Bioavailability of flumequine and diclofenac in mice exposed to a metal-drug chemical cocktail. Evaluation of the protective role of selenium.

BACKGROUND AND PURPOSE: Organisms, including humans, are subjected to the simultaneous action of a wide variety of pollutants, the effects of which should not be considered in isolation, as many synergies and antagonisms have been found between many of them. Therefore, this work proposes an in vivo study to evaluate the effect of certain metal contaminants on the bioavailability and metabolism of pharmacologically active compounds. Because the most frequent entry vector is through ingestion, the influence of the gut microbiota and the possible protective effects of selenium has been additionally evaluated. EXPERIMENTAL APPROACH: A controlled exposure experiment in mammals (Mus musculus) to a "chemical cocktail" consisting of metals and pharmaceuticals (diclofenac and flumequine). The presence of selenium has also been evaluated as an antagonist. Mouse plasma samples were measured by UPLC-QTOF. A targeted search of 48 metabolites was also performed. KEY RESULTS: Metals significantly affected the FMQ plasma levels when the gut microbiota was depleted. Hydroxy FMQ decreased if metals were present. Selenium minimized this decrease. The 3-hydroxy DCF metabolite was not found in any case. Changes in some metabolic pathways are discussed. CONCLUSIONS AND IMPLICATIONS: The presence of metals in the mouse diet as well as the prior treatment of mice with an antibiotic mixture (Abxs), which deplete the gut microbiota, has a decisive effect on the bioavailability and metabolism of the tested pharmaceuticals and dietary selenium minimize some of their effects.

Green strategies using solvent-free biodegradable membranes in microfluidic devices. Liquid phase microextraction and electromembrane extraction.

In this work, a novel solvent-free microfluidic method based liquid phase microextraction has been proposed for the first time. A comprehensive study of liquid phase microextraction (LPME) and electromembrane extraction (EME) implemented in microfluidic formats has been carried out to investigate the efficiency of biodegradable membranes (such as agarose) without organic solvent to develop fully environmental microfluidic methods. For this study, non-polar and polar basic compounds (five) were selected as model analytes and different agarose membrane compositions were synthesized and tested with and without organic solvent (solvent-free). Under optimal experimental conditions, the extraction efficiencies obtained using solvent-free LPME-chip devices were similar to the ones obtained using solvent-free EME-chip devices at very low voltages (0.25 V), however, LPME microfluidic format was selected due to its simplicity. The proposed green microfluidic device was successfully applied in urine samples with recoveries between 80 and 93% for all analytes and relative standard deviation below 7% for all analytes. Results were compared with experiments previously conducted using conventional (polypropylene) membranes, observing that solvent-free microfluidic systems based on biodegradable solid support materials have proven to be an attractive alternative and offered the same advantages in terms of membrane stability allowing consecutive extractions compared to supported liquid membranes (SLM) microfluidic methods.

Electromembrane extraction of peptides based on hydrogen bond interactions.

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.

An improved microfluidic device to enhance the enrichment factors in liquid phase microextraction: application to the simultaneous extraction of polar and non-polar acids in biological samples.

A new microfluidic device to enhance the enrichment factor in miniaturized systems is proposed. The microfluidic system was design for liquid phase microextractions, and it was applied to the simultaneous extraction of acidic compounds of a wide range of polarity (0.5 < log P < 3). The device operated under stagnant acceptor phase conditions and all the operational parameters involved were optimized. Tributyl phosphate was found to be a new highly efficient supported liquid membrane to simultaneously extract analytes of very different polarities. The optimal donor and acceptor phase were pH 2 and pH 13, respectively. The donor flow rate and the extraction time were investigated simultaneously, offering great versatility with high enrichment factors (EFs). Limits of quantitation were within 0.02 and 0.09 µg mL-1 for all compounds at 10 µL min-1 as donor flow rate and 20-min extractions, offering EFs between 11 and 18 with only 200-µL sample volume consumption. The method was successfully applied to human urine samples, observing recoveries between 47 and 90% for all compounds. This new proposed microfluidic system increases the wide range of applications, especially when the analytes are present in lower concentrations in the sample.

Solid supports and supported liquid membranes for different liquid phase microextraction and electromembrane extraction configurations. A review.

Liquid phase microextraction (LPME) and electromembrane microextraction (EME) can be considered as two of the most popular techniques in sample treatment today. Both techniques can be configurated as membrane-assisted techniques to carry out the extraction. These supports provide the required geometry and stability on the contact surface between two phases (donor and acceptor) and improve the reproducibility of sample treatment techniques. These solid support pore space, once is filled with organic solvents, act as a selective barrier acting as a supported liquid membrane (SLM). The SLM nature is a fundamental parameter, and its selection is critical to carry out successful extractions. There are numerous SLMs that have been successfully employed in a wide variety of application fields. The latter is due to the specificity of the selected organic solvents, which allows the extraction of compounds of a very different nature. In the last decade, solid supports and SLM have evolved towards "green" and environmentally friendly materials and solvents. In this review, solid supports implemented in LPME and EME will be discussed and summarized, as well as their applications. Moreover, the advances and modifications of the solid supports and the SLMs to improve the extraction efficiencies, recoveries and enrichment factors are discussed. Hollow fiber and flat membranes, including microfluidic systems, will be considered depending on the technique, configuration, or device used.

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.

A green microfluidic method based liquid phase microextraction for the determination of parabens in human urine samples.

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.

Optofluidic systems enabling detection in real samples: A review.

Optofluidics, understood as the synergistic combination between microfluidics and photonics, has been at the forefront of the scientific research due to its outmatching properties: on the one hand, microfluidics allows the handling of minute amounts of liquid samples at the microscale. On the other hand, photonics has proved to outmatch other detection methods (e.g. electrochemistry) in terms of sensitivity and selectivity. From the initial single analyte or spiked samples, currently the technology is mature enough for selective detection of a variety of analytes in raw, complex liquid samples. This will pave the way for the applicability of optofluidic devices for applications in the field or at the point of care. Here, we will revisit the current state of the art of optofluidic and photonic lab-on-a-chip systems for the analysis of real and biologically relevant samples: body fluids and water.

Microfluidic liquid-phase microextraction based on natural deep eutectic solvents immobilized in agarose membranes.

In liquid-phase microextraction (LPME), the sample and the acceptor are separated by a synthetic organic solvent, which is immobilized in a porous polymeric membrane of polypropylene or polyvinylidene fluoride. The organic solvent serves as extraction phase, while the polymeric membrane serves as support membrane. The combination of extraction phase and support membrane is termed supported liquid membrane (SLM). In this paper, we developed for the first time fully green and biodegradable supported SLMs, based on natural deep eutectic solvents as extraction phase and agarose as support membrane. This highly green approach was developed and studied with sulfonamide pharmaceuticals as model analytes, and performance was compared with LPME using conventional SLMs. All experiments were conducted in a microfluidic device. Model analytes were extracted from acidic sample (pH1.0) and into alkaline acceptor (pH12.0). Both sample and acceptor were pumped at 1 µL min-1 into the microfluidic device, and the optimal SLM was based on 3 µL of coumarin and thymol (1:2 molar ratio) as the extraction phase. The proposed green microfluidic device was successfully applied for the determination of sulfonamides in urine samples with spiking recoveries in the range of 77-100%. LPME with deep eutectic solvent immobilized in agarose showed similar performance as with conventional SLMs. Thus, the data presented in this paper demonstrate that highly green microextraction systems may be developed in the future, based on natural solvents and biodegradable materials.

A microchip device based liquid-liquid-solid microextraction for the determination of permethrin and cypermethrin in water samples.

In this work, for the first time, a microchip device integrating liquid-liquid-solid phase microextraction is presented. As a novel approach to microchip systems, liquid-liquid-solid microextraction was performed in a sandwiched microchip device. The microchip device consisted of three poly(methyl methacrylate) layers along with a double "Y"-shaped microchannel. As the stationary phase, polyacrylonitrile-C18 was synthesized and immobilized in the upper channel, while the beneath channel was used as a reservoir for the stagnant volume ratio of sample-to-extraction solvent phase. In this way, analytes were extracted from an aqueous sample through an organic phase into the stationary phase. The analytes were finally desorbed with a minimum amount of acetonitrile as the desorption solvent. Permethrin and cypermethrin were selected as the model analytes for extraction and subsequent analysis by gas chromatography-flame ionization detection. Under optimum conditions (extraction solvent; n-hexane, sample -to-extraction solvent volume ratio; 2:1, extraction time; 20 min, desorption solvent; acetonitrile, desorption volume; 200 µL, and desorption time; 15 min) detection limits were 3.5 and 6.0 ng mL-1 for permethrin and cypermethrin, respectively. Relative standard deviations for intra- and inter-day reproducibility were below 8.3%. Device-to-device precision was in the range of 8.1-9.6%. The proposed microchip device was successfully applied to determine permethrin and cypermethrin in water samples with recoveries in the range of 73-96%.

Monitoring of pharmaceuticals in aquatic biota (Procambarus clarkii) of the Doñana National Park (Spain).

In this work the presence of different pharmaceuticals at Doñana National Park (Spain) and their main entry sources (input source or entry points) have been stated over the 2011-2016 years period. Twenty-three selected pharmaceuticals (corresponding to eight therapeutic families) were evaluated in crayfish and water samples from Doñana National Park (Spain) (six sampling points selected in order to cover different possible pollution sources into and surrounding the Park). The multiresidue determination was carried out using enzymatic-microwave assisted extraction prior to high performance liquid chromatography mass spectrometry detection. Sulphonamides (sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxazole); trimethoprim, an antibiotic that is frequently co-administered with sulfamethoxazole; amphenicols (chloramphenicol, florfenicol and thiamphenicol); fluoroquinolones (ciprofloxacin, enrofloxacin, flumequine, danofloxacin, gatifloxacin, norfloxacin, marbofloxacin and grepafloxacin); penicillins (amoxicillin); tetracyclines (chlortetracycline and oxytetracycline); non-steroidal anti-inflammatory drugs (salicylic acid and ibuprofen); beta-blocker drugs (atenolol); and antiepileptics (carbamazepine) were analysed. Ciprofloxacin, ibuprofen, salicylic acid, flumequine, and carbamazepine were detected and/or quantified at some of the selected sampling points. A clear ecotoxicological risk to the ecosystem was demonstrated from the occurrence of ciprofloxacin in samples obtained after the punctual and massive presence of people inside the Park. Furthermore, flumequine and carbamazepine have been detected in Procambarus clarkii specimens in concentrations around 30 ng g-1 and 14 ng g-1, respectively, and their occurrence in the specimens could indicate the persistence of the discharge sources. The main source of pharmaceuticals into the Park might be the livestock farming activities, and the influence of urban wastewaters from surrounding villages does not seem to be very important.

Green microfluidic liquid-phase microextraction of polar and non-polar acids from urine.

In this work, hippuric acid (log P = 0.5), anthranilic acid (log P = 1.3), ketoprofen (log P = 3.6), and naproxen (log P = 3.0) were simultaneously extracted by a green microfluidic device based on the principles of liquid-phase microextraction (LPME). Different deep eutectic solvents (DESs) were investigated as supported liquid membrane (SLM), and a mixture of camphor and menthol as eutectic solvents in the molar ratio 1:1 was found to be highly efficient for the simultaneous extraction of non-polar and polar acidic drugs. LPME was conducted for 6 min per sample. Urine sample was delivered to the system at 1 µL min-1, and target analytes were extracted exhaustively (75-100% recovery) across the DES SLM, and into pure aqueous phosphate buffer pH 11.0 delivered as acceptor at 1 µL min-1. The acceptor was analyzed with liquid chromatography-UV detection. Interestingly, the DES enabled extraction of both the polar and non-polar model analytes at the same time; all chemicals were green and non-hazardous, and the chemical waste was less than 1 mg per sample.

An efficient microfluidic device based on electromembrane extraction for the simultaneous extraction of acidic and basic drugs.

The simultaneous extraction of acidic and basic compounds is considered a great challenge. In this work, an efficient and fast microfluidic device is described for the simultaneous determination of acidic and basic drugs by two electromembrane extraction, offering extraction efficiencies over 98% for all analytes in human urine samples and solving the difficulties encountered to date. The sample is submitted into the device and the collected acceptor phase is directly analyzed by diode array detector and high-pressure liquid chromatography (HPLC). The device consisted of three poly(methylmethacrylate) layers and four electrodes to perform EME in two steps in a single device. Two acidic analytes (ketoprofen and naproxen) and two basic analytes (amitriptyline and loperamide) were selected as model analytes. The device proposed works under stable electric field conditions, low current intensities that confers great stability to the supported liquid membrane. After a comprehensive study of the SLM, 1:1 2-nitrophenyl octhyl ether:dodecanol was selected as optimal. This device has also been successfully applied in 1:2 diluted bovine plasma samples with recoveries over 84% and a relative standard deviation below 6%. This microfluidic device needs small sample volumes (lower than 50 µL) and offers short extraction times (10 min) and excellent clean-up. Furthermore, it has proven to be a robust and reproducible device after more than 30 consecutive extractions, and thanks to the low potential required (5 V), it allows its compatibility with a single battery.

Electromembrane extraction using deep eutectic solvents as the liquid membrane.

In this work, we investigated for the first time hydrophobic deep eutectic solvents (DES) as supported liquid membrane (SLM) for electromembrane extraction (EME). Camphor, coumarin, DL-menthol, and thymol were used as non-ionic DES components. Different DESs compositions were tested, to study systematically the importance of hydrogen bonding and dispersion/aromatic interactions during mass transfer across the SLM. Unexpectedly, mixtures of coumarin and thymol were highly efficient SLMs, and provided exhaustive or near-exhaustive extraction of non-polar bases, non-polar acids, and polar bases. SLMs with such performance for both bases and acids, in a large polarity window, are not found in current literature. The SLMs were highly aromatic, very strong hydrogen bonding donors, and moderately strong hydrogen bonding acceptors. Aromatic (π type) interactions were apparently very important for transfer of bases, while hydrogen bonding were dominant for acids. EME of six polar basic drugs from plasma, with a coumarin and thymol mixture as SLM, and combined with UHPLC-MS/MS analysis, was evaluated to test the potential for analytical applications. Plasma was diluted 1:1 with phosphate buffer pH 2.0. Calibration curves were linear in the therapeutic ranges (0.970 < R2 < 0.999), recoveries ranged between 47 and 93%, and repeatability was within 1.6-10.7% RSD. The clean-up efficiency was excellent and no matrix effects from plasma were seen. Presence of trace levels of coumarin in the acceptor phase was however found to cause some ion enhancement. Based on the current work, we foresee more research on the use of DES in EME.

An overview on the recent applications of agarose as a green biopolymer in micro-extraction-based sample preparation techniques.

Introducing a myriad array of chemicals in different industrial fields has made sample preparation inevitable for trace analysis. Classical extraction techniques such as solid phase extraction (SPE) and liquid-liquid extraction (LLE) techniques often suffer from tedious procedures (huge workload) and hazards to personnel and environment (samples and reagents are often user-unfriendly and processed in high amounts). For addressing these problems, microextraction techniques have been introduced. These systems benefit from using a minute amount of sample, reduced consumption of organic solvents, enhanced clean-up, high recovery and high enrichment factors. Moreover, approaches based on the use of natural materials have emerged during the last 10 years. Agarose is a natural biopolymer used as a green material in the form of gel-based separation medium. It has been recently utilized in the microextraction schemes. Easy fabrication, adjustability to get various dimensions and shapes, high inertness and biodegradability are of its main attributes. The present overview is focused on applications of agarose in solid phase microextraction (SPME), micro-solid phase extraction (µ-SPE) and liquid phase microextraction (LPME) - agarose film-liquid phase microextraction (AF-LPME) and gel electromembrane extraction (G-EME) since 2012. Besides, the pros and cons of agarose employment in the mentioned techniques will be described in depth.

Comparison of three electromembrane-based extraction systems for NSAIDs analysis in human urine samples.

A comparative study on the extraction efficiency of five non-steroidal anti-inflammatories was carried out using three different electromembrane extraction (EME) devices with different geometries. The employed setups were (a) a hollow fiber configuration (HF-EME), (b) a microfluidic device that allows working in semi-dynamic mode (µF-EME), and (c) a static miniaturized flat membrane device (FM-EME). Each system was applied to the extraction of salicylic acid (SAC), ketoprofen (KTP), naproxen (NAX), diclofenac (DIC), and ibuprofen (IBU) and subsequent determination by high-performance liquid chromatography with UV and fluorescence detection (HPLC/UV-DAD-FLD). Voltage, pH composition, and extraction time were optimized for all devices. Additionally, volume ratio was investigated for HF-EME and FM-EME and flow rate for the microfluidic device. HF-EME provides the best result in terms of sensitivity with a limit of detection (LOD) between 0.1 and 1.5 ng mL-1 for SAC and KTP, respectively, while LODs for µF-EME were between 100 ng mL-1 and 400 ng mL-1 for SAC and DIC, respectively; however, a lower amount of sample was required. Finally, the obtained results, in terms of enrichment factors and extraction recoveries, were discussed to establish the advantages and disadvantages of each device. The proposed EME methods were successfully applied to the determination of the target analytes in fortified human urine samples. Graphical abstract.

Impedance model for voltage optimization of parabens extraction in an electromembrane millifluidic device.

In sample pre-treatment, millifluidic electromembrane platforms have been developed to extract and pre-concentrate target molecules with good clean-up that minimize matrix effects. Optimal operation conditions are normally determined experimentally, repeating the extractions at different conditions and determining the efficiencies by an analytical technique. To shorten and simplify the optimization protocol, millifluidic platforms have been electrically characterized by impedance spectroscopy. The magnitude of the resistance of the electromembrane has been found very predictive of the migration capacity and extraction efficiency of three different parabens on real time. The optimal conditions (4 V of applied potential) (Electromembrane extraction low voltage) have been successfully applied in the extraction of parabens from urine samples, that not only improves the extraction efficiency (100% for all compounds) but also provides a very low current intensity (7 µA), which is very important in electromembrane to minimize electrolysis phenomena. The possibility to optimize one of the most critical and important parameters such as the voltage with a simple electrical model may accelerate the production of application-specific millifluidic electromembrane platforms in a short development time. The results showed that millifluidic electromembrane extraction based low voltage has a future potential as a simple, selective, and time-efficient sample preparation technique allowing a simple battery as power supply.

A Method for the Determination of Veterinary Drugs from Different Therapeutic Classes in Animal Urine.

A rapid, precise and robust HPLC separation procedure has been developed and optimized for the determination of a series of drugs of different therapeutic classes: chlortetracycline, oxitetracycline, cefoperazone, diclofenac, tiamphenicol, marbofloxacin, ciprofloxacin, danofloxacin, enrofloxacin and flumequine. The chromatographic method used a monolithic C18 column and both diode array and fluorescence detection. This procedure was validated for the analysis of drugs in cow urine, using a simple and fast procedure with methanol/acetonitrile, allowing the simultaneous and efficient extraction of most of the studied drugs. The proposed method was successfully applied to the determination of enrofloxacin in cow urine, collected after the administration of this antibiotic.

Liquid - Phase microextraction and electromembrane extraction in millifluidic devices:A tutorial.

This tutorial discusses how to integrate different microextraction procedures into millifluidic platforms and the applicability of such systems for the determination of acidic and basic drugs. Sample preparation techniques have been downscaled into a millifluidic format and the replacement of conventional analytical systems by miniaturized alternatives has increased during recent years due to the small volume consumption of toxic solvents and sample required, shorter extraction times, simple-handling and low cost, among others. This review comprehensively summarizes the development of liquid-liquid extraction into a millifluidic device in a three-phase configuration, with focus on (a) historical development, (b) extraction mechanisms and performance, (c) operation modes and automatization, (d) operational parameters, (e) applications, and (f) future directions and perspectives.

On-chip electromembrane extraction of acidic drugs.

In the present work, a new supported liquid membrane (SLM) has been developed for on-chip electromembrane extraction of acidic drugs combined with HPLC or CE, providing significantly higher stability than those reported up to date. The target analytes are five widely used non-steroidal anti-inflammatory drugs (NSAIDs): ibuprofen (IBU), diclofenac (DIC), naproxen (NAX), ketoprofen (KTP) and salicylic acid (SAL). Two different microchip devices were used, both consisted basically of two poly(methyl methacrylate) (PMMA) plates with individual channels for acceptor and sample solutions, respectively, and a 25 µm thick porous polypropylene membrane impregnated with the organic solvent in between. The SLM consisting of a mixture of 1-undecanol and 2-nitrophenyl octyl ether (NPOE) in a ratio 1:3 was found to be the most suitable liquid membrane for the extraction of these acidic drugs under dynamic conditions. It showed a long-term stability of at least 8 hours, a low system current around 20 µA, and recoveries over 94% for the target analytes. NPOE was included in the SLM to significantly decrease the extraction current compared to pure 1-undecanol, while the extraction properties was almost unaffected. Moreover, it has been successfully applied to the determination of the target analytes in human urine samples, providing high extraction efficiency.