Key factors in electromembrane microextraction systems for metals analysis in natural waters

This is an original manuscript of an article published by Taylor & Francis in International Journal of Environmental Analytical Chemistry o 2018, available at: https://doi.org/10.1080/03067319.2018.1533006].Application of an electric potential to hollow fibre liquid phase microextraction (HF-LPME) systems previously optimised for metals preconcentration from natural waters could improve their analytical performance increasing enrichment factors and reducing operation times. Nevertheless, the effectiveness of the direct application of an electric potential to these systems may be limited due to the effects produced by other operational parameters. In this work, the effect of a variable electric potential on the enrichment factors of four HF-LPME systems used for the analysis of trace metals in natural waters (Cd, Ni, Ag and Cu) has been studied. In addition, the effect of organic phase composition, distance between electrodes and electrodes diameter has been also studied. From the results obtained, composition of organic phase can be considered as the key factor in electromembrane (EME) systems, since its polarity determine the operational range of the applied electric potential and consequently the enrichment factor that could be achieved. EMEs have demonstrated to be a real alternative to preconcentrate Cd, Ag and Cu from natural water samples in very short times (30 min). In fact, enrichment factors increased up to one order of magnitude if compared with HF-LPME methodology without application of an electrical potential

Chitosan biofilms: Insights for the selective electromembrane extraction of fluoroquinolones from biological samples

A selective electromembrane extraction procedure for the extraction of Enrofloxacin, Marbofloxacin and Flumequine, usually employed as antibiotic in veterinarian use, is proposed by using a chitosan biofilm, composed by 60% (w/w) chitosan and 40% (w/w) Aliquat®336, as active biopolymeric support. The interaction mechanism occurring between the target drugs and the biopolymer has been deeply studied using the Quantum Theory of Atoms in Molecules. The obtained results show the interaction between the extracted fluoroquinolones and the biomembrane is stabilized by two hydrogen bonds formed between both the carboxyl and keto groups of the drugs with both the amine and hydroxyl groups of glucosamine in the biopolymer. The energetic results agree with the high extraction efficiency obtained for Marbofloxacin, Enrofloxacin and Flumequine in terms of enrichment factors (83, 82 and 58, respectively) in presence of other fluoroquinolones. Under optimum conditions, the proposed electromembrane extraction method exhibits wide linear ranges of 4.2e200 mg L1 , 5.6e200 mg L1 and 5.1e200 mg L1 , respectively; low limits of detection close to 1.3 mg L1 and appropriate repeatability (relative standard deviation values 4e7%).Fondos Europeos FEDER, Ministerio de Ciencia e Innovación y Agencia Estatal de Investigación, de España - PGC2018-096608- B-C22Ministerio de Ciencia, Innovación y Universidades de España - RED2018-102522-TJunta de Andalucía - 2019/FQM-106Premio Mensual Publicación Científica Destacada de la US. Facultad de Químic

Effect of Aliquat®336 on supported liquid membrane on electromembrane extraction of non-steroidal anti-inflammatory drugs

Up to now, most electromembrane extraction methods describe the use of pure organic solvents or mixtures as supported liquid membrane. However, the need to incorporate carriers in the supported liquid membrane to achieve the extraction of high polar compounds, seems to indicate that the presence of certain additives in the organic solvent may improve the extraction yield. For this reason, some studies have tried to enhance electrokinetic migration in different ways, modifying either the supported liquid membrane or even the donor solution. In this work, it has been studied and optimized an electromembrane extraction of five widely used non-steroidal anti-inflammatory drugs: salicylic acid, ketoprofen, naproxen, diclofenac and ibuprofen. The thickness and porosity of the support, the supported liquid membrane composition, the donor and acceptor phase pH, the voltage, the extraction time and the electrode configuration were optimized. supported liquid membrane was modified by adding different amounts of Aliquat®336, a cationic carrier commonly used in electromembrane extraction procedure for anionic compounds. The results compared with those obtained in the same extraction conditions using the pure organic solvent as supported liquid membrane, showed better extraction recoveries. The highest recoveries were achieved using a pH 5 donor phase and an acceptor phase at pH 12. The recoveries were within the range of 39 and 53% after 12 min extraction, using a voltage of 80 V, a stirring speed of 400 rpm and 1-nonanol modified with Aliquat®336 2.5% (w/v) as support liquid membrane. Detection and quantitation limits were within 0.02–1.0 ng mL−1 and 0.05–3.0 ng mL−1, respectively. The selected analytes were extracted by electromembrane extraction using a home-made device designed with a flat configuration. The analyses were carried out by high performance liquid chromatography with diode array and fluorescence detection and finally, applied to the analysis of human urine samples.Ministerio de Educación y Ciencia (MEC). España CTM2015-67902-C-1-

Chitosan tailor-made membranes as biopolymeric support for electromembrane extraction

El período de embargo ha expirado ya al ser del año 2019A chitosan membrane composed by 60% (w/w) chitosan and 40% (w/w) Aliquat®336 has been proposed as a new biopolymeric support for electromembrane extraction. The new support has been characterized by Scanning Electron Microscopy, resulting a 30–35 µm thickness. Amoxicillin, nicotinic acid, hippuric acid, salicylic acid, anthranilic acid, ketoprofen, naproxen and ibuprofen have been successfully extracted using the proposed support. Better enrichment factors were obtained for the acidic polar analytes than for the non-steroidal anti-inflammatory compounds (ranging from 118 for hippuric acid and 20 for ibuprofen). Electromembrane extraction was developed applying a DC voltage of 100 V, 1-octanol as supported liquid membrane and 20 min of extraction. The target analytes have also been satisfactorily extracted from human urine samples, providing high extraction efficiencies. The chitosan membrane is presented as a promising alternative for supporting liquid membrane compared to commonly used materials for this purpose.Ministerio de Educación y Ciencia (MEC). España CTM2015–67902-C-1-

Use of Polymer Inclusion Membranes (PIMs) as Support for Electromembrane Extraction of Non-steroidal Anti-inflammatory Drugs and Highly Polar Acidic Drugs

The use of polymer inclusion membranes (PIMs) as support of 1-octanol liquid membrane in electromembrane extraction (EME) procedure is proposed. Synthesis of PIMs were optimized to a composition of 29% (w/w) of cellulose triacetate as base polymer and 71% (w/w) of Aliquat®336 as cationic carrier. Flat PIMs of 25 µm thickness and 6 mm diameter were used. EME protocol was implemented for the simultaneous extraction of four non-steroidal anti-inflammatory drugs (NSAIDs) (salicylic acid, ketoprofen, naproxen and ibuprofen) and four highly polar acidic drugs (anthranilic acid, nicotinic acid, amoxicillin and hippuric acid). Posterior HPLC separation of the extracted analytes was developed with diode array detection. Recoveries in the 81–34% range were obtained. EME procedure was applied to human urine samples.Ministerio de Educación y Ciencia TM2015-67902-C-1-PPremio Mensual Publicación Científica Destacada de la US. Facultad de Químic

Green electromembrane extraction procedure based on biodegradable chitosan films for determination of polyphenolic compounds in food samples: greenness assessment of the sample preparation approach

A simple, rapid and environmentally friendly method for the electromembrane extraction of polyphenolic compounds has been developed using chitosan films (60% (w/w) chitosan, 40% (w/w)-Aliquat®336, 10–11 μm thickness) as biopolymeric membrane. In this work for the first time with this type of chitosan-based support, the use of organic solvents has been completely eliminated, which allows considering the proposed methodology as a green solvent-free procedure, as demonstrated by performing analytical greenness metric for sample preparation (AGREEprep). Under optimal experimental conditions (10 mL donor phase, pH 7; 50 μL acceptor phase, pH 9; 100 V applied voltage for 15 min) high enrichment factors (EF ≥ 60) were obtained for all the target analytes. Wide concentration ranges between 52.8 μg L− 1 and 1000 μg L− 1 , good linearity (R2 ≥ 0.996), low limit of detection (15.9–37.1 μg L− 1 ), and repeatability (relative standard deviation (RSD) values 4–10%) were achieved. Polyphenolic compounds have been successfully extracted from coffee- and tea-based dietary food supplements in different formats (pills and ampoules). For comparison purposes, target analytes have additionally been determined in green coffee beans and tea.Ministerio de Ciencia e Innovación de España (MCIN) - PGC 2018- 096608-B-C2

A comprehensive study of a new versatile microchip device based liquid phase microextraction for stopped-flow and double-flow conditions

A new geometry for a versatile microfluidic-chip device based liquid phase microextraction was developed in order to enhance the preconcentration in microfluidic chips and also to enable double-flow and stopped-flow working modes. The microchip device was combined with a HPLC procedure for the simultaneous determination of two different families as model analytes, which were parabens and non-steroidal anti-inflammatories (NSAIDs): Ethyl 4-hydroxybenzoate (Et-P), Propyl 4-hydroxybenzoate (Pr-P), Butyl 4-hydroxybenzoate (Bu-P), IsoButyl 4-hydroxybenzoate (iBu-P), salycilic acid (SAC), ketoprofen (KET), naproxen (NAX), diclofenac (DIC) and ibuprofen (IBU) in urine samples. The new miniaturized microchip proposed in this work allows not only the possibility of working in double-flow conditions, but also under stagnant conditions (stopped-flow) (SF-μLPME). The sample (pH 1.5) was delivered to the SF-μLPME at 20 μL min−1 while keeping the acceptor phase (pH 11.75) under stagnant conditions during 20 min. The highest enrichment factors (between 16 and 47) were obtained under stopped-flow conditions at 20 μL min−1 (sample flow rate) after 20 min extraction; whereas the extraction efficiencies were within the range of 27–81% for all compounds. The procedure provided very low detection limits between 0.7 and 8.5 μg L−1 with a sample volume consumption of 400 μL. Parabens and NSAIDs have successfully been extracted from urine samples with excellent clean up and recoveries over 90% for all compounds. In parallel, the new device was also tested under double flow conditions, obtaining good but lower enrichment factors (between 9 and 20) and higher extraction efficiencies (between 45 and 95) after 7 min extraction, consuming a volume sample of 140 μL. The versatile device offered very high extraction efficiencies and good enrichment factor for double flow and stopped-flow conditions, respectively. In addition, this new miniaturized SF-μLPME device significantly reduced costs compared to the existing analytical techniques for sample preparation since this microchip require few microliters of sample and reagents and it is reusabl

A rapid and versatile microfluidic method for the simultaneous extraction of polar and non-polar basic pharmaceuticals from human urine

In sample preparation, simultaneous extraction of analytes of very different polarity from biological matrixes represents a challenge. In this work, verapamil hydrochloride (VRP), amitriptyline (AMP), tyramine (TYR), atenolol (ATN), metopropol (MTP) and nortriptyline (NRP) were used as basic model analytes and simultaneously extracted from urine samples by liquid-phase microextraction (LPME) in a microfluidic device. The model analytes (target compounds) were pharmaceuticals with 0.4 < log P < 5. Different organic solvents and mixtures of them were investigated as supported liquid membrane (SLM), and a mixture of 2:1 (v/v) tributyl phosphate (TBP) and dihexyl ether (DHE) was found to be highly efficient for the simultaneous extraction of the non-polar and polar model analytes. TBP reduced the intrinsic hydrophobicity of the SLM and facilitated extraction of polar analytes, while DHE served to minimize trapping of non-polar analytes. Sample and acceptor phase composition were adjusted to pH 12 and pH 1.5, respectively. Urine samples were pumped into the microfluidic system at 1 μL min-1 and the extraction was completed in 7 min. Recoveries exceeded 78% for the target analytes, and the relative standard deviation (n = 4) was below 7% in all cases. Using five microliters of SLM, the microfluidic extraction system showed good long-term stability, and the same SLM was used for more than 18 consecutive extractions.Agencia de Gestió d'Ajusts Universitaris i the Recerca 2017-SGR-329Ministerio de Ciencia e Innovación PGC2018-096608-B-C2

Electromembrane extraction of immunosuppressants

Tofacitinib (TFB) and cyclosporine A (CsA) are two immunosuppressants that can cause toxic adverse effects or treatment failure if not dosed properly. Both these drugs have the potential to be affected by individual variability in pharmacokinetics, and interactions with other drugs and nutrients. Therapeutic drug monitoring (TDM), based on serum concentration measurements, could benefit patients in need of these drugs, to ensure safe treatment. Effective sample preparation techniques are essential to precisely determine the concentration of a drug within pharmaceutical bioanalysis. This is to avoid interference from matrix components and prevent contamination or damage of the analytical instrument. Electromembrane extraction (EME) is a sample preparation technique that was developed in 2006. Over the years, this technique has proven to be efficient for both acidic, basic, polar and non-polar analytes. The concept of the extraction is electrokinetic migration of the analyte by an external power supply over a three-phase system consisting of two aqueous solutions (donor and acceptor), separated by a supported liquid membrane (SLM) comprised of an organic solvent. EME has several advantages, including high sample clean-up and selectivity, enrichment with the possibility of pre-concentration, and low consumption of organic solvents. In this study, EME was for the first time investigated as a sample preparation technique for the immunosuppressants CsA and TFB. The EME method development for CsA was obstructed by the lower limit of detection with HPLC-UV, at 2 µg/mL, and the solubility of the analyte. CsA was attempted to be extracted as an anion with highly alkaline conditions using a 10 mM NaOH solution with pH 10 in both donor and acceptor, and 1-octanol as SLM. CsA was not detected in the acceptor solution, and the highest mean recovery of analyte from the donor solution and SLM was 24% at 20 V. For the method development of TFB, a range of different conditions, i.e. pH, SLMs, voltage and extraction time, were tested and optimized in order to yield high recoveries of the analyte. The aqueous samples without plasma were analyzed by HPLC-UV at 40˚C with an isocratic mobile phase of 10 mM ammonium acetate pH 5 and acetonitrile (60:40). An absolute recovery (100%) of TFB was obtained after 45 minutes of extraction as a cation from diluted plasma with pH 2.1 at 30 V, using an acceptor solution of 100 mM formic acid with pH 2.4 and a SLM comprised of 6-methylcoumarin and thymol mixed in a weight to weight ratio (1:2). A similar method yielded 79% recovery after 15 minutes extraction from a donor solution of 100 mM formic acid with pH 2.4. In conclusion, EME extraction appears as a promising sample preparation technique for TFB, but further optimization is needed to conclude if it is viable also for CsA.Masteroppgave i FarmasiFARM399/05HMATF-FAR