Seth D Currie, David Blake Benson, Zhong-Ru Xie, Jia-Sheng Wang, Lili Tang
{"title":"Utilization of Artificial Intelligence Coupled with a High-Throughput, High-Content Platform in the Exploration of Neurodevelopmental Toxicity of Individual and Combined PFAS.","authors":"Seth D Currie, David Blake Benson, Zhong-Ru Xie, Jia-Sheng Wang, Lili Tang","doi":"10.3390/jox15010024","DOIUrl":"10.3390/jox15010024","url":null,"abstract":"<p><p>Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in various products, such as firefighting foams and non-stick cookware, due to their resistance to heat and degradation. However, these same properties make them persistent in the environment and human body, raising public health concerns. This study selected eleven PFAS commonly found in drinking water and exposed Caenorhabditis elegans to concentrations ranging from 0.1 to 200 µM to assess neurodevelopmental toxicity using a high-throughput, high-content screening (HTS) platform coupled with artificial intelligence for image analysis. Our findings showed that PFAS such as 6:2 FTS, HFPO-DA, PFBA, PFBS, PFHxA, and PFOS inhibited dopaminergic neuron activity, with fluorescence intensity reductions observed across concentrations from 0.1 to 100 µM. PFOS and PFBS also disrupted synaptic transmission, causing reduced motility and increased paralysis in aldicarb-induced assays, with the most pronounced effects at higher concentrations. These impairments in both neuron activity and synaptic function led to behavioral deficits. Notably, PFOS was one of the most toxic PFAS, affecting multiple neurodevelopmental endpoints. These results emphasize the developmental risks of PFAS exposure, highlighting the impact of both individual compounds and mixtures on neurodevelopment. This knowledge is essential for assessing PFAS-related health risks and informing mitigation strategies.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rosaria Scudiero, Teresa Chianese, Patrizia Cretì, Luigi Rosati
{"title":"Risk Assessment Arising from the Exposure of Terrestrial Vertebrates to Soil Contamination: Learning from Field Lizards of the <i>Podarcis</i> Genus.","authors":"Rosaria Scudiero, Teresa Chianese, Patrizia Cretì, Luigi Rosati","doi":"10.3390/jox15010021","DOIUrl":"10.3390/jox15010021","url":null,"abstract":"<p><p>The soil environment has been considered capable of storing toxic substances without serious consequences for the inhabitants since plants are able to bioaccumulate pollutants without compromising their survival. The application of chemicals to increase soil productivity and the dumping of waste have worsened soil quality. Recently, following a greater awareness of the importance of monitoring the damage deriving from the consumption of contaminated crops for humans and of the protection of biodiversity, studies aimed at identifying the effects of soil contamination on terrestrial animals have increased considerably. Studies using field lizards as model organisms fit into this scenario; this research has shed light on the uptake, accumulation, and toxicity of soil pollutants on reptiles. This review summarizes data collected on lizards of the <i>Podarcis</i> genus, a group of resilient wild species capable of living in both pristine and anthropized areas; the data reveal that many of the effects recorded in lizard tissues at the molecular, biochemical, and histological levels are independent of the chemical composition of the contaminants and are mostly linked to the type of cellular response. Overall, these studies confirm <i>Podarcis</i> lizards as a good model system in ecotoxicological and cytotoxicological research, providing an accurate description of the effects of pollutants, clarifying the defense mechanisms activated in relation to different exposure routes and, finally, providing predictive information on the risks faced by other animals. Since the effects recorded in lizards have often also been observed in mammals, it can be concluded that the results obtained from studies on these animals can be translated to other terrestrial vertebrates, including mammals.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11855989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Remodeling of Embryo Architecture in Response to Vanadium and Increased Temperatures: From Morphometric to Molecular Changes.","authors":"Roberto Chiarelli, Chiara Martino, Rosaria Scudiero, Alessio Terenzi, Fabiana Geraci","doi":"10.3390/jox15010022","DOIUrl":"10.3390/jox15010022","url":null,"abstract":"<p><p>The study of ecotoxicity induced by vanadium (V) represents an area of increasing interest due to the growing use of V in both the industrial and pharmaceutical areas. This leads to its introduction into water environments, marking a developing problem, especially since rising global temperatures appear to intensify its toxic properties. Cytotoxicological approaches carried out on whole marine embryos represent a valid research tool since they grow directly in contact with the pollutants and are equipped with highly responsive cells to stressors. Here, we discuss the detrimental impact on <i>Paracentrotus lividus</i> sea urchin embryos resulting from the combination of V and higher temperatures, reflecting the effects of climate variation. The results demonstrate the remodeling of embryonic architecture at the morphometric level, revealing developmental delays and anomalies. These malformations involve variations in the total skeletal mass due to the almost total absence of the skeleton, with the exception of small calcareous aggregates. Furthermore, both a modulation in total tissue remodeling enzymatic activities and a variation in the amount of three MMP-like gelatinases (MMP-2, -9, and -14) were observed. This research demonstrates that climate change significantly increases the harmful effects of V, emphasizing the necessity for comprehensive toxicity assessments in environmental evaluations.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kari A Gaither, Guihua Yue, Dilip Kumar Singh, Julia Trudeau, Kannapiran Ponraj, Nadezhda Y Davydova, Philip Lazarus, Dmitri R Davydov, Bhagwat Prasad
{"title":"Effects of Chronic Alcohol Intake on the Composition of the Ensemble of Drug-Metabolizing Enzymes and Transporters in the Human Liver.","authors":"Kari A Gaither, Guihua Yue, Dilip Kumar Singh, Julia Trudeau, Kannapiran Ponraj, Nadezhda Y Davydova, Philip Lazarus, Dmitri R Davydov, Bhagwat Prasad","doi":"10.3390/jox15010020","DOIUrl":"10.3390/jox15010020","url":null,"abstract":"<p><p>In this study, to better understand the mechanisms of the profound impact of alcohol consumption on drug pharmacokinetics, efficacy, and toxicity, we characterized the alcohol-induced changes in the ensemble of drug-metabolizing enzymes and transporters (DMETs) in the human liver by performing global proteomic analysis of human liver microsomes from 94 donors. DMET protein levels were analyzed concerning alcohol consumption, smoking history, and sex using non-parametric tests, which were further strengthened by correlational analysis. To this end, we used a provisional index of alcohol exposure formulated based on the relative abundances of four marker proteins best correlating with the level of alcohol consumption. Alcohol-induced changes in the cytochrome P450 pool include significant increases in CYP2E1, CYP2B6, CYP2J2, and NADPH-cytochrome P450 reductase levels and the lowering of CYP1A2, CYP2C8, CYP2C9, CYP4A11, and cytochrome b<sub>5</sub>. Changes in UDP-glucuronosyltransferase (UGT) abundances comprise elevated UGT1A6, UGT1A9, and UGT2A1, and reduced UGT1A3, UGT1A4, UGT2B7, UGT2B10, and UGT2B15 levels. Tobacco smokers showed elevated CYP1A2, UGT1A6, and UGT2B4 and reduced FMO3, FMO4, and FMO5 levels, while in females, CYP1A2, UGT2B17, and UGT2B15 levels were lower, and UGT2A3 and STS were higher compared to males. The alcohol-induced changes in the DMET ensemble at the protein level reported herein provide deep insights into how alcohol impacts drug and xenobiotic metabolism.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdus Sabur, Angkan Khan, B Borphukan, Abdur Razzak, M Salimullah, Muslima Khatun
{"title":"The Unique Capability of Endolysin to Tackle Antibiotic Resistance: Cracking the Barrier.","authors":"Abdus Sabur, Angkan Khan, B Borphukan, Abdur Razzak, M Salimullah, Muslima Khatun","doi":"10.3390/jox15010019","DOIUrl":"10.3390/jox15010019","url":null,"abstract":"<p><p>The lack of new antibacterial medicines and the rapid rise in bacterial resistance to antibiotics pose a major threat to individuals and healthcare systems. Despite the availability of various antibiotics, bacterial resistance has emerged for almost every antibiotic discovered to date. The increasing prevalence of multidrug-resistant bacterial strains has rendered some infections nearly untreatable, posing severe challenges to health care. Thus, the development of alternatives to conventional antibiotics is critical for the treatment of both humans and food-producing animals. Endolysins, which are peptidoglycan hydrolases encoded by bacteriophages, represent a promising new class of antimicrobials. Preliminary research suggests that endolysins are more effective against Gram-positive bacteria than Gram-negative bacteria when administered exogenously, although they can still damage the cell wall of Gram-negative bacteria. Numerous endolysins have a modular domain structure that divides their binding and catalytic activity into distinct subunits, which helps maximize their bioengineering and potential drug development. Endolysins and endolysin-derived antimicrobials offer several advantages as antibiotic substitutes. They have a unique mechanism of action and efficacy against bacterial persisters (without requiring an active host metabolism); subsequently, they target both Gram-positive and Gram-negative bacteria (including antibiotic-resistant strains), and mycobacteria. Furthermore, there has been limited evidence of endolysin being resistant. Because these enzymes target highly conserved links, resistance may develop more slowly compared to traditional antibiotics. This review provides an overview and insight of the potential applications of endolysins as novel antimicrobials.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Klimowska, Joanna Jurewicz, Michał Radwan, Paweł Radwan, Paweł Pol, Bartosz Wielgomas
{"title":"Distribution of Environmental Phenols into Follicular Fluid and Urine of Women Attending Infertility Clinic.","authors":"Anna Klimowska, Joanna Jurewicz, Michał Radwan, Paweł Radwan, Paweł Pol, Bartosz Wielgomas","doi":"10.3390/jox15010017","DOIUrl":"10.3390/jox15010017","url":null,"abstract":"<p><p>Infertility and environmental pollution are two globally prevalent and related issues. To explore women's reproductive health, the composition of follicular fluid (FF) has been studied and it was found that changes to its composition, including the presence of exogenous chemicals, can adversely affect the fertilization process. Two groups of women (idiopathic infertility and controls) who were patients at a fertility clinic were recruited for this study. Samples of urine and FF were gathered from each participant to determine the concentration of 14 common phenols (four parabens, six bisphenols, two benzophenones, and two naphthols). Associations between phenol concentrations (free and total) in both matrices were described using Spearman's correlation coefficient and were compared between two groups by the Mann-Whitney U test. Eight phenols were quantified in more than 50% of the urine samples, while only three parabens were quantified in hydrolyzed FF samples, and only methylparaben was quantified in non-hydrolyzed FF samples. Conjugates were the predominant form in FF samples. However, a significant correlation of 0.533 (<i>p</i> < 0.0001) was observed between free and total methylparaben concentrations in FF. Differences in concentrations between cases and controls in both matrices were not statistically significant, except for benzophenone-3 in urine, with a higher median observed in the control group (<i>p</i> = 0.04). The total paraben concentrations in urine and FF samples were rather weakly correlated (r = 0.232-0.473), implying that urine concentrations may not be appropriate for predicting their concentration in FF.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>Apis mellifera</i> as a Model Species to Evaluate Toxicological Effects of Fungicides Used in Vineyard Agroecosystems.","authors":"Tommaso Campani, Ginevra Manieri, Ilaria Caliani, Agata Di Noi, Silvia Casini","doi":"10.3390/jox15010018","DOIUrl":"10.3390/jox15010018","url":null,"abstract":"<p><p>Agroecosystems provide habitats, food, and water for many pollinators and insects, but they are also heavily exposed to threats from the widespread use of pesticides and fertilizers. Managed honeybees and wild bees encounter pesticides in vineyards by collecting morning dew from vine leaves and accessing sugars from grapes, particularly during dry periods. This study assessed the toxicological effects of the commercial fungicide formulations Fantic FNCWG<sup>®</sup> and Ramedit combi<sup>®</sup>, both individually and in combination, on honeybees. Using a multi-biomarker approach, we evaluated neurotoxicity, metabolic disturbances, phase II detoxification processes, and immune system function. Our findings revealed that commercial fungicide mixtures with multiple active ingredients affect bees differently than single active compounds. Biomarker responses highlighted how these complex mixtures disrupt various enzymatic pathways; including immune function; altering critical enzyme kinetics involved in detoxification and potentially impairing essential bee functions. This study emphasizes the need for more comprehensive research into the sublethal effects of commercial pesticides, particularly those used in vineyards, which are understudied compared to pesticides used in orchards.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11856139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heba M Abdou, Ghada M Abd Elmageed, Hussein K Hussein, Imane Yamari, Samir Chtita, Lamia M El-Samad, Mohamed A Hassan
{"title":"Antidiabetic Effects of Quercetin and Silk Sericin in Attenuating Dysregulation of Hepatic Gluconeogenesis in Diabetic Rats Through Potential Modulation of PI3K/Akt/FOXO1 Signaling: In Vivo and In Silico Studies.","authors":"Heba M Abdou, Ghada M Abd Elmageed, Hussein K Hussein, Imane Yamari, Samir Chtita, Lamia M El-Samad, Mohamed A Hassan","doi":"10.3390/jox15010016","DOIUrl":"10.3390/jox15010016","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is an intricate disease correlated with many metabolic deregulations, including disordered glucose metabolism, oxidative stress, inflammation, and cellular apoptosis due to hepatic gluconeogenesis aberrations. However, there is no radical therapy to inhibit hepatic gluconeogenesis disturbances yet. We thus sought to probe the effectiveness and uncover the potential mechanism of quercetin (QCT) and silk sericin (SS) in mitigating hyperglycemia-induced hepatic gluconeogenesis disorder, which remains obscure. Administration of QCT and SS to diabetic male albino rats markedly restored the levels of glucose, insulin, advanced glycation end-products (AGEs), liver function enzymes, alpha-fetoprotein (AFP), globulin, and glycogen, in addition to hepatic carbohydrate metabolizing enzymes and gluconeogenesis in comparison with diabetic rats. Furthermore, treatment with QCT and SS modulated hepatic malondialdehyde (MD), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), nitric oxide, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β), in addition to serum interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), implying their effectiveness in safeguarding cells against oxidative impairment and inflammation. Remarkably, QCT and SS treatments led to the upregulation of expression of phosphatidylinositol 3-kinases (PI3K), phospho-Akt (p-Akt), and forkhead box-O1 (FOXO1) genes in hepatic tissues compared to diabetic rats, orchestrating these singling pathways for curtailing hyperglycemia and pernicious consequences in hepatic tissues. Importantly, immunohistochemical investigations exhibited downregulation of caspase-3 expression in rats treated with QCT and SS compared to diabetic animals. Beyond that, the histopathological results of hepatic tissues demonstrated notable correlations with biochemical findings. Interestingly, the in silico results supported the in vivo findings, showing notable binding affinities of QCT and SS to PI3K, GPx, and TNF-α proteins. These results imply that QCT and SS could mitigate oxidative stress and inflammation and regulate hepatic gluconeogenesis in diabetic rats. However, QCT revealed greater molecular interactions with the studied proteins than SS. Overall, our results emphasize that QCT and SS have significant therapeutic effects on attenuating hyperglycemia-induced hepatic gluconeogenesis, with QCT showing superior effectiveness.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gracia Luque, Pilar Ortiz, Alfonso Torres-Sánchez, Alicia Ruiz-Rodríguez, Ana López-Moreno, Margarita Aguilera
{"title":"Impact of Ex Vivo Bisphenol A Exposure on Gut Microbiota Dysbiosis and Its Association with Childhood Obesity.","authors":"Gracia Luque, Pilar Ortiz, Alfonso Torres-Sánchez, Alicia Ruiz-Rodríguez, Ana López-Moreno, Margarita Aguilera","doi":"10.3390/jox15010014","DOIUrl":"10.3390/jox15010014","url":null,"abstract":"<p><p>Dietary exposure to the plasticiser bisphenol A (BPA), an obesogenic and endocrine disruptor from plastic and epoxy resin industries, remains prevalent despite regulatory restriction and food safety efforts. BPA can be accumulated in humans and animals, potentially exerting differential health effects based on individual metabolic capacity. This pilot study examines the impact of direct ex vivo BPA exposure on the gut microbiota of obese and normal-weight children, using 16S rRNA amplicon sequencing and anaerobic culturing combined methods. Results showed that direct xenobiotic exposure induced modifications in microbial taxa relative abundance, community structure, and diversity. Specifically, BPA reduced the abundance of bacteria belonging to the phylum <i>Bacteroidota</i>, while taxa from the phylum <i>Actinomycetota</i> were promoted. Consistently, <i>Bacteroides</i> species were classified as sensitive to BPA, whereas bacteria belonging to the class <i>Clostridia</i> were identified as resistant to BPA in our culturomics analysis. Some of the altered bacterial abundance patterns were common for both the BPA-exposed groups and the obese non-exposed group in our pilot study. These findings were also corroborated in a larger cohort of children. Future research will be essential to evaluate these microbial taxa as potential biomarkers for biomonitoring the effect of BPA and its role as an obesogenic substance in children.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karolina Nowak, Agnieszka Chłopaś-Konowałek, Paweł Szpot, Marcin Zawadzki
{"title":"The Issue of \"Smart Drugs\" on the Example of Modafinil: Toxicological Analysis of Evidences and Biological Samples.","authors":"Karolina Nowak, Agnieszka Chłopaś-Konowałek, Paweł Szpot, Marcin Zawadzki","doi":"10.3390/jox15010015","DOIUrl":"10.3390/jox15010015","url":null,"abstract":"<p><p>Cognitive enhancement through stimulants such as modafinil is becoming increasingly popular, with many individuals using prescription stimulants for non-medical purposes to improve alertness, attention, and mood. The misuse of such substances has raised concerns, particularly in forensic toxicology. The UHPLC-QqQ-MS/MS method was developed to quantify modafinil in evidentiary samples and biological materials. Additionally, the authors noted the presence of sodium adducts during the analysis of samples with high concentrations of modafinil. The method was validated for accuracy, precision, and linearity, with a concentration range of 0.1-10.0 µg/mL for the evidences and 1.0-100.0 ng/mL for blood. The method successfully detected modafinil as the sole substance in all evidences, with concentrations ranging from 90.7 to 120.8 mg, corresponding to 45.5% to 80.5% of the labeled dose. The method was applied to real post-mortem human cases, where, among others, the concentration of modafinil in blood was 110 ng/mL, whereas, in another case, the concentration of modafinil in the putrefaction fluid exceeded 1000 ng/mL. The developed UHPLC-QqQ-MS/MS method is effective for the quantification of modafinil in evidentiary samples and biological materials, offering a reliable tool for forensic toxicology applications. This method can be used to evaluate modafinil use in both legal and illicit contexts, including cases of overdose or misuse.</p>","PeriodicalId":42356,"journal":{"name":"Journal of Xenobiotics","volume":"15 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}