A comprehensive HRMS methodology using LC-(ESI)-/GC-(APCI)-QTOF MS complementary platforms for wide-scope target screening of >750 pesticides in olive oil.

This study presents the development and validation of a comprehensive high-resolution mass spectrometry (HRMS) methodology for the detection of 771 pesticides in olive oil, using liquid chromatography with electrospray ionization, operating in positive and negative mode, and gas chromatography with atmospheric-pressure chemical ionization in positive mode, both coupled to quadrupole-time-of-flight mass spectrometry (LC-(ESI)-/GC-(APCI)-QTOF MS). Special reference is made to the post-acquisition evaluation step, in which all LC/GC-HRMS analytical evidence (i.e. mass accuracy, retention time, isotopic pattern, MS/MS fragmentation) is taken into account in order to successfully identify the compounds. The sample preparation of the method involves a QuEChERS-based protocol, common for both techniques, differentiated only on the reconstitution step, making the method highly applicable in routine analysis. A smart evaluation of method's performance was carried out, with 65 representative analytes comprising the validation set. The method was validated in terms of linearity, accuracy, matrix effect and precision, while the limits of detection and quantification of the method were estimated. Finally, twenty Greek olive oil samples were analysed in both analytical platforms and the findings included the pesticides lambda-cyhalothrin, chlorpyrifos, phosphamidon, pirimiphos-methyl and esprocarb at low ng g-1 level.

Evaluating an integrated nano zero-valent iron column system for emerging contaminants removal from different wastewater matrices - Identification of transformation products.

The presence of micropollutants in water bodies has become a growing concern due to their persistence, bioaccumulation and potential toxicological effects on aquatic life and humans. In this study, the performance of a column system consisting of zero-valent iron nanoparticles (nZVI) incorporated into a cationic resin and synthesized from green tea extract with the addition of persulfate for the elimination of selected pharmaceuticals and endocrine disruptors from wastewater is evaluated. Ibuprofen, naproxen, diclofenac and ketoprofen were the target pharmaceuticals from non-steroidal anti-inflammatory drugs group, while bisphenol A was the target endocrine disruptor. In this context, different real wastewater effluent matrices were investigated: anaerobic membrane bioreactor (AnMBR), upflow anaerobic sludge blanket reactor (UASB) after microfiltration, tertiary treated by conventional activated sludge system and saturated vertical constructed wetland followed by a sand filtration unit effluent (hybrid). The transformation products of diclofenac and bisphenol A were also identified. The experimental results indicated that the performance of the R-nFe/PS system towards the removal efficiency of the target compounds was enhanced in the order of effluents: tertiary > AnMBR ≈ hybrid > UASB. More than 70% removal was obtained for almost all target compounds when conventional tertiary effluent was used, while the maximum removal efficiency was about 50% in the case of filtered UASB. As far as we know, this is the first time that nZVI has been assessed in combination with persulfate for the removal of micropollutants in a continuous flow system receiving various types of real wastewater with different matrix characteristics.

Development and validation of a high-throughput headspace solid-phase microextraction gas chromatography-mass spectrometry methodology for target and suspect determination of honey volatiles.

The determination of volatile compounds is essential for the chemical characterisation of honey's aroma and its correlation to its sensory profile and botanical origin. The present study describes the development, optimization and validation of a new, simple and reliable method for the determination of volatile compounds in honey using headspace solid-phase microextraction combined with gas chromatography/mass spectrometry (HS-SPME-GC-MS). The optimization of the SPME conditions showed that the ratio of honey: water (2:1) and the incubation temperature (60 °C) are the most critical parameters. Gas chromatography was performed with medium polar Varian CP-Select 624 column and the experimental Retention Index for a number of compounds was determined as an additional identification feature for suspect analysis. The simultaneous use of four internal standards chlorobenzene, benzophenone, 2-pentanol and 4-methyl-2-pentanone and matrix matched calibration enhanced method accuracy achieving recoveries 73-114 % and repeatability ranging between 3.9 and 19 % relative standard deviations. Furthermore, the superiority of the HS-SPME to static head space technique was verified exhibiting four-to nine-fold higher sensitivity. Target and suspect screening were applied to 30 Greek honey samples and 53 volatile compounds belonging to different chemical classes, such as alkanes, aldehydes, ketones, alcohols, and esters were identified with quantified concentrations ranging between 3.1 µg kg-1 (Limonene) up to 20 mg kg-1 (Benzeneacetaldehyde). Among the new findings is the detection of Myrtenol in Greek pine honey and 2,3-butanediol in Greek oak honey. The developed analytical protocol can be a valuable tool in order to chemically characterize honey based on the volatile content.

First-Row Transition Metal Complexes Incorporating the 2-(2'-pyridyl)quinoxaline Ligand (pqx), as Potent Inflammatory Mediators: Cytotoxic Properties and Biological Activities against the Platelet-Activating Factor (PAF) and Thrombin.

Inflammatory mediators constitute a recently coined term in the field of metal-based complexes with antiplatelet activities. Our strategy targets Platelet-Activating Factor (PAF) and its receptor, which is the most potent lipid mediator of inflammation. Thus, the antiplatelet (anti-PAF) potency of any substance could be exerted by inhibiting the PAF-induced aggregation in washed rabbit platelets (WRPs), which internationally is a well-accepted methodology. Herein, a series of mononuclear (mer-[Cr(pqx)Cl3(H2O]) (1), [Co(pqx)Cl2(DMF)] (2) (DMF = N,N'-dimethyl formamide), [Cu(pqx)Cl2(DMSO)] (3) (DMSO = dimethyl sulfoxide), [Zn(pqx)Cl2] (4)) and dinuclear complexes ([Mn(pqx)(H2O)2Cl2]2 (5), [Fe(pqx)Cl2]2 (6) and [Ni(pqx)Cl2]2 (7)) incorporating the 2-(2'-pyridyl)quinoxaline ligand (pqx), were biologically evaluated as inhibitors of the PAF- and thrombin-induced aggregation in washed rabbit platelets (WRPs). The molecular structure of the five-co-ordinate analog (3) has been elucidated by single-crystal X-ray diffraction revealing a trigonal bipyramidal geometry. All complexes are potent inhibitors of the PAF-induced aggregation in WRPs in the micromolar range. Complex (6) displayed a remarkable in vitro dual inhibition against PAF and thrombin, with IC50 values of 1.79 µM and 0.46 µM, respectively. Within the series, complex (5) was less effective (IC50 = 39 µM) while complex (1) was almost 12-fold more potent against PAF, as opposed to thrombin-induced aggregation. The biological behavior of complexes 1, 6 and 7 on PAF's basic metabolic enzymatic pathways reveals that they affect key biosynthetic and catabolic enzymes of PAF underlying the anti-inflammatory properties of the relevant complexes. The in vitro cytotoxic activities of all complexes in HEK293T (human embryonic kidney cells) and HeLa cells (cervical cancer cells) are described via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The results reveal that complex 3 is the most potent within the series.

Development of a novel apigenin prodrug programmed for alkaline-phosphatase instructed self-inhibition to combat cancer.

Elevated levels of alkaline phosphatase (ALP) in the tumor microenvironment (TME) are a hallmark of cancer progression and thus inhibition of ALP could serve as an effective approach against cancer. Herein, we developed a novel prodrug approach to tackle cancer that bears self-inhibiting alkaline phosphatase-responsiveness properties that can enhance at the same time the solubility of the parent compound. To probe this novel concept, we selected apigenin as the cytotoxic agent since we first unveiled, that it directly interacts and inhibits ALP activity. Consequently, we rationally designed and synthesized, using a self-immolative linker, an ALP responsive apigenin-based phosphate prodrug, phospho-apigenin. Phospho-apigenin markedly increased the stability of the parent compound apigenin. Furthermore, the prodrug exhibited enhanced antiproliferative effect in malignant cells with elevated ALP levels, compared to apigenin. This recorded potency of the developed prodrug was further confirmed in vivo where phospho-apigenin significantly suppressed by 52.8% the growth of PC-3 xenograft tumors.Communicated by Ramaswamy H. Sarma.

Alzheimer's disease: using gene/protein network machine learning for molecule discovery in olive oil.

Alzheimer's disease (AD) poses a profound human, social, and economic burden. Previous studies suggest that extra virgin olive oil (EVOO) may be helpful in preventing cognitive decline. Here, we present a network machine learning method for identifying bioactive phytochemicals in EVOO with the highest potential to impact the protein network linked to the development and progression of the AD. A balanced classification accuracy of 70.3 ± 2.6% was achieved in fivefold cross-validation settings for predicting late-stage experimental drugs targeting AD from other clinically approved drugs. The calibrated machine learning algorithm was then used to predict the likelihood of existing drugs and known EVOO phytochemicals to be similar in action to the drugs impacting AD protein networks. These analyses identified the following ten EVOO phytochemicals with the highest likelihood of being active against AD: quercetin, genistein, luteolin, palmitoleate, stearic acid, apigenin, epicatechin, kaempferol, squalene, and daidzein (in the order from the highest to the lowest likelihood). This in silico study presents a framework that brings together artificial intelligence, analytical chemistry, and omics studies to identify unique therapeutic agents. It provides new insights into how EVOO constituents may help treat or prevent AD and potentially provide a basis for consideration in future clinical studies.

Ultrasound-Assisted Extraction of Total Phenolic Compounds and Antioxidant Activity Evaluation from Oregano (Origanum vulgare ssp. hirtum) Using Response Surface Methodology and Identification of Specific Phenolic Compounds with HPLC-PDA and Q-TOF-MS/MS.

Oregano is native to the Mediterranean region and it has been reported to contain several phenolic compounds particularly flavonoids that have been related with multiple bioactivities towards certain diseases. Oregano is cultivated in the island of Lemnos where the climate promotes its growth and thus it could be further used in promoting local economy. The aim of the present study was to establish a methodology for the extraction of total phenolic content along with the antioxidant capacity of oregano by using response surface methodology. A Box-Behnken design was applied to optimize the extraction conditions with regard to the extraction time, temperature, and solvent mixture with the use of ultrasound-assisted extraction. For the optimized extracts, identification of the most abundant flavonoids (luteolin, kaempferol, and apigenin) was performed with an analytical HPLC-PDA and UPLC-Q-TOF MS methodology. The predicted optimal conditions of the statistical model were identified, and the predicted values confirmed. The linear factors evaluated, temperature, time, and ethanol concentration, all showed significant effect (p < 0.05), and the regression coefficient (R2) presented a good correlation between predicted and experimental data. Actual values under optimum conditions were 362.1 ± 1.8 and 108.6 ± 0.9 mg/g dry oregano with regard to total phenolic content and antioxidant activity based on 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay, respectively. Additionally, further antioxidant activities by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) (115.2 ± 1.2 mg/g dry oregano), Ferric Reducing Antioxidant Power (FRAP) (13.7 ± 0.8 mg/g dry oregano), and Cupric Reducing Antioxidant Capacity (CUPRAC) (1.2 ± 0.2 mg/g dry oregano) assays were performed for the optimized extract. The extract acquired under the optimum conditions contain an adequate quantity of phenolic compounds that could be used in the production of functional foods by food enrichment procedure.

Wide-scope target screening characterization of legacy and emerging contaminants in the Danube River Basin by liquid and gas chromatography coupled with high-resolution mass spectrometry.

A state-of-the-art wide-scope target screening of 2,362 chemicals and their transformation products (TPs) was performed in samples collected within the Joint Danube Survey 4 (JDS4) performed in 2019. The analysed contaminants of emerging concern (CECs) included three major categories: plant protection products (PPPs), industrial chemicals and pharmaceuticals and personal care products (PPCPs). In total, 586 CECs were detected in the samples including 158 PPPs, 71 industrial chemicals, 348 PPCPs, and 9 other chemicals. A wide-variety of sample matrices were collected including influent and effluent wastewater, groundwater, river water, sediment and biota. Forty-five CECs (19 PPPs, 8 industrial chemicals, 18 PPCPs) were detected at levels above their ecotoxicological thresholds (lowest predicted no-effect concentration (PNEC) values) in one or more of the investigated environmental compartments, indicating potential adverse effects on the impacted ecosystems. Among them 12 are legacy substances; 33 are emerging and qualify as potential Danube River Basin Specific Pollutants (RBSPs). Moreover, the efficiency of the wastewater treatment plants (WWTPs) was evaluated using 20 selected performance indicator chemicals. WWTPs showed effective removal (removal rate ≥80%) and medium removal (removal rate 25-80%) for 6 and 8 of the indicator chemicals, respectively. However, numerous contaminants passed the WWTPs with a lower removal rate. Further investigation on performance of WWTPs is suggested at catchment level to improve their removal efficiency. WWTP effluents are proven to be one of the major sources of contaminants in the Danube River Basin (DRB). Other sources include sewage discharges, industrial and agricultural activities. Continuous monitoring of the detected CECs is suggested to ensure water quality of the studied area.

Socioeconomic status and public health in Australia: A wastewater-based study.

Analysis of untreated municipal wastewater is recognized as an innovative approach to assess population exposure to or consumption of various substances. Currently, there are no published wastewater-based studies investigating the relationships between catchment social, demographic, and economic characteristics with chemicals using advanced non-targeted techniques. In this study, fifteen wastewater samples covering 27% of the Australian population were collected during a population Census. The samples were analysed with a workflow employing liquid chromatography high-resolution mass spectrometry and chemometric tools for non-target analysis. Socioeconomic characteristics of catchment areas were generated using Geospatial Information Systems software. Potential correlations were explored between pseudo-mass loads of the identified compounds and socioeconomic and demographic descriptors of the wastewater catchments derived from Census data. Markers of public health (e.g., cardiac arrhythmia, cardiovascular disease, anxiety disorder and type 2 diabetes) were identified in the wastewater samples by the proposed workflow. They were positively correlated with descriptors of disadvantage in education, occupation, marital status and income, and negatively correlated with descriptors of advantage in education and occupation. In addition, markers of polypropylene glycol (PPG) and polyethylene glycol (PEG) related compounds were positively correlated with housing and occupation disadvantage. High positive correlations were found between separated and divorced people and specific drugs used to treat cardiac arrhythmia, cardiovascular disease, and depression. Our robust non-targeted methodology in combination with Census data can identify relationships between biomarkers of public health, human behaviour and lifestyle and socio-demographics of whole populations. Furthermore, it can identify specific areas and socioeconomic groups that may need more assistance than others for public health issues. This approach complements important public health information and enables large-scale national coverage with a relatively small number of samples.

First Novel Workflow for Semiquantification of Emerging Contaminants in Environmental Samples Analyzed by Gas Chromatography-Atmospheric Pressure Chemical Ionization-Quadrupole Time of Flight-Mass Spectrometry.

The ionization efficiency of emerging contaminants was modeled for the first time in gas chromatography-high-resolution mass spectrometry (GC-HRMS) which is coupled to an atmospheric pressure chemical ionization source (APCI). The recent chemical space has been expanded in environmental samples such as soil, indoor dust, and sediments thanks to recent use of high-resolution mass spectrometric techniques; however, many of these chemicals have remained unquantified. Chemical exposure in dust can pose potential risk to human health, and semiquantitative analysis is potentially of need to semiquantify these newly identified substances and assist with their risk assessment and environmental fate. In this study, a rigorously tested semiquantification workflow was proposed based on GC-APCI-HRMS ionization efficiency measurements of 78 emerging contaminants. The mechanism of ionization of compounds in the APCI source was discussed via a simple connectivity index and topological structure. The quantitative structure-property relationship (QSPR)-based model was also built to predict the APCI ionization efficiencies of unknowns and later use it for their quantification analyses. The proposed semiquantification method could be transferred into the household indoor dust sample matrix, and it could include the effect of recovery and matrix in the predictions of actual concentrations of analytes. A suspect compound, which falls inside the application domain of the tool, can be semiquantified by an online web application, free of access at http://trams.chem.uoa.gr/semiquantification/.

Comparative Evaluation of Different Targeted and Untargeted Analytical Approaches to Assess Greek Extra Virgin Olive Oil Quality and Authentication.

Extra virgin olive oil (EVOO) is a key component of the Mediterranean diet, with several health benefits derived from its consumption. Moreover, due to its eminent market position, EVOO has been thoroughly studied over the last several years, aiming at its authentication, but also to reveal the chemical profile inherent to its beneficial properties. In the present work, a comparative study was conducted to assess Greek EVOOs' quality and authentication utilizing different analytical approaches, both targeted and untargeted. 173 monovarietal EVOOs from three emblematic Greek cultivars (Koroneiki, Kolovi and Adramytiani), obtained during the harvesting years of 2018-2020, were analyzed and quantified as per their fatty acids methyl esters (FAMEs) composition via the official method (EEC) No 2568/91, as well as their bioactive content through liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) methodology. In addition to FAMEs analysis, EVOO samples were also analyzed via HRMS-untargeted metabolomics and optical spectroscopy techniques (visible absorption, fluorescence and Raman). The data retrieved from all applied techniques were analyzed with Machine Learning methods for the authentication of the EVOOs' variety. The models' predictive performance was calculated through test samples, while for further evaluation 30 commercially available EVOO samples were also examined in terms of variety. To the best of our knowledge, this is the first study where different techniques from the fields of standard analysis, spectrometry and optical spectroscopy are applied to the same EVOO samples, providing strong insight into EVOOs chemical profile and a comparative evaluation through the different platforms.

Chemical characterisation of Pelargonium sidoides root based on LC-QToF-MS non-target screening strategies.

INTRODUCTION: Pelargonium sidoides is a member of the Geraniaceae family and it originates from the coastal regions of South Africa. In the last decades, Pelargonium sidoides root has been subjected to several surveys due to the assertion of its health benefits, such as the relief of symptoms of acute bronchitis, common cold and acute rhinosinusitis. Many studies have been conducted to reveal its naturally occurring bioactive chemicals, yet no wide-scope chemical characterisation strategies have been done using mass spectrometry. OBJECTIVE: This research aimed to comprehensively characterise the chemical profile of Pelargonium sidoides root via high-resolution mass spectrometry. METHODOLOGY: The Pelargonium sidoides root was extracted by a mixture of methanol: water in the proportion of 80:20. The extraction procedure included vortexing, shaking as well as the use of an ultrasound sonication bath under 40°C. After centrifugation, the supernatant was evaporated to dryness. The dry residue was reconstituted with a mixture of methanol/water (50:50, v/v), filtered and injected into an ultra-high-pressure liquid chromatography-quadruple time-of-flight mass spectrometer. RESULTS: Overall, 33 compounds were identified in the root using suspect and non-target screening. These compounds were originated from different classes of compounds such as amino acids, phenolic acids, α-hydroxy-acids, vitamins, polyphenols, flavonoids, coumarins, coumarins glucosides, coumarin sulphates and nucleotides. Quantitative results were provided for the identified compounds, where their reference standards were available. CONCLUSION: Some important compounds were elucidated, belonging to different classes of compounds such as antioxidants (coumarins and phenolic compounds), amino acids, nucleotides and vitamins revealing the importance of the bioactive content of this root.

Trapped Ion Mobility Incorporated in LC-HRMS Workflows as an Integral Analytical Platform of High Sensitivity: Targeted and Untargeted 4D-Metabolomics in Extra Virgin Olive Oil.

Trapped ion mobility spectrometry (TIMS) is a promising technique for the separation of isomers based on their mobility. In the present work, TIMS coupled to liquid chromatography (LC) and high-resolution mass spectrometry (HRMS) was applied as a comprehensive analytical platform to address authenticity challenges, focusing on extra virgin olive oil (EVOO). Isomers detected in EVOO's phenolic fraction, classified into secoiridoids group, were successfully separated. Thanks to parallel accumulation serial fragmentation (PASEF) acquisition mode, high-quality spectra were obtained, facilitating identification. Moreover, a four-dimensional (4D) untargeted metabolomics approach was implemented to evaluate EVOO's global profile in cases of both variety and geographical origin discrimination. Potential authenticity markers, attributed to isomers, were successfully identified through the proposed workflow that incorporates ion mobility information along with LC-HRMS analytical evidence (i.e., mass accuracy, retention time, isotopic pattern, MS/MS fragmentation). Our study establishes LC-TIMS-HRMS in food authenticity and highlights mobility-enhanced metabolomics in four dimensions.

Assessment of Environmental Pollution and Human Exposure to Pesticides by Wastewater Analysis in a Seven-Year Study in Athens, Greece.

Pesticides have been used in large amounts around the world for decades and are responsible for environmental pollution and various adverse effects on human health. Analysis of untreated wastewater can deliver useful information on pesticides' use in a particular area and allow the assessment of human exposure to certain substances. A wide-scope screening method, based on liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry, was applied, using both target and suspect screening methodologies. Daily composite influent wastewater samples were collected for seven or eight consecutive days in Athens between 2014 and 2020 and analyzed for 756 pesticides, their environmental transformation products and their human metabolites. Forty pesticides were quantified at mean concentrations up to 4.9 µg/L (tralkoxydim). The most abundant class was fungicides followed by herbicides, insect repellents, insecticides and plant growth regulators. In addition, pesticide transformation products and/or metabolites were detected with high frequency, indicating that research should be focused on them. Human exposure was evaluated using the wastewater-based epidemiology (WBE) approach and 3-ethyl-carbamoyl benzoic acid and cis-1,2,3,6-tetrahydrophthalimide were proposed as potential WBE biomarkers. Wastewater analysis revealed the presence of unapproved pesticides and indicated that there is an urgent need to include more transformation products in target databases.

Characterization of the Phenolic Fingerprint of Kolovi Extra Virgin Olive Oils from Lesvos with Regard to Altitude and Farming System Analyzed by UHPLC-QTOF-MS.

Extra virgin olive oil (EVOO) is recognized for its nutritional virtues and the beneficial health effects deriving from its hydrophilic fraction (phenolic acids, phenolic alcohols, flavonoids, and secoiridoids). The phenolic compounds of EVOOs possess multiple biological properties such as antioxidant, antimicrobial, anticarcinogenic, and anti-inflammatory properties, among others. Considering that EVOOs produced in Greece are recognized as high-quality products due to their rich phenolic content, it is imperative to characterize Greek monovarietal EVOOs and ensure that their uniqueness is closely linked to their botanical and territorial origin. In this work, an ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS) analytical method combined with target and suspect screening was used to characterize monovarietal EVOOs of the Kolovi variety from Lesvos, and thereby establish their phenolic fingerprint. Overall, 25 phenols were determined, and the total quantification and semi-quantification results ranged between 251 and 1230 mg/kg, highlighting the high phenolic content of the Kolovi variety from the island of Lesvos in the North Aegean.

Change in the chemical content of untreated wastewater of Athens, Greece under COVID-19 pandemic.

COVID-19 pandemic spread rapidly worldwide with unanticipated effects on mental health, lifestyle, stability of economies and societies. Although many research groups have already reported SARS-CoV-2 surveillance in untreated wastewater, only few studies evaluated the implications of the pandemic on the use of chemicals by influent wastewater analysis. Wide-scope target and suspect screening were used to monitor the effects of the pandemic on the Greek population through wastewater-based epidemiology. Composite 24 h influent wastewater samples were collected from the wastewater treatment plant of Athens during the first lockdown and analyzed by liquid chromatography mass spectrometry. A wide range of compounds was investigated (11,286), including antipsychotic drugs, illicit drugs, tobacco compounds, food additives, pesticides, biocides, surfactants and industrial chemicals. Mass loads of chemical markers were estimated and compared with the data obtained under non-COVID-19 conditions (campaign 2019). The findings revealed increases in surfactants (+196%), biocides (+152%), cationic quaternary ammonium surfactants (used as surfactants and biocides) (+331%), whereas the most important decreases were estimated for tobacco (-33%) and industrial chemicals (-52%). The introduction of social-restriction measures by the government affected all aspects of life.

Patterns of pharmaceuticals use during the first wave of COVID-19 pandemic in Athens, Greece as revealed by wastewater-based epidemiology.

Since 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), impaired public health with considerable morbidity and mortality due to the lack of vaccines and effective treatment. The severe disease mainly harmed adults with predisposing medical comorbidities (such as heart disease, hypertension, chronic lung disease), while it can occur in healthy individuals that may be asymptomatic. Wastewater-based Epidemiology (WBE), a non-invasive, objective, chemical tool was used to monitor and estimate the changes in drug's consumption and prescription patterns under normal conditions (2019) and under COVID-19 pandemic conditions (2020). NSAIDs, antihypertensives, diuretics, antiepileptics, antilipidemics, antibiotics, analgesics, antivirals, anticancer drugs, contrast iodinated drugs, antidiabetics, antiallergic drugs, antiulcers and other pharmaceuticals were studied in wastewater and revealed the application of various treatments during the first wave of the pandemic in Athens, Greece. Data were correlated with COVID-19 infection therapeutical plans. The result of the analysis revealed a remarkable increase for antiviral drugs (170%), hydroxychloroquine (387%), and antibiotics (57%), which were the most applied treatments against COVID-19 during the first wave in Greece. In agreement with related authorities urge, NSAIDs presented decrease (27%) during the first lockdown, while paracetamol demonstrated a remarkable increase (198%). The use levels for Angiotensin II receptor blockers such as valsartan, and co-administrated diuretics, such as hydrochlorothiazide, were reduced during 2020, by 32% and 26% respectively.

Application of High Resolution Mass Spectrometric methods coupled with chemometric techniques in olive oil authenticity studies - A review.

Extra Virgin Olive Oil (EVOO), the emblematic food of the Mediterranean diet, is recognized for its nutritional value and beneficial health effects. The main authenticity issues associated with EVOO's quality involve the organoleptic properties (EVOO or defective), mislabeling of production type (organic or conventional), variety and geographical origin, and adulteration. Currently, there is an emerging need to characterize EVOOs and evaluate their genuineness. This can be achieved through the development of analytical methodologies applying advanced "omics" technologies and the investigation of EVOOs chemical fingerprints. The objective of this review is to demonstrate the analytical performance of High Resolution Mass Spectrometry (HRMS) in the field of food authenticity assessment, allowing the determination of a wide range of food constituents with exceptional identification capabilities. HRMS-based workflows used for the investigation of critical olive oil authenticity issues are presented and discussed, combined with advanced data processing, comprehensive data mining and chemometric tools. The use of unsupervised classification tools, such as Principal Component Analysis (PCA) and Hierarchical Clustering Analysis (HCA), as well as supervised classification techniques, including Linear Discriminant Analysis (LDA), Support Vector Machine (SVM), Partial Least Square Discriminant Analysis (PLS-DA), Orthogonal Projection to Latent Structure-Discriminant Analysis (OPLS-DA), Counter Propagation Artificial Neural Networks (CP-ANNs), Self-Organizing Maps (SOMs) and Random Forest (RF) is summarized. The combination of HRMS methodologies with chemometrics improves the quality and reliability of the conclusions from experimental data (profile or fingerprints), provides valuable information suggesting potential authenticity markers and is widely applied in food authenticity studies.

Antihypertensive activity and molecular interactions of irbesartan in complex with 2-hydroxypropyl-ß-cyclodextrin.

Irbesartan (IRB) exerts beneficial effects either alone or in combination with other drugs on numerous diseases, such as cancer, diabetes, and hypertension. However, due to its high lipophilicity, IRB does not possess the optimum pharmacological efficiency. To circumvent this problem, a drug delivery system with 2-hydroxypropyl-ß-cyclodextrin (2-HP-ß-CD) was explored. The 1:1 complex between IRB and 2-HP-ß-CD was identified through ESI QTF HRMS. Dissolution studies showed a higher dissolution rate of the lyophilized IRB-2-HP-ß-CD complex than the tablet containing IRB at pH = 1.2. DSC results revealed the differences of the thermal properties between the complex and various mixtures consisting of the two components, namely IRB and 2-HP-ß-CD. Interestingly, depending on the way the mixture preparation was conducted, different association between the two components was observed. Molecular dynamics (MD) simulations predicted the favorable formation of the above complex and identified the dominant interactions between IRB and 2-HP-ß-CD. In vitro pharmacological results verified that the inclusion complex not only preserves the binding affinity of IRB for AT1R receptor, but also it slightly increases it. As the complex formulation lacks the problems of the tablet, our approach is a promising new way to improve the efficiency of IRB.

Review on fresh and dried figs: Chemical analysis and occurrence of phytochemical compounds, antioxidant capacity and health effects.

Fig fruit (Ficus carica L.) is one of the most important agricultural products of the tropic and subtropics areas. In the Middle East and the Mediterranean region, the fig is included in diet since the ancient years and it is considered as the symbol of longevity. This review presents the main phytochemical compounds found in fresh and dried figs of different varieties, describes the analytical methods used for their determination and discuss the antioxidant capacity and the potential effects of figs in human health. Phenolic acids and flavonoids are the major types of phytochemical compounds that have been found in fresh and dried figs. Their levels are strongly influenced by various factors such as the color, the part of fruit, the maturity and the drying process. Gallic acid, chlorogenic acid, rutin, quercetin-3-O-rutinoside and epicatechin are the most predominant phenolic acids and flavonoids in dried and fresh fig varieties. Extracts of dark-colored varieties contain higher amount of phenolic compounds than the light-colored varieties. Fruit skin contributes most to the amount of phenolic compounds compared to the fruit pulp. The ripening stage affects the concentrations of phenolic compounds in figs, the maximum have been found in ripe fruit. On the other hand, contradictory results have been reported in the literature regarding the effect of air- and sun- drying on the total content of phytochemical compounds, as well as on the concentrations of individual phenolic compounds and carotenoids in figs. The antioxidant capacity of figs is highly correlated with their amount of phenolic compounds. The leaves, roots, fruit and latex of the plant are known for their health properties including acetyl cholinesterase inhibition, antifungal, anti-helminthic and anticarcinogenic activities. Future efforts should be focused on the application of fig extracts as functional ingredients of food products, on clinical trials in order to confirm the beneficial effect of plant extracts in human health and, on the valorization of the waste material produced during figs' processing.