Analytical control of imatinib in bioanalytical samples using graphene quantum dots sensing.

An analytical method for the determination of imatinib (IMA, the primary treatment for chronic myeloid leukemia), based on the fluorescence properties of graphene quantum dots (GQDs), is reported in this work. The method is addressed to the analytical control of IMA in biological and pharmaceutical samples, due to the present interest in the control of the doses of this anticancer drug, as well as the therapeutic monitoring. The whole method involves the use of a solid-phase extraction (SPE) procedure, followed by an evaporation step, for the treatment of biological samples. For that, tC18 sorbent cartridges were used. After the sample treatment, the solution containing the analyte was mixed with an aqueous solution of GQDs at pH 7.2, and the fluorescent quenching of GQDs was measured. IMA was determined in the 10-250 µg L-1 range, with a limit of detection of 21 µg L-1 and a precision of 1.5% as relative standard deviation, measured in terms of reproducibility. The recovery for biological samples was in the 84-113% range.

Selective dual sensing strategy for free and vitamin D3 micelles in food samples based on S,N-GQDs photoinduced electron transfer.

A reliable nanotechnological sensing strategy, based on an S,N-co-doped graphene quantum dot (GQD) platform, has been developed to distinctly detect two key variants of vitamin D3, specifically the free (VD3) and the nanoencapsulated form (VD3Ms). For this purpose, food-grade vitamin D3 micelles were self-assembled using a low-energy procedure (droplet size: 49.6 nm, polydispersity index: 0.34, ζ-potential: -33 mV, encapsulation efficiency: 90 %) with an innovative surfactant mixture (Tween 60 and quillaja saponin). Herein, four fluorescent nanoprobes were also synthesized and thoroughly characterized: S,N-co-doped GQDs, α-cyclodextrin-GQDs, ß-cyclodextrin-GQDs, and γ-cyclodextrin-GQDs. The goal was to achieve a selective dual sensing strategy for free VD3 and VD3Ms by exploiting their distinctive quenching behaviors. Thus, the four nanosensors allowed the individual sensing of both targets to be performed (except α-CD-GQD for VD3Ms), but S,N-GQDs were finally selected due to selectivity and sensitivity (quantum yield, QY= 0.76) criteria. This choice led to a photoinduced electron transfer (PET) mechanism associated with static quenching, where differentiation was evidenced through a displayed 13-nm hypsochromic (blue) shift when interacting with VD3Ms. The reliability of this dual approach was demonstrated through an extensive evaluation of analytical performance characteristics. The feasibility and accuracy were proven in commercial food preparations and nutritional supplements containing declared nanoencapsulated and raw VD3, whose results were validated by a paired Student's t-test comparison with a UV-Vis method. To the best of our knowledge, this represents the first non-destructive analytical approach addressing the groundbreaking foodomic trend to distinctly detect different bioactive forms of vitamin D3, while also preserving their native nanostructures as a chemical challenge, thus providing reliable information about their final stability and bioavailability.

Full kinetic modeling analysis of [18F]fluorocholine Positron Emission Tomography (PET) at initial diagnosis of high-grade glioma.

PURPOSE: The main objective was to characterize the tracer uptake kinetics of [18F]fluoromethylcholine ([18F]F-CHO) in high-grade gliomas (HGG) through a full PET kinetic modeling approach. Secondarily, we aimed to explore the relationship between the PET uptake measures and the HGG molecular features. MATERIALS AND METHODS: Twenty-four patients with a suspected diagnosis of HGG were prospectively included. They underwent a dynamic brain [18F]F-CHO-PET/CT, from which a tumoral time-activity curve was extracted. The plasma input function was obtained through arterial blood sampling with metabolite correction. These data were fitted to 1- and 2-tissue-compartment models, the best of which was selected through the Akaike information criterion. We assessed the correlation between the kinetic parameters and the conventional static PET metrics (SUVmax, SUVmean and tumor-to-background ratio TBR). We explored the association between the [18F]F-CHO-PET quantitative parameters and relevant molecular biomarkers in HGG. RESULTS: Tumoral time-activity curves in all patients showed a rapid rise of [18F]F-CHO uptake followed by a plateau-like shape. Best fits were obtained with near-irreversible 2-tissue-compartment models. The perfusion-transport constant K1 and the net influx rate Ki showed strong correlation with SUVmax (r = 0.808-0.861), SUVmean (r = 0.794-0.851) and TBR (r = 0.643-0.784), p < 0.002. HGG was confirmed in 21 patients, of which those with methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter showed higher mean Ki (p = 0.020), K1 (p = 0.025) and TBR (p = 0.001) than the unmethylated ones. CONCLUSION: [18F]F-CHO uptake kinetics in HGG is best explained by a 2-tissue-compartment model. The conventional static [18F]F-CHO-PET measures have been validated against the perfusion-transport constant (K1) and the net influx rate (Ki) derived from kinetic modeling. A relationship between [18F]F-CHO uptake rate and MGMT methylation is suggested but needs further confirmation.

Implications of analytical nanoscience in pharmaceutical and biomedical fields: A critical view.

This review summarizes recent progress performed in the design and application of analytical tools and methodologies using nanomaterials for pharmaceutical analysis, and specifically new nanomedicines at distinct phases of development and translation from preclinical to clinical stages. Over the last 10-15 years, a growing number of studies have utilized various nanomaterials, including carbon-based, metallic nanoparticles, polymeric nanomaterials, materials based on biological molecules, and composite nanomaterials as tools for improving the analysis of pharmaceutical products. New and more complex nanomaterials are currently being explored to influence different stages of the analytical process. These materials provide unique properties to support the extraction of analytes in complex samples, increase the selectivity and efficiency of chromatographic separations, and improve the analytical properties of many sensor applications. Indeed, nanomaterials, including electrochemical detection approaches and biosensing, are expanding at a remarkable rate. Furthermore, the analytical performance of numerous approaches to determine drugs in different matrices can be significantly improved in terms of precision, detection limits, selectivity, and time of analysis. However, the quality control and metrological characterization of the currently synthesized nanomaterials still depend on the development of new and improved analytical methodologies, and the application of specific and improved instrumentation. Therefore, there is still much to explore about the properties of nanomaterials which need to be determined even more precisely and accurately.

An ICP-MS-Based Analytical Strategy for Assessing Compliance with the Ban of E 171 as a Food Additive on the EU Market.

A method was developed for the determination of total titanium in food and food supplements by inductively coupled plasma mass spectrometry (ICP-MS) after microwave-assisted acid digestion of samples. Five food supplements, including one certified reference material, and 15 food products were used for method development. Key factors affecting the analytical results, such as the composition of the acid mixture for sample digestion and the bias from spectral interferences on the different titanium isotopes, were investigated. Resolution of interferences was achieved by ICP-MS/MS with ammonia adduct formation and viable conditions for control laboratories equipped with standard quadrupole instruments were identified. The method was successfully validated and enables rapid screening of samples subject to confirmatory analysis for the presence of TiO2 particles. For the latter, single-particle ICP-MS (spICP-MS) analysis after chemical extraction of the particles was used. The two methods establish a viable analytical strategy for assessing the absence of titania particles in food products on the EU market following the E 171 ban as a food additive.

Fluorescent dual-mode sensor for the determination of graphene oxide and catechin in environmental or food field.

The novel fluorescent sensor is proposed in this work based on the competitive interactions between the known bioactive compounds, riboflavin and catechin, which act as guests, and graphene oxide (GO) material that acts as host. Specifically, this proposal is based on an indicator displacement assay which allows the detection of GO and catechin (fluorescence quenching of riboflavin signal by GO and increase in fluorescence by catechin on the GO-riboflavin system). Three GO structures with different lateral dimensions and thickness were synthesized and tested, being able to be the three differentiated depending on the attenuation capacity of the fluorescent signal that each one possesses. The environmental analytical control of GO is more and more important, being this method sensitive and selective in the presence of other potential interferent substances. On the other hand, the other sensing capacity of the sensor also allows the determination of catechin in food samples based on the formation of riboflavin-GO complex. It is a rapid, simple and non-expensive procedure. Thus, the same 2D nanomaterial (GO) is seen to play a double role in this sensing strategy (analyte and analytical tool for the determination of another compound).

Advanced oxidation and a metrological strategy based on CLC-MS for the removal of pharmaceuticals from pore & surface water.

In this work, it is studied the photolysis, electrolysis, and photo-electrolysis of a mixture of pharmaceutics (sulfadiazine, naproxen, diclofenac, ketoprofen and ibuprofen) contained in two very different types of real water matrices (obtained from surface and porewater reservoirs), trying to clarify the role of the matrix on the degradation of the pollutants. To do this, a new metrological approach was also developed for screening of pharmaceuticals in waters by capillary liquid chromatography mass spectrometry (CLC-MS). This allows the detection at concentrations lower than 10 ng mL-1. Results obtained in the degradation tests demonstrate that inorganic composition of the water matrix directly influences on the efficiency of the drugs removal by the different EAOPs and better degradation results were obtained for experiments carried out with surface water. The most recalcitrant drug studied was ibuprofen for all processes evaluated, while diclofenac and ketoprofen were found to be the easiest drugs for being degraded. Photo-electrolysis was found to be more efficient than photolysis and electrolysis, and the increase in the current density was found to attain a slight improvement in the removal although with an associated huge increase in the energy consumption. The main reaction pathways for each drug and technology were also proposed.

Feeding volume advancement in preterm neonates: A level 4 neonatal intensive care unit quality improvement initiative.

INTRODUCTION: Because of provider variability in feeding guideline application, a quality improvement (QI) initiative was begun to better standardize feeding initiation and advancement for preterm infants. Our specific, measurable, achievable, relevant, and timely aims included decreasing the time to reach full feeds by 35% and reducing the duration of central lines by 30% over 12 months in infants born between 25 and 30 weeks' gestation or with birth weight between 600 and 1250 g. METHODS: Registered dietitians tracked central line days, parenteral nutrition (PN), enteral nutrition, fortification, guideline adherence, anthropometrics, necrotizing enterocolitis (NEC) cases, and central line-associated bloodstream infections (CLABSIs). QI progress charts were reviewed monthly. RESULTS: Mean central line days decreased from 7.3 to 5.8. Days of PN decreased from 6.7 to 5.1. The day of life that enteral feeds were started decreased from 1.1 to 0.5. The number of days between starting enteral feeds and adding fortification decreased from 3.4 to 2.3 days. Full enteral feeds were achieved on average 2 days earlier. Birth weight was regained at around 10.2 days of life before the guideline was implemented and at a mean of 9.6 days after the guideline. There was no increase in cases of CLABSI or diagnoses of NEC. CONCLUSION: After implementation of this feeding QI initiative at a level 4 neonatal intensive care unit, central line duration and PN use were decreased and infants reached full enteral feeds earlier without changes in cases of NEC, CLABSI, or time to regain birth weight.

Bacterial Colonization of Microplastics at the Beaches of an Oceanic Island, Tenerife, Canary Islands.

(1) Isolated systems, such as oceanic islands, are increasingly experiencing important problems related to microplastic debris on their beaches. The formation of microbial biofilm on the surface of microplastics present in marine environments provides potential facilities for microorganisms to survive under the biofilm. Moreover, microplastics act as a vehicle for the dispersion of pathogenic organisms, constituting a new route of exposure for humans. (2) In this study, the microbial content (FIO and Vibrio spp. and Staphylococcus aureus) of microplastics (fragments and pellets) collected from seven beaches of the oceanic island of Tenerife, in the Canary Islands (Spain), was determined. (3) Results showed that Escherichia coli was present in 57.1% of the fragments and 28.5% of the pellets studied. In the case of intestinal Enterococci, 85.7% of the fragments and 57.1% of the pellets tested positive for this parameter. Finally, 100% of the fragments and 42.8% of the pellets analyzed from the different beaches contained Vibrio spp. (4) This study shows that microplastics act as reservoirs of microorganisms that can increase the presence of bacteria indicating faecal and pathogenic contamination in bathing areas.

Rapid determination of malondialdehyde in serum samples using a porphyrin-functionalized magnetic graphene oxide electrochemical sensor.

An electrochemical sensor based on a screen-printed carbon electrode (SPCE) modified with porphyrin-functionalized magnetic graphene oxide (TCPP-MGO) was developed for the sensitive and selective determination of malondialdehyde (MDA), an important biomarker of oxidative damage, in serum samples. The coupling of TCPP with MGO allows the exploitation of the magnetic properties of the material for separation, preconcentration, and manipulation of analyte, which is selectively captured onto the TCPP-MGO surface. The electron-transfer capability in the SPCE was improved through derivatization of MDA with diaminonaphthalene (DAN) (MDA-DAN). TCPP-MGO-SPCEs have been employed to monitor the differential pulse voltammetry (DVP) levels of the whole material, which is related to the amount of the captured analyte. Under optimum conditions, the nanocomposite-based sensing system has proved to be suitable for the monitoring of MDA, presenting a wide linear range (0.01-100 µM) with a correlation coefficient of 0.9996. The practical limit of quantification (P-LOQ) of the analyte was 0.010 µM, and the relative standard deviation (RSD) was 6.87% for 30 µM MDA concentration. Finally, the developed electrochemical sensor has demonstrated to be adequate for bioanalytical applications, presenting an excellent analytical performance for the routine monitoring of MDA in serum samples.

γ-Cyclodextrin-graphene quantum dots-chitosan modified screen-printed electrode for sensing of fluoroquinolones.

An innovative electrochemical approach based on screen-printed carbon electrodes (SPCEs) modified with graphene quantum dots (GQDs) functionalized with γ-cyclodextrin (γ-CD) and assembled to chitosan (CHI) is designed for the assessment of the total content of fluoroquinolones (FQs) in animal source products. For the design of the bionanocomposite, carboxylated graphene quantum dots synthesized from uric acid as precursor were functionalized with γ-CD using succinic acid as a linker. Physic-chemical and nanostructural characterization of the ensuing nanoparticles was performed by high-resolution transmission scanning microscopy, dynamic light scattering, Z potential measurement, Fourier transformed infrared spectroscopy and X-ray diffraction. Electrochemical properties of assembled bionanocomposite like potential difference, kinetic electronic transfer constant and electroactive area among other parameters were assessed by cyclic voltammetry and differential pulse voltammetry using potassium ferricyanide as redox probe. The oxidation behaviour of four representative quinolones with distinctive structures was studied, obtaining in all cases the same number of involved e- (2) and H+ (2) in their oxidation. These results led us to propose a single and consistent oxidation mechanism for all the checked analytes. The γ-CD-GQDs-CHI/SPCE sensor displayed a boosted electroanalytical performance in terms of linear range (4-250 µM), sensibility (LOD = 1.2 µM) and selectivity. This electrochemical strategy allowed the determination of FQs total amount in complex processed food like broths, bouillon cubes and milkshakes at three concentration levels (150, 75 and 37.5 µM) for both equimolar and different ratio FQs mixtures with recovery values ranging from 90 to 106%.

Assessment by a multi-technique approach of PtNPs' transformations in waters under relevant environmental concentrations and conditions.

Once released to the environment, platinum nanoparticles (PtNPs) can undergo different transformations and are affected by several environmental conditions. An only analytical technique cannot provide all the information required to understand those complex processes, so new analytical developments are demanded. In the present work, the potential of asymmetric flow field flow fractionation hyphenated to inductively coupled plasma mass spectrometry (AF4-ICP-MS) for these studies, has been investigated, and classical dynamic and electrophoretic light scattering (DLS & ELS) have been used as complementary techniques. The role of ionic strength, ionic water composition, and natural organic matter (NOM) in the behaviour of PtNPs of different sizes (5 and 50 nm) has been specifically studied. Dynamic and electrophoretic light scattering have been used to track changes in the hydrodynamic diameters (dh) and polydispersity index (PdI) for 50 nm PtNPs (5 nm cannot be studied by DLS) and Z-potential values (for all sizes) to monitor aggregation. AF4-ICP-MS has been also employed to have a solid insight of aggregation at low environmental concentrations for different sizes of PtNPs simultaneously. The information gathered with those techniques was useful to observe changes as the ionic strength increases, which induces aggregation. Also, it was observed that this aggregation process was attenuated in the presence of organic matter. This approach, based on complementary analytical techniques, is needed for a comprehensive study of such complex interactions of NPs in the environment. AF4-ICP-MS is still under-exploited but shows a great potential for this purpose, especially low size NPs and concentrations.

Distinctive sensing nanotool for free and nanoencapsulated quercetin discrimination based on S,N co-doped graphene dots.

A selective and sensitive fluorescent nanoprobe (sulfur and nitrogen co-doped graphene quantum dots, S,N-GQDs) was designed for both detection and discrimination between free and quercetin-loaded nanoemulsion in food samples of diverse nature. Quercetin nanoemulsions (Q-NEs) were synthesized by a phase inversion temperature (PIT) procedure, while S,N-GQDs were synthesized using a bottom-up methodology by means of simple hydrothermal treatment of citric acid and cysteamine. Both synthetized nanomaterials (analyte and fluorescent probe), were carefully characterized through advanced spectroscopic and high-resolution microscopic techniques. It was observed that fluorescence intensity of S,N-GQDs could be markedly and distinctively quenched by the addition of both quercetin forms through inner filter effect (IFE) mechanisms, exhibiting static quenching events for free quercetin and Q-NEs but with a characteristic 13 nm red-shift spectra in presence of Q-NEs. Linear dynamic ranges between 0.05 and 10 mg L-1 and 0.025-70 mg L-1, with detection limits of 17 and 8 µg L-1 were revealed for free and nanoquercetin, respectively. After nanostructural and physic-chemical optimization, the discrimination strategy was metrologically validated and applied to nutraceutical supplements containing nanoencapsulated quercetin and on diverse free quercetin products such as onion peels and dietary supplements. Accuracy and reliability were proved by means of a statistical comparison with the results obtained by a µHPLC-DAD method (paired Student's t-test at 95% confidence level). The method provides the exciting prospect of analyzing new designed nanoencapsulated bioactives without altering their native nanostructure, as well as being able to accomplish the challenge to distinguish between both forms of quercetin.

Detection of Porphyrins in Hair Using Capillary Liquid Chromatography-Mass Spectrometry.

Unlike humans, some animals have evolved a physiological ability to deposit porphyrins, which are pigments produced during heme synthesis in cells, in the skin and associated integument such as hair. Given the inert nature and easiness of collection of hair, animals that present porphyrin-based pigmentation constitute unique models for porphyrin analysis in biological samples. Here we present the development of a simple, rapid, and efficient analytical method for four natural porphyrins (uroporphyrin I, coproporphyrin I, coproporphyrin III and protoporphyrin IX) in the Southern flying squirrel Glaucomys volans, a mammal with hair that fluoresces and that we suspected has porphyrin-based pigmentation. The method is based on capillary liquid chromatography-mass spectrometry (CLC-MS), after an extraction procedure with formic acid and acetonitrile. The resulting limits of detection (LOD) and quantification (LOQ) were 0.006-0.199 and 0.021-0.665 µg mL-1, respectively. This approach enabled us to quantify porphyrins in flying squirrel hairs at concentrations of 3.6-353.2 µg g-1 with 86.4-98.6% extraction yields. This method provides higher simplicity, precision, selectivity, and sensitivity than other methods used to date, presenting the potential to become the standard technique for porphyrin analysis.

SERS-Based Methodology for the Quantification of Ultratrace Graphene Oxide in Water Samples.

The extensive use of graphene materials in real-world applications has increased their potential release into the environment. To evaluate their possible health and ecological risks, there is a need for analytical methods that can quantify these materials at very low concentrations in environmental media such as water. In this work, a simple, reproducible, and sensitive method to detect graphene oxide (GO) in water samples using the surface-enhanced Raman spectroscopy (SERS) technique is presented. The Raman signal of graphene is enhanced when deposited on a substrate of gold nanoparticles (AuNPs), thus enabling its determination at low concentrations with no need for any preconcentration step. The practical limit of quantification achieved with the proposed method was 0.1 ng mL-1, which is lower than the predicted concentrations for graphene in effluent water reported to date. The optimized procedure has been successively applied to the determination of ultratraces of GO in water samples.

Rapid Sample Screening Method for Authenticity Controlling of Vanilla Flavours Using Liquid Chromatography with Electrochemical Detection Using Aluminium-Doped Zirconia Nanoparticles-Modified Electrode.

A rapid and sensitive technique for frauds determination in vanilla flavors was developed. The method comprises separation by liquid chromatography followed by an electrochemical detection using a homemade screen-printed carbon electrode modified with aluminium-doped zirconia nanoparticles (Al-ZrO2-NPs/SPCE). The prepared nanomaterials (Al-ZrO2-NPs) were characterized by using X-ray diffraction (XRD), transmission electron microscopy (TEM) and energy dispersive X-ray (EDX). This method allows for the determination of six phenolic compounds of vanilla flavors, namely, vanillin, p-hydroxybenzoic acid, p-hydroxybenzaldehyde, vanillyl alcohol, vanillic acid and ethyl vanillin in a linear range between 0.5 and 25 µg g-1, with relative standard deviation values from 2.89 to 4.76%. Meanwhile, the limits of detection and quantification were in the range of 0.10 to 0.14 µg g-1 and 0.33 to 0.48 µg g-1, respectively. In addition, the Al-ZrO2-NPs/SPCE method displayed a good reproducibility, high sensitivity, and good selectivity towards the determination of the vanilla phenolic compounds, making it suitable for the determination of vanilla phenolic compounds in vanilla real extracts products.

Graphene quantum dots an efficient nanomaterial for enhancing the photostability of trans-resveratrol in food samples.

Given the health-promoting properties associated with trans-resveratrol consumption and knowing its photochemical instability, as it rapidly isomerizes to the less biologically active conformer, the photoprotective role of a carbon-based nanomaterial was investigated. The resveratrol adsorption on graphene quantum dots (GQDs), synthesized from uric acid, produces a considerable inhibition in the trans- to cis-resveratrol conversion process under light-induced radiation, conferring photostability to the bioactive. The influence of different parameters affecting the adsorption efficiency and loading capacity of resveratrol on GQDs was explored. Several characterization techniques confirmed this interaction, even proving to be non-toxic at the concentration at which the maximum inhibition of isomerization occurs. This adsorption also implies an increase in the antioxidant capacity of the polyphenol. The photoprotective effect was evaluated in food samples, resulting in a considerable slowing down of isomerization. This fact confirms the potential of GQDs to be an effective vehicle of trans-resveratrol to supplement food systems.