Basal release and relaxation responses to 6-nitrodopamine in swine carotid, coronary, femoral, and renal arteries.

Mammalian and reptilian vascular tissues present basal release of 6-nitrodopamine, which is reduced when the tissues are pre-incubated with the NO synthase inhibitor L-NG-Nitro arginine methyl ester (L-NAME), or when the endothelium is mechanically removed. 6-Nitrodopamine induces vasorelaxation in pre-contracted vascular rings by antagonizing the dopaminergic D2-like receptor. Here it was investigated whether male swine vessels (including carotid, left descendent coronary, renal, and femoral arteries) release 6-nitrodopamine, dopamine, noradrenaline, and adrenaline, as measured by liquid chromatography coupled to tandem mass spectrometry. The in vitro vasorelaxant action of 6-nitrodopamine was evaluated in carotid, coronary, renal, and femoral arteries precontracted by U-46619 (3 nM), and compared to that induced by the dopamine D2-receptor antagonist L-741,626. Expression of tyrosine hydroxylase and the neuromaker calretinin was investigated by immunohistochemistry. All vascular tissues presented basal release of endothelium-derived catecholamines. The relaxation induced by 6-nitrodopamine was not affected by preincubation of the tissues with either L-NAME (100 µM, 30-min preincubation) or the heme-site inhibitor of soluble guanylyl cyclase ODQ (100 µM, 30-min preincubation). Electrical field stimulation (EFS)-induced contractions were significantly potentiated by previous incubation with L-NAME, but unaffected by ODQ preincubation. The contractions induced by EFS were reduced by preincubation with either 6-nitrodopamine or L-741,626. Immunohistochemistry in all arteries revealed the presence of tyrosine hydroxylase in the endothelium, whereas immunoreactivity for calretinin was negative. Swine vessels present basal release of endothelium-derived catecholamines and expression of tyrosine hydroxylase in the endothelium. The vasodilation induced by 6-nitrodopamine is due to blockade of dopaminergic D2-like receptors.

Characterizing lipid constituents of B. moojeni snake venom: a comparative approach for chemical and biological investigations.

Snake venoms are complex mixtures majorly composed of proteins with well-studied biological effects. However, the exploration of non-protein components, especially lipids, remains limited despite their potential for discovering bioactive molecules. This study compares three liquid-liquid lipid extraction methods for both chemical and biological analyses of Bothrops moojeni snake venom. The methods evaluated include the Bligh and Dyer method (methanol, chloroform, water), considered standard; the Acunha method, a modification of the Bligh and Dyer protocol; and the Matyash method (MTBE/methanol/water), featuring an organic phase less dense than the aqueous phase. Lipidomic analysis using liquid chromatography with high-resolution mass spectrometry (LC-HRMS) system revealed comparable values of lipid constituents' peak intensity across different extraction methods. Our results show that all methods effectively extracted a similar quantity of lipid species, yielding approximately 17-18 subclasses per method. However, the Matyash and Acunha methods exhibited notably higher proportions of biologically active lipids compared to the Bligh and Dyer method, particularly in extracting lipid species crucial for cellular structure and function, such as sphingomyelins and phosphatidylinositol-phosphate. In conclusion, when selecting a lipid extraction method, it is essential to consider the study's objectives. For a biological approach, it is crucial to evaluate not only the total quantity of extracted lipids but also their quality and biological activity. The Matyash and Acunha methods show promise in this regard, potentially offering a superior option for extracting biologically active lipids compared to the Bligh and Dyer method.

A miniaturized QuEChERS and UPLC-MS/MS method for the determination of mycotoxins in cashew nuts.

This study aimed to develop and validate a multi-mycotoxin analysis method applied to cashew nuts by employing a miniaturized QuEChERS method followed by determination by ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Satisfactory recoveries for the concentrations 1, 10 and 30 ng g-1, ranging from 66% (fumonisin B1) to 110% (ochratoxin A) and relative standard deviations lower than 9% (fumonisin B2) were obtained for the target compounds. Limits of quantification ranged from 0.004 ng g-1 (sterigmatocystin) to 0.59 ng g-1 (alternariol). The applicability of the analytical method was verified by analyzing 30 cashew nut samples from the city of Rio de Janeiro, RJ, southeastern Brazil. Aflatoxins M1, G2, G1, B2, B1, ochratoxin A and sterigmatocystin were detected, respectively, in 27%, 10%, 17%, 30%, 30%, 30% and 50% of the analyzed samples, at maximum concentrations of 0.56, 0.67, 1.43, 2.02, 4.93, 4.81, and 0.35 ng g-1. The maximum limit established by Brazilian legislation for aflatoxins was not exceeded by any of the analyzed samples.

Occurrence of a "forever chemical" in the atmosphere above pristine Amazon Forest.

Per- and polyfluoroalkyl substances (PFAS), often referred to as "forever chemicals", are a class of man-made, extremely stable chemicals, which are widely used in industrial and commercial applications. Exposure to some PFAS is now known to be detrimental to human health. By virtue of PFAS long residence times, they are widely detected in the environment, including remote locations such as the Arctics, where the origin of the PFAS is poorly understood. It has been suggested that PFAS may be transported through contaminated waters, leading to accumulation in coastal areas, where they can be aerosolised via sea spray, thereby extending their geographical distribution far beyond their original source regions. The aim of this work is to investigate, for the first time, whether "forever chemicals" could be transported to areas considered to be pristine, far from coastal sites. This study was performed at the Amazonian Tall Tower Observatory (ATTO), a unique remote site situated in the middle of the Amazon rainforest, where a restricted PFAS, perfluorooctanoic acid (PFOA), was observed with concentrations reaching up to 2 pg/m3. A clear trend of increasing concentration with sampling height was observed and air masses from the south over Manaus had the highest concentrations. Atmospheric lifetime estimations, removal mechanisms supported by measurements at two heights (320 and 42 m above the rainforest), and concentration spikes indicated a long-range transport of PFOA to pristine Amazon rainforest. Potential sources, including industrial activities in urban areas, were explored, and historical fire management practices considered. This research presents the first measurements of PFAS in the atmosphere of Amazon rainforest. Remarkably, even in this remote natural environment, appreciable levels of PFAS can be detected. This study provides valuable insights into the long-range transport of the anthropogenic "forever chemical" into a remote natural ecosystem and should raise awareness of potential environmental implications.

Secondary Metabolites and Antioxidant Activity against Moko Disease as a Defense Mechanism of Musa spp. from the Ecuadorian Coast Area.

The Musa spp. represents the most commonly produced, transitioned, and consumed fruit around the globe, with several important applications in the biotechnology, pharmaceutical, and food industries. Moko disease is produced by Ralstonia solanacearum-a factor with a high impact on all crops in Ecuador, representing one of the biggest phytosanitary problems. Four of the most common varieties of Musa spp. were tested to identify the metabolic reaction of plants facing Moko disease. The phenolic and flavonoid content has been evaluated as a defense system, and the α-diphenyl-α-picrylhydrazyl free-radical-scavenging method (DPPH), free-radical-scavenging activity (ABTS), ferric-reducing antioxidant power (FRAP) assays, and liquid chromatography and mass spectrometry (LC-MS) have been adapted to analyze the active compounds with the antioxidant capacity necessary to counteract the pathogenic attack. Our results indicate that all the studied varieties of Musa spp. react in the same way, such that the diseased samples showed a higher accumulation of secondary metabolites with antioxidant capacity compared with the healthy ones, with high active compound synthesis identified during the appearance of Moko disease symptoms. More than 40 compounds and their derivatives (from kaempferol and quercetin glycosides) with protective roles demonstrate the implication of the Musa spp. defense system against R. solanacearum infection.

Determination of pesticide residues in urine by chromatography-mass spectrometry: methods and applications.

Introduction: Pollution has emerged as a significant threat to humanity, necessitating a thorough evaluation of its impacts. As a result, various methods for human biomonitoring have been proposed as vital tools for assessing, managing, and mitigating exposure risks. Among these methods, urine stands out as the most commonly analyzed biological sample and the primary matrix for biomonitoring studies. Objectives: This review concentrates on exploring the literature concerning residual pesticide determination in urine, utilizing liquid and gas chromatography coupled with mass spectrometry, and its practical applications. Method: The examination focused on methods developed since 2010. Additionally, applications reported between 2015 and 2022 were thoroughly reviewed, utilizing Web of Science as a primary resource. Synthesis: Recent advancements in chromatography-mass spectrometry technology have significantly enhanced the development of multi-residue methods. These determinations are now capable of simultaneously detecting numerous pesticide residues from various chemical and use classes. Furthermore, these methods encompass analytes from a variety of environmental contaminants, offering a comprehensive approach to biomonitoring. These methodologies have been employed across diverse perspectives, including toxicological studies, assessing pesticide exposure in the general population, occupational exposure among farmers, pest control workers, horticulturists, and florists, as well as investigating consequences during pregnancy and childhood, neurodevelopmental impacts, and reproductive disorders. Future directions: Such strategies were essential in examining the health risks associated with exposure to complex mixtures, including pesticides and other relevant compounds, thereby painting a broader and more accurate picture of human exposure. Moreover, the implementation of integrated strategies, involving international research initiatives and biomonitoring programs, is crucial to optimize resource utilization, enhancing efficiency in health risk assessment.

Differential Extraction and Preliminary Identification of Polyphenols from Ugni candollei (White Murta) Berries.

Ugni candollei, commonly known as white murta, is a native Chilean berry with a polyphenol composition that has been underexplored. This study aimed to establish a comprehensive profile of white murta polyphenols using ultra-performance liquid chromatography electrospray ionization Orbitrap mass spectrometry (UPLC-ESI-ORBITRAP MS). Additionally, it compared the efficacy of conventional extraction methods with emerging techniques such as deep eutectic solvent (DES) extraction and hot pressurized water extraction (HPWE). The analysis tentatively identified 107 phenolic compounds (84 of them reported for the first time for this cultivar), including 25 phenolic acids, 37 anthocyanins, and 45 flavonoids. Among the prominent and previously unreported polyphenols are ellagic acid acetyl-xyloside, 3-p-coumaroylquinic acid, cyanidin 3-O-(6'-caffeoyl-glucoside, and phloretin 2'-O-xylosyl-glucoside. The study found HPWE to be a promising alternative to traditional extraction of hydroxybenzoic acids, while DES extraction was less effective across all categories. The findings reveal that white murta possesses diverse phenolic compounds, potentially linked to various biological activities.

Analysis of the UV filter Benzophenone-3 assimilation in Crossostrea gigas oysters post-exposure in a controlled environment by LC-MS/MS.

Benzophenone-3 (BP-3), utilized as a UV filter in cosmetic products, is an emerging contaminant that constitutes a threat to natural resources and environmental health. This study investigated the assimilation of the UV filter BP-3 in Crassostrea gigas oysters collected in Florianópolis, Santa Catarina, Brazil. Lyophilized oyster tissue extracts were prepared using the QuEChERS method, and LC-MS/MS was employed to determine the BP-3 concentration in the samples. The method was applied to specimens intentionally exposed to two concentrations of the contaminant, for different periods of exposure (1 and 7 days). Samples from treatment 1 (T1) were exposed to a concentration of 1 µg L-1 of the BP-3 standard, and samples from treatment 2 (T2) were exposed to a concentration of 100 µg L-1 of the BP-3 standard. The results revealed rapid absorption of BP-3, with an increase of 126% for lower concentrations, reaching 1.13 µg of BP-3 per gram of oyster tissue, and 17% for higher concentrations, reaching 34.6 µg of BP-3 per gram of oyster tissue after 7 days. The presence of BP-3 even in samples not directly exposed to the contaminant indicates its widespread environmental distribution. The rapid bioaccumulation suggests the need to consider seasonal variations, such as increased tourism in the summer. The validated analytical method demonstrated efficacy in quantifying BP-3, providing an integrated approach for long-term monitoring of pollution levels and their dynamic variations over time. In addition, variation in BP-3 levels in the samples may be related to transport patterns influenced by tides and discharges from septic system, highlighting the need to improve wastewater treatment. These findings underscore the necessity for continuous biomonitoring and effective environmental management to safeguard the health of marine ecosystems and humans.

Determination of high-intensity sweeteners in bakery products marketed in Brazil and dietary exposure assessment.

Bakery products, including biscuits, cakes and breads, generally present a high content of simple sugars of rapid absorption, high fat content and low amount of dietary fiber, which make them highly caloric foods. Although sucrose is a very important ingredient in bakery products for its preservation characteristics and a significant source of energy, there is a growing interest in replacing this sugar with alternative substances, such as high-intensity sweeteners (HIS) that provide sweetness with no or low calories. In Brazil, there is no data on the use of HIS in this class of food. Therefore, the objective of this study was to evaluate the presence of HIS in baked food commercially available in the country and estimate the dietary exposure to these food additives. For that, an analytical method was established for the simultaneous determination of nine HIS in bakery products using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Sample preparation steps were required based on mechanical kneading for homogenization, hexane extraction of fats, dilution in mobile phase and vortex homogenization, prior to injection into the system. The results obtained during validation showed that coefficients of variation (CV%) for precision were lower than 13.8% and the accuracy was between 91.6% and 109.1%. Aspartame, acesulfame potassium, sodium cyclamate, saccharin, sucralose and steviol glycosides were found in the samples, used alone or in combinations of up five substances. Steviol glycosides were the most found HIS in biscuit samples, while sucralose was the most common sweetener in cake and bread samples. Analysis of product labels revealed only three different claims, .i.e. 'no sugar', 'no added sugar' and 'zero sugar', with the latter being found in 70% of the samples. Exposure to HIS through the consumption of bakery products estimated per eating occasion showed no concerns regarding toxicological risk.

Dereplication of 4-Quinolone Alkaloids from Waltheria Indica (Malvaceae) Tissues Using Molecular Network Tools.

Waltheria indica (Malvaceae) is a plant popularly used in folk medicine by traditional African and indigenous communities, and in various countries worldwide, to treat general inflammation. Several biological activities of this plant have been reported, including acetylcholinesterase inhibition and potential anti-human immunodeficiency virus (HIV), antinociceptive, analgesic, antifungal, anticancer, anti-inflammatory, leishmanicidal, trypanocidal, antioxidant, and antibacterial activities. The chemical profile of Waltheria indica was assessed by dereplication analysis using UPLC-MS/MS, and data acquisition was performed using chemoinformatics tools, such as Mass Spectrometry-Data Independent AnaLysis (MS-DIAL) and MS-FINDER softwares. The preprocessed data were sent to the GNPS to build a feature-based molecular network (FBMN). Thirty-three 4-quinolone alkaloids were annotated in the extracts and fractions of stems and roots, whereas 12 were annotated in the extracts and fractions of flowers and leaves. This represents an inaugural chemical investigation study employing UPLC-Q-TOF-MS/MS analysis, along with a molecular network approach, within this species and genus.

Identification and Characterization of Rotigotine Degradation Products by HPLC Coupled DAD and CAD Detectors and HRMS Through Q-Orbitrap and Electrospray Ionization.

Rotigotine (RTG) is a dopamine agonist used in the treatment of Parkinson's disease. As it is susceptible to oxidation, stability studies must be carefully designed for the identification and characterization of all possible degradation products. Here, RTG degradation was evaluated according to the International Conference on Harmonization guidelines under various stress conditions, including acidic and basic hydrolysis, oxidative, metallic, photolytic, and thermal conditions. Additionally, more severe stress conditions were applied to induce RTG degradation. Significant degradation was only observed under oxidative and photolytic conditions. The samples were analyzed by high performance liquid chromatography coupled to photodiode array detectors, charged aerosol, and high-resolution mass spectrometry. Chromatographic analyses revealed the presence of eight substances related to RTG, four of which were already described and were qualified impurities (impurities B, C, K and E) and four new degradation products (DP-1 - DP-4), whose structures were characterized by high-resolution mass spectrometry through Q-Orbitrap and electrospray ionization. In the stress testing of the active pharmaceutical ingredient in solid form, significant RTG degradation was observed in the presence of the oxidative matrix. The results corroborate the literature that confirm the high susceptibility of RTG to oxidation and the importance of using different detectors to detect degradation products in forced degradation studies.

A LC-MS/MS method for the simultaneous determination of 6-cyanodopamine, 6-nitrodopamine, 6-nitrodopa, 6-nitroadrenaline and 6-bromodopamine in human plasma and its clinical application in patients with chronic kidney disease.

The aim of this study was to develop a high-performance liquid chromatography-tandem mass spectrometry method for the determination of 6-cyanodopamine, 6-nitrodopamine, 6-nitrodopa, 6-nitroadrenaline and 6-bromodopamine in human plasma samples. Strata-X 33 µm solid-phase extraction cartridges were used for the extraction of the catecholamines from human plasma samples. The catecholamines were separated in a 150 × 3 mm Shim-pack GIST C18-AQ column with 3 µm particle size, placed in an oven at 40°C and perfused with 82% mobile phase A (acetonitrile-H2O; 90:10, v/v) + 0.4% acetic acid and 18% mobile phase B (deionized H2O) + 0.2% formic acid at a flow rate of 340 µl/min in isocratic mode. The injected volume was 4 µl and the run lasted 4 min. The method was linear from 0.1 to 20 ng/ml and the lower limit of quantification was 0.1 ng/ml for all analytes. The method was applied to evaluate the plasma levels of catecholamines in plasma of patients with chronic kidney disease and allowed the detection for the first time of circulating levels of the novel catecholamines 6-bromodopamine and 6-cyanodopamine.

Comprehensive analysis of contaminants in Brazilian infant formulas: Application of QuEChERS coupled with UHPLC-QqQ-MS/MS and suspect screening-unknown analysis by UHPLC-Q-Orbitrap-MS.

Infant formulas (IF) can contain harmful chemical substances, such as pesticides and mycotoxins, resulting from the contamination of raw materials and inputs used in the production chain, which can cause adverse effects to infants. Therefore, the quick, easy, cheap, effective, rugged, and safe (QuEChERS) methodology prior ultra-high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPL-QqQ-MS/MS) analysis was applied for the determination of 23 contaminants, in 30 samples of Brazilian IF. The method was validated in terms of limit of detection (0.2 to 0.4 µg/kg), limits of quantification (1 and 10 µg/kg), and recovery (64 % to 122 %); precision values, in terms of relative standard deviation (RSD), were ≤ 20 %. Fenitrothion, chlorpyrifos, and bifenthrin were the pesticides detected in the samples, but the values did not exceed the limit set by the European Union (EU), and ANVISA, and they were detected under their limits of quantification. Additionally, suspect screening and unknown analysis were conducted to tentatively identify 32 substances, including some compounds not covered in this study, such as pesticides, hormones, and veterinary drugs. Carbofuran was identified, confirmed and quantified in 10 % of the samples.

New records on toxic cyanobacteria from Brazil: Exploring their occurrence and geography.

Cyanobacterial Harmful Algal Blooms (CyanoHABs) pose a significant threat to communities globally, impacting ecosystems and public health. This study provides an in-depth review of the current state of cyanotoxins and the distribution of CyanoHABs species in Brazil, while also detailing the methods used for their detection. Four hundred and twenty-one incidents were analyzed from 1993 to 2021, compiling cyanotoxin records and toxic CyanoHABs occurrences. The investigation begins with the first detection of microcystins in 1994 and highlights pivotal moments, like the 1996 "Caruaru Syndrome" outbreak. This event encouraged research and updated cyanotoxin-monitoring guidelines. The Brazilian drought period of 2015-2016 exacerbated cyanobacterial growth and saxitoxin levels, coinciding with Zika-related microcephaly. This study delves into methods used for cyanotoxin analysis, including ELISA, bioassays, HPLC, and LC-MS. Additionally, we investigated the toxicity of 37 cyanobacterial strains isolated from various Brazilian environments. Extracts were tested against Artemia salina and analyzed by LC-MS. Results revealed toxicity in extracts from 49 % of cyanobacterial strains. LC-MS results were analyzed using GNPS MS/MS molecular networking for comparing experimental spectra with those of cyanotoxin standards against in-house databases and the existing literature. Our research underscores the variability in cyanotoxin production among species and over time, extending beyond microcystins. LC-MS results, interpreted through the GNPS platform, revealed six cyanotoxin groups in Brazilian strains. Yet, compounds present in 75 % of the toxic extracts remained unidentified. Further research is crucial for fully comprehending the impact of potentially harmful organisms on water quality and public health management strategies. The study highlights the urgent need for continuously monitoring cyanobacteria and the cyanotoxin inclusion of management in public health policies.

Development of an innovative analytical method for forensic detection of cocaine, antidepressants, and metabolites in postmortem blood using magnetic nanoparticles.

Cocaine and antidepressants rank high globally in substance consumption, emphasizing their impact on public health. The determination of these compounds and related substances in biological samples is crucial for forensic toxicology. This study focused on developing an innovative analytical method for the determination of cocaine, antidepressants, and their related metabolites in postmortem blood samples, using unmodified commercial Fe3O4 nanoparticles as a sorbent for dispersive magnetic solid-phase extraction (m-d-SPE), coupled with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. An aliquot of 100 µL of whole blood and 5 µL of the internal standard pool were added to 30 mg of nanoparticles. The nanoparticles were separated from the sample using a neodymium magnet inserted into a 3D-printed microtube rack. The liquid was then discarded, followed by desorption with 300 µL of 1/1/1 acetonitrile/methanol/ethyl acetate. The sample was vortexed and separated, and 1.5 µL of the organic supernatant was injected into the LC-MS/MS. The method was acceptably validated and successfully applied to 263 postmortem blood samples. All samples evaluated in this study were positive for at least one substance. The most frequent analyte was benzoylecgonine, followed by cocaine and cocaethylene. The most common antidepressants encountered in the analyzed samples were citalopram and fluoxetine, followed by fluoxetine's metabolite norfluoxetine. This study describes the first report of this sorbent in postmortem blood analysis, demonstrating satisfactory results for linearity, precision, accuracy, and selectivity for all compounds. The method's applicability was confirmed, establishing it as an efficient and sustainable alternative to traditional techniques for forensic casework.

Ecotoxicological strategies employing biochemical markers and organisms to monitor the efficacy of malathion photolysis treatment.

The objective of this study was to assess the photolysis-mediated degradation of malathion in standard and commercial formulations, and to determine the toxicity of these degraded formulations. Degradation tests were carried out with 500 µg L-1 of malathion and repeated three times. The initial and residual toxicity was assessed by using Lactuca sativa seeds for phytotoxicity, Stegomyia aegypti larvae for acute toxicity, and Stegomyia aegypti mosquitoes (cultivated from the larval stage until emergence as mosquitoes) to evaluate the biochemical markers of sublethal concentrations. For the standard formulations the photolytic process efficiently reduced the initial concentration of malathion to levels below the regulatory limits however, the formation of byproducts was revealed by chromatography, which allowed for a more complete proposal of photolytic-mediated malathion degradation route. The degraded formulations inhibited the growth of L. sativa seeds, while only the untreated formulations showed larvicidal activity and mortality. Both formulations slightly inhibited acetylcholinesterase activity in S. aegypti mosquitoes, while the standard formulation decreased and the commercial formulation increased glutathione S-transferase activity. However, there were no significant differences for superoxide dismutase, esterase-α, esterase-ß and lipid peroxidation. These findings indicate that in the absence of the target compound, the presence of byproducts can alter the enzymatic activity. In general, photolysis effectively degrade malathion lower than the legislation values; however, longer treatment times must be evaluated for the commercial formulation.

Enhancing oral bioavailability of an antifungal thiazolylhydrazone derivative: Development and characterization of a self-emulsifying drug delivery system.

RN104 (2-[2-(cyclohexylmethylene)hydrazinyl)]-4-phenylthiazole) is a thiazolylhydrazone derivative with prominent antifungal activity. This work aimed to develop a self-emulsifying drug delivery system (SEDDS) loaded with RN104 to improve its biopharmaceutical properties and enhance its oral bioavailability. Medium chain triglycerides, sorbitan monooleate, and polysorbate 80 were selected as components for the SEDDS formulation based on solubility determination and a pseudo-ternary phase diagram. The formulation was optimized using the central composite design in response surface methodology. The optimized condition consisted of medium chain triglycerides, sorbitan monooleate, and polysorbate 80 in a mass ratio of 65.5:23.0:11.5, achieving maximum drug loading (10 mg/mL) and minimum particle size (118.4 ± 0.7 nm). The developed RN104-SEDDS was fully characterized using dynamic light scattering, in vitro release studies, stability assessments, polarized light microscopy, and transmission electron microscopy. In vivo pharmacokinetic studies in mice demonstrated that RN104-SEDDS significantly improved oral bioavailability compared to free RN104 (the relative bioavailability was 2133 %). These results clearly indicated the successful application of SEDDS to improve the pharmacokinetic profile and to enhance the oral bioavailability of RN104, substantiating its potential as a promising antifungal drug candidate.

A peptide dataset for target analysis of human complement system proteins.

The targeted LC-MS/MS method has been widely applied for peptide quantification, offering sensibility, specificity, and reproducibility to the analysis. However, it requires the prior selection of targets, including the construction of a spectral library. Here, we present a dataset comprising peptide mass spectra for targeted LC-MS/MS method setup, applied to a set of human complement system proteins. Additionally, we selected a group of peptides and demonstrated their stability and reproducibility in quantification. This dataset is invaluable for studies aiming at the quantification of the complement system proteins by targeted LC-MS/MS, as it provides data for spectral library construction and a list of selected peptides.

Behavior of diclofenac from contaminated fish after cooking and in vitro digestion.

BACKGROUND: Seafood consumers are widely exposed to diclofenac due to the high contamination levels often present in aquatic organisms. It is a potential risk to public health due its endocrine disruptor properties. Limited information is available about diclofenac behavior after food digestion to enable a more realistic scenario of consumer exposure. This study aimed to evaluate cooking effects on diclofenac levels, and determine diclofenac bioaccessibility by an in vitro digestion assay, using commercial fish species (seabass and white mullet) as models. The production of the main metabolite 4'-hydroxydiclofenac was also investigated. Fish hamburgers were spiked at two levels (150 and 1000 ng g-1) and submitted to three culinary treatments (roasting, steaming and grilling). RESULTS: The loss of water seems to increase the diclofenac levels after cooking, except in seabass with higher levels. The high bioaccessibility of diclofenac (59.1-98.3%) observed in both fish species indicates that consumers' intestines are more susceptible to absorption, which can be worrisome depending on the level of contamination. Contamination levels did not affect the diclofenac bioaccessibility in both species. Seabass, the fattest species, exhibited a higher bioaccessibility of diclofenac compared to white mullet. Overall, cooking decreased diclofenac bioaccessibility by up to 40% in seabass and 25% in white mullet. The main metabolite 4'-hydroxydiclofenac was not detected after cooking or digestion. CONCLUSION: Thus, consumption of cooked fish, preferentially grilled seabass and steamed or baked white mullet are more advisable. This study highlights the importance to consider bioaccessibility and cooking in hazard characterization studies. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Computational prediction of retention times of veterinary antibiotics obtained by liquid chromatography-mass spectrometry.

BACKGROUND: Veterinary antibiotics are chemical compounds used to kill or inhibit the growth of pathogenic bacteria associated with animal diseases. These molecules can be defined by their retention times (tR) in liquid chromatography-mass spectrometry (LC-MS). One strategy to predict the tR of new veterinary antibiotics is the development of predictive quantitative structure-property relationships (QSPRs), which were used in this study. RESULTS: A database of 122 antibiotics was selected in which the tR was measured using a Hypersil GOLD column. An optimal three-feature model was developed by integrating the unsupervised variable reduction, replacement method variable subset selection, and multiple linear regression. The negligible differences among the coefficient of determination and the root-mean-square error for the training set (R2 = 0.902 and RMSEC = 0.871) and test set (Q2 = 0.854 and RMSEP = 1.064) indicate a stable and predictive model. In a further step, a more in-depth explanation of the mechanism of action of each descriptor in predicting the tR is provided, with the construction of the theoretical chemical space for accurate predictions of new antibiotics. CONCLUSION: The in silico model developed in this work identified three molecular descriptors associated with aqueous solubility, octanol-water partition coefficient, and the presence of negative and lipophilic atom pairs. The QSPR developed here could be implemented by agricultural and food chemists to identify and monitor existing and new antibiotics within the framework of LC-MS. The computational model was developed in accordance with five principles outlined by the Organization for Economic Co-operation and Development. © 2024 Society of Chemical Industry.