated into approximately one-third of the epithelium, and it therefore appears that the main permeability barrier for mannitol is located in the outer epithelium. MALDI-MSI was shown to be a useful method for imaging spatial distribution of drugs and permeations enhancers in buccal mucosa.

Two-phase micro-electromembrane extraction across free liquid membrane for determination of acidic drugs in complex samples

A dynamic two-phase micro-electromembrane extraction (μ-EME) using electrically induced transfer of charged analytes directly into free liquid membrane (FLM) is proposed as a novel technique for improving enrichment capabilities of μ-EME. The presented set-up employs aqueous sample as donor solution and water immiscible organic solvent (1-octanol) as FLM, which form the two-phase μ-EME system for efficient extraction of model acidic drugs (ibuprofen, ketoprofen, naproxen and diclofenac) from standard solutions, human urine, human serum and wastewater samples. The FLM eliminates migration of matrix components from the complex samples and simultaneously it acts as an acceptor solution for selective trapping and enrichment of the analyte ions. Electrodes are immersed directly into the sample and the FLM and replenishment of analyte ions at the sample/FLM phase interface is accomplished by stirring the sample solution using a conventional laboratory stirrer. At optimized two-phase μ-EME conditions (100 V, 15 min, 1000 rpm) and optimized volume ratio of sample to FLM (480:16 μL), extraction recoveries of 60–97% and enrichment factors up to 29.1 were achieved. Determination of the acidic drugs in resulting FLMs was achieved by capillary electrophoresis with ultraviolet detection with good linearity (r2 ≥ 0.9998) and low limits of detection (4–20 ng/mL).

The use of the novel glycosyl acceptor and supramer analysis in the synthesis of sialyl-α(2–3)-galactose building block

A new glycosyl acceptor to be used in sialylation was designed as a 3-hydroxy derivative of 4-methoxyphenyl β-d-galactopyranoside with 2-O-acetyl group and O-4 and O-6 protected as benzylidene acetal. Two alternative syntheses of this compound were compared. Sialylation of 3-OH group of the glycosyl acceptor with O-chloroacetylated N-trifluoroacetylneuraminic acid phenyl thioglycoside (NIS, TfOH, MeCN, MS 3 Å, −40 °C) was studied in a wide concentration range (5–150 mmol L−1). The outcome of sialylation generally followed the predictions of supramer analysis of solutions of sialyl donor in MeCN, which was performed by polarimetry and static light scattering and revealed two concentration ranges differing in solution structure and the structures of supramers of glycosyl donor. The optimized conditions of sialylation (C = 50 mmol L−1) were used to synthesize protected Neu-α(2–3)-Gal disaccharide (78%, α:β = 13:1), which was then converted to sialyl-α(2–3)-galactose imidate building block useful for the synthesis of complex sialo-oligosaccharides.

Design of a Hollow Fiber Supported Liquid Membrane System for Zn Speciation in Natural Waters.

A supported liquid membrane-hollow fiber system (HFSLM) has been developed to determine zinc speciation in aquatic environments. The liquid membrane consisted of an organic solution of bis-(2-ethylhexyl)phosphoric acid (D2EHPA) impregnated in the microporous of a polypropylene hollow fiber. The membrane contacted both the donor solution, that contained the metal and the stripping solution, placed in the lumen of the hollow fiber, where the metal was preconcentrated. Different parameters affecting the Zn2+ transport efficiency have been evaluated such as the composition of both the donor and stripping solutions as well as the membrane phase. Extraction and transport efficiencies of free Zn(II) higher than 90% were obtained with a liquid membrane consisting of a 0.1 M D2EHPA solution in dodecane and a 0.1 M HNO3 solution as the stripping phase. The developed HFSLM was used to study the effect of different ligands (EDTA and citric acid) in the donor phase of Zn(II) transport and to investigate the selectivity of the membrane towards Zn when other metals were also present. Finally, the HFSLM system was successfully applied to estimate the free Zn(II) concentrations in three water samples from a mining area. Moreover, the HFSLM system facilitates the analytical determination of trace Zn(II) levels allowing the achievement of enrichment factors of around 700 in the stripping phase.

Extraction of glycyrrhizin from licorice (Glycyrrhiza Glabra L.) by bulk liquid membrane

Abstract In this work, the extraction of glycyrrhizin from Licorice using bulk liquid membrane technique was developed and optimized. The effect of various parameters such as pH of stripping and donor solutions, temperature, stirring speed and kinetic parameters were investigated. Moreover, to study the impact of the polarity of membrane solvent, two types of extraction solvents were used as a membrane solvent: n-Hexane was used as a non-polar solvent and 1-Hexanol was as a polar solvent. The optimum extraction condition was found (95.53%) using 1-Hexanol, rotating speed was 400 rpm, and pH of the acceptor and donor solutions were 8 and 5.5, respectively. The reaction kinetics constants ( K 1 and K 2 ) for the transport of glycyrrhizin from the donor phase to BLM phase then to acceptor phase were evaluated. In addition, the accumulation of glycyrrhizin in bulk liquid membrane phase and rate controlling step under different experimental conditions were also discussed. The results showed that the proposed liquid membrane was effectively applied for glycyrrhizin extraction from the aqueous phase.

In vitro meningeal permeation of MnFe2O4 nanoparticles

MnFe2O4 nanoparticles (NPs) are commonly produced in some occupational settings and may reach high concentration in activities such as arc-welding or ferroalloy metallurgy. Manganese is an essential cofactor in enzyme activities but it has been demonstrated that long-term exposure to excessive levels can lead to “manganism”, a neurodegenerative disease resembling Parkinson features.Inhaled NPs deposit partially in pharynx and nasopharynx and may reach the central nervous system through the olfactory nerve, which is completely enveloped by the meningeal membranes throughout its course from the nasal cavity to the olfactory bulb or through the trigeminal nerves. This study investigated in vitro the transmeningeal absorption of 50 nm MnFe2O4NPs, using excised porcine meninges mounted on Franz diffusion cells. We tested two donor solutions: the first containing MnFe2O4NPs (2.0 g/L) and the second obtained by the ultrafiltration of the first one, in order to test only the NPs water soluble fraction. Each experiment was carried separately for 4 h. Results showed that no Mn flux permeation through the meninges occurred, since only trace of the metal was found in receivers solutions of cells exposed to MnFeNPs (5.5 ± 2.2 ng/cm2), ultrafiltered solution (3.5 ± 1.5 ng/cm2) and blank cells. (2.1 ± 0.6 ng/cm2) (mean and SE). Differences did not reach the statistical significance.Our study shows – for the first time - that MnFe2O4NPs penetrate the meningeal membrane in a negligible amount, thus making unlikely the hypothesis of a transcellular and paracellular absorption through the olfactory nerve but not excluding the hypothesis of an active intraneuronal absorption.

Comparison of different speciation techniques to measure Zn availability in hydroponic media

Four analytical techniques are compared: AGNES (Absence of Gradients and Nernstian Equilibrium Stripping), LASV (Anodic Stripping Voltammetry with Linear stripping), DGT (Diffusive Gradients in Thin films) and PIM (Polymer Inclusion Membranes). These techniques have been designed to provide the free ion concentration or a labile fraction, complementarily contributing to an integrated description of speciation and availability. Their simultaneous application to the determination of free Zn concentrations or labile fluxes in seven solutions of a hydroponic medium reveals characteristics of each technique and correlations between their results. All dynamic results can be interpreted in terms of a general theoretical framework on fluxes. Indeed, in techniques under diffusion-limited conditions in the sample, the flux can be split into the free contribution (linearly proportional to the free fraction), plus the contribution of the complexes (where mobility, lability and abundance of complexation are intertwined). A methodology to compute lability degrees is developed. Measurements with PIM devices confirm that diffusion in the sample solution is not rate limiting, so its flux is proportional to the free metal in the donor solution. A proportionality between the responses of any given two techniques is observed, which suggests that, for the low ligand-to-metal concentration ratios used in the present work, any of these techniques would correlate similarly with uptake, toxic or nutritional measurements.

New supported liquid membrane for electromembrane extraction of polar basic endogenous metabolites

Extraction of polar endogenous compounds remains an important issue in bioanalysis although different techniques have been evaluated. Among them, electromembrane extraction (EME) is a relevant approach but supported liquid membranes (SLMs) dedicated to polar molecules are still lacking. In this study 22 organic solvents were evaluated as SLMs on a set of 45 polar basic metabolites (log P from −5.7 to 1.5) from various biochemical families. To investigate a large variety of organic solvents, a parallel electromembrane extraction device was used and a constant current approach was applied to circumvent the heterogeneous conductivities of the different SLMs. Among the tested organic solvents, 2-nitrophenyl pentyl ether (NPPE) appeared the most efficient SLM with the extraction of a large variety of polar cationic metabolites, high extraction yields, and low extraction variabilities. The applied current and the composition of the acceptor and donor solutions were also evaluated and 300 μA per well and acetic acid 1% (v/v), both as acceptor and donor compartments, were the most efficient conditions. The new SLM and the optimized experimental parameters were successfully applied to the extraction of precipitated plasma samples. Although the extraction recovery decreased for most compounds in the biological matrix, process efficiency (PE) up to 90% and low extraction variability (RSD between 2 and 18%) were obtained for several very polar compounds such as choline or acetylcholine, emphasizing the potential of EME for polar compounds.