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Background: Electromembrane extraction (EME) of peptides reported in the scientific literature involve transfer of net positively charged peptides from an aqueous sample, through a liquid membrane, and into an aqueous acceptor solution, under the influence of an electrical field. The liquid membrane comprises an organic solvent, containing an ionic carrier. The purpose of the ionic carrier is to facilitate peptide solvation in the organic solvent based on ionic interactions. Unfortunately, ionic carriers increase the conductivity of the liquid membrane; the current in the system increases, the electrolysis in sample and acceptor is accelerated, and the extraction system tend to be unstable and suffers from drifting pH. Results: In the present work, a broad selection of organic solvents were tested as pure liquid membrane for EME of peptides, without ionic carrier. Several phosphates provided high mass transfer, and tri(pentyl) phosphate was selected since this solvent also provided high operational stability. Among 16 different peptides used as model analytes, tri(pentyl) phosphate extracted those with net charge +1 and with no more than two polar side chains. Tri(pentyl) phosphate served as a very strong hydrogen bond acceptor, while the protonated peptides were hydrogen bond donors. By such, hydrogen bonding served as the primary interactions responsible for mass transfer. Tri(pentyl) phosphate as liquid membrane, could exhaustively extract leu-enkephalin, met-enkephalin, and endomorphin from human blood plasma and detected by LC-MS/MS. Calibration curves were linear (r2 > 0.99) within a concentration range from 1 to 500 ng/mL, and a relative standard deviation within 12% was observed for precision studies. Significance: The current experiments are important because they indicate that small peptides of low polarity may be extracted selectively in EME based on hydrogen bond interactions, in systems not suffering from electrolysis.

Development of green approaches have emerged as a challenge that highlight the pressing need for nontoxic solvents, miniaturized method and bio-degradable materials. In this regard, an environmentally-friendly microfluidic system based on natural deep eutectic solvents (DESs) immobilized in agarose membranes was developed to extract parabens from urine samples for the first time. A comprehensive study of the support liquid membrane showed that only 3 µL of camphor and thymol (2:1 molar ratio) was an interesting option as a substitute for conventional (toxic) solvents used to date. Other experimental conditions were optimized and pH 4 (HCl) and 12 (NaOH) were selected as sample and acceptor solution, respectively. Both solutions (sample and acceptor) were fixed at 1 µL min⁻¹ as flow rate. The proposed green microfluidic device was successfully applied for the determination of parabens in urine samples with relative recoveries between 86 and 100% for all analytes. Detection limits and quantitation limits were between 0.011–0.093 and 0.31–0.38 µg mL⁻¹, respectively. Relative standard deviation was below 7% for all analytes. Furthermore, the environmentally-friendly solvent (Ca:Ty 2:1) used as SLM offered the same advantages in terms of membrane stability allowing consecutive extractions. Results were compared with experiments previously conducted using conventional (polypropylene) membranes, observing that highly green microextraction systems based on natural and biodegradable materials have proven to be an attractive alternative in microfluidic systems.

Frequent consumption of pharmaceuticals and personal care products (PPCPs) have emerged as a current problem that highlights the pressing need for new multi-residue analytical methods that allow their simultaneous determination to assess their overall effect on human health. In this regard and for the first time, a versatile microfluidic based- liquid phase microextraction (LPME) method was developed for simultaneous monitoring of ten compounds from six different classes: amoxicillin, sulfadiazine, sulfamerazine, tiamphenicol, ethyl 4-hydroxybenzoate, flumequine, propyl 4-hydroxybenzoate, 5-hydroxydiclofenac, 3-hydroxydiclofenac and diclofenac. The microfluidic device was combined with a HPLC-UV system for the separation and determination of the model analytes in the sample. Optimal conditions were reached using 2-nitrophenyl octyl ether as supported liquid membrane, pH 3.5 as donor phase, pH 11.5 as acceptor phase, 0.5 µL min−1 as donor flow rate and 1 µL min−1 as acceptor flow rate. Under optimal method conditions, the extraction efficiency was between 85 and 100% for most compounds after 10 min extraction, and it was successfully applied in non-diluted human urine, with recoveries between 70 and 100% for all analytes except for sulfamerazine (52% recovery). In addition, the extraction of metabolites (3-hydroxydiclofenac and 5-hydroxydiclofenac) was also demonstrated in microfluidic systems with recoveries between 71 and 100% in human urine. The proposed method allowed consecutive extraction and only requires 5 µL of organic solvent and less than 15 µL of sample volume.

Liquid phase microextraction (LPME) into a microfluidic has undergone great advances focused on downscaled and miniaturized devices. In this work, a microfluidic device was developed for the extraction of sulfonamides in order to accelerate the mass transfer and passive diffusion of the analytes from the donor phase to the acceptor phase. The subsequent analysis was carried out by high performance liquid chromatography with UV-DAD (HPLC-DAD). Several parameters affecting the extraction efficiency of the method such as the supported liquid membrane, composition of donor and acceptor phase and flow rate were investigated and optimized. Tributyl phosphate was found to be a good supported liquid membrane which confers not only great affinity for analytes but also long-term stability, allowing more than 20 consecutive extractions without carry over effect. Under optimum conditions, extraction efficiencies were over 96 % for all sulfonamides after 10 minutes extraction and only 10 µL of sample was required. Relative standard deviation was between 3-5 % for all compounds. Method detection limits were 45, 57, 54 and 33 ng mL−1 for sulfadiazine (SDI), sulfamerazine (SMR), sulfamethazine (SMT) and sulfamethoxazole (SMX), respectively. Quantitation limits were 0.15, 0.19, 0.18 and 0.11 µg mL−1 for SDI, SMR, SMT SMX, respectively. The proposed microfluidic device was successfully applied for the determination of sulfonamides in urine samples with extraction efficiencies within the range of 86-106 %. The proposed method improves the procedures proposed to date for the determination of sulfonamides in terms of efficiency, reduction of the sample volume and extraction time.