Pharmaceuticals and personal care products (PPCPs) exhibit varying biodegradability during the acidogenic and methanogenic phases of anaerobic digestion. However, there is limited information regarding the end products generated during these processes. This work investigates the biotransformation products (BTPs) generated in a two-phase (TP) acidogenic-methanogenic (Ac-Mt) bioreactor using advanced suspect and nontarget strategies. Fourteen BTPs were confidently identified from ten parent PPCPs including carbamazepine (CBZ), naproxen (NPX), diclofenac (DCF), ibuprofen (IBU), acetaminophen (ACT), metoprolol (MTP), sulfamethoxazole (SMX), ciprofloxacin (CIP), methylparaben (MPB) and propylparaben (PPB). These BTPs were linked with oxidation reactions such as hydroxylation, demethylation and epoxidation. Their generation was related to organic acid production, since all metabolites were detected during acidogenesis, with some being subsequently consumed during methanogenesis, e.g., aminothiophenol and kynurenic acid. Another group of BTPs showed increased concentrations under methanogenic conditions, e.g., hydroxy-diclofenac and epoxy-carbamazepine. The most PPCPs showed high removal efficiencies (> 90 %) - SMX, CIP, NPX, MTP, ACT, MPB, PPB, while DCF, CBZ and IBU demonstrated higher persistence - DCF (42 %); CBZ (40 %), IBU (47 %). The phase separation of anaerobic digestion provided a deeper understanding of the biotransformation pathways of PPCPs, in addition to enhancing the biodegradability of the most persistent compounds, i.e., DCF, CBZ and IBU.

Exposomics aims to measure human exposures throughout the lifespan and the changes they produce in the human body. Exposome-scale studies have significant potential to understand the interplay of environmental factors with complex multifactorial diseases widespread in our society and whose origin remain unclear. In this framework, the study of the chemical exposome aims to cover all chemical exposures and their effects in human health but, today, this goal still seems unfeasible or at least very challenging, which makes the exposome for now only a concept. Furthermore, the study of the chemical exposome faces several methodological challenges such as moving from specific targeted methodologies towards high-throughput multitargeted and non-targeted approaches, guaranteeing the availability and quality of biological samples to obtain quality analytical data, standardization of applied analytical methodologies, as well as the statistical assignment of increasingly complex datasets, or the identification of (un)known analytes. This review discusses the various steps involved in applying the exposome concept from an analytical perspective. It provides an overview of the wide variety of existing analytical methods and instruments, highlighting their complementarity to develop combined analytical strategies to advance towards the chemical exposome characterization. In addition, this review focuses on endocrine disrupting chemicals (EDCs) to show how studying even a minor part of the chemical exposome represents a great challenge. Analytical strategies applied in an exposomics context have shown great potential to elucidate the role of EDCs in health outcomes. However, translating innovative methods into etiological research and chemical risk assessment will require a multidisciplinary effort. Unlike other review articles focused on exposomics, this review offers a holistic view from the perspective of analytical chemistry and discuss the entire analytical workflow to finally obtain valuable results.

Vitis vinifera L. is a natural source of bioactive compounds that is already used for cosmeceutical and nutraceutical approaches. However, their phytochemical and antioxidant properties, although studied, have not been fully explored. We aimed to characterize V. vinifera L. cv. Falanghina seed extracts in different polarity solvents (hexane, ethyl acetate, ethanol, and a mixture of acetone-water) for their phytochemical contents, including the total phenolic compound content (TPC), free radical scavenging capacities, and antioxidant ability on HepG2 cells. We directly profiled the functional quality of V. vinifera seed extracts against H2O2-induced oxidative stress in HepG2 cells, focusing on mitochondrial functions. The content of bioactive compounds was characterized by LC-MS. To assess the cytocompatibility of the extracts, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted. Results showed that extraction with ethyl acetate (18.12 mg GAE·g-1) and ethanol solvents (18.07 mg GAE·g-1), through Soxhlet, and with an acetone-water mixture (14.17 mg GAE·g-1), through maceration, yielded extracts rich in (poly)phenols, with good scavenging and antioxidant activity (98.32 I% for ethanol solvents and 96.31 I% for acetone-water mixture). The antioxidant effect of polyphenols is at least partially due to their capacity to maintain mitochondrial biogenesis and mitophagy, which elevates mitochondrial efficiency, resulting in diminished ROS production, hence re-establishing the mitochondrial quality control. These findings highlight the valorization of Vitis by-products to improve food functional characteristics.

Estrogen related receptors (ERRs) agonist GSK-9089 (DY-131) reported to pose a potential in increasing exercise endurance. High resolution mass spectrometry (HRMS) based analysis has utmost importance in the detection, identification, or characterization of a molecule including its metabolites in human body. In this study, in vitro metabolism profile of GSK-9089 was investigated after incubation with liver microsomes and S9 fractions. Additionally, in vivo metabolites of the molecule were identified in plasma, urine, and faeces samples of rats. Structures of all the potential metabolites were revealed by employing an in silico tool and HRMS based analysis through data-dependent and data-independent mining strategies. Nine unknown metabolites of GSK-9089 have been identified which were found to be present in a trace amount in in vivo matrices. Most of the in vitro and in vivo phase I metabolites of the molecule were formed after imine bond hydrolysis followed by deamidation, oxidation, and N-oxidation. The molecule underwent phase II metabolism to generate more polar metabolites mainly through glucuronide, sulfate conjugation biotransformation reactions. The in vitro and in vivo metabolites of GSK-9089 could be useful to identify the abuse of this ERRs agonist in the future.

Aim: To synthesize novel more potent anti-diabetic agents. Methodology: A simple cost effective Hantzsch\'s synthetic strategy was used to synthesize 2-(2-arylidenehydrazinyl)thiazol-4(5H)-ones. Results: Fifteen new 2-(2-arylidenehydrazinyl)thiazol-4(5H)-ones were established to check their anti-diabetic potential. From alpha(α)-amylase inhibition, anti-glycation and anti-oxidant activities it is revealed that most of the compounds possess good anti-diabetic potential. All tested compounds were found to be more potent anti-diabetic agents via anti-glycation mode. The results of α-amylase and anti-oxidant inhibition revealed that compounds are less active against α-amylase and anti-oxidant assays. Conclusion: This study concludes that introduction of various electron withdrawing groups at the aryl ring and substitution of different functionalities around thiazolone nucleus could help to find out better anti-diabetic drug.
Diabetes is a most spreading chronicle disease effecting millions of peoples across the globe every year and this number increases day by day. To cure the human population from this dilemma, we had synthesized, characterized and evaluated the anti-diabetic behavior of our synthesized compounds. α-Amylase, in vitro anti-glycation and anti-oxidant assays were performed to find out good lead for Diabetes Mellitus. All tested compounds were found to be excellent anti-glycating agents with IC50 values far better than standard amino-guanidine (IC50 = 3.582 ± 0.002 μM). Compound 4m was most efficient glycation inhibitor (IC50 = 1.095 ± 0.002 μM). Cytotoxicity of all compounds was determined with in vitro hemolytic assay and found all compounds safe and bio-compatible to humans at all tested concentrations. The inhibition potential was also examined with theoretical docking studies to support our experimental results against human pancreatic alpha-amylase (HPA) and human serum albumin (HSA) proteins. All compounds showed excellent binding affinity with HSA active pockets however, only compound 4h and 4k binding affinity was good with HPA.

Efforts to regulate and monitor emerging contaminants are insufficient because new chemicals are continually brought to market, and many are unregulated and potentially harmful. Domestic wastewater treatment plants are not designed to remove micropollutants and are important sources of emerging contaminants in the aquatic environment. In this study, non-target screening, an unbiased method for analyzing compounds without prior information, was used to identify compounds that may be emitted in wastewater treatment plant effluent and should be monitored. Nine wastewater treatment plants using different treatment methods were studied, and a non-target screening data-processing method was used. The frequencies at which the contaminants were detected and contaminant persistence through the treatment processes were considered, and then the contaminants were prioritized. The predicted no-effect concentration of each prioritized contaminant was used to determine whether further analysis and monitoring of the contaminant was necessary. Quantitative analyses of five compounds (amantadine, atenolol, benzotriazole, diphenhydramine, and sulpiride) were performed using reference standards. Probable molecular formulae and structures were proposed for 17 contaminants, and the risks posed by the contaminants were estimated using predicted no-effect concentrations. The results provide valuable insights into how unregulated micropollutants can be identified and prioritized for monitoring in future studies.

High resolution mass spectrometry (HRMS) has become an important tool in environmental and food safety analysis. This review highlights how HRMS has been used to analyze chemical contaminants in fish. Measuring and documenting chemical contaminants in fish serves not only as an indicator of environmental conditions but can also monitor the health of these animals and help protect an important source of human food. The incidence and significance of contaminants including veterinary drugs, human drugs and personal care products, pesticides, persistent organic pollutants, per- and poly fluorinated substances, and marine toxins will be reviewed. The advantage of HRMS over traditional MS is its ability to expand the number of compounds that can be detected and identified. This is true whether HRMS is used for targeted analytes, or more broadly for suspect screening and nontargeted analyses. The classes of compounds, types of fish or seafood, options for data acquisition and analysis, and reports of unexpected findings from recent HMRS methods for chemical contaminants in fish are summarized.

Cannabidiol (CBD) is the main non-psychoactive phytocannabinoid derived from Cannabis sativa L. It is now an active pharmaceutical ingredient (API), given its usage in treating some types of pediatric epilepsy. For this reason, this compound requires a deep characterization in terms of purity and origin. Previous research work has shown two impurities in CBD samples from hemp inflorescences, namely, cannabidivarin (CBDV) and cannabidibutol (CBDB), while abnormal-cannabidiol (abn-CBD) has been described as the primary by-product that is generated from CBD synthesis. Both natural and synthetic CBD samples exhibit the presence of Δ9-tetrahydrocannabinol (Δ9-THC) and Δ8-THC. This study aimed to develop a new analytical method based on high-performance liquid chromatography (HPLC) with different detection systems to study the purity of CBD and to define its origin based on the impurity profile. In addition to the above-mentioned cannabinoids, other compounds, such as cannabigerovarin (CBGV), cannabigerol (CBG), cannabichromevarin (CBCV), and cannabichromene (CBC), were examined as potential discriminating impurities. Qualitative and quantitative analyses were carried out by UHPLC-HRMS and HPLC-UV/Vis, respectively. Principal component analysis was applied for statistical exploration. Natural CBD samples exhibited purities ranging between 97.5 and 99.7%, while synthetic samples were generally pure, except for three initially labeled as synthetic, revealing natural-derived impurities. To further confirm the origin of CBD samples, the presence of other two minor impurities, namely cannabidihexol (CBDH) and cannabidiphorol (CBDP), was assessed as unequivocal for a natural origin. Finally, an enantioselective HPLC analysis was carried out and the results confirmed the presence of the (-)-trans enantiomer in all CBD samples. In conclusion, the HPLC method developed represents a reliable tool for detecting CBD impurities, thus providing a clear discrimination of the compound origin.

Over the past few years, the implementation of mass spectrometry (MS) in QC laboratories has become a more common occurrence. The multi-attribute method (MAM), and emerging intact multi-attribute method (iMAM), are powerful analytical tools utilising liquid chromatography-mass spectrometry (LC-MS) methods that enable the monitoring of critical quality attributes (CQAs) in biotherapeutic proteins in compliant settings. Both MAM and iMAM are intended to replace or supplement several conventional assays with a single LC-MS method utilising MS data in combination with robust, semi-automated data processing workflows. MAM and iMAM workflows can also be implemented into current Good Manufacturing Practices environments due to the availability of CFR 11 compliant chromatography data system software. In this study, MAM and iMAM are employed for the analysis of 4 batches of a glucagon-like peptide-Fc fusion protein. MAM approach involved a first the discovery phase for the identification of CQAs and second, the target monitoring phase of the selected CQAs in other samples. New peak detection was performed on the data set to determine the appearance, absence or change of any peak. For native iMAM workflow both size exclusion and strong cation exchange chromatography were optimized for the identification and monitoring of CQAs at the intact level.

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain compounds with fewer side effects, at the same time effectively overcoming the problem of antimicrobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important support for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of Fourier transform-ion cyclotron resonance (FT-ICR) and Linear Trap Quadrupole (LTQ) mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribution and MSn spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds\' antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents.