Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 41
Filtrar
1.
J Chromatogr A ; 1734: 465286, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39191185

RESUMO

This study pioneers a comparison of the application of biomimetic techniques, immobilised artificial membrane liquid chromatography (IAM LC) and liposome electrokinetic capillary chromatography (LEKC), for the prediction of pulmonary drug permeability. The pulmonary absorption profiles of 26 structurally unrelated drug-like molecules were evaluated using their IAM hydrophobicity index (CHI IAM) measured in IAM LC, and the logarithm of distribution constants (log KLEKC) derived from the LEKC experiments. Lipophilicity (phospholipids) parameters obtained from IAM LC and most LEKC analyses were linearly related to the n-octanol/water partitioning coefficients of the neutral forms (i.e., log Po/w values) to a moderate extent. However, the relationship with distribution coefficients at the experimental pH (7.4) (i.e., log D7.4) were weaker overall for IAM LC data and sigmoidal for some liposome compositions (phosphatidyl choline (PC): phosphatidyl inositol (PI) 85:15 mol% and 90:10 mol%) and concentrations (4 mM) in LEKC. This suggests that phospholipid partitioning supports both hydrophobic and electrostatic interactions occurring between ionised drugs and charged phospholipid moieties. The latter interactions are original when compared to those taking place in the more established n-octanol/water partitioning systems. A stronger correlation (R2 > 0.65) was identified between the LEKC retention parameters, and the experimental apparent lung permeability (i.e., log Papp values) as opposed to the values obtained by IAM LC. Therefore, LEKC offers unprecedented advantages over IAM LC in simulating cell membrane partitioning processes in the pulmonary delivery of drugs. Although LEKC has the advantage of more effectively simulating the electrostatic and hydrophobic forces in drug/pulmonary membrane interactions in vitro, the technique is unsuitable for analysing highly hydrophilic neutral or anionic compounds at the experimental pH. Conversely, IAM LC is useful for analysing compounds spanning a wider range of lipophilicity. Its simpler and more robust implementation, and propensity for high-throughput automation make it a favourable choice for researchers in drug development and pharmacological studies.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Lipossomos , Membranas Artificiais , Lipossomos/química , Preparações Farmacêuticas/química , Mucosa Respiratória/metabolismo , Mucosa Respiratória/química , Cromatografia Líquida/métodos , Cromatografia Capilar Eletrocinética Micelar/métodos , Permeabilidade , Animais , 1-Octanol/química
2.
Arch Toxicol ; 98(8): 2441-2461, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38864942

RESUMO

In this review article, the research works covering the analytical determination of bisphenol A (BPA) and its structural analogues published from 2018 to present (February 2024) were examined. The review offers an overview of the concentration levels of these xenoestrogens in food and beverages, and discusses concerns that these may possibly pose to the human health and scrutinises, from an analytical perspective, the main biomonitoring approaches that are applied. This comes as a natural evolution of a previous review that covered the same topic but in earlier years (up to 2017). As compared to the past, while the volume of published literature on this topic has not necessarily decreased, the research studies are now much more homogeneous in terms of their geographical origin, i.e., Southern Europe (mainly Italy and Spain). For this reason, an estimated daily intake of the European population could not be calculated at this time. In terms of the analytical approaches that were applied, 67% of the research groups exploited liquid chromatography (LC), with a detection that was prevalently (71%) afforded by mass spectrometry, with over one-fourth of the research teams using fluorescence (26%) and a minority (3%) detecting the analytes with diode array detection. One-third of the groups used gas chromatography (GC)-mass spectrometry achieving comparatively superior efficiency as compared to LC. Derivatisation was performed in 59% of the GC studies to afford more symmetrical signals and enhanced sensitivity. Although the contamination levels are well below the threshold set by governments, routinely biomonitoring is encouraged because of the possible accumulation of these contaminants in the human body and of their interplay with other xenoestrogens.


Assuntos
Compostos Benzidrílicos , Contaminação de Alimentos , Fenóis , Compostos Benzidrílicos/análise , Fenóis/análise , Contaminação de Alimentos/análise , Humanos , Europa (Continente) , Monitoramento Biológico/métodos , Disruptores Endócrinos/análise , Monitoramento Ambiental/métodos
3.
Sci Total Environ ; 917: 170461, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38286290

RESUMO

Five parabens (PBs) i.e., Methylparaben (MP), Ethylparaben (EP), Isopropylparaben (iPrP), Isobutylparaben (iBuP), Benzylparaben (BzP), and their parent compound i.e., para-hydroxy Benzoic Acid (pHBA), were studied both in vitro and in silico. Specifically, we determined their retention on several both protein- (Human Serum Albumin and α1-acidic glycoprotein) and (phospho) lipid- (immobilized artificial membrane (IAM)) based biomimetic stationary phases to evaluate their penetration potential through the biomembranes and their possible distribution in the body. The IAM phases were based either on phosphatidylcholine (PC) analogues i.e., PC.MG and PC.DD2 or on sphingomyelin (SPH). We also assessed their viability effect on breast cancer cells (MCF-7) via MTT assay subjecting the cells to five different PB concentrations i.e., 100 µM, 10 µM, 1 µM, 0.1 µM and 0.01 µM. Finally, their pharmacokinetics and toxicity were assessed by the ADMET Predictor™ software. Isopropylparaben was found to be more active than 17ß estradiol (E2) employed as positive control, on the screened cell line inducing cell proliferation up to 150 % more of untreated cells. Other analogues showed only a slight/moderate cell proliferation activity, with parabens having longer/branched side chain showing, on average, a higher proliferation rate. Significant linear direct relationships (for PC.DD2 r2 = 0.89, q2 = 0.86, for SPH r2 = 0.89, q2 = 0.85, for both P value < 0.05) were observed between the difference in proliferative effect between the readout and the control at 0.01 µM concentration and the retention on the IAM phases measured at pH 5.0 for all compounds but pHBA, which is the only analyte of the dataset supporting a carboxylic acid moiety. IAM affinity data measured at pH 7.0 were found to be related to the effective human jejunal permeability as predicted by the software ADMET® Predictor, which is relevant when PBs are added to pharmaceutical and food commodities.


Assuntos
Biomimética , Parabenos , Humanos , Parabenos/toxicidade , Sobrevivência Celular , Cromatografia Líquida/métodos , Membranas Artificiais
4.
J Pharm Biomed Anal ; 235: 115604, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37531733

RESUMO

The charge state of a molecule is the single most prominent attribute ruling out its interactions with the surrounding environment. In a previous study, the retention of acids on the new Celeris™ Arginine (ARG) column was found to be predominantly driven by electrostatics and, specifically, their charge state. Therefore, we analysed 41 compounds in liquid chromatography with ultraviolet detection to study possible relationships between the analytical retention on this phase and the pKa of the acidic solutes. Highly significant relationships were observed indicating either a linear (r2 = 0.86) or a quadratic (r2= 0.89) trend. To improve the throughput of the method, this was transferred to LC mass spectrometry, allowing the analysis of a molecule every 3 mins. The developed method was found to be fast, reliable, accurate, easily automatable and simple to set up. Finally, the analytical column's being industrially manufactured and commercially available offers broad applicability.


Assuntos
Arginina , Compostos Orgânicos , Cromatografia Líquida de Alta Pressão/métodos , Concentração de Íons de Hidrogênio , Cromatografia Líquida/métodos , Espectrometria de Massas
5.
Chemosphere ; 337: 139361, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37392796

RESUMO

Implementing effective environmental management strategies requires a comprehensive understanding of the chemical composition of environmental pollutants, particularly in complex mixtures. Utilizing innovative analytical techniques, such as high-resolution mass spectrometry and predictive retention index models, can provide valuable insights into the molecular structures of environmental contaminants. Liquid Chromatography-High-Resolution Mass Spectrometry is a powerful tool for the identification of isomeric structures in complex samples. However, there are some limitations that can prevent accurate isomeric structure identification, particularly in cases where the isomers have similar mass and fragmentation patterns. Liquid chromatographic retention, determined by the size, shape, and polarity of the analyte and its interactions with the stationary phase, contains valuable 3D structural information that is vastly underutilized. Therefore, a predictive retention index model is developed which is transferrable to LC-HRMS systems and can assist in the structural elucidation of unknowns. The approach is currently restricted to carbon, hydrogen, and oxygen-based molecules <500 g mol-1. The methodology facilitates the acceptance of accurate structural formulas and the exclusion of erroneous hypothetical structural representations by leveraging retention time estimations, thereby providing a permissible tolerance range for a given elemental composition and experimental retention time. This approach serves as a proof of concept for the development of a Quantitative Structure-Retention Relationship model using a generic gradient LC approach. The use of a widely used reversed-phase (U)HPLC column and a relatively large set of training (101) and test compounds (14) demonstrates the feasibility and potential applicability of this approach for predicting the retention behaviour of compounds in complex mixtures. By providing a standard operating procedure, this approach can be easily replicated and applied to various analytical challenges, further supporting its potential for broader implementation.


Assuntos
Misturas Complexas , Cromatografia Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas/métodos , Isomerismo
6.
Environ Pollut ; 316(Pt 1): 120478, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36306887

RESUMO

Bisphenol A (BPA) is a widespread thyroid disruptor, but evidence about an association with thyroid cancer is weak. Excess body weight is a risk factor for thyroid cancer and affects activity of endocrine disruptors. Aim of the study was to investigate the association between BPA exposure and thyroid cancer, verifying the effect modification related to body weight. We performed a multicentre, cross-sectional study including consecutive patients referring for nodular goiter. The quantitative determination of BPA in serum samples was performed through high performance liquid chromatography system, coupled in tandem with ultraviolet and fluorescence detection. Ninety-six patients were included: 55 benign nodules, 41 thyroid cancers, 28 normal weight, and 68 overweight/obese. BPA was detected in 79 subjects. In the overall study population and in the group with BMI<25 kg/m2 BPA exposure was not significantly correlated to thyroid cancer (p = 0.08 and 0.759, respectively). In the group with BMI≥25 kg/m2, BPA-exposed subjects showed significantly higher risk of malignancy (OR: 5.3, p = 0.028). At multivariate analysis, such association was independent of smoking, alcohol consumption, occupational exposure, and phthalates exposure (p = 0.021 and 0.016, respectively), but was lost after adjustment for the presence of metabolic syndrome (p = 0.089). In overweight/obese subjects, BPA exposure was significantly associated with higher thyroid stimulating hormone levels. Our study suggests that BPA exposure is a risk factor for thyroid cancer in overweight/obese subjects.


Assuntos
Disruptores Endócrinos , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/induzido quimicamente , Nódulo da Glândula Tireoide/epidemiologia , Sobrepeso/epidemiologia , Estudos Transversais , Compostos Benzidrílicos , Disruptores Endócrinos/efeitos adversos , Obesidade/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Fatores de Risco
7.
Chemosphere ; 313: 137569, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36535497

RESUMO

Endocrine disruptors are chemicals widely used worldwide by industries in a variety of applications. Routinely exposure to these chemicals, even if at low doses, can cause damage effects on human health. In the present study, we evaluated toxic effects of nine chemicals, among which phthalates, using various cell lines to inspect their capability to interfere with cell proliferation and viability. Alongside, we investigated their affinity for phospholipids to assess the possible passage through biomembranes. Experimentally determined logkwIAM.MG values ranged from 1.37 to 3.49 whilst calculated log kwIAM.DD2 spanned from 1.80 to 5.21, supporting the target contaminants to exhibit lipophilicity moderate or very high. The achieved results were related to pharmacokinetic and toxicological properties by ADMET predictor™ and EPI Suite™ software. Triclosan and 4-Nonylphenol were found to be the most toxic against all cell lines screened, showing an IC50 of 30 µM for triclosan on human keratinocytes and of 50 µM for 4-Nonylphenol on human colorectal adenocarcinoma cells. Overall, even if the phthalates showed higher IC50 values (ranging from 170 µM to 280 µM), we can assert that all contaminants herein tested were able to interfere with cell growth and viability.


Assuntos
Disruptores Endócrinos , Triclosan , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Disruptores Endócrinos/toxicidade , Triclosan/toxicidade , Sobrevivência Celular , Membranas Artificiais , Interações Hidrofóbicas e Hidrofílicas
8.
Biomedicines ; 10(10)2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36289598

RESUMO

The illicit drug market of novel psychoactive substances (NPSs) is expanding, becoming an alarming threat due to increasing intoxication cases and insufficient (if any) knowledge of their effects. Phenethylamine 2-chloro-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) and synthetic cathinone 3,4-methylenedioxy-α-pyrrolidinohexanophenone (3,4-MDPHP) are new, emerging NPSs suggested to be particularly dangerous. This study verified whether these two new drugs (i) possess abuse liability, (ii) alter plasma corticosterone levels, and (iii) interfere with dopaminergic transmission; male and female adolescent rats were included to evaluate potential sex differences in the drug-induced effects. Findings show that the two NPSs are not able to sustain reliable self-administration behavior in rats, with cumulatively earned injections of drugs being not significantly different from cumulatively earned injections of saline in control groups. Yet, at the end of the self-administration training, females (but not males) exhibited higher plasma corticosterone levels after chronic exposure to low levels of 3,4-MDPHP (but not of 2-Cl-4,5-MDMA). Finally, electrophysiological patch-clamp recordings in the rostral ventral tegmental area (rVTA) showed that both drugs are able to increase the firing rate of rVTA dopaminergic neurons in males but not in females, confirming the sex dimorphic effects of these two NPSs. Altogether, this study demonstrates that 3,4-MDPHP and 2-Cl-4,5-MDMA are unlikely to induce dependence in occasional users but can induce other effects at both central and peripheral levels that may significantly differ between males and females.

9.
Materials (Basel) ; 15(13)2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35806753

RESUMO

This study investigated the improvement in the behaviour of a clay soil due to the addition of alkali-activated fly ash as a stabilising agent, and the effects of different activation factors such as alkali dosages and silica moduli. The alkali activator solution used was a mixture of sodium silicate and sodium hydroxide. Class F fly ash was used as the precursor material for the geopolymerisation process. Soil samples stabilised with non-activated class F fly ash were prepared and tested to compare the results with samples stabilised with alkali-activated fly ash. Compaction tests, unconfined compressive strength tests, X-ray diffraction analysis, and scanning electron microscopy analysis were carried out on samples cured 1, 7, and 28 days at room conditions. The results showed that the compressive strength of stabilised soil significantly increased when the fly ash was activated. The optimal activation parameters to stabilise the soil were found to be alkali dosages in the range of 12% to 16% and a silica modulus of 1.25. The highest compressive strength recorded was at 1293 kPa with an alkali dosage of 16% and a silica modulus of 1.25, while for the non-stabilised soil, it was at 204 kPa at 28 days of curing. Mineralogical analysis showed a decrease in the peak intensities of kaolinite and illite, while microstructural analysis indicated an alteration in soil texture with the addition of the alkali-activated fly ash.

10.
Molecules ; 27(13)2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35807230

RESUMO

The concentration levels of thirteen organic pollutants and selected heavy metals were investigated in 40 plastics bottled and tap water samples. Some of the selected contaminants have an ascertained or suspected endocrine disrupting activity, such as Bisphenol A (BPA) and its analogs, and Bis 2-ethylhexyl phthalate (DEHP), which are used by industries as plasticizers. The most frequently detected pollutants were Bisphenol AF (BPAF) (detection frequency (DF) = 67.5%, mean 387.21 ng L-1), DEHP (DF = 62.5%, mean 46.19 µg L-1) and BPA (DF = 60.0%, mean 458.57 ng L-1), with higher concentration levels found in tap waters. Furthermore, a possible level of exposure to thirteen pollutants via drinking water intake was calculated. Our findings show that, even though the occurrence of contaminants and heavy metals in drinking waters does not pose an immediate, acute health risk for the population, their levels should be constantly monitored and "hard-wired" into everyday practice. Indeed, the health impact to the continuous and simultaneous intake of a huge variety of xenobiotics from various sources by humans is complex and still not fully understood.


Assuntos
Dietilexilftalato , Água Potável , Disruptores Endócrinos , Poluentes Ambientais , Poluentes Químicos da Água , Compostos Benzidrílicos/análise , Dietilexilftalato/análise , Disruptores Endócrinos/análise , Humanos , Plastificantes/análise , Plásticos , Poluentes Químicos da Água/análise
11.
Molecules ; 27(13)2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35807508

RESUMO

Parabens (PBs) are used as preservatives to extend the shelf life of various foodstuffs, and pharmaceutical and cosmetic preparations. In this work, the membrane barrier passage potential of a subset of seven parabens, i.e., methyl-, ethyl-, propyl- isopropyl, butyl, isobutyl, and benzyl paraben, along with their parent compound, p-hydroxy benzoic acid, were studied. Thus, the Franz cell diffusion (FDC) method, biomimetic liquid chromatography (BLC), and in silico prediction were performed to evaluate the soundness of both describing their permeation through the skin. While BLC allowed the achievement of a full scale of affinity for membrane phospholipids of the PBs under research, the permeation of parabens through Franz diffusion cells having a carbon chain > ethyl could not be measured in a fully aqueous medium, i.e., permeation enhancer-free conditions. Our results support that BLC and in silico prediction alone can occasionally be misleading in the permeability potential assessment of these preservatives, emphasizing the need for a multi-technique and integrated experimental approach.


Assuntos
Parabenos , Absorção Cutânea , Biomimética , Cromatografia Líquida , Parabenos/química , Conservantes Farmacêuticos/química
13.
J Chromatogr A ; 1651: 462316, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34139386

RESUMO

CelerisTM Arginine (ARG) is a mixed-mode stationary phase recently released on the market. To characterize its analytical behavior, the retention factors of a pool (n=100, of which 36 neutrals, 26 acids and 38 bases) of pharmaceutically relevant compounds have been measured on this phase over eight percentages (from 10 to 90% v/v) of acetonitrile (MeCN) as organic modifier. The ARG phase exhibited enhanced affinity for the molecules that are in their anionic form at the experimental pH, whilst basic compounds, albeit over a wide range of lipophilicity and pKa values, were on average poorly retained. To dissect the separation mechanism of the ARG phase, the overall analytical retention has been deconvoluted into the individual contributions of intermolecular forces by a QSPR/ Partial Least Square (PLS)/Block Relevance (BR) analysis tool recently developed by us. For the neutrals, the most relevant blocks were found to be Size, describing the interaction due to the dimension of the molecule, and O, representing the solute's hydrogen bond donor properties. The change in sign from positive to negative of the Size block, which occurs between 10% and 20% MeCN, allowed to visually appreciate the switch in the separation mode from reversed phase to normal phase. Some good statistic models for rationalizing the analytical behaviour of neutrals were developed from VS+ descriptors. However, their performance in modelling the analytical retention of acids was substandard, probably due to the intrinsic inefficacy of VS+ descriptors in handling electric charges. This instance was addressed by a complimentary MLR strategy, which led to successfully model the retention of acids on the ARG column and to shed light into their retention mechanism, which seemed to be substantially driven by electrostatics.


Assuntos
Arginina/química , Preparações Farmacêuticas/análise , Cromatografia/métodos , Ligação de Hidrogênio , Análise dos Mínimos Quadrados , Análise de Componente Principal
14.
Water Environ Res ; 93(10): 1944-1958, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33794056

RESUMO

Endocrine-disrupting chemicals (EDCs) are agents able to exert perturbation toward the endocrine system via a broad array of signalling pathways. Some EDCs are released into the environment as a result of antropogenic activities. Analytical surveillance plays a critical role in investigating the prevalence of such chemicals in environmental samples. A study was carried out in a lagoon in Southern Italy, a water basin relates to the sea through a mouth channel, making this water body a "dynamic environment". The screening of fourteen EDCs in surface waters and sediments, includes a fast and cost-effective sample preparation, based on a solid-liquid (sediments) and liquid-liquid (surface waters) extraction and a chromatographic analysis by liquid chromatography tandem UV and fluorescence detection. Only four chemicals out the fourteen investigated EDCs were detected in both matrices with a frequency higher than 60%. The average concentrations of the single EDC were higher in sediments (730-155.000 ng kg-1  dw) than in surface waters (132-28.000 ng L-1 ). Limited to the assayed EDCs, the ecosystem has a low risk regarding to the conservation of biodiversity of the animal species living thereby, since the total estrogenic activity does not exceed 1 ng L-1 . PRACTITIONER POINTS: Occurrence of selected EDCs was investigated in an Italian lagoon in Southern Italy. BPAF, BADGE, and BPA were the most frequently and highly detected compounds in both waters and sediments. Concentration levels were greater in the sediment than in water samples. Low risk for the ecosystem biodiversity concerning investigated EDCs.


Assuntos
Disruptores Endócrinos , Poluentes Químicos da Água , Animais , Ecossistema , Disruptores Endócrinos/análise , Monitoramento Ambiental , Itália , Água , Poluentes Químicos da Água/análise
15.
Eur J Pharm Sci ; 162: 105825, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33813038

RESUMO

A new isoform of human manganese superoxide dismutase (SOD) has been recently isolated and obtained in a synthetic recombinant form and termed rMnSOD. As compared to other SODs, this isoform exhibits a dramatically improved cellular uptake and an intense antioxidant and antitumoral activity. Unfortunately, its use is severely hampered as this active pharmaceutical ingredient (API) in solution suffers from remarkable instability, which realizes as an interplay of unfolding and aggregation phenomena. This leads the API to be ineffective after three weeks only when stored at 4°C. A formulation strategy was undertaken to mitigate this instability. This was based on the incorporation of the API in hyaluronic acid and its layer-by-layer deposition over a chitosan-n-acetyl cysteine- monolayer nanoemulsion (NE) and its subsequent coverage with a further external interface of a chitosan-n-acetyl cysteine. The obtained constructs were tested over a selected panel of healthy and cancerous cell lines. The undertaken formulation strategy enhanced the API's effect in vitro already at time zero, maintaining the efficacy of this anticancer agent until up to 30 weeks when stored at 4°C.


Assuntos
Neoplasias , Superóxido Dismutase , Antioxidantes , Humanos , Polímeros , Isoformas de Proteínas
16.
Mar Pollut Bull ; 166: 112241, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33711611

RESUMO

The occurrence of endocrine disrupting chemicals (EDCs) has been determined in two widely consumed fish species from Persian Gulf i.e., Epinephelus coioides and Platycephalus indicus by applying a validated analytical for the simultaneous detection of fourteen EDCs. The concentrations of all detected EDCs were greater in the liver than in the muscle (except for bisphenol A in P. indicus), suggesting a prolonged exposure of the fishes to these pollutants in the Persian Gulf. Specifically, the results showed that di (2-ethylhexyl) phthalate (DEHP) was the compound detected most frequently and at the highest concentration in both species. DEHP levels in ranged from 6.68 to 297.48 µg g-dw-1 and from 13.32 to 350.52 µg g-dw-1, in muscle and in liver, respectively. A risk assessment study was conducted, and demonstrated that consuming two fish based- meals per week may result in a moderate risk especially for vulnerable population groups.


Assuntos
Disruptores Endócrinos , Poluentes Químicos da Água , Animais , Disruptores Endócrinos/análise , Monitoramento Ambiental , Humanos , Oceano Índico , Medição de Risco , Poluentes Químicos da Água/análise
17.
ADMET DMPK ; 9(4): 267-281, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35300371

RESUMO

56 compounds, whose log BB values were known from the scientific literature, were considered and their phospholipophilicity values were calculated in silico. These values, along with either experimentally determined or calculated lipophilicity values, were used to extract cΔ/Δ'log k w IAM parameters. cΔ/Δ'log k w IAM values were found inversely related to data of blood-brain barrier passage, especially in the < -0.20 log BB range and on the IAM.PC.DD2 phase (r2 = 0.79). In multiple linear regression, satisfactory statistic models (r2 (n-1) = 0.76), based on cΔ/Δ'log k w IAM.MG along with other in silico calculated descriptors, were achieved. This method brings the potential to be applied, along with other methodologies, to filter out solutes whose BBB permeation is foreseen to be substandard, thus allowing pharmaceutical companies/research institutes to focus on candidates that are more likely to concentrate in the brain.

18.
Eur J Pharm Sci ; 156: 105585, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33045369

RESUMO

STATE OF THE ART: Sphingomyelin (SPH) is a type of sphingolipid found in animal nerve tissues, especially in the membranous myelin sheath that surrounds some nerve cell axons. Because of its characteristics, SPH stationary phase represents an ideal tool to mimic the interactions taking place between active pharmaceutical ingredients and neurons. METHOD: The IAM.SPH stationary phase (0.821 mg) was suspended in methanol (7.0 mL) and the resulting slurry packed (600 bar) in an HPLC column (10 cm x 2.1 mm). The column was operated at 300 µL min-1 at 25°C using a mobile phase consisting of 60/25/15 (v/v/v) Dulbecco's phosphate buffer saline pH 7.4/methanol/acetonitrile. The elution was achieved isocratically and monitored by UV detection at 220 nm. The investigated dataset consisted of 88 compounds (36 neutrals, 26 bases and 26 acids). The block relevance (BR) analysis was accomplished starting by calculating 82 descriptors using the software VS+ and submitting the data matrices to Matlab. Multiple linear regression and related descriptors were obtained with Vega ZZ 64. RESULTS AND DISCUSSION: The method developed allowed to achieve a solid and reproducible SPH affinity scale for the assayed compounds. Computational studies produced statistically significant models for the prediction and mechanism elucidation of the retentive behavior of pharmaceutically relevant compounds on the SPH stationary phase. CONCLUSIONS: For ionizable compounds, the IAM.SPH exhibited an original selectivity when compared to the commercially available IAM.PC. Moreover, apart from its suitability to surrogate log BB, IAM.SPH was also found relate significantly with the drugs' fraction unbound in plasma, a crucial parameter in pharmacokinetics.


Assuntos
Preparações Farmacêuticas , Esfingomielinas , Animais , Biomimética , Biofarmácia , Cromatografia Líquida de Alta Pressão , Membranas Artificiais
19.
Anal Chim Acta ; 1142: 157-168, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33280693

RESUMO

A comprehensive two-dimensional liquid chromatography-based biomimetic platform (LCxLC) has been developed and validated for drug diffusion studies. Human serum albumin (HSA) and immobilized artificial membrane (IAM) were thereby used in the first (1D) and second (2D) separation dimension, respectively. While the former was meant to emulate the blood, the latter was instead intended to mimic the intestinal mucosa epithelium. Therefore, the experimental conditions, i.e. pH, temperature and buffer composition, were modulated to reflect faithfully in vivo conditions. 30 compounds, whose effective intestinal permeability (Peff) assayed in situ on humans by a validated technique was known from the literature, were used as model drugs. A good and orthogonal separation was achieved for the whole dataset, although for a better distribution of the most polar compounds in the elution window a segmented gradient elution program had to be employed. Interestingly, the passively uptaken compounds having the most favourable Peff populated a specific area of the 2D plots, implying that the affinity for HSA and IAM has to lie in specific ranges in order for a compound to be satisfactorily absorbed from the intestinal lumen. Although these results should be regarded as preliminary, this work paves an entirely new and unprecedented way to profile pharmaceutically relevant compounds for their in vivo absorption and distribution potential.


Assuntos
Biomimética , Membranas Artificiais , Cromatografia Líquida de Alta Pressão , Desenvolvimento de Medicamentos , Humanos , Permeabilidade
20.
J Food Sci ; 84(11): 3303-3311, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31671224

RESUMO

Seven bisphenols, endocrine-disruptor chemicals, were analytically determined for risk assessment in 52 large-consumption beverages collected from the Italian market. The analytes under examination were bisphenol A, bisphenol F, bisphenol E, bisphenol B, bisphenol AF, bisphenol A diglycidyl ether, and bisphenol M. The concentration levels of all bisphenols detected ranged from

Assuntos
Compostos Benzidrílicos/análise , Bebidas/análise , Disruptores Endócrinos/análise , Fenóis/análise , Cerveja/análise , Compostos de Epóxi/análise , Contaminação de Alimentos/análise , Alimentos em Conserva/análise , Humanos , Itália
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA