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Exposure to environmental pollutants or contaminants is correlated with detrimental effects on human health, such as neurodegenerative diseases. Adopting hair as a biological matrix for biomonitoring is a significant innovation, since it can reflect the long-term chemical exposome, spanning months to years. However, only a limited number of studies have developed analytical strategies for profiling the chemical exposome in this heterogeneous biological matrix. In this study, a systematic investigation of the chemical extraction procedure from human hair was conducted, using a design of experiments and a high-resolution mass spectrometry (HRMS)-based suspect screening approach. The PlackettBurman (PB) design was applied to identify the significant variables influencing the number of detected features. Then, a central composite design was implemented to optimize the levels of each identified significant variable. Under the optimal conditions-15-minute pulverization, 25 mg of hair weight, 40 min of sonication, and a sonication temperature of 35 °C-approximately 32,000 and 15,000 aligned features were detected in positive and negative ion modes, respectively. This optimized analytical procedure was applied to hair samples from patients with Alzheimer's disease (AD) and individuals with normal cognitive function. Overall, 307 chemicals were identified using the suspect screening approach, with 37 chemicals differentiating patients with AD from controls. This study not only optimized an analytical procedure for characterizing the long-term chemical exposome in human hair but also explored the associations between AD and environmental factors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The increasing recognition of the health impacts from human exposure to per- and polyfluorinated alkyl substances (PFAS) has surged the need for sophisticated analytical techniques and advanced data analyses, especially for assessing exposure by food of animal origin. Despite the existence of nearly 15,000 PFAS listed in the CompTox chemicals dashboard by the US Environmental Protection Agency, conventional monitoring and suspect screening methods often fall short, covering only a fraction of these substances. This study introduces an innovative automated data processing workflow, named PFlow, for identifying PFAS in environmental samples using direct infusion Fourier transform ion cyclotron resonance mass spectrometry (DI-FT-ICR MS). PFlow's validation on a bream liver sample, representative of low-concentration biota, involves data pre-processing, annotation of PFAS based on their precursor masses, and verification through isotopologues. Notably, PFlow annotated 17 PFAS absent in the comprehensive targeted approach and tentatively identified an additional 53 compounds, thereby demonstrating its efficiency in enhancing PFAS detection coverage. From an initial dataset of 30,332 distinct m/z values, PFlow thoroughly narrowed down the candidates to 84 potential PFAS compounds, utilizing precise mass measurements and chemical logic criteria, underscoring its potential in advancing our understanding of PFAS prevalence and of human exposure., (© 2024. The Author(s).)

Fish feed is essential in aquaculture fish production because, along with beneficial nutrients and components, many suspected compounds can be transferred to fish and ultimately to humans. In this context, a comprehensive analysis was conducted to monitor various pesticides and pharmaceutical compounds in aquaculture fish feed through target analysis and many other groups of chemicals via suspect screening approaches. In this study, the QuEChERS extraction method was optimized, validated, and applied to fifty-four fish feed samples collected from different production batches. This was followed by liquid chromatography-high-resolution linear ion trap/Orbitrap mass spectrometry (LC-HR-IT/Orbitrap-MS) for targeted and suspect screening purposes. In general, pesticides provided satisfactory recoveries (70-105.5 %), with quantification limits lower than 5 ng g -1 , whereas pharmaceuticals displayed recoveries ranging from 70.5 to 120.2 %, with quantification limits below 25 ng g -1 . In addition, the matrix effects and measurement uncertainty were assessed to provide more accurate and high-confidence results. Pirimiphos-methyl was detected and quantified in 20 of 54 fish feed samples (37 %) at concentrations <77 ng g -1 . Finally, suspect screening revealed the occurrence of 10 mycotoxins (e.g., citrinin, aflatoxin G2, zearalenone, and alternariol), two pesticides excluding the target pesticides (tebuconazole and fenazaquin), perfluorooctane sulfonic acid (PFOS) in almost 2 % of the samples, and ethoxyquin (antioxidant), with 12 of its Transformation Products (TPs). Finally, suspect analysis incorporated in routine analyses have proven to have great potential for complete monitoring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Antioxidants are ubiquitous in various environmental samples, leading to increasing concern regarding their potential risk to environments or humans. However, there is dearth of information regarding the environmental fate of antioxidants and unknown/unexpected antioxidants in the environment. Here, we established a compound database (CDB) containing 320 current-used antioxidants by collecting the chemicals from EPA's functional use database and published documents. Physical-chemical characteristics of these antioxidants were estimated, and 19 ones were considered as persistent and bioaccumulative (P&B) substances. This CDB was further coupled with high resolution mass spectrometry (HRMS) technique, which was employed for suspect screening of antioxidants in extracts of sediments (n = 88) collected from Taihu Lake basin. We screened 119 HRMS features that can match 135 chemical formulas in the CDB, and 20 out of them exhibited the detection frequencies ≥ 90%. The total concentrations of suspect antioxidants in sediments ranged from 6.41 to 830 ng/g dw. Statistical analysis demonstrated that concentrations of suspect antioxidants in Taihu Lake were statistically significantly lower than those in Shihu and Jiulihu Lake, but greater than those from other small lakes. Collectively, this study provided a CDB that could be helpful for further monitoring studies of antioxidant in the environments, and also provided the first evidence regarding the ubiquity of antioxidants in aquatic environment of Taihu Lake basin., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The process of cheese-making has long been part of human food culture and nowadays dairy represents a large sector of the food industry. Being the main byproduct of cheese-making, the revalorization of milk whey is nowadays one of the primary goals in alignment with the principles of the circular economy. In the present paper, a deep and detailed investigation of short endogenous peptides in milk and its byproducts (whole whey, skimmed whey, and whey permeate) was carried out by high-resolution mass spectrometry, with a dedicated suspect screening data acquisition and data analysis approach. A total of 79 short peptides was tentatively identified, including several sequences already known for their exerted biological activities. An unsupervised chemometric approach was then employed for highlighting the differences in the short peptide content among the four sets of samples. Whole and skimmed whey showed not merely a higher content of short bioactive peptides compared to whole milk, but also a peculiar composition of peptides that are likely generated during the process of cheese-making. The results clearly demonstrate that whey represents a valuable source of bioactive compounds and that the set-up of processes of revalorization of milk byproducts is a promising path in the obtention of high revenue-generating products from dairy industrial waste.

Since 2011, the World Health Organization has encouraged a global phase-down of the use of dental amalgam and actively supported the use of alternative, resin-based dental materials. The resins consist of (meth)acrylate monomers derived from Bisphenol A (BPA), such as Bisphenol A glycidyl methacrylate (BisGMA) and Bisphenol A ethoxylate methacrylate (BisEMA) or triethylene glycol dimethacrylate (TEGDMA) and urethane dimethacrylate (UDMA) which lack the BPA backbone. Besides monomers, other compounds such as photoinitiators and stabilizing agents can be present in the dental resin matrices. The current study consists in the development of an analytical method for the separation and identification of dental material components using LC-QTOF-MS. The developed method was applied on several dental material ingredients, unpolymerized composite resins, and a common dental sealant. The acquired high resolution accurate-mass data was analyzed using suspect screening with an in-house developed library. Next to the main components, various isomers and impurities related to the production of the main component have been detected and identified in the dental material ingredients. In total, 39 chemicals have been identified in the analyzed dental materials. On average 15 chemicals have been identified. Major components, such as BisEMA, BisGMA and TEGDMA were identified although they were not always stated in the material safety data sheets. Minor components included photoinitiators, such as ethyl 4-dimethyl aminobenzoate (EDMAB) and (meth)acrylates impurities originating from production of main ingredients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A new mass spectrometric method for evaluating metabolite formation of the pesticides thiacloprid, azoxystrobin, and difenoconazole was developed for the Brassica species pak choi and broccoli. Both, distribution and transformation kinetics of the active compounds and their metabolites were analyzed by UPLC-TWIMS-QTOF-MS. Additionally, HR-MS analysis and structure elucidation tools such as diagnostic ions, isotopic matches, and collision cross sections were applied for metabolites identification. Following the application of two plant protection products (containing the above-mentioned active compounds) in a greenhouse study plant material was cryo-milled and extracted with water/methanol. The residual levels of active compounds were identified at certain timepoints during pre-harvest intervals and in the final products. Different phase I and phase II metabolites of the pesticides were identified in different plant organs such as leaves, stems, (broccoli) heads, and roots. Three individual degradation pathways and distribution profiles are suggested including eight thiacloprid, eleven azoxystrobin and three difenoconazole metabolites., (Copyright © 2017. Published by Elsevier Ltd.)

Retrospective in silico screening of analytical data for the identification of new or emerging disinfection by-products in drinking waters could be useful to assess quality and potential hazards, as well as help implement mitigation procedures more rapidly. Herein, the first study coupling ion exchange chromatography (IC) with high resolution mass spectrometry (HRMS) for the determination of halogenated carboxylic acid disinfectant by-products is reported. Separation was achieved using a Metrohm A Supp 5 column and a Na 2 CO 3 /NaHCO 3 gradient eluent from 1/0.31 to 10/3.1mM. A variety of solid phase extraction (SPE) sorbents were tested for added selectivity to organic ions and Isolute ENV+ cartridges were selected because of their best overall extraction performance. Method LODs were in the μgL -1 concentration range, with R 2 ≥ 0.99 for all the analytes, and isobaric ions could be easily discriminated using HRMS. The method was applied to municipal drinking water. Targeted quantitative analysis revealed the presence of 10 haloacetic acids at levels not exceeding the limits set by WHO and USEPA. Furthermore, suspect screening for additional halogenated carboxylic acids via retrospective HRMS data analysis also indicated the presence of other iodinated HAAs and chlorinated propionic acids, of which one (i.e. monochloropropionic acid) is discussed here for the first time. Most importantly, several potential suspects could be eliminated from further consideration through HRMS data analysis alone. To our knowledge, this represents the first time that a retrospective IC-HRMS screen of halogenated carboxylic acids in drinking water has been reported., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Access to clean, safe drinking water poses a serious challenge to regulators, and requires analytical strategies capable of rapid screening and identification of potentially hazardous chemicals, specifically in situations when threats to water quality or security require rapid investigations and potential response. This study describes a fast and efficient chemical hazard screening strategy for characterising trace levels of polar organic contaminants in water matrices, based on liquid chromatography high resolution mass spectrometry with post-acquisition 'case-control' data processing. This method allowed for a rapid response time of less than 24 h for the screening of target, suspect and non-target unknown chemicals via direct injection analysis, and a second, more sensitive analysis option requiring sample pre-concentration. The method was validated by fortifying samples with a range of pesticides, pharmaceuticals and personal care products (n = 46); with >90% of target compounds positively screened in samples at 1 ng mL -1 , and 46% at 0.1 ng mL -1 when analysed via direct injection. To simulate a contamination event samples were fortified with compounds not present in the commercial library (designated 'non-target compounds'; fipronil and fenitrothion), tentatively identified at 0.2 and 1 ng mL -1 , respectively; and a compound not included in any known commercial library or public database (designated 'unknown' compounds; 8Cl - perfluorooctanesulfonic acid), at 0.8 ng mL -1 . The method was applied to two 'real-case' scenarios: (1) the assessment of drinking water safety during a high-profile event in Brisbane, Australia; and (2) to screen treated, re-circulated drinking water and pre-treated (raw) water. The validated workflow was effective for rapid prioritisation and screening of suspect and non-target potential hazards at trace levels, and could be applied to a wide range of matrices and investigations where comparison of organic contaminants between an affected and control site and or timeframe is warranted., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

One of the difficulties encountered when monitoring groundwater quality is low and fluctuating concentration levels and complex mixtures of micropollutants, including emerging substances or transformation products. Combining passive sampling techniques with analysis by high resolution mass spectrometry (HRMS) should improve environmental metrology. Passive samplers accumulate compounds during exposure, which improves the detection of organic compounds and integrates pollution fluctuations. The Polar Organic Chemical Integrative Sampler (POCIS) were used in this study to sequester polar to semi-polar compounds. The methodology described here improves our knowledge of environmental pollution by highlighting and identifying pertinent compounds to be monitored in groundwater. The advantage of combining these two approaches is demonstrated on two different sites impacted by agricultural and/or urban pollution sources where groundwater was sampled for several months. Grab and passive sampling were done and analyzed by liquid chromatography coupled to a hybrid quadrupole time-of-flight mass spectrometer (LC-QTOF). Various data processing approaches were used (target, suspect and non-target screening). Target screening was based on research from compounds listed in a homemade database and suspect screening used a database compiled using literature data. The non-target screening was done using statistical tools such as principal components analysis (PCA) with direct connections between original chromatograms and ion intensity. Trend plots were used to highlight relevant compounds for their identification. The advantage of using POCIS to improve screening of polar organic compounds was demonstrated. Compounds undetected in water samples were detected with these tools. The subsequent data processing identified sentinel molecules, molecular clusters as compounds never revealed in these sampling sites, and molecular fingerprints. Samples were compared and multidimensional visualization of chemical patterns such as molecular fingerprints and recurrent or specific markers of each site were given., (Copyright © 2016 Elsevier B.V. All rights reserved.)

For the prioritization of more than 5200 anthropogenic chemicals authorized on the European market, we use a large scale liquid chromatography-high resolution mass spectrometry (LC-HRMS) suspect screening study. The prioritization is based on occurrence in 151 water samples including effluent, surface water, ground water and drinking water. The suspect screening linked over 700 detected compounds with known accurate masses to one or multiple suspects. Using a prioritization threshold and removing false positives reduced this to 113 detected compounds linked to 174 suspects, 24 compounds reflect a confirmed structure by comparison with the pure reference standard. The prioritized compounds and suspects are relevant for detailed risk assessments after confirmation of their identity. Only one of the 174 prioritized compounds and suspects is mentioned in water quality regulations, and only 20% is mentioned on existing lists of potentially relevant chemicals. This shows the complementarity to commonly used target-based methods. The semi-quantitative total concentration, expressed as internal standard equivalents of detected compounds linked to suspects, in effluents is approximately 10 times higher than in surface waters, while ground waters and drinking waters show the lowest response. The average retention time, a measure for hydrophobicity, of the detected compounds per sample decreased from effluent to surface- and groundwater to drinking water, confirming the occurrence of more polar compounds in drinking water. The semi-quantitative total concentrations exceed the conservative and precautionary threshold of toxicological concern. Therefore, adverse effects of mixtures cannot be neglected without a more thorough risk assessment., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

High-resolution mass spectrometry (HRMS) has become an important tool for monitoring chemical residues in food, but the time and effort required to evaluate the large amount of data generated by HRMS can be a limiting factor in the widespread application of this tool. Suspect screening, i.e., searching HRMS data against large compound databases or mass lists, represents a practical compromise between using HRMS data to only look for target compounds and performing full non-target analysis. Several different approaches for suspect screening using HRMS data were tested using data from shrimp and eel spiked with veterinary drugs and pesticides as well as from imported aquaculture samples. Most of the analytes (>70%) in the spiked samples were detected and identified by searching against compound databases. To query larger databases and on-line resources such as mzCloud, it was necessary to use software capable of differential analysis and selective filtering, such as Compound Discoverer. Using selective filtering, the number of compounds detected in fish sample extracts could be reduced from tens of thousands to a few hundred by subtracting method blanks and comparing to matrix blank extracts. This smaller list of potential compounds could be further evaluated and compared to available databases and libraries. Analysis of imported aquaculture samples resulted in detection of unexpected contaminants including the dewormer levamisole, the insecticide buprofezin, and potentially the plant alkaloid ricinine. [ABSTRACT FROM AUTHOR]

Our proof-of-concept study develops a suspect screening workflow to identify and prioritize potentially ubiquitous chemical exposures in matched maternal/cord blood samples, a critical period of development for future health risks. We applied liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF/MS) to perform suspect screening for ∼3500 industrial chemicals on pilot data from 30 paired maternal and cord serum samples (n = 60). We matched 662 suspect features in positive ionization mode and 788 in negative ionization mode (557 unique formulas overall) to compounds in our database, and selected 208 of these for fragmentation analysis based on detection frequency, correlation in feature intensity between maternal and cord samples, and peak area differences by demographic characteristics. We tentatively identified 73 suspects through fragmentation spectra matching and confirmed 17 chemical features (15 unique compounds) using analytical standards. We tentatively identified 55 compounds not previously reported in the literature, the majority which have limited to no information about their sources or uses. Examples include (i) 1-(1-acetyl-2,2,6,6-tetramethylpiperidin-4-yl)-3-dodecylpyrrolidine-2,5-dione (known high production volume chemical) (ii) methyl perfluoroundecanoate and 2-perfluorooctyl ethanoic acid (two PFAS compounds); and (iii) Sumilizer GA 80 (plasticizer). Thus, our workflow demonstrates an approach to evaluating the chemical exposome to identify and prioritize chemical exposures during a critical period of development.

[Display omitted] • Q Exactive-Orbitrap MS used for targeted quantification and untargeted exploration. • Accuracy profile enabled HS-SPME- vs. SHS-GC-HRMS for furan quantification. • SHS-GC-HRMS was more precise and sensitive for furan quantification in infant food. • SHS-GC-HRMS was validated for quantification of furan, 2-MF and 3-MF in infant food. • Furan, 2MF and 3MF were quantified in the main classes of commercial infant food. • Untargeted screening of HS-SPME-GC-HRMS data underlined 13 more furan derivatives. The aim of the present study was to assess the performance and complementarity of methods capable of both quantifying furan, 2-Methylfuran (2-MF) and 3-Methylfuran (3-MF) in infant foods, but also to comprehensively explore other furan derivatives. It is more particularly a question of validating and comparing the couplings of the two headspace extraction methods most used for the analysis of furan compounds − Headspace Solid Phase Microextraction (HS-SPME) and Static HeadSpace (SHS) – with gas chromatography hyphenated to a high-resolution mass detector (Q Exactive-Orbitrap MS) which allows both targeted quantification and suspect screening. Firstly, the accuracy profile approach was implemented to assess, validate and compare HS-SPME- and SHS-GC-Q Exactive-Orbitrap MS for the quantification of furan in two model infant foods, apple puree and first infant formula. SHS-GC-Q Exactive-Orbitrap MS, showed better accuracy (uncertainty < 17.2 % vs 22.5 % for HS-SPME GC-Q Exactive-Orbitrap MS) and better sensitivity (LOQ < 2.8 vs LOQ < 4.0 µg/kg) over a broader validation range (2–100 µg/kg vs 5–100 µg/kg in apple puree). Secondly, SHS-GC-Q Exactive-Orbitrap MS was assessed and validated by accuracy profile for the quantification of 2-MF and 3-MF, with performance close to those for furan except for 3-MF in apple puree. Thirdly, SHS-GC-Q Exactive-Orbitrap MS was used to quantify the levels of these compounds in 20 commercial samples (n = 3) belonging to the four main categories of infant food (infant formulae, fruit purees, infant cereals, vegetable/fish baby meals). Furan was quantified in 75 % of the samples, with maximum levels in the vegetable/fish-based infant foods (up to 127 µg/kg) while 2-MF and 3-MF were quantified in 45 % and 15 % of products respectively, with maximum levels of 14.1 µg/kg in follow-on formula 3rd age and 9.2 µg/kg in apple puree. Finally, SHS- and HS-SPME-GC-Q Exactive-Orbitrap MS data of the 20 infant products were processed in suspect screening mode using Compound DiscovererTM software. Coupling with HS-SPME, it made it possible to identify 13 additional furan derivatives, i.e. 5 more than with SHS. The relevance and safety status of the compounds identified are discussed. [ABSTRACT FROM AUTHOR]

Plasticizers are chemicals that make plastics flexible, and phthalates are commonly used. Due to the toxic effects of phthalates, there is increasing use of non-phthalate plasticizers like acetyl tributyl citrate (ATBC). ATBC has emerged as a safer alternative, yet concerns about its long-term safety persist due to its high leachability and potential endocrine-disrupting effects. This study aims to identify ATBC metabolites using human liver microsomes and suspect screening methods, and to explore potential urinary biomarkers for ATBC exposure. Using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry, we identified ATBC metabolites, including acetyl dibutyl citrate (ADBC), tributyl citrate (TBC), and dibutyl citrate (DBC). Urine samples from 15 participants revealed the presence of ADBC in 5, TBC in 11, and DBC in all samples, with DBC concentrations pointedly higher than the other metabolites. These metabolites show promise as biomarkers for ATBC exposure, though further validation with human data is required. Our results underscore the need for comprehensive studies on ATBC metabolism, exposure pathways, and urinary excretion to accurately assess human exposure levels. [Display omitted] • LC-HRMS-based suspect screening method was applied to identify metabolites of ATBC. • ADBC, DBC, and TBC were identified as putative metabolites of ATBC from in vitro experiments using human liver microsomes. • Quantitative analytical methods for metabolites of ATBC in human urine were developed. • ADBC specific for ATBC exposure was detected in low concentrations and only a few, while DBCs were found in all participants. • Further research is needed on urinary excretion fractions and metabolic pathways to accurately assess human exposure to ATBC. [ABSTRACT FROM AUTHOR]

The use and advantages of high-resolution mass spectrometry (MS) as a discovery tool for environmental chemical monitoring has been demonstrated for environmental samples but not for biological samples. We developed a method using liquid chromatography-quadrupole time-of-flight MS (LC-QTOF/MS) for discovery of previously unmeasured environmental chemicals in human serum. Using non-targeted data acquisition (full scan MS analysis) we were able to screen for environmental organic acids (EOAs) in 20 serum samples from second trimester pregnant women. We define EOAs as environmental organic compounds with at least one dissociable proton which are utilized in commerce. EOAs include environmental phenols, phthalate metabolites, perfluorinated compounds, phenolic metabolites of polybrominated diphenyl ethers and polychlorinated biphenyls, and acidic pesticides and/or predicted acidic pesticide metabolites. Our validated method used solid phase extraction, reversed-phase chromatography in a C18 column with gradient elution, electrospray ionization in negative polarity and automated tandem MS (MS/MS) data acquisition to maximize true positive rates. We identified "suspect EOAs" using Agilent MassHunter Qualitative Analysis software, to match chemical formulas generated from each sample run with molecular formulas in our unique database of 693 EOAs assembled from multiple environmental literature sources. We found potential matches for 282 (41%) of the EOAs in our database. Sixty-five of these suspect EOAs were detected in at least 75% of the samples; only 19 of these compounds are currently biomonitored in National Health and Nutrition Examination Survey. We confirmed two of three suspect EOAs by LC-QTOF/MS using a targeted method developed through LC-MS/MS, reporting the first confirmation of benzophenone-1 and bisphenol S in pregnant women's sera. Our suspect screening workflow provides an approach to comprehensively scan environmental chemical exposures in humans. This can provide a better source of exposure information to help improve exposure and risk evaluation of industrial chemicals.

Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for "suspect screening" lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide. Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA's CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101). Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the "one substance, one assessment" approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/). [ABSTRACT FROM AUTHOR]

Pancreatic lipase (PNLIP, EC 3.1.1.3) plays a pivotal role in the digestion of dietary lipids, a metabolic pathway directly related to obesity. One of the effective strategies in obesity treatment is the inhibition of PNLIP, which is possible to be achieved by specific phenolic compounds occurring in high abundance in some plants. In this study, a multidisciplinary approach is presented investigating the PNLIP inhibitory effect of 33 plants belonging in the Asteraceae botanical family. In the first stage of the study, a rapid and cost-efficient PNLIP assay in a 96-microwell plate format was developed and important parameters were optimized, e.g., the enzyme substrate. Upon PNLIP assay optimization, aqueous and dichloromethane Asteraceae plant extracts were tested and a cut-off inhibition level was set to further analyze only the samples with a significant inhibitory effect (inhibitory rate > 40%), using an ultra-high-performance liquid chromatography hybrid quadrupole time-of-flight mass spectrometry (UHPLC-q-TOF-MS) method. Specifically, a metabolomic suspect screening was performed and 69 phenolic compounds were tentatively identified, including phenolic acids, flavonoids, flavonoid-3-O-glycosides, and flavonoid-7-O-glycosides, amongst others. In the case of aqueous extracts, phytochemicals known for inducing PNLIP inhibitory effect, e.g., compounds containing galloyl molecules or caffeoylquinic acids, were monitored in Chrysanthemum morifolium, Grindella camporum and Hieracium pilosella extracts. All in all, the presented approach combines in vitro bioactivity measurements to high-end metabolomics to identify phenolic compounds with potential medicinal and/or dietary applications. [ABSTRACT FROM AUTHOR]

Short peptides have been spiking interest owing to their significant contribution to the taste and functional properties of dry-cured ham. In this study, a suspect screening approach based on high-resolution mass spectrometry was employed for the comprehensive characterization of the short endogenous peptidome in dry-cured ham samples at different processing stages (14, 22, and 34 months). After careful manual spectra interpretation, a chemometric approach based on principal component analysis was employed for highlighting the differences between the three sets of samples. A total of 236 short peptide sequences was tentatively identified, including 173 natural short peptides and 63 sequences containing non-proteinogenic amino acids, the highest number ever reported for endogenous sequences in dry-cured ham. Samples in the latest processing stages presented a generally higher abundance of dipeptides, indicating residual proteolytic activity. Moreover, the several annotated modified short peptides, mainly pyroglutamination and lactoyl conjugation, allowed hypothesizing several reactions occurring over time. For the first time, several lactoyl-dipeptides were tentatively identified in dry-cured ham samples with maximum concentration in the late processing stage samples. The presented results significantly contribute to the understanding of the reaction involving short peptides that affect the sensory and functional properties of dry-cured ham. [ABSTRACT FROM AUTHOR]

The global manufacturing of clothing is usually composed of multistep processes, which include a large number of chemicals. However, there is generally no information regarding the chemical content remaining in the finished clothes. Clothes in close and prolonged skin contact may thus be a significant source of daily human exposure to hazardous compounds depending on their ability to migrate from the textiles and be absorbed by the skin. In the present study, twenty-four imported garments on the Swedish market were investigated with respect to their content of organic compounds, using a screening workflow. Reversed-phase liquid chromatography coupled to electrospray ionization/high-resolution mass spectrometry was used for both suspect and non-target screening. The most frequently detected compound was benzothiazole followed by quinoline. Nitroanilines with suspected mutagenic and possible skin sensitization properties, and quinoline, a carcinogenic compound, were among the compounds occurring at the highest concentrations. In some garments, the level of quinoline was estimated to be close to or higher than 50,000 ng/g, the limit set by the REACH regulation. Other detected compounds were acridine, benzotriazoles, benzothiazoles, phthalates, nitrophenols, and organophosphates. Several of the identified compounds have logP and molecular weight values enabling skin uptake. This pilot study indicates which chemicals and compound classes should be prioritized for future quantitative surveys and control of the chemical content in clothing as well as research on skin transfer, skin absorption, and systemic exposure. The results also show that the current control and prevention from chemicals in imported garments on the Swedish market is insufficient. [ABSTRACT FROM AUTHOR]

Thousands of chemicals are potentially contaminating the environment and food resources, covering a wide spectrum of molecular structures, physico-chemical properties, sources, environmental behavior and toxic profiles. Beyond the description of the individual chemicals, characterizing contaminant mixtures in related matrices has become a major challenge in ecological and human health risk assessments. Continuous analytical developments, in the fields of targeted (TA) and non-targeted analysis (NTA), have resulted in ever larger sets of data on associated chemical profiles. More than ever, the implementation of advanced data analysis strategies is essential to elucidate profiles and extract new knowledge from these large data sets. Specifically focusing on the data analysis step, this review summarizes the recent progress in integrating data analysis tools into TA and NTA workflows to address the challenging characterization of chemical mixtures in environmental and food matrices. As fish matrices are relevant in both aquatic pollution and consumer exposure perspectives, fish was chosen as the main theme to illustrate this review, although the present document is equally relevant to other food and environmental matrices.The key features of TA and NTA data sets were reviewed to illustrate the challenges associated with their analysis. Advanced filtering strategies to mine NTA data sets are presented, with a particular focus on chemical filters and discriminant analysis. Further, the applications of supervised and unsupervised multivariate analysis methods to characterize exposure to chemical mixtures, and their associated challenges, is discussed.

The combination of qualitative methods with quantitative analysis of pharmaceuticals and their metabolites in wastewater treatment plants using liquid chromatography coupled with quadrupole time-of-flight high-resolution mass spectrometry is presented. The selected pharmaceuticals were found at a low or medium level in raw wastewater, compared with previous studies around the world. The removal efficiencies of sulfamethoxazole in the four parallel biological treatment processes were similar. Data-independent and data-dependent mass spectrometry acquisition methods (All Ions MS/MS and auto MS/MS) were employed for qualitative analysis. Five of the 18 tentatively identified compounds resulted from data-independent acquisition mode were confirmed with standards. Thirty-nine pharmaceuticals and seven metabolites were tentatively identified using data-dependent acquisition mode. The parent pharmaceuticals and their metabolites, such as caffeine and its three metabolites (3-methylxanthine, 1,7-dimethyluric acid, and paraxanthine), were detected in wastewater. Irbesartan and valsartan were tentatively identified in both positive and negative modes. The present study demonstrates that both data-dependent and data-independent acquisitions are suitable and reliable for tentative determination of pharmaceuticals and their metabolites in municipal wastewater. [ABSTRACT FROM AUTHOR]

[Display omitted] • Suspect screening identified polyphenol profiles in nine plant and fungi species. • Overall, 401 features were annotated with 221 flavonoids and 180 non-flavonoids. • 64% of flavonoids and 17% of non-flavonoids were conjugated with a sugar moiety. • Quantitative analysis with 90 polyphenol standards was applied to the samples. • The most abundant class was flavanones, mainly conjugated with sugar moieties. Polyphenols are a broad molecular family whose occurence patterns in an organism are often only partially known. They are secondary metabolites exhibiting antioxidant properties and are involved in a wide range of biological actions. Moreover, polyphenol oxidases, metalloenzymes present in various plants and fungi, play a role in metabolic pathways by catalyzing the hydroxylation and oxidation of polyphenols. Functional studies on these enzymes are greatly hampered by the lack of information on the polyphenols present in a specific organisms, meaning the physiological substrate is unknown for most polyphenol oxidases. Therefore, seven commercially available fungal and two plant species were examined in detail for the presence of polyphenols using an LC-HRMS-based suspect screening workflow. A total of 401 features were annotated, composed of 221 flavonoids and 180 non-flavonoids. As 64% of the flavonoids were conjugated with a glycone, (semi-)quantification was applied when a reference standard of the aglycone was available. Isomers of hesperetin-O-glucoside were ubiquitous in all investigated samples. The samples were then additionally investigated by a quantitative, targeted LC-MS/MS assay that covers 90 polyphenols from 13 distinct polyphenol classes. The targeted assay showed phenolic acids as prevalent analytes. Overall, this pilot study provides new insights into the complex polyphenol profiles of nine mushroom and plant species. [ABSTRACT FROM AUTHOR]

Indoor dust can contribute substantially to human exposure to known and contaminants of emerging concern (CECs). Novel compounds with high structural variability and different homologues are frequently discovered through screening of the indoor environment, implying that constant monitoring is required. The present study aimed at the identification and semi-quantification of CECs in 46 indoor dust samples collected in Belgium by liquid chromatography high-resolution mass spectrometry. Samples were analyzed applying a targeted and suspect screening approach; the latter based on a suspect list containing >4000 CECs. This allowed the detection of a total of 55 CECs, 34 and 21 of which were identified with confidence level (CL) 1/2 or CL 3, respectively. Besides numerous known contaminants such as di(2-ethylhexyl) phthalate (DEHP), di(2-ethylhexyl) adipate (DEHA) or tris(2-butoxyethyl) phosphate (TBOEP) which were reported with detection frequencies (DFs) > 90%, several novel CECs were annotated. These included phthalates with differing side chains, such as decyl nonyl and decyl undecyl phthalate detected with DFs >80% and identified through the observation of characteristic neutral losses. Additionally, two novel organophosphate flame retardants not previously described in indoor dust, i.e. didecyl butoxyethoxyethyl phosphate (DDeBEEP) and bis(butoxyethyl) butyl phosphate (BBEBP), were identified. The implementation of a dedicated workflow provided semi-quantitative concentrations for a set of suspects. Such data obtained for novel phthalates were in the same order of magnitude as the concentrations observed for legacy phthalates indicating their high relevance for human exposure. From the semi-quantitative data, estimated daily intakes and resulting hazard quotients (HQs) were calculated to estimate the exposure and potential health effects. Neither of the obtained HQ values exceeded the risk threshold, indicating no expected adverse health effects. [Display omitted] • Suspect screening allowed the identification of 55 contaminants of emerging concern in indoor dust. • This study reported on novel phthalate and organophosphate homologues in dust. • Identified contaminants were semi-quantified to estimate daily intake. • Human exposure to identified contaminants was estimated below the risk threshold. [ABSTRACT FROM AUTHOR]

The recent advances of novel methodologies such as non-targeted and suspect screening based on high-resolution mass spectrometry (HRMS) have paved the way to a new paradigm for exposure assessment. These methodologies allow to profile simultaneously thousands of small unknown molecules present in environmental and biological samples, and therefore hold great promises in order to identify more efficiently hazardous contaminants potentially associated with increased risks of developing adverse health outcomes. In order to further explore the potential of these methodologies and push the transition from research applications towards regulatory purposes, robust harmonized quality standards have to be implemented. Here, we discuss the feasibility of using ISO/IEC 17025: 2017 as a guideline to implement non-targeted and suspect screening methodologies in laboratories, whether it is for accreditation purposes or not. More specifically, we identified and then discussed how specificities of non-targeted HRMS methodology can be accounted for in order to comply with the specific items of ISO/IEC 17025: 2017. We also discussed other specificities of HRMS methodologies (e.g., need for digital storage capacity) that are so far not included in the ISO/IEC 17025 requirements but should be considered. This works aims to fuel and expand the discussion in order to subsidize new opportunities of harmonization for non-targeted and suspect screening. [ABSTRACT FROM AUTHOR]

The information acquired by high resolution quadrupole-time of flight mass spectrometry (QTOF-MS) allows target analysis as well as retrospective screening for the presence of suspect or unknown emerging pollutants which were not included in the target analysis. Targeted quantification of eight azole antifungal drugs in wastewater effluent as well as new and relatively simple retrospective suspect and non-target screening strategy for emerging pollutants using UHPLC-QTOF-MS is described in this work. More than 300 (parent compounds and transformation products) and 150 accurate masses were included in the retrospective suspect and non-target screening, respectively. Tentative identification of suspects and unknowns was based on accurate masses, peak intensity, blank subtraction, isotopic pattern (mSigma value), compound annotation using data bases such as KEGG and CHEBI, and fragmentation pattern interpretation. In the targeted analysis, clotrimazole, fluconazole, itraconazole, ketoconazole and posaconazole were detected in the effluent wastewater sample, fluconazole being with highest average concentration (302.38 ng L−1). The retrospective screening resulted in the detection of 27 compounds that had not been included in the target analysis. The suspect compounds tentatively identified included atazanavir, citalopram, climbazole, bezafibrate estradiol, desmethylvenlafaxine, losartan carboxylic acid and cetirizine, of which citalopram, estradiol and cetirizine were confirmed using a standard. Carbamazepine, atrazine, efavirenz, lopinavir, fexofenadine and 5-methylbenzotriazole were among the compounds detected following the non-targeted screening approach, of which carbamazepine was confirmed using a standard. Given the detection of the target antifungals in the effluent, the findings are a call for a wide assessment of their occurrence in aquatic environments and their role in ecotoxicology as well as in selection of drug resistant fungi. The findings of this work further highlights the practical benefits obtained for the identification of a broader range of emerging pollutants in the environment when retrospective screening is applied to high resolution and high accuracy mass spectrometric data. Image 1 • LC-MS target azole antifungal quantification and retrospective screening for untargeted compounds were applied to wastewater. • Target analysis revealed the occurrence of fluconazole at relatively higher concentration than the other azoles. • Retrospective suspect and non-target screening enabled further detection of 27 emerging pollutants. • Estradiol, atrazine and carbamazepine were among the compounds detected using the retrospective screening. The work provides practical evidence for the potential of retrospective screening on detecting wider range of emerging pollutants in the environment. [ABSTRACT FROM AUTHOR]

A platform for archiving liquid chromatography high-resolution mass spectrometry (LC-HRMS) data was developed for the retrospective suspect screening of thousands of environmental pollutants with the ambition of becoming a European and possibly global standard. It was termed Digital Sample Freezing Platform (DSFP) and incorporates all the recent developments in the HRMS screening methods within the NORMAN Network. In the workflow, raw mass spectral data are converted into mzML, then mass spectral and chromatographic information on thousands of peaks of each sample is extracted into Data Collection Templates. The 'digitally frozen' samples can be retrospectively screened for the presence of virtually any compound amenable to LC–MS using a combination of information on its (i) exact mass, (ii) predicted retention time window in the chromatogram, (iii) isotopic fit and (iv) qualifier fragment ions. Its potential was demonstrated on monitoring of 670 antibiotics and 777 REACH chemicals from the Joint Black Sea Surveys (JBSS). Image 1 • An overview of the current HRMS screening steps is presented in an automatized tool. • Digital archiving and retrospective suspect screening were integrated in DSFP. • DSFP enables enhanced data mining and visualization capabilities. • 54 seawater, 19 sediment and 12 biota samples were screened for 1447 substances. • 80 chemicals from the REACH registry and 12 antibiotics were detected. [ABSTRACT FROM AUTHOR]

Abstract A customizable in silico tool (SusTool) for generating high resolution mass spectrometry (HRMS) suspect screening lists, specifically designed for the detection of hazardous organic compounds in various environmental compartments, was created. A database consisting of ∼32 000 environmentally relevant organic compounds was constructed, including data on their physicochemical properties, environmental fate characteristics, and endocrine disruption potential, along with emissions and quantity indices. Well-defined customized suspect lists were generated by systematic ranking using a scoring and weighting procedure. For demonstration purposes, three suspect screening lists were created, one for water (SL Water) and two for biota covering less (SL Biota Kow <5) or more hydrophobic chemicals (SL Biota Kow >3). Scrutiny of overlaps between compounds within these lists and the SusDat database (20 suspect lists comprising ∼58 000 compounds compiled by the Norman network) showed that approximately half of the compounds in the three suspect lists were also listed in one of the SusDat database lists. This indicates that SusTool is able to include highly relevant emerging pollutants, but also captures other compounds of potential concern that have been less well studied or not yet investigated. Overall, our in silico prioritization approach enables systematic creation of suspect screening lists and provides new opportunities for suspect screening for environmentally relevant compounds. Graphical abstract Image 1 Highlights • A flexible tool for creating suspect list was developed. • The database used contains over 31 000 compounds. • The model includes Quantity Index data to increase detection frequency. [ABSTRACT FROM AUTHOR]

Abstract The hyporheic zone (HZ), located at the interface of surface and groundwater, is a natural bioreactor for attenuation of chemical contaminants. Engineered HZs can be incorporated into stream restoration projects to enhance hyporheic exchange, with flowpaths optimized to promote biological habitat, water quantity, and water quality improvements. Designing HZs for in-stream treatment of stormwater, a significant source of flow and contaminant loads to urban creeks, requires assessment of both the hydrology and biogeochemical capacity for water quality improvement. Here, we applied tracer tests and high resolution mass spectrometry (HRMS) to characterize an engineered hyporheic zone unit process, called a hyporheic design element (HDE), in the Thornton Creek Watershed in Seattle, WA. Dye, NaCl, and bromide were used to hydrologically link downwelling and upwelling zones and estimate the hydraulic retention time (HRT) of hyporheic flowpaths. We then compared water quality improvements across hydrologically-linked surface and hyporheic flowpaths (3–5 m length; ∼30 min to >3 h) during baseflow and stormflow conditions. We evaluated fate outcomes for 83 identified contaminants during stormflow, including those correlated with an urban runoff mortality syndrome in coho salmon. Non-target HRMS analysis was used to assess holistic water quality improvements and evaluate attenuation mechanisms. The data indicated substantial water quality improvement in hyporheic flowpaths relative to surface flow and improved contaminant removal with longer hyporheic HRT (for ∼1900 non-target compounds detected during stormflow, <17% were attenuated >50% via surface flow vs. 59% and 78% via short and long hyporheic residence times, respectively), and strong contributions of hydrophobic sorption towards observed contaminant attenuation. Graphical abstract Image 1 Highlights • Engineered hyporheic zones (HZs) can treat non-point source pollution in-stream. • Hydraulically linked hyporheic flowpaths were identified with non-reactive tracers. • Hyporheic flow attenuates many organic contaminants detected in urban runoff. • Longer residence times in the HZ promote removal, particularly of polar compounds. • Non-target HRMS data can estimate hydrophobicity to evaluate sorption potential. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Visualization of ToxCast data availability and density, including water relevant mechanisms of toxicity. • Efficient prioritization strategy for suspect screening data combining occurrence and hazard data. • High throughput approach allows automation. • Little overlap between exposure only and exposure/hazard ratio based prioritization. Abstract Advancements in high-resolution mass spectrometry based methods have enabled a shift from pure target analysis to target, suspect and non-target screening analyses to detect chemicals in water samples. The multitude of suspect chemicals thereby detected needs to be prioritized for further identification, prior to health risk assessment and potential inclusion into monitoring programs. Here, we compare prioritization of chemicals in Dutch water samples based on relative intensities only to prioritization including hazard information based on high-throughput in vitro toxicity data. Over 1000 suspects detected in sewage treatment plant effluent, surface water, groundwater and drinking water samples were ranked based on their relative intensities. Toxicity data availability and density in the ToxCast database were determined and visualized for these suspects, also in regard to water relevant mechanisms of toxicity. More than 500 suspects could be ranked using occurrence/hazard ratios based on more than 1000 different assay endpoints. The comparison showed that different prioritization strategies resulted in significantly different ranking, with only 2 suspects prioritized based on occurrence among the top 20 in the hazard ranking. We therefore propose a novel scheme that integrates both exposure and hazard data, and efficiently prioritizes which features need to be confidently identified first. [ABSTRACT FROM AUTHOR]

In this study we developed a systematic method for suspect screening and target quantification of the human pharmaceutical residues in water, via solid phase extraction (SPE) followed by liquid chromatography-high resolution mass spectrometry (LC-HRMS). We then proceeded to study the occurrences and distribution of the pharmaceuticals in the surface waters of Wuhan, China, by analyzing water samples from lakes, rivers and municipal sewage. Initially, 33 human pharmaceuticals were identified from East Lake without using purchasing standards. Of these, 29 were later confirmed by using standards, and quantified using the aforementioned SPE pretreatment method and LC-HRMS analysis in full MS scan mode. The 29 compounds included 8 antibiotics, 9 metabolites, and 12 miscellaneous pharmaceuticals. The highest proportions of pharmaceutical residues were detected downstream of the Yangtze River and in the lakes close to the central city. Metformin, cotinine, and trans-3-hydroxy cotinine, were frequently encountered in all the surface water samples. High concentrations (>120 ng/l) of caffeine, metformin, theobromine, and valsartan were detected in the surface water samples; the removal rates of these compounds in the municipal sewage treatment plant were also high. In contrast, although the concentrations of 4-AAA and metoprolol acid in the surface water were high, the removal rates of these residues in the sewage treatment plant were low. [ABSTRACT FROM AUTHOR]

Humans are at risk of exogenous exposure to exogenous chemicals. Challenges exist for the comprehensive monitoring of residues with different physical and chemical properties in serum. Here, an on-line two-dimensional liquid chromatography (2D-LC) - high resolution mass spectrometry system (HRMS) was developed, expanding the range of the partition coefficient in octanol/water of the residue analysis from −8 to 12. A high-coverage serum residue screening strategy was further designed by integrating 2D-LC system with HRMS full MS/data independent acquisition and automatic spectral library searching. This strategy enables to simultaneously screen 1210 pesticides, veterinary/human drugs, other chemical pollutants and their metabolites in serum with a single analysis. Method validation showed 92% and 81% of 1022 residues spiked in serum could be detected at 50 ng/mL and 5 ng/mL, respectively. The developed method was applied to the analysis of 24 separately pooled serum samples, 58 suspect residues were found, some of them were detected at high frequencies over than 50%. Among them, 4,6-Dinitro-O-cresol and probable carcinogenic folpet are highly toxic, and cimaterol is banned in China. Collectively, this study developed a 2D-LC-HRMS -based screening strategy for screening pesticides, veterinary/human drugs, and other chemical pollutants in serum, it is helpful for studying the effect of exogenous exposures on human health. [Display omitted] • Relatively polar residue analysis was enabled using the novel 2D-LC-HRMS system. • An in-house database of 1210 exogenous chemicals and metabolites was constructed. • An efficient screening method integrated 2D-LC-HRMS analysis and database retrieval. • High-coverage screening was performed, 58 exogenous residues were detected from human sera. [ABSTRACT FROM AUTHOR]

Hair has recently emerged as a biospecimen for characterizing the long-term chemical exposome in biomonitoring investigations spanning several months, as chemical compounds circulating in the bloodstream accumulate in hair. Although there has been interest in using human hair as a biospecimen for exposome studies, it has yet to be widely adopted compared to blood and urine. Here, we applied a high-resolution mass spectrometry (HRMS)-based suspect screening strategy to characterize the long-term chemical exposome in human hair. Hair samples were collected from 70 subjects and cut into 3 cm segments, which were then mixed to prepare pooled samples. The pooled hair samples underwent a sample preparation procedure, and the hair extracts were further analyzed using an HRMS-based suspect screening approach. An in-house chemical suspect list containing 1227 chemical entries from National Report on Human Exposure to Environmental Chemicals (Report) published by the U.S. CDC and the Exposome-Explorer 3.0 database developed by the WHO was subsequently used to screen and filter the suspect features against the HRMS dataset. Overall, we matched 587 suspect features in the HRMS dataset to 246 unique chemical formulas in the suspect list, and the structures of 167 chemicals were further identified through a fragmentation analysis. Among these, chemicals such as mono-2-ethylhexyl phthalate, methyl paraben, and 1-naphthol, which have been detected in the urine or blood for exposure assessment, were also identified in human hair. This suggests that hair reflects the accumulation of environmental compounds to which an individual is exposed. Exposure to exogenous chemicals may exert adverse effects on cognitive function, and we discovered 15 chemicals in human hair that may contribute to the pathogenesis of Alzheimer's disease. This finding suggests that human hair may be a promising biospecimen for monitoring long-term exposure to multiple environmental chemicals and perturbations in endogenous chemicals in biomonitoring investigations. [Display omitted] • Using a HRMS-based suspect screening approach enabled the identification of 167 chemicals in human hair. • The 167 exposure markers identified in hair implied that hair analysis could be used for biomonitoring investigations. • A total of 15 environmental chemicals in human hair might contribute to pathogenesis of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Non-target analysis (NTA) employing high-resolution mass spectrometry (HRMS) coupled with liquid chromatography is increasingly being used to identify chemicals of biological relevance. HRMS datasets are large and complex making the identification of potentially relevant chemicals extremely challenging. As they are recorded in vendor-specific formats, interpreting them is often reliant on vendor-specific software that may not accommodate advancements in data processing. Here we present InSpectra, a vendor independent automated platform for the systematic detection of newly identified emerging chemical threats. InSpectra is web-based, open-source/access and modular providing highly flexible and extensible NTA and suspect screening workflows. As a cloud-based platform, InSpectra exploits parallel computing and big data archiving capabilities with a focus for sharing and community curation of HRMS data. InSpectra offers a reproducible and transparent approach for the identification, tracking and prioritisation of emerging chemical threats. [Display omitted] • Open-source/access high-resolution mass spectrometry data processing platform was built. • Automated vendor independent non-target analysis and suspect screening workflows. • Archival of HRMS data and metadata in a relational database for retrospective processing. • Access to largest community curated high-resolution mass spectrometry library. [ABSTRACT FROM AUTHOR]

• First characterization of quaternary ammonium compounds (QACs) in European dust. • Detection and semi-quantification of 21 targeted QACs. • Identification of 17 additional QACs through suspect screening. • Report of reference collision cross section values (CCS) for targeted QACs. • Use of CCS- m / z trendlines for compound identification. Quaternary ammonium compounds (QACs) are a class of surfactants commonly used in disinfecting and cleaning products. Their use has substantially increased during the COVID-19 pandemic leading to increasing human exposure. QACs have been associated with hypersensitivity reactions and an increased risk of asthma. This study introduces the first identification, characterization and semi-quantification of QACs in European indoor dust using ion-mobility high-resolution mass spectrometry (IM-HRMS), including the acquisition of collision cross section values (DTCCS N2) for targeted and suspect QACs. A total of 46 indoor dust samples collected in Belgium were analyzed using target and suspect screening. Targeted QACs (n = 21) were detected with detection frequencies ranging between 4.2 and 100 %, while 15 QACs showed detection frequencies > 90 %. Semi-quantified concentrations of individual QACs showed a maximum of 32.23 µg/g with a median ∑QAC concentration of 13.05 µg/g and allowed the calculation of Estimated Daily Intakes for adults and toddlers. Most abundant QACs matched the patterns reported in indoor dust collected in the United States. Suspect screening allowed the identification of 17 additional QACs. A dialkyl dimethyl ammonium compound with mixed chain lengths (C16:C18) was characterized as a major QAC homologue with a maximum semi-quantified concentration of 24.90 µg/g. The high detection frequencies and structural variabilities observed call for more European studies on potential human exposure to these compounds. For all targeted QACs, drift tube IM-HRMS derived collision cross section values (DTCCS N2) are reported. Reference DTCCS N2 values allowed the characterization of CCS- m / z trendlines for each of the targeted QAC classes. Experimental CCS- m / z ratios of suspect QACs were compared with the CCS- m / z trendlines. The alignment between the two datasets served as an additional confirmation of the assigned suspect QACs. The use of the 4bit multiplexing acquisition mode with consecutive high-resolution demultiplexing confirmed the presence of isomers for two of the suspect QACs. [ABSTRACT FROM AUTHOR]

The inclusion of new psychoactive substances (NPS) in the wastewater-based epidemiology approach presents challenges, such as the reduced number of users that translates into low concentrations of residues and the limited pharmacokinetics information available, which renders the choice of target biomarker difficult. The sampling during special social settings, the analysis with improved analytical techniques, and data processing with specific workflow to narrow the search, are required approaches for a successful monitoring. This work presents the application of a qualitative screening technique to wastewater samples collected during a city festival, where likely users of recreational substances gather and consequently higher residual concentrations of used NPS are expected. The analysis was performed using liquid chromatography coupled to high-resolution mass spectrometry. Data were processed using an algorithm that involves the extraction of accurate masses (calculated based on molecular formula) of expected m/z from an in-house database containing about 2,000 entries, including NPS and transformation products. We positively identified eight NPS belonging to the classes of synthetic cathinones, phenethylamines and opioids. In addition, the presence of benzodiazepine analogues, classical drugs and other licit substances with potential for abuse was confirmed. The screening workflow based on a database search was useful in the identification of NPS biomarkers in wastewater. The findings highlight the specific classical drugs and low NPS use in the Netherlands. Additionally, meta -chlorophenylpiperazine (mCPP), 2,5-dimethoxy-4-bromophenethylamine (2C-B), and 4-fluoroamphetamine (FA) were identified in wastewater for the first time. [ABSTRACT FROM AUTHOR]

Up until now, the methods used for determination of hydroxylated polycyclic aromatic hydrocarbons in air particulate samples have been target methods, only determining compounds with available reference standards. In this present study, a combined target and suspect screening strategy for the analysis of hydroxylated polycyclic aromatic hydrocarbons was developed, utilizing liquid chromatography coupled to orbitrap high resolution mass spectrometry. The target screening included simultaneous determination of nine hydroxylated polycyclic aromatic hydrocarbons, while additional eight hydroxylated polycyclic aromatic hydrocarbon masses were screened for using the suspect screening. The target screening was validated with respect to linearity, limits of detection and quantification and matrix effects. The calibration curves ranged from 0.01 to 10 ng/mL, the method limits of detection and quantification were in the rage of 0.001– 0.018 pg/m 3 and 0.006 – 0.061 pg/m 3 , respectively, while matrix effects ranged from 83% to 104%. For the suspect screening, a list with expected precursor ions created from suspect monoisotopic masses was used. The suspects were then identified by the accurate exact mass, with a mass accuracy threshold <5 ppm, molecular formula, isotopic pattern, and mass spectra (fragments) and also semi-quantified in order to obtain information on their relative levels in different matrixes. The developed strategy was applied on five air particulate samples collected from an urban background and five samples from a car tunnel in Stockholm (Sweden). In total 20 hydroxylated polycyclic aromatic hydrocarbons were detected, of which nine compounds were determined using the target screening and 11 were tentatively identified and semi-quantified using the suspect screening strategy. The concentrations of the target compounds ranged from 20.7 to 96.9 pg/m 3 , for most of the analytes the concentrations in particles from car tunnel were slightly higher than in urban air particles. The levels of most of the tentatively identified compounds were also slightly higher in particles from the car tunnel. [ABSTRACT FROM AUTHOR]

Riverine fish in densely populated areas is constantly exposed to wastewater-borne contaminants from effluent discharges. These can enter the organism through the skin, gills or by ingestion. Whereas most studies assessing the contaminant burden in exposed fish have focused either on muscle or a limited set of tissues. Here we set out to generate a more comprehensive overview of the distribution of pollutants across tissues by analyzing a panel of matrices including liver, kidney, skin, brain, muscle, heart, plasma and bile. To achieve a broad analyte coverage with a minimal bias towards a specific contaminant class, sample extracts from four fish species were analyzed by High-Performance Liquid Chromatography (HPLC) - high-resolution mass spectrometry (HRMS) for the presence of 600 wastewater-borne pharmaceutically active compounds (PhACs) with known environmental relevance in river water through a suspect-screening analysis. A total of 30 compounds were detected by suspect screening in at least one of the analyzed tissues with a clear prevalence of antidepressants. Of these, 15 were detected at confidence level 2.a (Schymanski scale), and 15 were detected at confidence level 1 following confirmation with authentic standards, which furthermore enabled their quantification. The detected PhACs confirmed with level 1 of confidence included acridone, acetaminophen, caffeine, clarithromycin, codeine, diazepam, diltiazem, fluoxetine, ketoprofen, loratadine, metoprolol, sertraline, sotalol, trimethoprim, and venlafaxine. Among these substances, sertraline stood out as it displayed the highest detection frequency. The values of tissue partition coefficients for sertraline in the liver, kidney, brain and muscle were correlated with its physicochemical properties. Based on inter-matrix comparison of detection frequencies, liver, kidney, skin and heart should be included in the biomonitoring studies of PhACs in riverine fish. [Display omitted] • Six fish tissues and 2 body fluids were analyzed for 600 pharmaceuticals. • Sertraline is present as bound form in non-target fish tissues. • Low concentrations of pollutants were detected in muscle. • Kidney, liver, skin and heart are proposed for detection of PhACs in fish. [ABSTRACT FROM AUTHOR]

There is a growing need in the field of exposure science for monitoring methods that rapidly screen environmental media for suspect contaminants. Measurement and analysis platforms, based on high resolution mass spectrometry (HRMS), now exist to meet this need. Here we describe results of a study that links HRMS data with exposure predictions from the U.S. EPA's ExpoCast™ program and in vitro bioassay data from the U.S. interagency Tox21 consortium. Vacuum dust samples were collected from 56 households across the U.S. as part of the American Healthy Homes Survey (AHHS). Sample extracts were analyzed using liquid chromatography time-of-flight mass spectrometry (LC–TOF/MS) with electrospray ionization. On average, approximately 2000 molecular features were identified per sample (based on accurate mass) in negative ion mode, and 3000 in positive ion mode. Exact mass, isotope distribution, and isotope spacing were used to match molecular features with a unique listing of chemical formulas extracted from EPA's Distributed Structure-Searchable Toxicity (DSSTox) database. A total of 978 DSSTox formulas were consistent with the dust LC–TOF/molecular feature data (match score ≥ 90); these formulas mapped to 3228 possible chemicals in the database. Correct assignment of a unique chemical to a given formula required additional validation steps. Each suspect chemical was prioritized for follow-up confirmation using abundance and detection frequency results, along with exposure and bioactivity estimates from ExpoCast and Tox21, respectively. Chemicals with elevated exposure and/or toxicity potential were further examined using a mixture of 100 chemical standards. A total of 33 chemicals were confirmed present in the dust samples by formula and retention time match; nearly half of these do not appear to have been associated with house dust in the published literature. Chemical matches found in at least 10 of the 56 dust samples include Piperine, N,N-Diethyl-m-toluamide (DEET), Triclocarban, Diethyl phthalate (DEP), Propylparaben, Methylparaben, Tris(1,3-dichloro-2-propyl)phosphate (TDCPP), and Nicotine. This study demonstrates a novel suspect screening methodology to prioritize chemicals of interest for subsequent targeted analysis. The methods described here rely on strategic integration of available public resources and should be considered in future non-targeted and suspect screening assessments of environmental and biological media. [ABSTRACT FROM AUTHOR]

[Display omitted] • A harmonized multi-laboratory suspect screening for pesticide metabolites was performed on 2,088 urine samples from five countries. • A strategy is presented on how to perform screening and confirmation analyses with a high number of suspects. • Pesticide metabolites were confirmed by comparing to reference information generated by human liver S9 incubation. • 498 tentative annotations for pesticide metabolites were obtained and prioritized; 14 parent pesticides and 71 pesticide metabolites related to a total of 46 parent pesticides could be confirmed. Within the Human Biomonitoring for Europe initiative (HBM4EU), a study to determine new biomarkers of exposure to pesticides and to assess exposure patterns was conducted. Human urine samples (N = 2,088) were collected from five European regions in two different seasons. The objective of the study was to identify pesticides and their metabolites in collected urine samples with a harmonized suspect screening approach based on liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) applied in five laboratories. A combined data processing workflow included comprehensive data reduction, correction of mass error and retention time (RT) drifts, isotopic pattern analysis, adduct and elemental composition annotation, finalized by a mining of the elemental compositions for possible annotations of pesticide metabolites. The obtained tentative annotations (n = 498) were used for acquiring representative data-dependent tandem mass spectra (MS2) and verified by spectral comparison to reference spectra generated from commercially available reference standards or produced through human liver S9 in vitro incubation experiments. 14 parent pesticides and 71 metabolites (including 16 glucuronide and 11 sulfate conjugates) were detected. Collectively these related to 46 unique pesticides. For the remaining tentative annotations either (i) no data-dependent MS2 spectra could be acquired, (ii) the spectral purity was too low for sufficient matching, or (iii) RTs indicated a wrong annotation, leaving potential for more pesticides and/or their metabolites being confirmed in further studies. Thus, the reported results are reflecting only a part of the possible pesticide exposure. [ABSTRACT FROM AUTHOR]

Identification of new psychoactive substances (NPS) is challenging. Developing targeted methods for their analysis can be difficult and costly due to their impermanence on the drug scene. Accurate-mass mass spectrometry (AMMS) using a quadrupole time-of-flight (QTOF) analyzer can be useful for wide-scope screening since it provides sensitive, full-spectrum MS data. Our article presents a qualitative screening workflow based on data-independent acquisition mode (all-ions MS/MS) on liquid chromatography (LC) coupled to QTOFMS for the detection and identification of NPS in biological matrices. The workflow combines and structures fundamentals of target and suspect screening data processing techniques in a structured algorithm. This allows the detection and tentative identification of NPS and their metabolites. We have applied the workflow to two actual case studies involving drug intoxications where we detected and confirmed the parent compounds ketamine, 25B-NBOMe, 25C-NBOMe, and several predicted phase I and II metabolites not previously reported in urine and serum samples. The screening workflow demonstrates the added value for the detection and identification of NPS in biological matrices. [ABSTRACT FROM AUTHOR]

Identification of transformation products (TPs) of emerging pollutants is challenging, due to the vast number of compounds, mostly unknown, the complexity of the matrices and their often low concentrations, requiring highly selective, highly sensitive techniques. We compile background information on biotic and abiotic formation of TPs and analytical developments over the past five years. We present a database of biotic or abiotic TPs compiled from those identified in recent years. We discuss mass spectrometric (MS) techniques and workflows for target, suspect and non-target screening of TPs with emphasis on liquid chromatography coupled to MS (LC-MS). Both low- and high-resolution (HR) mass analyzers have been applied, but HR-MS is the technique of choice, due to its high confirmatory capabilities, derived from the high resolving power and the mass accuracy in MS and MS/MS modes, and the sophisticated software developed. [ABSTRACT FROM AUTHOR]