Coupling Miniaturized Stir Bar Sorptive Dispersive Microextraction to Needle-Based Electrospray Ionization Emitters for Mass Spectrometry: Determination of Tetrahydrocannabinol in Human Saliva as a Proof of Concept.

Direct coupling of sample preparation with mass spectrometry (MS) can speed up analysis, enabling faster decision-making. In such combinations, where the analysis time is mainly defined by the extraction procedure, magnetic dispersive solid-phase extraction emerges as a relevant technique because of its rapid workflow. The dispersion and retrieval of the magnetic sorbent are typically uncoupled stages, thus reducing the potential simplicity. Stir bar sorptive dispersive microextraction (SBSDME) is a novel technique that integrates both stages into a single device. Its miniaturization (mSBSDME) makes it more portable and compatible with low-availability samples. This article reports the direct combination of mSBSDME and MS using a needle-based electrospray ionization (NESI) emitter as the interface. This combination is applied to determine tetrahydrocannabinol in saliva samples, a relevant societal problem if the global consumption rates of cannabis are considered. The coupling requires only the transference of the magnet (containing the sorbent and the isolated analyte) from the mSBSDME to the hub of a hypodermic needle, where the online elution occurs. The application of 5 kV on the needle forms an electrospray on its tip, transferring the ionized analyte to the MS inlet. The excellent performance of mSBSDME-NESI-MS/MS relies on the sensitivity (limits of detection as low as 2.25 ng mL-1), the precision (relative standard deviation lower than 15%), and the accuracy (relative recoveries ranged from 87 to 127%) obtained. According to the results, the mSBSDME-NESI-MS/MS technique promises faster and more efficient chemical analysis in MS-based applications.

Analysis of microsamples by miniaturized magnetic-based pipette tip microextraction: determination of free cortisol in serum and urine from very low birth weight preterm newborns.

Miniaturized magnetic-based pipette tip microextraction is presented as a sample preparation approach for microsamples. It involves quick dispersion of a diminutive amount of a magnetic sorbent material in a low-volume sample (10 µL) to entrap the target analytes. Next, the dispersion is aspirated using a (semi)automatic pipette through a pipette tip with a small cubic neodymium magnet inside, which retrieves the magnetic sorbent containing the analytes. After discarding the rest of the sample, the sorbent is properly rinsed by aspirating/dispensing deionized water, and then, the analytes are eluted by aspirating/dispensing an appropriate solvent. This approach was employed for the determination of free cortisol in serum and urine from very low birth weight preterm newborns, a vulnerable patient group who present low availability for sampling biological fluids. A magnetic immunosorbent made of a cortisol antibody was employed for the selective extraction, followed by liquid chromatography-tandem mass spectrometry. Good analytical features were obtained, such as limits of detection and quantification of 0.08 and 0.27 ng mL-1, respectively, linearity up to 50 ng mL-1 (R2 > 0.999), RSD values under 15% and relative recoveries between 91 and 111%. The cross-reactivity with other glucocorticoids (i.e., cortisone and prednisolone) was evaluated to show the selectivity of the extraction. Finally, the method applicability was demonstrated towards the determination of free cortisol in the serum and urine samples from low birth weight preterm newborns.

Ultramicroextraction as a miniaturization of the already miniaturized. A step toward nanoextraction and beyond.

Miniaturization of the analytical process has been a widespread trend, and the sample preparation stage is not exempted from this downscaling. Since the introduction of microextraction techniques as miniaturization of classical extraction techniques, they have become one of the strengths in this field. However, some of the original approaches to these techniques did not fully cover all the current principles of Green Analytical Chemistry. For this reason, during the last years, much emphasis has been placed on reducing/eliminating toxic reagents, reducing the amount of the extraction phase, and searching for new greener, and more selective extractant materials. On the other hand, even though high accomplishments have been achieved, the same attention has not always been paid to reducing the amount of sample, which is essential when treating low-availability samples such as biological samples, or in developing portable devices. In this review, we intend to give the readership an overview of the advances toward further miniaturization of microextraction techniques. Finally, a brief reflection is made on the terminology used, or that should, in our opinion, be used to term these new generation of miniaturized microextraction approaches. To this regard, the term, 'ultramicroextraction' is proposed to refer to those approaches beyond microextraction.

Use of green alternative solvents in dispersive liquid-liquid microextraction: A review.

Dispersive liquid-liquid microextraction is one of the most widely used microextraction techniques currently in the analytical chemistry field, mainly due to its simplicity and rapidity. The operational mode of this approach has been constantly changing since its introduction, adapting to new trends and applications. Most of these changes are related to the nature of the solvent employed for the microextraction. From the classical halogenated solvents (e.g., chloroform or dichloromethane), different alternatives have been proposed in order to obtain safer and non-pollutants microextraction applications. In this sense, low-density solvents, such as alkanols, switchable hydrophobicity solvents, and ionic liquids were the first and most popular replacements for halogenated solvents, which provided similar or better results than these classical dispersive liquid-liquid microextraction solvents. However, despite the good performances obtained with low-density solvents and ionic liquids, researchers have continued investigating in order to obtain even greener solvents for dispersive liquid-liquid microextraction. For that reason, in this review, the evolution over the last five years of the three types of solvents already mentioned and two of the most promising solvent alternatives (i.e., deep eutectic solvents and supramolecular solvents), have been studied in detail with the purpose of discussing which one provides the greenest alternative.

Stir bar sorptive-dispersive microextraction by a poly(methacrylic acid-co-ethylene glycol dimethacrylate)-based magnetic sorbent for the determination of tricyclic antidepressants and their main active metabolites in human urine.

A poly(methacrylic acid-co-ethylene glycol dimethacrylate)-based magnetic sorbent was used for the rapid and sensitive determination of tricyclic antidepressants and their main active metabolites in human urine. This material was characterized by magnetism measurements, zeta potential, scanning electron microscopy, nitrogen adsorption-desorption isotherms, and thermogravimetric analysis. The proposed analytical method is based on stir bar sorptive-dispersive microextraction (SBSDME) followed by liquid chromatography-tandem mass spectrometry. The main parameters involved in the extraction step were optimized by using the response surface methodology as a multivariate optimization method, whereas a univariate approach was employed to study the desorption parameters. Under the optimized conditions, the proposed method was properly validated showing good linearity (at least up to 50 ng mL-1) and enrichment factors (13-22), limits of detection and quantification in the low ng L-1 range (1.4-7.0 ng L-1), and good intra- and inter-day repeatability (relative standard deviations below 15%). Matrix effects were observed for the direct analysis of urine samples, but they were negligible when a 1:1 v/v dilution with deionized water was performed. Finally, the method was successfully applied to human urine samples from three volunteers, one of them consuming a prescribed drug for depression that tested positive for clomipramine and its main active metabolite. Quantitative relative recoveries (80-113%) were obtained by external calibration. The present work expands the applicability of the SBSDME to new analytes and new types of magnetic sorbents.

A paper-based polystyrene/nylon Janus platform for the microextraction of UV filters in water samples as proof-of-concept.

A new mix-mode cellulose-based sorptive phase is described that combines two different polymeric domains (i.e., nylon and polystyrene), thus providing simultaneous hydrophilic and hydrophobic features as a result. By analogy with Janus materials, the new paper-based sorptive phase has been named paper-based polystyrene/nylon Janus-platform (P-Ps/Ny-JP). The main advantages of the proposed P-Ps/Ny-JP are the sustainability, simplicity in synthesis, and low cost of this extraction device. The main parameters affecting the synthesis (i.e., coating procedure and polymers proportion) have been studied, and the resulting material has been characterized via scanning electron microscopy and infrared spectroscopy. As a proof-of-concept, the simultaneous extraction of fourteen UV filters of a wide range of polarity, with log P values ranging from - 0.234 to 16.129, from water samples and their determination by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been performed. The proposed methodology enables the determination of these chemicals with limits of detection from 12 to 71 ng L-1, and the precision, expressed as a relative standard deviation, was below 15%. The extraction device was applied to the analysis of real water samples likely to contain UV filters (i.e., two private swimming pool water and one seawater) and the recovery values were in the range 73-121%.

Use of Nanomaterial-Based (Micro)Extraction Techniques for the Determination of Cosmetic-Related Compounds.

The high consumer demand for cosmetic products has caused the authorities and the industry to require rigorous analytical controls to assure their safety and efficacy. Thus, the determination of prohibited compounds that could be present at trace level due to unintended causes is increasingly important. Furthermore, some cosmetic ingredients can be percutaneously absorbed, further metabolized and eventually excreted or bioaccumulated. Either the parent compound and/or their metabolites can cause adverse health effects even at trace level. Moreover, due to the increasing use of cosmetics, some of their ingredients have reached the environment, where they are accumulated causing harmful effects in the flora and fauna at trace levels. To this regard, the development of sensitive analytical methods to determine these cosmetic-related compounds either for cosmetic control, for percutaneous absorption studies or for environmental surveillance monitoring is of high interest. In this sense, (micro)extraction techniques based on nanomaterials as extraction phase have attracted attention during the last years, since they allow to reach the desired selectivity. The aim of this review is to provide a compilation of those nanomaterial-based (micro)extraction techniques for the determination of cosmetic-related compounds in cosmetic, biological and/or environmental samples spanning from the first attempt in 2010 to the present.

Determination of N-nitrosamines in cosmetic products by vortex-assisted reversed-phase dispersive liquid-liquid microextraction and liquid chromatography with mass spectrometry.

A new analytical method for the simultaneous determination of trace levels of seven prohibited N-nitrosamines (N-nitrosodimethylamine, N-nitrosoethylmethylamine, N-nitrosopyrrolidine, N-nitrosodiethylamine, N-nitrosopiperidine, N-nitrosomorpholine, and N-nitrosodiethanolamine) in cosmetic products has been developed. The method is based on vortex-assisted reversed-phase dispersive liquid-liquid microextraction, which allows the extraction of highly polar compounds, followed by liquid chromatography with mass spectrometry. The variables involved in the extraction process were studied to obtain the highest enrichment factor. Under the selected conditions, 75 µL of water as extraction solvent was added to 5 mL of n-hexane sample solution and assisted by vortex mixing during 30 s to form the cloudy solution. The method was successfully validated showing good linearity (0.5-50 ng/mL), enrichment factors up to 65 depending on the target compound, limits of detection values of 1.8-50 ng/g, and good repeatability (RSD < 9.8%). Finally, the proposed method was applied to different cosmetic samples. Quantitative relative recovery values (80-113%) were obtained, thus showing that matrix effects were negligible. The achieved analytical features of the proposed method, besides of its simplicity and affordability, make it useful to perform the quality control of cosmetic products to ensure the safety of consumers.

Vortex-assisted emulsification semimicroextraction for the analytical control of restricted ingredients in cosmetic products: determination of bronopol by liquid chromatography.

Vortex-assisted emulsification semimicroextraction is proposed as a one-step solution-extraction procedure for sample preparation in cosmetic products. The procedure allows rapid preparation based on dispersion of the sample in a mixture of 1 mL of n-hexane and 0.5 mL of ethanol, followed by the addition of 0.5 mL of water and centrifugation to obtain two separated phases. This procedure provides good sample clean-up with minimum dilution and is very useful for the determination of ingredients with restricted concentrations, such as bronopol. The procedure was applied to the determination of bronopol by liquid chromatography with UV detection. The best chromatographic separation was obtained by using a C18 column set at 40 °C and performing a stepwise elution with a mixture of ethanol/aqueous 1 % acetic acid solution as mobile phase pumped at 0.5 mL min(-1). The detection wavelength was set at 250 nm and the total run time required was 12 min. The method was successfully applied to 18 commercial cosmetic samples including creams, shampoos, and bath gels. Good recoveries and repeatability were obtained, with a limit of detection of 0.9 µg mL(-1), which makes the method suitable for the analytical control of cosmetic products. Moreover, it could be considered environmentally friendly, because water, ethanol, and only a low volume of n-hexane are used as solvents.

A miniaturized stir bar sorptive dispersive microextraction method for the determination of bisphenols in follicular fluid using a magnetic covalent organic framework.

BACKGROUND: Bisphenols, particularly bisphenol A (BPA), are the primary monomers used as additives in the manufacturing of many consumer products. The exposure to these compounds is related to endocrine-disrupting and reproductive effects, among others. For this reason, the development of analytical methods for their determination in biological matrixes is needed to monitor the population exposure to these compounds. Their quantification at ovarian level (i.e., follicular fluid) is interesting for the assessment of the bisphenol content to draw conclusions about infertility problems. However, the background does not meet all requirements by focusing mainly on BPA. RESULTS: In this work, a miniaturized stir bar sorptive dispersive microextraction (mSBSDME) approach has been developed for the determination of BPA and eight analogues in follicular fluid. In the proposed method, the sample is previously cleaned-up using a zirconia-based solid-phase extraction cartridge, removing proteins and phospholipids, and then subjected to the mSBSDME for the preconcentration of the analytes. For this purpose, a magnetic covalent organic framework was used as sorbent. A Plackett-Burman design was applied to select the significant variables affecting the mSBSDME. Afterwards, the only significant variable (i.e., sorbent amount) was optimized. Under the optimized conditions, the proposed method was properly validated, and satisfactory analytical parameters in terms of linearity (up to 50 ng mL-1), enrichment factors (8.5-14.3), limits of detection in the low ng mL-1 range, and precision (relative standard deviations below 11.5 %) were obtained. Finally, the method was successfully applied to five samples, detecting BPA and other two analogues. SIGNIFICANCE: This method expands the potential applicability of the mSBSDME to other low-availability complex matrixes, which would otherwise be difficult to analyze. Moreover, it offers a valuable tool for monitoring the female population's exposure to bisphenols with the final aim of evaluating if infertility problems of women might be associated to the exposure to these highly endocrine disrupting compounds.

Determination of nine prohibited N-nitrosamines in cosmetic products by vortex-assisted dispersive liquid-liquid microextraction prior to gas chromatography-mass spectrometry.

An analytical method for the simultaneous determination of nine prohibited N-nitrosamines in cosmetic products is presented. N-nitrosamines are banned compounds in cosmetic products due to their harmful effects. Therefore, these compounds are not intentionally added to these products but, however, small amounts of them may be present due to unintentional causes, and thus sensitive methods for their analytical control are required. The proposed method is based on vortex-assisted dispersive liquid-liquid microextraction (VA-DLLME) to extract and preconcentrate the analytes, followed by gas chromatography-mass spectrometry (GC-MS) for their determination. The variables involved in the VA-DLLME process were optimized by using a Box-Behnken design and, due to the different polarity of the N-nitrosamines studied, several approaches for sample treatment were compared to achieve the best results. The method was successfully validated, showing a good linearity at least up to 20 ng mL-1, enrichment factors from 2 to 100 depending on the target analyte, limits of detection and quantification at the low µg kg-1 level, and good repeatability values (<13%). Finally, the proposed analytical method was applied to the determination of N-nitrosamines in commercial cosmetic samples of different nature, avoiding the matrix effect by means of standard addition calibration. Significant amounts of some of the N-nitrosamines, even exceeding the established regulatory limit, were found in the samples. The resulting method is fast, simple, and affordable to carry out the quality control of cosmetic products to ensure consumer safety for most laboratories.

New challenges in sample preparation: Miniaturized stir bar sorptive dispersive microextraction as a high-throughput and feasible approach for low-availability sample preparation.

The miniaturization of stir bar sorptive dispersive microextraction (mSBSDME) for the analysis of low-availability samples is presented. This new methodology is based on the principles of stir bar sorptive dispersive microextraction, but the amount of sorbent and, most importantly, the amount of sample are considerably reduced to a tiny amount and a few microliters, respectively. Thus, affordable 400-µL flat-base glass inserts and minute bar-shape neodymium magnets (3 mm length x 2 mm diameter) were used as extraction devices hold by a specifically designed multiextraction assembly, which comprises a high-rate stirring plate and a 3D-printed support to treat 15 samples simultaneously. This new approach allows a fast, affordable, portable, and high-throughput analysis of low-volume samples, expanding the potential of the technique. The same extraction device is used along the different stages, thus avoiding transfers, which reduces sample handling. Besides, the reduction in the sample, sorbent and organic solvent amounts allows a considerable decrease of the waste generation, and thus pursues a green sample preparation for bioanalysis. As a proof-of-concept of this new methodology, cortisone and cortisol were determined in human saliva using a composite material made of a reversed phase polymer (Strata™-X-RP) and CoFe2O4 magnetic nanoparticles. Liquid chromatography coupled to tandem mass spectrometry was used to measure both analytes obtaining good analytical features in terms of linearity (R2 > 0.997), method limits of detection and quantification (22.6 and 75.5 ng L-1 for cortisone, and 19.3 and 64.3 ng L-1 for cortisol, respectively), repeatability (RSD ≤11%) and relative recoveries (78-134%).

Trace determination of tetrahydrocannabinol (THC) in cosmetic products by stir bar sorptive dispersive microextraction followed by liquid chromatography-tandem mass spectrometry.

An analytical method for the determination of tetrahydrocannabinol (THC) at trace level in cosmetics is presented. As psychoactive compound, the presence of THC in consumer products should be avoided. However, it might be unintentionally present in cannabidiol-rich or hemp-based products by contamination or isomerization of cannabidiol. Due to the low concentrations expected, a sensitive and selective method is necessary for the analytical control of these products. In this sense, the presented method is based on stir bar sorptive dispersive microextraction (SBSDME) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this work, a magnetic composite made of CoFe2O4 magnetic nanoparticles embedded in a commercial reverse-phase polymer (Strata™-X-RP) was employed as magnetic sorbent material taking advantage of its affinity to the target analyte. Under the optimized conditions, the method was validated and showed good analytical features in terms of linearity (at least up to 10 ng mL-1), limits of detection and quantification (2.2 and 7.2 ng g-1, respectively) and repeatability (RSD <10%). Moreover, relative recoveries between 99 and 109% were obtained, showing matrix effects were negligible using deuterated THC (THC-D3) as surrogate. This new approach was successfully applied to ten commercially-available cosmetic samples of different matrices, thus showing it is suitable for the analytical control of THC in cosmetic products. The proposed methodology overcomes some of the drawbacks of the previous works with the same purpose, such as the higher limits of detection, time-consuming procedures, and consumption of large volumes of organic solvents.

Solid-phase immunoextraction followed by liquid chromatography-tandem mass spectrometry for the selective determination of thyroxine in human serum.

In this work, an analytical method based on solid-phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry analysis (LC-MS/MS) has been developed for the selective determination of thyroxine (T4) in human serum. For this purpose, two immunosorbents (ISs) specific to T4 were synthesized by grafting two different T4-specific monoclonal antibodies on a cyanogen bromide (CNBr)-activated-Sepharose® 4B solid support. The grafting yields obtained from the immobilization of each antibody on the CNBr-activated-Sepharose® 4B were over 90%, demonstrating that most of the antibodies were covalently bound to the solid support. The SPE procedure was optimized by studying the retention capability and selectivity of the two ISs in pure media fortified with T4. Under the optimized conditions, high elution efficiencies were achieved in the elution fraction for both specific ISs (i.e., 85%), whereas low ones were obtained in the control ISs (ca. 2%), showing the selectivity of the specific ISs. The ISs were also characterized by studying extraction and synthesis repeatability (RSD <8%), and capacity (104 ng of T4 per 35 mg of ISs, i.e., 3 µg g-1). Finally, the methodology was applied to a pooled human serum sample in order to study its analytical utility and accuracy. Relative recovery (RR) values between 81 and 107% were obtained, showing no matrix effects during the global methodology. Furthermore, the need to perform the immunoextraction was evidenced by comparing the LC-MS scan chromatograms and RR values with and without applying the immunoextraction procedure on a serum sample submitted to protein precipitation. This works exploits, for the first time, the use of an IS on the selective determination of T4 in human serum samples.

Trace determination of prohibited acrylamide in cosmetic products by vortex-assisted reversed-phase dispersive liquid-liquid microextraction and liquid chromatography-tandem mass spectrometry.

An analytical method for the determination of residual acrylamide in cosmetic products containing potential acrylamide-releasing ingredients is presented. The method is based on vortex-assisted reversed-phase dispersive liquid-liquid microextraction (VA-RP-DLLME) to extract and preconcentrate acrylamide by using water as extraction solvent taking advantage the highly polar behavior of this analyte, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for its determination. Under optimized conditions (5 mL toluene as supporting solvent, 50 µL of water as extraction solvent, 1 min for vortex extraction time) the method was properly validated obtaining good analytical features (linearity up to 20 ng mL-1, method limits of detection and quantification of 0.51 and 1.69 ng g-1, respectively, enrichment factor of 52, and good repeatability (RSD < 4.1%)). The proposed analytical method was applied to the determination of acrylamide in commercial samples that were weighed and dispersed in the minimum quantity of methanol (50 µL) by vortex stirring before applying the VA-RP-DLLME procedure. Through the pretreatment of the sample and the use of acrylamide-d3 as surrogate, the matrix effect was overcome, obtaining good relative recovery values (88-108%). The proposed method has shown efficacy, simplicity, and speed, and it allows the determination of acrylamide at trace levels easily, which could make it very useful for companies in the quality control of cosmetic products containing potential acrylamide-releasing ingredients to fulfill the safety limits imposed by European Regulation.

Determination of hexanal and heptanal in saliva samples by an adapted magnetic headspace adsorptive microextraction for diagnosis of lung cancer.

In this work, an analytical method for the determination of two endogenous aldehydes (hexanal and heptanal) as lung cancer biomarkers in saliva samples is presented for the first time. The method is based on a modification of magnetic headspace adsorptive microextraction (M-HS-AME) followed by gas chromatography coupled to mass spectrometry (GC-MS). For this purpose, an external magnetic field generated by a neodymium magnet is used to hold the magnetic sorbent (i.e., CoFe2O4 magnetic nanoparticles embedded into a reversed-phase polymer) in the headspace of a microtube to extract the volatilized aldehydes. Subsequently, the analytes are desorbed in the appropriate solvent and the extract is injected into the GC-MS system for separation and determination. Under the optimized conditions, the method was validated and showed good analytical features in terms of linearity (at least up to 50 ng mL-1), limits of detection (0.22 and 0.26 ng mL-1 for hexanal and heptanal, respectively), and repeatability (RSD ≤12%). This new approach was successfully applied to saliva samples from healthy volunteers and those with lung cancer, obtaining notably differences between both groups. These results reveal the prospect of the method as potential diagnostic tool for lung cancer by saliva analysis. This work contributes to the Analytical Chemistry field presenting a double novelty: on the one hand, the use of M-HS-AME in bioanalysis is unprecedentedly proposed, thus expanding the analytical potential of this technique, and, on the other hand, the determination of hexanal and heptanal is carried out in saliva samples for the first time.

Green, rapid and simultaneous determination of 'alternative preservatives' in cosmetic formulations by gas chromatography-mass spectrometry.

Some hydroxylated compounds commonly used in cosmetic formulations including short chain glycols, benzylic alcohols, and organic acids show antimicrobial activity, although they are not considered as preservatives according to the existing European legislation. These 'alternative preservatives' are not exempt of potential side-effects for cosmetics users. The aim of this work is to develop a simple and affordable analytical method useful for the simultaneous and green determination of fourteen compounds used as 'alternative preservatives' in cosmetic samples with different matrices. The proposed method allows a rapid sample preparation by simple dissolution or dispersion of the sample in ethanol using ultrasound-assisted leaching of the analytes from the cosmetic matrix. Gas chromatography coupled to mass spectrometry (GC-MS) is used for the analysis of the samples. Working conditions for the instrumental measure and the quantification of analytes were studied. The method was found to have high sensitivity and good precision (relative standard deviation below 13%) as well as low limits of detection (i.e., 0.01·10-3-2.14·10-3% w/w) and quantification (i.e., 0.04·10-3-7.14·10-3% w/w). The method was successfully applied to five commercial cosmetic samples of different composition. Recovery values near 100% were obtained. Each sample was found to contain at least three of the analytes of the study and their concentrations were determined with low standard deviations. The analytical features of the proposed method and the obtained results agree with the principles of Green Analytical Chemistry and make it a useful tool for controlling these alternative preservatives in the cosmetic industry in order to guarantee quality and safety of the products.

A high-throughput magnetic-based pipette tip microextraction as an alternative to conventional pipette tip strategies: Determination of testosterone in human saliva as a proof-of-concept.

In this work, a lab-made and affordable high-throughput pipette tip microextraction strategy is presented. In this approach, a magnetic sorbent is quickly dispersed in the sample by means of a disperser solvent and the resulting dispersion is immediately aspirated into a pipette tip containing a small neodymium magnet inside, which entraps the magnetic sorbent containing the analytes. The sample is then discarded, and the subsequent cleaning and desorption steps are conducted by aspirating/dispensing the suitable solvents. This methodology provides satisfactory results when compared with previous pipette tip extraction strategies (i.e., pipette-tip solid-phase extraction and dispersive pipette extraction). Furthermore, it requires a minimum number of aspirating/dispensing cycles, thus benefiting the ergonomics for the operator, and it is not commercially dependent. This new approach has been tested by measuring testosterone levels in saliva of volunteers as a proof-of-concept. In this regard, a magnetic composite made of CoFe2O4 magnetic nanoparticles embedded in octadecyl bonded silica microparticles was employed as sorbent material. Testosterone was quantified by liquid chromatography coupled to tandem mass spectrometry. Under the optimized conditions, low limits of detection and quantification (7.5 ng L-1 and 24.8 ng L-1, respectively), good repeatability (RSD <9%) and relative recoveries between 82 and 106% were obtained with just one adsorption and two desorption cycles, which requires few seconds per sample. In order to increase even more the sample throughput, a multichannel pipette was also evaluated.

Low toxicity deep eutectic solvent-based ferrofluid for the determination of UV filters in environmental waters by stir bar dispersive liquid microextraction.

In this work, a low toxicity deep eutectic solvent-based ferrofluid is presented for the first time as magnetic fluid to be used as an efficient solvent in liquid-based microextraction techniques. This ferrofluid is made of a hydrophobic deep eutectic solvent, composed by menthol and thymol in a 1:5 molar ratio as carrier solvent, and oleic acid-coated cobalt ferrite (CoFe2O4@oleic acid) magnetic nanoparticles. This material was characterized via magnetism measurement, scanning electron microscopy, infrared spectroscopy and density measurement. The determination of UV filters in environmental water samples was selected as model analytical application to test the extraction performance of this new ferrofluid by employing stir bar dispersive liquid microextraction, prior to liquid chromatography-tandem mass spectrometry analysis. The response surface methodology was used as a multivariate optimization method for extraction step. Under the optimized conditions, good analytical features were obtained, such as low limits of detection between 7 and 83 ng L-1, good repeatability (relative standard deviations, RSD (%) below 15%), enrichment factors between 46 and 101 and relative recoveries between 80 and 117%, proving the good extraction capability of this ferrofluid. Finally, the method was successfully applied to three environmental waters (beach and river waters), finding trace amounts of the target UV filters. The presented low toxicity deep eutectic solvent-based ferrofluid results to be a good alternative to conventional solvents used in liquid-phase microextraction techniques.

Development of a new three-phase membrane-assisted liquid-phase microextraction method: determination of nitrite in tap water samples as model analytical application.

A novel and simple device for membrane-assisted liquid-phase microextraction is used for the first time in a three-phase system. The device consists of a glass vial containing the aqueous acceptor phase, whose septum of its screw stopper has been replaced by a sized piece of polytetrafluoroethylene membrane impregnated with n-decane. The vial is assembled to a volumetric flask containing the aqueous donor phase, and the membrane comes in contact alternatively with both donor and acceptor aqueous phases by orbital agitation. The device has been tested for the determination of nitrite in tap water samples, which is extensively carried out in routine analysis, as model analytical application. Experimental variables, such as the organic solvent used to form the supported liquid membrane, the volumes of both donor and acceptor phases, the orbital agitation rate, and the extraction time were studied and optimized in terms of enrichment factor. Under the selected working conditions, the analytical figures of merit for nitrite determination were a linearity range up to 50 ng mL(-1), limits of detection and quantification of 0.15 and 0.50 ng mL(-1), respectively, and a good repeatability (RSD < 10%). The method has been applied to four tap water samples of different origins, and accurate and precise results were achieved. Besides, the very low volume of organic solvent used, its low cost and the no-risk of cross-contamination are significant operational advantages.