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.

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.

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.

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.

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.

A New Microchip Design. A Versatile Combination of Electromembrane Extraction and Liquid-Phase Microextraction in a Single Chip Device.

For the first time, a novel and versatile microfluidic device was developed to achieve the possibility of combining different extraction principles using a miniaturized approach for the extraction of different classes of analytes. This novel microchip is composed of a sandwich of three poly(methyl methacrylate) (PMMA) layers. Four channels allowed the combination of electromembrane extraction (EME) and liquid-phase microextraction (LPME) in three different ways: (I) EME and LPME, (II) EME and EME, or (III) LPME and LPME. The microchip can be used either (a) using a common acceptor phase (for both extractions) for the simultaneous extraction of drugs from different nature in a single step, or (b) a common sample solution (for both extractions) and two acceptor solutions for simultaneous drug separation. In this work, the performance of this novel microchip was demonstrated by simultaneous integration of EME and LPME using a common acceptor phase for both extractions. This configuration reduces the time of analysis allowing direct analysis in a single chip. The microchip was tested for extracting two different classes of analytes: five fluoroquinolones and four parabens as model analytes. All effective variables were optimized for EME and LPME. Under the optimized conditions, the reusable microchip enables simultaneous µ-EME/LPME with extraction efficiencies over 77% in only 8 min extraction and sample volume consumption lower than 40 µL. The optimized procedure was successfully applied to urine samples obtaining recoveries over 90% for all analytes.

Recent trends in capillary electrophoresis for complex samples analysis: A review.

CE has been a continuously evolving analytical methodology since its first introduction in the 1980s of the last century. The development of new CE separation procedures, the coupling of these systems to more sensitive and versatile detection systems, and the advances in miniaturization technology have allowed the application of CE to the resolution of new and complex analytical problems, overcoming the traditional disadvantages associated with this method. In the present work, different recent trends in CE and their application to the determination of high complexity samples (as biological fluids, individual cells, etc.) will be reviewed: capillary modification by different types of coatings, microfluidic CE, and online microextraction CE. The main advantages and disadvantages of the different proposed approaches will be discussed with examples of most recent applications.

Analysis of Hemoglobin Glycation Using Microfluidic CE-MS: A Rapid, Mass Spectrometry Compatible Method for Assessing Diabetes Management.

Diabetes has become a significant health problem worldwide with the rate of diagnosis increasing rapidly in recent years. Measurement of glycated blood proteins, particularly glycated hemoglobin (HbA1c), is an important diagnostic tool used to detect and manage the condition in patients. Described here is a method using microfluidic capillary electrophoresis with mass spectrometry detection (CE-MS) to assess hemoglobin glycation in whole blood lysate. Using denaturing conditions, the hemoglobin (Hb) tetramer dissociates into the alpha and beta subunits (α- and ß-Hb), which are then separated via CE directly coupled to MS detection. Nearly baseline resolution is achieved between α-Hb, ß-Hb, and glycated ß-Hb. A second glycated ß-Hb isomer that is partially resolved from ß-Hb is detected in extracted ion electropherograms for glycated ß-Hb. Glycation on α-Hb is also detected in the α-Hb mass spectrum. Additional modifications to the ß-Hb are detected, including acetylation and a +57 Da species that could be the addition of a glyoxal moiety. Patient blood samples were analyzed using the microfluidic CE-MS method and a clinically used immunoassay to measure HbA1c. The percentage of glycated α-Hb and ß-Hb was calculated from the microfluidic CE-MS data using peak areas generated from extracted ion electropherograms. The values for glycated ß-Hb were found to correlate well with the HbA1c levels derived in the clinic, giving a slope of 1.20 and an R(2) value of 0.99 on a correlation plot. Glycation of human serum albumin (HSA) can also be measured using this technique. It was observed that patients with elevated glycated Hb levels also had higher levels of HSA glycation. Interestingly, the sample with the highest HbA1c levels did not have the highest levels of glycated HSA. Because the lifetime of HSA is shorter than Hb, this could indicate a recent lapse in glycemic control for that patient. The ability to assess both Hb and HSA glycation has the potential to provide a more complete picture of a patient's glycemic control in the months leading up to blood collection. The results presented here demonstrate that the microfluidic CE-MS method is capable of rapidly assessing Hb and HSA glycation from low volumes of whole blood with minimal sample preparation and has the potential to provide more information in a single analysis step than current technologies.

Agar films containing silver nanoparticles as new supports for electromembrane extraction.

A new support containing silver nanoparticles to assist electromembrane extraction (EME) procedures is proposed. For the first time, synthesized agar films containing silver nanoparticles (AgNPs) have been used as a support for liquid membranes in EME. Agarose films of 20 µm thickness containing 107.9 mg Ag/g agar were synthesized and characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM), showing isolated spherical silver nanoparticles of 20-30 nm diameter with homogeneous distribution. Nanometallic films were cut and glued to narrow bore glass tubes and used as supports for a dihexyl ether liquid membrane for use in an EME procedure. EME conditions were optimized and applied to the extraction of selected non-steroidal anti-inflammatory drugs (NSAIDs). The results were compared to those using polypropylene membranes (450 µm and 100 µm thickness), achieving 10- to 70-fold higher extraction efficiency. This article opens a new line of research into electrically assisted microextraction systems by combining other possible kinds of nanometallic films, including different metals, film functionalization through metallic NPs, and the use of low polarity solvents. Also, very low currents are obtained during the extraction process, which lead to high electromigration of the analytes.

Hollow-fiber liquid-phase microextraction for the direct determination of flumequine in urban wastewaters by flow-injection analysis with terbium-sensitized chemiluminescence.

A flow-injection analysis chemiluminescence method based on the enhancement effect of the flumequine-Tb(III) complex on the weak native emission of the Ce(IV)-Na2SO3 system has been developed for the determination of flumequine. The method includes a cleanup and preconcentration stage (750-fold) of the sample by hollow-fiber liquid-phase microextraction using an Accurel(®) Q 3/2 polypropylene hollow fiber impregnated with 1-octanol as the supported liquid membrane. The obtained 50 µL acceptor phase was injected in a 1 mM Tb(III) + 4 mM Ce(IV) in 5% v/v H2 SO4 stream and mixed with a 2 mM Na2 SO3 stream before its introduction into the flow cell. The chemiluminescence signal was linear in the 0.3-15 ng/mL range, with detection and quantitation limits of 0.1 and 0.3 ng/mL, respectively. The method allows the selective extraction and determination of flumequine in wastewater samples, using simpler and lower-cost instrumentation and with shorter extraction and analysis times than traditional high-performance liquid chromatography analysis.

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.

Electromembrane extraction (EME)--an easy, novel and rapid extraction procedure for the HPLC determination of fluoroquinolones in wastewater samples.

For the first time, an electromembrane extraction combined with a HPLC procedure using diode array and fluorescence detection has been developed for the determination of seven widely used fluoroquinolones (FQs): marbofloxacin, norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, gatifloxacin and grepafloxacin. The drugs were extracted from acid aqueous sample solutions (pH 5), through a supported liquid membrane consisting of 1-octanol impregnated in the walls of a S6/2 Accurel® polypropylene hollow fiber, to an acid (pH 2) aqueous acceptor solution inside the lumen of the hollow fiber. The main operational parameters were optimized, and extractions were carried out in 15 min using a potential of 50 V. Enrichment factors of 40-85 have been obtained using only 15 min of extraction time versus 330 min used in a previously proposed hollow-fiber liquid-phase microextraction procedure. The procedure allows low detection and quantitation limits of 0.005-0.07 and 0.007-0.15 µg L(-1), respectively. The proposed method was successfully applied to the FQs analysis in urban wastewaters.

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.

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.

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.

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.

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.

Capillary electrophoresis determination of nonsteroidal anti-inflammatory drugs in wastewater using hollow fiber liquid-phase microextraction.

The presence of pharmaceuticals in the environment due to growing worldwide consumption has become an important problem that requires analytical solutions. This paper describes a CE determination for several nonsteroidal anti-inflammatory drugs (ibuprofen, naproxen, ketoprofen, diclofenac, ketorolac, aceclofenac and salicylic acid) in environmental waters using hollow fiber membrane liquid-phase microextraction. The extraction was carried out using a polypropylene membrane supporting dihexyl ether and the electrophoretic separation was performed in acetate buffer (30 mM, pH 4) using ACN as the organic modifier. Detection limits between 0.25 and 0.86 ng/mL were obtained, respectively. The method could be applied to the direct determination of the seven anti-inflammatories in wastewaters, and five of them have been determined or detected in different urban wastewaters.

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%.