bims-mebolo Biomed News
on Metabolomics
Issue of 2026–06–28
fifty-nine papers selected by
Daniel Méndez Rodríguez, Vbi-Ugent
  1. Practical Workflow for Building Local Mass Spectral Libraries for Untargeted Metabolomics.
  2. Metabolomic Signatures of Commercial Ready-to-Drink Beverages by Dual-Mode Untargeted LC-MS/MS.
  3. Integrated untargeted metabolomics and lipidomics reveals functional- and taste-related compounds in stir-fried Trichosanthis Semen.
  4. Comparative Metabolomic Analysis of Different Organs of Understory-Transplanted and Wild Dendropanax dentiger.
  5. Regions of interest multivariate curve resolution for liquid chromatography with ion mobility high-resolution tandem mass spectrometry: analysis of plastic additives.
  6. Rapid Detection and Deep Characterization of Adulterants in Fennel Essential Oil Using Electronic Nose With GC-MS/Chemometrics.
  7. Chemical composition and antioxidant properties of selected mangrove species from the Sine Saloum Delta (Senegal) using UHPLC-MS/MS and molecular networking.
  8. Metabolite Profiling and Pathway Elucidation of 2-Fluorodeschloroketamine and 2-Fluoro-N-ethylketamine in Rats Using HPLC-QTOF Mass Spectrometry.
  9. Pushing the Boundaries of Biomarker Discovery in Phenylketonuria: Metabolomic Profiling Reveals Novel Biomarkers and Their Associations with Phenylalanine.
  10. Larrea ameghinoi Speg. (Zygophyllaceae) "Jarilla Rastrera": UHPLC-ESI-QTOF-MS Analysis, Antioxidant, Antimicrobial Properties, and Inhibition of Enzymes of Interest to Human Health.
  11. Tissue-specific phenolic profiling of Castanopsis sieboldii: Validated quantification, metabolite annotation, and chemometric discrimination.
  12. Comparative Analysis of Components and Biological Activities in Different Parts of Gastrodia elata Blume.
  13. Qualitative gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry fingerprinting of tissue-specific phytochemicals in finnish Quercus robur L. acorns.
  14. Identification of Chemical Constituents and Metabolites of Shipi Powder In Vitro and In Vivo Based on Ultra-High-Performance Liquid Chromatography Coupled With Quadrupole Time-of-Flight Tandem Mass Spectrometry.
  15. Librarian: An Open-Access Web Application for High-Resolution Mass Spectral Library Assembly.
  16. Benchmarking Lipid Quantitation from Skin Swab Sebum-Rich Samples to Establish Mass Spectrometry-Based Diagnostic Methodology.
  17. LC-MS/MS Strategy Using Substructure Searching for the Annotation of Cyanopeptide Classes: Implications for New Compound Discovery and Environmental Monitoring.
  18. Integrated metabolomic and transcriptomic analysis identifies enhanced phosphatidylcholine metabolism in placenta accreta spectrum.
  19. Validation of a New LC-MS/MS Method for Rapid Quantification of Neferine: Application to Lipid Nanocarriers.
  20. Compositional Analysis of Polymeric Proanthocyanidins from Vitis amurensis Rupr. (Vitaceae) Seeds After Catechin-Assisted Sulfitolytic Cleavage.
  21. Metabolite profiling and in vitro assessment of skin-related pharmacological activities in Baccharis trimera (Less.) DC.
  22. Metabolomic Evidence for Bee-Driven Detoxification, Nutritional Remodeling, and Geographic Homogenization in Rapeseed Floral Products.
  23. Development of a validated UPLC-MS3 method for trace-level azoxystrobin determination in zebrafish liver tissues.
  24. Simultaneous Quantification of Colistin A and B in Human Plasma Using a Small Volume with a High-Throughput LC-MS/MS Method.
  25. Characterizing the molecular signature of obesity through urine metabolomics in a large Chinese population.
  26. Isotope-Coded Derivatization Enables Accurate LC-MS/MS Quantification of Urinary THC-COOH without Isotope-Labeled Cannabinoid Standards.
  27. A Validated LC-MS/MS Method for the Determination of Perospirone in Human Plasma and Its Pharmacokinetic Application in Healthy Volunteers.
  28. Rapid LC-MS/MS Method for Targeted Assay of Creatine Deficiency Syndromes in Morocco.
  29. Functional enhancement of fermented dairy-based tarhana with Thymus vulgaris: phytochemical characterisation and in vitro antidiabetic potential.
  30. Metabolomics Analysis of Aged Garlic Extract for the Identification of Novel Compounds.
  31. Effect of Leaf Extracts of Cornus sanguinea L., C. sericea L., and C. alba L. on Digestive Enzymes and Blood Coagulation In Vitro.
  32. Unveiling Hidden Aconitum Alkaloids in a Poisoning-Implicated Tincture by Untargeted Screening and Molecular Networking.
  33. Transformation-Aware Molecular Networking for Interpretation of Untargeted LC-HRMS Data.
  34. Metabolomic Profiling of Extracellular Vesicles from Flower and Leaf Tissues of Hibiscus syriacus.
  35. Searching for Amaranthin-A Multipotential Betacyanin from Natural Sources and In Vitro Cultures.
  36. Enzyme-Assisted Ultrasonic Extraction of Flavonoids from Pinus koraiensis Needle Litterfall: Process Optimization, Component Identification, and In Vitro Bioactivity Evaluation.
  37. Molecular Framework Modification in Mass Spectrometry: Atom Exchange, Insertion, and Deletion.
  38. Phenolic profiling, synergistic antibacterial and antioxidant potentials of various honey combinations: in vitro and in silico study.
  39. Molecular Profiling and Selective Pro-Apoptotic Activity of a Pruning-Derived Lavandula dentata Leaf-Surface Extract in Colorectal Cancer Cells.
  40. Bioactivity-Guided Identification of Metabolites from Syzygium polycephalum with Antioxidant and α-Glucosidase Inhibitory Activities.
  41. LC-MS/MS analysis of propofol in postmortem blood: propofol glucuronide as an indicator of exposure.
  42. Mass Spectrometry-Based Lipidomics in Coffee: Linking Lipid Transformation to Flavor Formation and Quality Control.
  43. Ultrasound-Treated Sweet Potato Peel Enhances Nutritional Quality and Antioxidant Potential of Gluten-Free Brownies: A Metabolomics and Cell-Based Approach.
  44. First-trimester plasma targeted metabolomics for eicosanoids reveals predictive potential and preventive targets for severe preeclampsia: a nested case-control study.
  45. Feature Down-Selection to Improve Supervised Classification by Machine Learning on Mass Spectrometry Imaging Data.
  46. Epidural-related maternal fever and metabolomic changes: a pilot exploratory study.
  47. Novel bioactive compounds from marine-derived endosymbiotic Penicillium fungi reported during 2020-2025.
  48. Improving Speed and Efficiency of DESI Imaging with the Xevo MRT Mass Spectrometer for Analyte Mapping.
  49. Chemical Profile and Evaluation of the Growth-Inhibitory, Anti-Inflammatory, and Antioxidant Activity Potential of Polar Extracts of Reseda alba L. (Resedaceae).
  50. Quantitative Lipidomics Reveals Dynamic Lipid Profiles in Cinnamomum camphora Seed Kernels at Different Developmental Stages.
  51. Integrated metabolomics, network pharmacology and molecular docking to reveal the effects of drying processes on the antioxidant activity of mulberry (Morus alba L.) leaves.
  52. Integrative multi-omics analysis identifies a robust 14-metabolite signature and reveals microbiome-metabolite-host interactions in atherosclerosis.
  53. Untargeted Metabolomics and Metabolite-Gene Network Analysis Predict NF-κB Inhibition in Artemisian B-Treated Triple-Negative Breast Cancer Cells.
  54. Single-Laboratory Validation of Simultaneous Determination of Aflatoxins in Nutraceuticals following immune-affinity Column Cleanup and Liquid Chromatography Tandem Mass Spectrometry Analysis.
  55. DeepMASS v2: An enhanced deep learning platform for large-scale discovery and structural annotation of unknown plant metabolites.
  56. Plasma or Serum? A Pilot Evaluation of Matrix Selection for Integrated Metabolomics and Exposomics of Clinical Samples.
  57. Integrated Multiomics Enabled by Sequential Extraction for Comprehensive Molecular Profiling of Small Extracellular Vesicles.
  58. Time-Resolved Secondary Metabolite Profiling of Seeded and Seedless Ougan at Commercial Harvest Maturity.
  59. DESI-MSI-Based Multi-Organ Distribution Mapping of Psilocin in Zebrafish.
  1. Metabolites. 2026 Jun 12. pii: 412. [Epub ahead of print]16(6):
    Practical Workflow for Building Local Mass Spectral Libraries for Untargeted Metabolomics.
    Torbjørn Norberg Myhre, Terkel Hansen, Tetiana Lutchyn, Marie Mardal, Terje Vasskog.
      Background: Metabolite identification and annotation remain major bottlenecks in untargeted metabolomics because mass spectral features often lack sufficient specificity. High-confidence annotation requires experimental validation using authentic standards analyzed under matched chromatographic and ionization conditions, providing greater reliability than in silico predictions or database matching alone. This study aimed to develop a practical and scalable workflow for constructing a high-quality mass spectral library using a commercially available analytical standards kit. Methods: A total of 603 metabolites from the MSMLS kit were organized into 42 mixtures, each containing approximately 15 compounds. Mixture design was based on molecular mass and distribution coefficient values, specifically logD at pH 3.1, with a minimum logD spacing of 0.15 to improve chromatographic separation and reduce co-elution. This strategy was used to minimize the total number of injections while maintaining spectral quality. The resulting spectra were evaluated against online spectral resources and in silico fragmentation predictions. A preliminary proof-of-concept analysis was also performed using human serum samples. Results: Using this workflow, 471 metabolites, corresponding to approximately 78% of the standards, were successfully detected and incorporated into the spectral library. Comparison with online resources and in silico fragmentation predictions demonstrated improved spectral quality and reliability. The proof-of-concept serum analysis enabled identification of endogenous metabolites using the constructed library. In addition, the robustness and applicability of the workflow were further supported by a method validation study using metabolites derived from this library. Conclusions: This workflow provides a scalable strategy for constructing mass spectral libraries that balances spectral quality with analytical throughput. By using rational mixture design and authentic standards analyzed under matched experimental conditions, the approach enables substantial metabolite coverage while maintaining data reliability and minimizing experimental effort.
    Keywords:  LC-MS/MS; MSMLS; compound discoverer; fragmentation spectra; mass spectral library; mzVault
    DOI:  https://doi.org/10.3390/metabo16060412
  2. Metabolites. 2026 Jun 10. pii: 404. [Epub ahead of print]16(6):
    Metabolomic Signatures of Commercial Ready-to-Drink Beverages by Dual-Mode Untargeted LC-MS/MS.
    Ivana Blaženović, Kara Bresnahan, Shunyang Wang.
      Background: The rapid expansion of functional ready-to-drink (RTD) beverages-formulated with prebiotic fibers, botanical extracts, and reduced sugar-has outpaced systematic characterization of their small-molecule composition. Methods: We applied dual-mode untargeted high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS), integrating hydrophilic interaction (HILIC) and reversed-phase C18 separations, to profile five commercial RTD beverages spanning distinct formulation categories: Coca-Cola®, Poppi® Orange, OLIPOP® Cream Soda, Pure Leaf® Unsweetened Black Tea, and BeePop™ Peach + Orange Blossom Honey. Results: Across all products, 478 compounds were structurally annotated at Metabolomics Standards Initiative (MSI) Levels 1 and 2, of which 42 matched compounds with reported bioactivity in a curated literature-based reference database. Seventeen compounds-including the NAD+ precursor trigonelline and multiple B vitamins-were detected across all five products. The number and diversity of compounds with reported bioactivity varied substantially by product and correlated with botanical ingredient complexity. Conclusions: This work presents a qualitative molecular survey of the RTD beverage category using standardized, dual-mode untargeted metabolomics, providing a reference dataset for future targeted quantitation studies.
    Keywords:  LC–MS/MS; bioactive compounds; functional beverages; molecular profiling; polyphenols; ready-to-drink beverages; untargeted metabolomics
    DOI:  https://doi.org/10.3390/metabo16060404
  3. Front Nutr. 2026 ;13 1754969
    Integrated untargeted metabolomics and lipidomics reveals functional- and taste-related compounds in stir-fried Trichosanthis Semen.
    Yuan Wang, Di Wu, Xin Zhang, Xin Jia, Lijuan Ha.
      Trichosanthis Semen (TS) is widely used as both a food and traditional medicine. It is rich in diverse compounds (e.g., fatty acids, amino acids, and terpenes), which contribute to its functional and sensory properties. Stir-frying alters the functional and sensory properties of TS, yet the underlying chemical basis remains unclear. In this study, an integrated untargeted metabolomics and lipidomics strategy based on liquid chromatography-high resolution mass spectrometry (LC-HRMS) was employed to characterize compositional differences between raw and stir-fried TS. A total of 144 metabolites and 295 lipids were identified. Omics analysis revealed that 29 metabolites and 54 lipids exhibited significant changes after stir-frying, of which 25 compounds showed increased abundance. Based on these differential compounds, molecular docking suggested that 19 upregulated compounds may have potential relevance to constipation-related regulation, while sensory analysis tentatively linked 39 altered compounds to taste-related attributes. Overall, this study provides a comprehensive chemical profiling of TS and offers a preliminary link between processing-induced chemical changes and functional as well as sensory properties.
    Keywords:  Trichosanthis Semen; lipidomics; liquid chromatography-high resolution mass spectrometry; metabolomics; molecular docking
    DOI:  https://doi.org/10.3389/fnut.2026.1754969
  4. Metabolites. 2026 May 25. pii: 354. [Epub ahead of print]16(6):
    Comparative Metabolomic Analysis of Different Organs of Understory-Transplanted and Wild Dendropanax dentiger.
    Jianshuang Shen, Yiyun Chen, Hang Zhang, Tianze Hu.
      Background: The artificial cultivation of Dendropanax dentiger under forest understory conditions offers a sustainable alternative to wild harvesting, yet the metabolic adaptations underlying transplantation stress and recovery remain poorly understood. Objectives: In this study, we performed a comparative metabolomics analysis of different organs (leaves, current-year stems, three-year-old stems, and roots) from wild D. dentiger plants and those transplanted to the understory. Methods and Results: Metabolite annotation and classification revealed that over 60% of the metabolites fell into the categories of lipids and lipid-like molecules, organoheterocyclic compounds, phenylpropanoids, and polyketides. Further differential analysis of metabolites showed that understory transplantation significantly altered the metabolic profiles of all organs, exhibiting organ-specific response patterns. For the metabolite components in the organs of transplanted and wild D. dentiger, these metabolites were mainly classified into eight categories: alkaloids and derivatives; benzenoids; lignans, neolignans and related compounds; lipids and lipid-like molecules; organic acids and derivatives; organoheterocyclic compounds; phenylpropanoids and polyketides; and organic oxygen compounds. Notably, the contents of (-)-asarinin, (Z)-1-(methylthio)-5-phenyl-1-penten-3-yne, and stearidonic acid (SDA, 18:4n-3) were higher in transplanted plants than in wild plants, indicating the potential of understory cultivation for the targeted extraction of these bioactive compounds. Conclusion: These findings provide a metabolomics basis for optimizing the artificial cultivation and quality control of D. dentiger. This study highlights the value of metabolomics in understanding the metabolic composition of D. dentiger and offers a reference for its artificial cultivation.
    Keywords:  Dendropanax dentiger; metabolic components; organ specificity; understory-transplanted; untargeted metabolomics
    DOI:  https://doi.org/10.3390/metabo16060354
  5. Anal Bioanal Chem. 2026 Jun 22.
    Regions of interest multivariate curve resolution for liquid chromatography with ion mobility high-resolution tandem mass spectrometry: analysis of plastic additives.
    Ana Torres-Agullo, Roma Tauler, Silvia Lacorte, Tytus D Mak, Yamil Simón-Manso.
      Ion mobility (IM) enhances liquid chromatography-mass spectrometry identification capabilities by providing an additional dimension that improves peak capacity, mass detection, and sensitivity, being particularly valuable for untargeted analysis. However, the high dimensionality and large amount of information in the datasets obtained in this type of analysis are a big challenge for data processing, slowing its broader application and potential. The regions of interest multivariate curve resolution (ROIMCR) is a chemometrics approach based on the bilinear model intrinsic structure of the data. It represents an effective strategy for efficient feature extraction, deconvolution, and resolution of overlapping signals in complex datasets without losing relevant information and maintaining instrumental mass accuracy. In this work, the application of ROIMCR is shown for the first time for liquid chromatography ion mobility mass spectrometry (LC-IM-MS) in data-dependent acquisition (DDA) mode, including MS1 and MS2 datasets for the analysis of plastic additives. An improvement in the discrimination of isomeric species and minimization of interferences was shown by working with mobility profiles. IM-MS data from five microsphere standards and three polyethylene (PE) plastic leachates, containing complex mixtures of unknown additives, were analyzed and resolved, and collision cross-section (CCS) values were calculated for each component. Using ROIMCR, 14 different plastic additives, including phthalates, siloxanes, and phosphates, present in the original PE polymers, were identified. Our findings highlight that ROIMCR provides an effective and scalable tool for resolving complex IM datasets and enhancing the identification of potential additives associated with microplastics.
    Keywords:  Collision cross-section; Ion mobility mass spectrometry; Microplastics; Non-targeted analysis; ROIMCR
    DOI:  https://doi.org/10.1007/s00216-026-06632-w
  6. J Food Sci. 2026 Jun;91(6): e71227
    Rapid Detection and Deep Characterization of Adulterants in Fennel Essential Oil Using Electronic Nose With GC-MS/Chemometrics.
    Chun-Lu Liu, Yan Jiang, Huan Wang, Ke Liu, Chun-Mei Qiu, Long Wang, Ping Li, Hui-Jun Li.
      As a classic typical of medicine and food homology, fennel essential oil (FEO) is at risk of fraud due to its high commercial value and soaring consumer demand. This study developed an integrated analysis strategy using electronic nose (E-nose), gas chromatography-mass spectrometry (GC-MS), and chemometrics to achieve rapid identification and quantitative analysis of FEO and its adulterants (anise essential oil [AEO], dill essential oil [DEO], caraway essential oil [CAEO], and cumin essential oil [CUEO]). E-nose combined with principal component analysis (PCA) successfully enabled rapid differentiation of FEO from four common adulterants. Using GC-MS-based untargeted metabolomics coupled with orthogonal partial least squares discriminant analysis (OPLS-DA), 17 differential metabolites were screened, of which 15 were further validated as key markers via gas chromatography-triple quadrupole mass spectrometry (GC-QQQ-MS)-targeted quantitative analysis. On this basis, partial least squares discriminant analysis (PLS-DA) and partial least squares regression (PLS-R) models were established to achieve adulterant type identification and adulteration ratio prediction. The results demonstrated that both established models exhibited good fitting and predictive capabilities. The PLS-DA model achieved 100% classification accuracy for samples with adulteration ratios exceeding 30%, whereas the prediction errors of the PLS-R models for all four adulteration systems were below 10%. This integrated strategy demonstrates the potential to detect FEO adulteration, thereby offering a valuable reference for the quality control of FEO in future studies.
    Keywords:  adulterant quantification; chemometrics; electronic nose; fennel essential oil; gas chromatography–mass spectrometry
    DOI:  https://doi.org/10.1111/1750-3841.71227
  7. Sci Rep. 2026 Jun 23.
    Chemical composition and antioxidant properties of selected mangrove species from the Sine Saloum Delta (Senegal) using UHPLC-MS/MS and molecular networking.
    Cheikhouna Gaye, Elnur Garayev, Yoro Tine, Fathi Mabrouki, Myriam Bertolotti, Charifat Saïd Hassane, Sok-Siya Bun-Llopet, Djibril Fall, Anne Bousquet-Mélou, Béatrice Baghdikian.
      Mangrove ecosystems are important sources of secondary metabolites with significant pharmacological potential. However, the chemical diversity of West African mangroves remains largely unexplored. This study investigated the phytochemical composition and antioxidant activity of aqueous and hydroethanolic extracts from Avicennia germinans, Laguncularia racemosa, and Conocarpus erectus leaves, harvested from the Sine Saloum Delta Biosphere Reserve (Senegal). Metabolic profiling was performed by UHPLC-MS/MS combined with Feature-Based Molecular Networking (FBMN) for metabolite annotation. Antioxidant activity was assessed by off-line and on-line DPPH and ABTS assays, while the total phenolic content (TPC) was determined by the Folin-Ciocalteu method. A total of 153 metabolites were tentatively annotated, primarily phenolic acids, flavonoids, hydrolysable tannins and terpenoids. L. racemosa and C. erectus exhibited the highest TPC and the strongest antioxidant activities, while A. germinans showed limited free radical scavenging activity despite its high triterpenoid content. On-line UHPLC-DPPH/ABTS-MS/MS analysis enabled the rapid identification of the main antioxidant metabolites such as ellagic acid, myricetin and quercetin glycosides. This metabolomics approach highlights the chemical richness and antioxidant potential of L. racemosa and C. erectus. This study contributes to the chemical characterization and valorization of Senegalese mangroves as promising sources of bioactive natural products.
    Keywords:  Antioxidant activity; Mangrove plants; Molecular networking; Sine Saloum Delta; UHPLC-MS/MS
    DOI:  https://doi.org/10.1038/s41598-026-59275-3
  8. Metabolites. 2026 Jun 05. pii: 394. [Epub ahead of print]16(6):
    Metabolite Profiling and Pathway Elucidation of 2-Fluorodeschloroketamine and 2-Fluoro-N-ethylketamine in Rats Using HPLC-QTOF Mass Spectrometry.
    Yujie Zhang, Qinghong Wang, Yanjun Wang, Yongfu Wu, Xun Tian, Yong Dai, Yugang Cai.
      Objectives: This study aimed to employ a High Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight Mass Spectrometry(HPLC-QTOF/MS) system to detect potential metabolites of 2-Fluorodeschloroketamine (2-FDCK) and 2-fluoro-N-ethylketamine (2-FXE) in rats, elucidate their metabolic pathways, and analyze the metabolic differences between the two compounds. Such exploration is vital for understanding their distinct drug effects and providing a reference for forensic toxicological assessment of new phencyclidine-class psychoactive substances. Methods: Twelve SD rats were randomly split into two groups. After a 12 h fast, each group was administered a single intraperitoneal injection of one drug at 0.045 mg/kg. At 1 h and 2 h post-dosing, the rats were euthanized, and blood, liver tissue, and urine samples were promptly collected. These samples underwent rapid solvent extraction for pretreatment and were then analyzed using HPLC-QTOF. Metabolites were identified through database searches and secondary mass spectrometry fragment ion analysis. Results: Comparative analysis of metabolite types, formation times, and chromatographic peak response intensities between the two groups showed that metabolic pathways were mostly consistent. However, significant differences were observed in metabolic reaction types, metabolite formation times, and response intensities, likely stemming from chemical structural disparities. Conclusions: The findings offer crucial insights into the drug effect differences between the two compounds and establish a valuable reference for forensic toxicological evaluation of new phencyclidine-class psychoactive substances.
    Keywords:  2-FDCK; 2-FXE; HPLC-Q-TOF/MS; metabolic differences; metabolic pathway profiling; metabolites
    DOI:  https://doi.org/10.3390/metabo16060394
  9. Molecules. 2026 Jun 08. pii: 2000. [Epub ahead of print]31(12):
    Pushing the Boundaries of Biomarker Discovery in Phenylketonuria: Metabolomic Profiling Reveals Novel Biomarkers and Their Associations with Phenylalanine.
    Reem AlMalki, Shereen M Aleidi, Maha Al Mogren, Shaima Almohsen, Khalid M Sumaily, Ahmed Alfares, Anas M Abdel Rahman.
       BACKGROUND: Phenylketonuria (PKU) is a rare genetic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene, resulting in a deficiency of the enzyme responsible for metabolizing phenylalanine (Phe) and its accumulation. PKU can be identified through newborn screening (NBS) or genetic sequencing; however, both approaches have limitations, including high false-discovery rates and variants of uncertain significance (VUS). This study aims to identify a PKU metabolomic profile using unique biomarkers to enhance early diagnosis and improve treatment outcomes.
    METHODS: Dried blood spot (DBS) samples from 65 patients diagnosed with PKU and matched healthy controls were collected through the NBS program. An untargeted metabolomics analysis was conducted using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to profile metabolites and investigate altered metabolic pathways in patients with PKU.
    RESULTS: A total of 418 significantly dysregulated metabolites were identified in PKU patients. Among them, 90 metabolites were identified as endogenous human metabolites. The most significantly affected pathways were those related to the metabolism of aromatic amino acids and polysaccharides. Moreover, lipid metabolic pathways were dysregulated, including those involved in fatty acid and phospholipid biosynthesis. In addition to phenylalanine (AUC = 0.994), 1,11-Undecanedicarboxylic acid (UDCA) (AUC = 0.969) was significantly elevated in patients with PKU, suggesting it is a promising potential biomarker for PKU.
    CONCLUSIONS: Untargeted metabolomics revealed distinct metabolic alterations in patients with PKU, providing insights into disease pathophysiology. The identification of UDCA as a consistently elevated metabolite supports its potential utility as a supplementary biomarker for PKU diagnosis and monitoring. Further validation in larger cohorts, using a targeted metabolomics approach, is warranted.
    Keywords:  biomarker; next-generation metabolic screening (NGMS); phenylalanine; phenylketonuria; untargeted metabolomics
    DOI:  https://doi.org/10.3390/molecules31122000
  10. Antioxidants (Basel). 2026 May 26. pii: 668. [Epub ahead of print]15(6):
    Larrea ameghinoi Speg. (Zygophyllaceae) "Jarilla Rastrera": UHPLC-ESI-QTOF-MS Analysis, Antioxidant, Antimicrobial Properties, and Inhibition of Enzymes of Interest to Human Health.
    Jessica Gómez, Silvana M Sede, Belén Ariza Sampietro, Daniel Zaragoza-Puchol, María Elisa Bressan Merlo, Duilio Caballero, Beatriz Lima, Alejandro Tapia, Mario J Simirgiotis.
      Larrea ameghinoi Speg., an endemic species of Argentine Patagonia traditionally used in folk medicine to treat fever, stomach disorders, respiratory conditions, back pain, and as an emmenagogue, among others, still remains chemically and biologically underexplored compared to the other four members of the genus. This study aimed to perform a comprehensive metabolomic characterization of methanolic extracts from two populations (EMLaSAO and EMLaMAQ) using ultra-high-resolution liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS) and to evaluate their antioxidant, antimicrobial, and enzyme-inhibitory activities of relevance to human health. Thirty-three compounds were tentatively identified by extensive UHPLC-MS analysis, including flavones, two major lignans, and oleanane-type triterpenes. Both extracts exhibited high phenolic content (215-239 mg of gallic acid equivalents (GAE)/g extract) and strong free radical scavenging activity, as evidenced by 2,2-diphenyl-1-picrylhydrazyl (DPPH, EC50 ≈ 10 μg/mL), ferric-reducing antioxidant power (FRAP), and Trolox equivalent antioxidant activity (TEAC) assays. In addition, significant inhibition of butyrylcholinesterase (IC50 ≈ 50 μg extract/mL) and α-glucosidase, together with selective antibacterial activity against methicillin-sensitive and resistant Staphylococcus aureus (MIC = 125 μg extract/mL), were recorded. These findings suggest that L. ameghinoi possesses a distinctive phytochemical composition conferring multitarget bioactivity, differing from other Larrea species dominated by lignans such as nordihydroguaiaretic acid (NDGA) and its derivatives. Overall, this work supports the potential of L. ameghinoi as a novel source of bioactive metabolites for managing oxidative stress-related disorders and opportunistic infections. This warrants future in vivo studies investigating biological activities associated with oxidative stress and their relevance to human health.
    Keywords:  antimicrobial; antioxidant; enzymes; lignans; phenolic characterization
    DOI:  https://doi.org/10.3390/antiox15060668
  11. J Pharm Biomed Anal. 2026 Jun 18. pii: S0731-7085(26)00289-X. [Epub ahead of print]280 117621
    Tissue-specific phenolic profiling of Castanopsis sieboldii: Validated quantification, metabolite annotation, and chemometric discrimination.
    Ji-Yeong Bae, Bharathi Avula, Kiran Kumar Tatapudi, Ye-Sol Kang, Kumar Katragunta, Sang Ho Lee, Ikhlas A Khan.
      Castanopsis sieboldii is a phenolic-rich evergreen species in the family Fagaceae, yet comprehensive quantitative and tissue-specific metabolite profiling remains limited. In this study, an integrated analytical workflow comprising UHPLC-PDA quantification, LC-QToF-MS identification, and chemometric analysis was developed to characterize phenolic constituents in leaves, flowers, fruits, and stems. A validated UHPLC-PDA method enabled the simultaneous quantification of six major phenolics, with limits of detection ranging from 0.01 to 0.05 μg/mL and limits of quantification from 0.025 to 0.1 μg/mL. Among all tissues, 3‑O‑galloylshikimic acid (Compound 1) was the predominant metabolite (0.1-204 mg/g), followed by caffeoylquinic acids (Compounds 2-3), ellagic acid (Compound 4), and flavonoid glycosides (Compounds 5-6). LC-QToF-MS analysis facilitated the tentative annotation of 185 metabolites, including phenolic acids, ellagitannins, galloylshikimic acids, and flavonoid glycosides, based on accurate mass measurements and characteristic MS/MS fragmentation patterns. Chemometric evaluation using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and hierarchical clustering analysis (HCA) revealed clear tissue-specific clustering, with leaves exhibiting the highest chemical diversity and phenolic abundance, whereas fruits showed minimal levels. PCA captured 80% of total variance in the first two components, and the PLS-DA model showed strong predictive performance (R²Y ≈ 1.00; Q² ≈ 0.98) although interpretation should consider the limited sample size. This study provides a comprehensive, tissue-resolved phenolic profile of C. sieboldii, establishing a robust chemical foundation for future pharmacological, ecological, and quality-control applications.
    Keywords:  Castanopsis sieboldii; Chemical profiling; Chemometrics; LC-QToF-MS; Method validation; UHPLC-PDA
    DOI:  https://doi.org/10.1016/j.jpba.2026.117621
  12. Metabolites. 2026 Jun 10. pii: 406. [Epub ahead of print]16(6):
    Comparative Analysis of Components and Biological Activities in Different Parts of Gastrodia elata Blume.
    Yuru Zhang, Hong Zhang, Xue Meng, Yu Zhang, Di Wang, Juan Chen.
      Background:Gastrodia elata Blume (GE) is a widely used plant with both medicinal and edible properties. Besides the underground tubers, its above-ground parts also have certain medicinal potential. However, most of these resources are frequently discarded during production and processing. The differences in chemical composition and bioactivity among different parts of GE remain unclear. Methods: In this research, the non-targeted metabolomics method was used to detect the metabolites in the stem (ST), capsule shell (CS), seed (SE), arrow end (AE), middle end (ME), and navel end (NE) of GE. Differential metabolites were screened by multivariate statistical analysis. The pathway enrichment analysis of differential metabolites was carried out by the Kyoto Encyclopedia of Genes and Genomes (KEGG) platform. The antioxidant and α-glucosidase inhibitory activities of extracts from six different parts of GE were determined in vitro, followed by correlation analysis between biological activities and key metabolites. Results: Metabolites in different parts of GE were significantly different, including lipids, organic acids, organoheterocyclic compounds, phenylpropanoids, benzenoids, and organic oxygen compounds. The characteristics of metabolites in the underground and above-ground parts of GE were clearly distinct. The contents of lipids, organoheterocyclic compounds, and organic acids were the highest in SE, SE and CS, ST, and AE, respectively. The KEGG pathway enrichment analysis preliminarily suggested that the differences in metabolites from different parts of GE might be related to the arginine biosynthesis pathway, which involves seven metabolites, including L-glutamic acid, L-arginine, L-ornithine, and L-aspartate. Compared with the tuber (the conventional medicinal part), ST and CS exhibited excellent antioxidant properties and inhibitory activity against α-glucosidase. Correlation analysis indicated that L-arginine and L-aspartate were positively correlated with the biological activity of GE and may be components preliminarily associated with its difference in activity. Conclusions: This study provided preliminary comparative evidence for the metabolite characteristics from different parts of GE, thereby facilitating the further development and utilization of its above-ground resources.
    Keywords:  Gastrodia elata Blume; antioxidant activity; different organs; enzyme inhibition; metabolomics; multivariate statistical analysis
    DOI:  https://doi.org/10.3390/metabo16060406
  13. Sci Rep. 2026 Jun 23.
    Qualitative gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry fingerprinting of tissue-specific phytochemicals in finnish Quercus robur L. acorns.
    Inga-Liina Järvinen, Rahim Ullah, Kari Hartonen, Susanne K Wiedmer.
      Acorns of Quercus robur L. are abundant in Finland but remain underutilized, and their chemical composition in high-latitude regions is not well documented. In this study, Finnish acorns were analyzed using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-high resolution mass spectrometry (LC-HRMS) to provide a qualitative overview of their nonpolar and polar compounds. We examined fresh whole acorns as well as dried acorn nuts and dried pericarp fractions. GC-MS analysis indicated that fresh whole acorns were characterized by signals corresponding to phytosterols and tocopherol-related compounds, whereas dried acorn nuts presented increased relative abundances of long-chain n-alkanes. Similarly, dried pericarp analysis showed sterol-related signals and long-chain aldehydes. LC-MS analysis suggested that polar fractions were characterized by ellagitannins, phenolic acids, flavonoids, and organic acids. Although the study is qualitative, it provides the first combined GC-MS and LC-MS fingerprint of the chemical profiles of Finnish Quercus robur L. acorns. Hence, our results provide a foundation for future quantitative studies and application-oriented research on acorn valorization.
    Keywords:   Quercus robur L; Acorn phytochemistry; GC–MS analysis; LC–MS analysis; Lipophilic and polar metabolites
    DOI:  https://doi.org/10.1038/s41598-026-58816-0
  14. J Sep Sci. 2026 Jul;49(7): e70476
    Identification of Chemical Constituents and Metabolites of Shipi Powder In Vitro and In Vivo Based on Ultra-High-Performance Liquid Chromatography Coupled With Quadrupole Time-of-Flight Tandem Mass Spectrometry.
    Jingmei Ma, Xiang Wang, Qi Qian, Yurou Tian, Yingchun Wang, Xinguo Wang, Liying Niu.
      Shipi powder (SPP) is a classical traditional Chinese medicine prescription used to warm yang, strengthen the spleen, promote qi movement, and eliminate retained fluid. It is widely used in the clinic for the treatment of edema caused by various conditions. However, the comprehensive and simultaneous characterization of the major constituents of SPP in vitro and in vivo has remained unclear, which has limited the identification of its active substances and its further clinical application. Therefore, in this study, a chemical composition database of SPP was established. An ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS) method was developed to characterize the constituents of SPP in vitro and in vivo. A total of 217 compounds were identified in vitro, including 57 alkaloids, 8 phenylpropanoid glycosides, 14 lignans, 41 flavonoids, 41 terpenoids, 15 gingerols, 7 lactones, 16 organic acids, and 18 other compounds. Meanwhile, 151 components were detected in vivo, including 93 prototype components and 58 metabolites, in rat plasma, bile, urine, and feces. In summary, this study systematically characterized the components of SPP in vitro and in vivo for the first time. These results provide a useful basis for identifying the pharmacodynamic substances of SPP and for guiding its clinical application.
    Keywords:  chemical constituents; mass spectrometry; metabolites; shipi powder; ultra‐high‐performance liquid chromatography
    DOI:  https://doi.org/10.1002/jssc.70476
  15. Metabolites. 2026 Jun 22. pii: 433. [Epub ahead of print]16(6):
    Librarian: An Open-Access Web Application for High-Resolution Mass Spectral Library Assembly.
    Jacob Ahlberg Weidenfors, Bénilde Bonnefille, Stefano Papazian.
      Background: Confident chemical annotation in nontarget small-molecule mass spectrometry critically depends on the availability of high-quality tandem mass spectral (MS2) reference libraries. While community efforts have driven significant expansion of open-access repositories, technical challenges in assembling standardized, metadata-rich records continue to limit broader participation, underscoring the need for improved computational tools to assist contributors. Methods: To promote the creation and sharing of standardized reference MS2 spectral records, we have developed Librarian, a free, open-access web application designed for rapid and scalable assembly of high-resolution MS2 libraries. Librarian integrates automated retrieval and harmonization of chemical identifiers and metadata from PubChem, compound mixture design for high-resolution mass spectrometry (HRMS) acquisition, and assembly of curated MS2 spectra into repository-ready records compatible with public spectral databases. Results: Through a simple in-browser interface, Librarian offers a flexible end-to-end workflow compatible with popular open-source pre-processing tools to lower technical barriers and facilitate broader community participation in library development. As a demonstration, we used Librarian to create and deposit a spectral library comprising over 1500 new MS2 records into MassBank, which was further applied in retrospective analysis of environmental datasets. Conclusions: Librarian streamlines the creation of standardized, metadata-rich and repository-ready MS2 reference records. Addressing a key bottleneck in community spectral library development and sharing, Librarian supports the continued growth of open-access resources for metabolomics, exposomics, and environmental mass spectrometry. The Librarian web application is publicly accessible via the SciLifeLab Serve platform.
    Keywords:  FAIR; HRMS; MS-DIAL; MassBank; NTA; exposomics; mass spectrometry; metabolomics; open-source; spectral database
    DOI:  https://doi.org/10.3390/metabo16060433
  16. Anal Chem. 2026 Jun 24.
    Benchmarking Lipid Quantitation from Skin Swab Sebum-Rich Samples to Establish Mass Spectrometry-Based Diagnostic Methodology.
    Minhui Zhu, Caitlin Walton-Doyle, Eleanor Sinclair, Katherine Hollywood, Monty Silverdale, Michael Morris, Perdita Barran.
      Skin swab sampling provides an accessible, noninvasive method for collecting lipid-rich material from the skin surface, with growing potential for biomarker discovery and diagnostic testing. However, quantitative sebum analysis remains challenging because of variability in the amount collected and the complexity of the lipid matrix. This study evaluates the robustness of skin swab sampling for lipid analysis and the feasibility of quantifying skin-surface components using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Multiple reaction monitoring was used to assess analytical linearity, matrix effects, and recovery following established protocols for swab collection, storage, and extraction. Robust linearity was observed for both spiked isotope-labeled internal standards (IS) and endogenous lipids across concentrations of 0.15-550 ng/mL (R2 > 0.97). IS recovery varied between lipid classes, with consistent under-recovery. Although IS corrected for analytical variability during extraction and analysis, it could not fully account for differences in the amount of material collected. Endogenous lipids were, therefore, evaluated as normalization markers. Ratios between selected triacylglycerol (TG) species were highly conserved across samples, with coefficients of variation below 15% for TG 45:1/TG 47:1, TG 46:1/TG 48:1, and TG 47:1/TG 48:1. These ratios were stable across individuals and were independent of disease status. The reproducibility of TG recovery and stability of TG ratios suggest that endogenous lipid normalization can mitigate sampling and extraction variability. This approach provides a framework for improving quantitative reliability in skin swab lipidomics and represents a big step toward the development of reproducible mass spectrometry workflows for skin-swat-based biomarker studies.
    DOI:  https://doi.org/10.1021/acs.analchem.5c08056
  17. Environ Sci Technol. 2026 Jun 20.
    LC-MS/MS Strategy Using Substructure Searching for the Annotation of Cyanopeptide Classes: Implications for New Compound Discovery and Environmental Monitoring.
    Runjie Xia, Lindsey Ahn, Michaela Burkhauser, Ross Youngs, Matthew J Bertin.
      Cyanobacterial harmful algal blooms (cyanoHABs) are a major ecological and public health concern, commonly monitored for hepatotoxic microcystins and cylindrospermopsins and neurotoxic anatoxins and saxitoxins. However, the broader suite of bioactive metabolites produced during blooms remains undercharacterized. Here, we interrogated a chromatography fraction library generated from a cyanoHAB in Muskegon, Michigan. From this library, we isolated two new micropeptins (1 and 2), including an analog bearing a bishomologated tyrosine residue, and we confirmed the structure of ferintoic acid C (3). Structures were established using complementary spectrometric and spectroscopic methods. To expand chemical space coverage beyond isolated compounds, we analyzed liquid chromatography-tandem mass spectrometry (LC-MS/MS) data using the Global Natural Products Social Molecular Networking 2 (GNPS2) Analysis Hub query language for product ion searching, enabling annotation of cyanopeptide classes and class-specific modifications across the fraction set, which provided a practical and user-friendly strategy for identifying cyanopeptide classes. One of the new micropeptins (1) exhibited moderate inhibition of neutrophil elastase, consistent with roles in ecological interactions and potential relevance to human exposure. Analysis of field samples from ongoing Lake Erie blooms showed recurring micropeptins but no evidence of microcystins. Together, these results challenge microcystin-centric assessments of bloom hazard and support expanded monitoring of nonmicrocystin cyanopeptides.
    Keywords:  LC-MS/MS; cyanoHABs; cyanopeptides; micropeptins; protease inhibition
    DOI:  https://doi.org/10.1021/acs.est.6c05607
  18. BMC Pregnancy Childbirth. 2026 Jun 23.
    Integrated metabolomic and transcriptomic analysis identifies enhanced phosphatidylcholine metabolism in placenta accreta spectrum.
    Zhenping Liu, Xijiang Liu, Wenxia Zhang, Chenggong Sun, Yuyan Ma, Hongyan Wang.
       BACKGROUND: Placenta accreta spectrum (PAS) is a serious obstetric complication with limited understanding of its molecular basis. This study investigates metabolic and transcriptomic alterations in PAS placentas to uncover potential mechanisms and biomarkers.
    METHODS: Placental tissues from PAS patients (n = 19) and controls (n = 10) underwent untargeted metabolomics via Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differential metabolites were analyzed for pathway enrichment. RNA sequencing was performed to identify differentially expressed genes (DEGs), followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) and disease ontology enrichment. Integrated metabolomic-transcriptomic analysis was used to identify key metabolic pathways, and findings were validated in an expanded cohort (22 PAS cases, 50 controls). Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance of Lecithin, phosphate cytidylyltransferase 1 beta (PCYT1B), and their combination for predicting PAS.
    RESULTS: A total of 203 metabolites were differentially expressed in PAS placentas, with lipid and lipid-like molecules comprising the largest class. Several phosphatidylcholine (PC) species were significantly upregulated, indicating dysregulated glycerophospholipid metabolism. Transcriptome analysis identified 578 DEGs, including upregulation of PCYT1B and endothelial lipase (LIPG), both involved in lipid metabolism. Enrichment analysis revealed activation of glycerolipid and glycosphingolipid pathways and the potential involvement with metabolic disorders. Integrated analysis highlighted enhanced phosphatidylcholine biosynthesis, supported by elevated PCYT1B expression and increased total PC levels in PAS placentas. Lecithin showed higher sensitivity but lower specificity, while PCYT1B displayed intermediate performance. Their combination yielded the best discrimination with an area under the curve (AUC) of 0.791 (95% CI: 0.684-0.899).
    CONCLUSIONS: PAS is characterized by significant alterations in lipid metabolism, particularly increased phosphatidylcholine biosynthesis via the Kennedy pathway. These findings provide new insights into the molecular pathogenesis of PAS and suggest potential metabolic targets for early diagnosis or intervention.
    Keywords:  Glycerophospholipid metabosim; Lipid metabolism; Metabolomics; Placenta accreta spectrum (PAS); Transcriptomics
    DOI:  https://doi.org/10.1186/s12884-026-09552-w
  19. ACS Omega. 2026 Jun 16. 11(23): 34010-34016
    Validation of a New LC-MS/MS Method for Rapid Quantification of Neferine: Application to Lipid Nanocarriers.
    Yash Patidar, Himanshu Kathuria, Murali Monohar Pandey.
      Neferine, a natural alkaloid, is known for its multifaceted properties, including antioxidant, neuroprotective, anti-inflammatory, and autophagy-regulating effects. A simple, robust, specific, and sensitive analytical method is a key requirement for quantifying an analyte. Although a few methods have been reported for simultaneous estimation, none are available for the quantification of neferine alone in pharmaceutical or nutraceutical formulations. Whereas, the quantification of drugs alone is considered as a valuable requirement in the preformulation and formulation studies. In this research work, we report the development and validation of a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the accurate quantification of neferine in bulk and formulations. The chromatographic separation was achieved using a UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm) under an isocratic elution method. The mobile phase consisted of acetonitrile (80%) and 10 mM ammonium acetate with 0.1% formic acid (20%). The flow rate of the mobile phase was set at 0.3 mL/min. The method exhibited good linearity (R 2 = 0.9944) over a range of 25-600 ng/mL. High sensitivity of the method was demonstrated by the limit of detection (LOD) and limit of quantification (LOQ) values of 1.29 and 3.90 ng/mL, respectively. Results of the accuracy and precision study were in complete alignment with the ICH guidelines. The analytical method was found to be robust under varied analytical conditions. Furthermore, the method was successfully applied for the quantification of neferine in nanostructured lipid carriers in the diffusion studies. In conclusion, the newly developed and validated LC-MS/MS method is specific, sensitive, rapid, accurate, and precise for the quantification of neferine in bulk and formulated products.
    DOI:  https://doi.org/10.1021/acsomega.6c00933
  20. Foods. 2026 Jun 06. pii: 2045. [Epub ahead of print]15(12):
    Compositional Analysis of Polymeric Proanthocyanidins from Vitis amurensis Rupr. (Vitaceae) Seeds After Catechin-Assisted Sulfitolytic Cleavage.
    Xiangyun Ren, Peixin Wang, Jing Lan, Zhangcheng Liang, Zhigang He, Hao Su, Weixin Li.
      Polymeric procyanidins (PPCs) constitute the major fraction of procyanidins, but they have poor bioactivity. The purpose of this study is to clarify the composition and content of PPCs from Vitis amurensis Rupr. (Vitaceae) seeds before and after depolymerization, thereby providing a theoretical basis for activity evaluation and application of proanthocyanidins (PCs). PPCs extracted from V. amurensis seeds were depolymerized by catechin-assisted sulfitation. The compositions and contents of PCs before and after depolymerization were qualitatively and quantitatively analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), high-performance liquid chromatography (HPLC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results showed that twenty-eight components were identified (7 monomers, 13 dimers, 5 trimers, 1 tetramer and 2 unknowns). Before depolymerization, tetrameric and higher polymers dominated, accounting for 58.81% of the relative content. After depolymerization, these high-molecular-weight compounds declined to <1% or became undetectable, while monomers and dimers (with minor trimers) surged to 42.89%. Among them, the relative content of two monomers and three dimers, catechin, epicatechin gallate and procyanidin B1-B3, increased by 37.00, 3.75, 10.98, 3.72 and 9.74 times, respectively. In conclusion, the method utilizing catechin-assisted sulfitation effectively depolymerizes PPCs from V. amurensis seeds into oligomeric components such as monomers and dimers.
    Keywords:  Vitis amurensis seeds; catechin; depolymerization; polymeric proanthocyanidins; sulfitation
    DOI:  https://doi.org/10.3390/foods15122045
  21. J Ethnopharmacol. 2026 Jun 25. pii: S0378-8741(26)00971-2. [Epub ahead of print] 122117
    Metabolite profiling and in vitro assessment of skin-related pharmacological activities in Baccharis trimera (Less.) DC.
    Philipp Gabor, Wéldion G Mesquita Júnior, Kyuri Ribeiro, Romário Pereira da Costa, Quezia B Cass, Vanessa Gisele Pasqualotto Severino, Richele P Severino, Geísa Ferreira Costa Makishi, Gislane Florambel Siqueira, Matthias F Melzig, Alexander Weng, Lorena R F de Sousa.
       ETHNOPHARMACOLOGICAL RELEVANCE: Baccharis trimera (Less.) DC. (Asteraceae), commonly known as "carqueja", is a medicinal plant traditionally used in Brazil as an herbal remedy for gastrointestinal disorders. In some regions, its aerial parts are also used to treat skin-related diseases, including wounds. Despite growing interest in discovering new cosmeceutical ingredients from traditionally used medicinal plants, knowledge of this species and its potential skin-related applications remains limited.
    AIM OF THE STUDY: We investigated the aerial parts of B. trimera for their anti-inflammatory, anti-aging, and skin-whitening properties.
    MATERIALS AND METHODS: The ethanolic extract (BtE) was fractionated via liquid-liquid extraction into hexane (BtEH), dichloromethane (BtED), ethyl acetate (BtEA), and hydroalcoholic (BtEHy) fractions. Chemical dereplication of BtE and active fractions (BtEA and BtED) was performed using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). Enzyme inhibitory activity against tyrosinase and elastase was evaluated spectrophotometrically. Anti-inflammatory activity was assessed in lipopolysaccharide (LPS)-stimulated THP-1 macrophages by quantifying TNF-α, IL-1β, and IL-6 levels using ELISA.
    RESULTS: The crude extract inhibited elastase activity, while its fractions reduced cytokine production and enhanced tyrosinase inhibition. Among these, the dichloromethane fraction showed the most pronounced effects, including tyrosinase inhibition, reduced secretion of TNF-α, IL-1β and IL-6, and a significant decrease in LPS-induced LDH release. Twenty compounds, including flavonoids, hydroxycinnamic acid derivatives, diterpenes, phenylpropanoids, and fatty acids, were annotated in the active ethanolic extract and its fractions from Baccharis trimera, several of which have previously shown anti-inflammatory activity. After fractionation, cirsimaritin, eupatorin, and jaceosidin were found exclusively in the dichloromethane fraction and may have contributed to its anti-inflammatory activity. In addition, the anti-tyrosinase activity observed in the medium-polarity fractions may be associated with the presence of rutin, apigenin flavone glucoside, and 3-hydroxy-copalic acid.
    CONCLUSION: Overall, this study expands the chemical characterization of this medicinal plant and underscores its potential for skincare applications. Notably, anti-tyrosinase activity was identified in the medium-polar fractions for the first time, highlighting their potential as a source of bioactive metabolites relevant for cosmetic and skin-related applications.
    Keywords:  Anti-inflammatory; THP-1; cosmeceutical; elastase; tyrosinase
    DOI:  https://doi.org/10.1016/j.jep.2026.122117
  22. Metabolites. 2026 Jun 10. pii: 403. [Epub ahead of print]16(6):
    Metabolomic Evidence for Bee-Driven Detoxification, Nutritional Remodeling, and Geographic Homogenization in Rapeseed Floral Products.
    Wei-Min Gao, Chun-Mei Xiong, Jing-Juan Li, Lu Lu.
      Background: Rapeseed (Brassica napus L.)-derived pollen, pollen-containing anther, bee pollen, and honey are natural health products with both nutritional and functional value. Bee processing plays a key role in the dynamic transformation process of bee product formation. Existing research has mostly focused on static analyses of single product types and has not systematically elucidated the hierarchical differences in metabolites from plant pollen to bee products, the remodeling mechanism during bee processing, or the impact of geographical origin and agricultural practices on product metabolic profiles. These research gaps limit the precise development and quality control of rapeseed-derived bee products. Methods: This study employed UPLC-MS/MS-based untargeted metabolomics to analyze differential metabolites among rapeseed pollen, pollen-containing anther, bee pollen, and honey and elucidated functional differences via KEGG pathway enrichment analysis. Results: A total of 1308 metabolites were identified, primarily consisting of active components such as flavonoids and terpenoids. Origin-related differences caused by agricultural practices and companion plants were significant in raw pollen but were markedly attenuated by bee processing. Bee pollen showed increased levels of phospholipids and sugars along with reduced toxic substances, forming a safer and more balanced nutritional profile, making it suitable as a nutritional supplement. Honey was highly enriched in monosaccharides and disaccharides, combining flavor with functionality, and is suitable for the development of energy foods. Conclusions: Bee processing actively reshapes the pollen metabolome, attenuates geographical origin differences in raw materials, and enhances the safety and nutritional balance of bee products.
    Keywords:  bee pollen; bee processing; honey; rapeseed pollen; untargeted metabolomics
    DOI:  https://doi.org/10.3390/metabo16060403
  23. Anal Methods. 2026 Jun 22.
    Development of a validated UPLC-MS3 method for trace-level azoxystrobin determination in zebrafish liver tissues.
    Yufeng Guo, Chunpeng Feng, Mengchuan Lai, Meichen Liu, Yalin Xi, Lei Yin, Meiyun Shi.
      Azoxystrobin is a widely used strobilurin fungicide. Its environmental persistence and potential toxicity to aquatic organisms demand accurate trace-level quantification in biological tissues. However, its sensitive and specific determination in small tissue samples using conventional methods remains challenging. In this study, a novel high-sensitivity analytical method based on ultra-performance liquid chromatography coupled with triple-stage mass spectrometry (UPLC-MS3) was established for the trace determination of azoxystrobin in zebrafish liver tissues. Following protein precipitation extraction, chromatographic separation was performed on a C18 column using a gradient of 0.1% aqueous formic acid and acetonitrile. Detection relied on an optimized MS3 transition (m/z 404.0 → 371.9 → 344.2). The method exhibited excellent linearity (r > 0.9984) from 0.1 to 20 ng mL-1, with accuracy between -3.33% and 3.67% and precision (CV) between 5.57 and 10.19%. Consistent recoveries (94.93-106.64%) and minimal matrix effects (99.45-104.79%) were achieved across all tissue matrices. Compared to conventional MRM, MS3 scanning significantly enhanced specificity by reducing endogenous interference. The validated approach was successfully applied to tissue distribution studies in zebrafish, confirming its reliability for environmental toxicology research and providing a robust platform for investigating fungicide biodistribution in aquatic organisms.
    DOI:  https://doi.org/10.1039/d6ay00445h
  24. Pharmaceuticals (Basel). 2026 Jun 12. pii: 924. [Epub ahead of print]19(6):
    Simultaneous Quantification of Colistin A and B in Human Plasma Using a Small Volume with a High-Throughput LC-MS/MS Method.
    Jimin Yoon, Won Gun Kwack, Kyung-Tae Lee, Eunseo Song, Hyeon Su Kim, Ki-Ho Park, Eun Kyoung Chung.
      Background/Objectives: Colistin is a complex polymyxin antibiotic with a narrow therapeutic window and significant interindividual pharmacokinetic variability, necessitating precise concentration monitoring. Current analytical methods often utilize colistin mixtures or require large sample volumes, potentially limiting the precision and resolution of individual component quantification. This study aimed to develop a sensitive and component-specific bioanalytical assay for the simultaneous quantification of colistin A and colistin B in human plasma. Methods: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed using pure, component-specific reference standards to ensure rigorous independent quantification of each component. Analytes were efficiently extracted from a small volume of plasma (50 µL) using solid-phase extraction. Chromatographic separation was achieved on a C18 column with a total runtime of 4 min, and detection was performed using negative-ion multiple reaction monitoring (MRM). Results: Calibration curves showed excellent linearity over a range of 0.1-20 µg/mL for both colistin A and B (R2 > 0.99). The precision (%CV ≤ 8.8%) and accuracy (86.4-105.7%) for both components met the predefined regulatory criteria. This method was clinically validated using 60 plasma samples from 15 patients, demonstrating its applicability for capturing individual concentration-time profiles within the clinically relevant range (0.323-19.579 µg/mL for colistin A and 0.065-6.132 µg/mL for colistin B). Conclusions: This validated bioanalytical assay enables precise clinical pharmacokinetic assessments in a high-throughput workflow using a small plasma volume. Therefore, it serves as a practical tool for therapeutic drug monitoring (TDM)-guided dose optimization and further clinical investigations of colistin therapy.
    Keywords:  LC–MS/MS; colistin; colistin A; colistin B; pharmacokinetics; therapeutic drug monitoring
    DOI:  https://doi.org/10.3390/ph19060924
  25. J Chromatogr B Analyt Technol Biomed Life Sci. 2026 Jun 20. pii: S1570-0232(26)00284-9. [Epub ahead of print]1281 125195
    Characterizing the molecular signature of obesity through urine metabolomics in a large Chinese population.
    Xiaoyi Yi, Enhui Luan, Jie Luo, Congjie Zhong, Jiaping Song, Tiancai Liu, Jingxin Wang.
      Human obesity is a growing public health problem and has been considered as a pandemic non-communicable disease. Obesity and its related comorbidities have become a major health concern worldwide, but the metabolic factors underlying obesity are not well-understood. In the present study, we conducted large-scale untargeted metabolomics to clarify the metabolic links between obesity and the urinary metabolome. In total, 340 candidate urinary metabolites from 5831 Chinese individuals were identified by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QToF MS). The cross-sectional associations between urinary metabolites and body mass index (BMI) were examined. Height, weight, dietary and lifestyle habits of the participants were collected by questionnaire. The urinary metabolome was profiled by LC-QToF MS. The potential associations were evaluated by multiple linear regression adjusted for age and gender. Results revealed that 32 urinary metabolites were significantly associated with BMI, including 16 amino acids and peptides, 3 nucleotides, 1 carbohydrate, 1 lipid, 7 food components, and 4 exposure chemicals (Q < 0.01). Many of these potential associations have not been reported previously, including several peptides and exposure chemicals. In total, 59 candidate metabolites were associated with BMI at the P < 0.05 level. These findings provide a comprehensive view of metabolic phenotyping of obesity in the Chinese population. The untargeted metabolomic results suggest a broadly modifiable metabolic profile during the progress of obesity for future research.
    Keywords:  Body mass index; Liquid chromatography quadrupole time-of-flight mass spectrometry; Metabolomics; Obesity; Urine
    DOI:  https://doi.org/10.1016/j.jchromb.2026.125195
  26. J Am Soc Mass Spectrom. 2026 Jun 24.
    Isotope-Coded Derivatization Enables Accurate LC-MS/MS Quantification of Urinary THC-COOH without Isotope-Labeled Cannabinoid Standards.
    Maiko Kusano, Shimba Kawasue, Yu-Ki Sakamoto, Mahiro Yoshida, Taka-Aki Matsuyama.
      Quantitative determination of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in urine is the internationally accepted approach for verifying cannabis use in forensic toxicology. Accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis typically relies on stable isotope-labeled internal standards; however, isotope-labeled cannabinoid reference materials are costly, tightly regulated, and not uniformly accessible across laboratories. We report an isotope-coded derivatization (ICD) strategy that enables isotope-dilution-equivalent quantification of urinary THC-COOH without reliance on commercially available isotope-labeled cannabinoid standards. THC-COOH was derivatized with isopropyl-piperidine carboxylic acid hydrazide (IPPAH) and its deuterated analogue (IPPAH-d6), generating a chemically matched analyte/internal standard pair through parallel derivatization. The derivatives exhibited stable chromatographic coelution and closely matched ionization behavior under positive electrospray ionization. Quantitative LC-MS/MS analysis demonstrated linearity over 1-500 ng/mL (r2 > 0.999), with intra- and interday accuracy of 81.8-108.6% and precision below 10%. Internal standard-normalized matrix factors ranged from 97-109% with minimal variability, indicating effective compensation for matrix effects. This compensation enabled reliable quantification without extensive sample cleanup, allowing a simplified sample preparation workflow compared with conventional methods. Derivatized samples remained stable for at least 72 h in the autosampler without detectable isotopic exchange. This ICD strategy provides a quantitatively reliable alternative to conventional isotope dilution while eliminating dependence on isotope-labeled cannabinoid standards, thereby expanding the accessibility of high-confidence LC-MS/MS quantification and illustrating the broader potential of isotope-coded derivatization in forensic mass spectrometry.
    Keywords:  11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC−COOH); isotope-coded derivatization; liquid chromatography-tandem mass spectrometry; Δ9-tetrahydrocannabinol (Δ9-THC)
    DOI:  https://doi.org/10.1021/jasms.6c00110
  27. ACS Omega. 2026 Jun 16. 11(23): 34621-34635
    A Validated LC-MS/MS Method for the Determination of Perospirone in Human Plasma and Its Pharmacokinetic Application in Healthy Volunteers.
    Benkai Qin, Huina Zhang, Hangyu Zhao, Yuchen Su, Yifu Kong, Shengshuo Zhang, Luwei Wang, Yonghua Yu, Jie Gu, Tingting Lou.
      Perospirone hydrochloride hydrate is an atypical antipsychotic widely used in the management of schizophrenia. Reliable quantification of its plasma concentrations remains essential for pharmacokinetic characterization and dose optimization. A rapid, specific, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and fully validated for the quantification of perospirone in human EDTA-K2 plasma using perospirone-d 8 as the internal standard (IS). Chromatographic separation was achieved on a Kinetex C18 analytical column (100 Å, 50 mm × 2.1 mm, 5 μm, 100 Å). The mobile phase consisted of an aqueous solution of 0.1% formic acid and 1 mM ammonium formate (MPA) and a solution of 95% acetonitrile containing 0.1% formic acid and 1 mM ammonium formate (MPB), delivered at a flow rate of 0.300 mL/min. The injection volume was 10 μL. Mass spectrometric detection was performed using electrospray ionization in positive-ion mode with multiple reaction monitoring (MRM). The method exhibited linearity over a concentration range of 0.0200-12.0 ng/mL. The validated method was successfully applied to fasting and postprandial pharmacokinetic studies following oral administration of perospirone hydrochloride tablets. The method demonstrates strong performance characteristics and practical utility, supporting its application in pharmacokinetic investigations, bioequivalence assessment, and clinical drug monitoring.
    DOI:  https://doi.org/10.1021/acsomega.6c02906
  28. Metabolites. 2026 Jun 03. pii: 388. [Epub ahead of print]16(6):
    Rapid LC-MS/MS Method for Targeted Assay of Creatine Deficiency Syndromes in Morocco.
    Faïza Meiouet, François Boemer.
      Background: Creatine deficiency syndromes (CDS) are rare neurometabolic disorders caused by defects in creatine biosynthesis (AGAT and GAMT deficiencies) or creatine transport (SLC6A8 deficiency). Early biochemical recognition is crucial for timely treatment of AGAT and GAMT deficiencies and for improving neurodevelopmental outcomes. In Morocco, expanding the liquid chromatography-tandem mass spectrometry (LC-MS/MS) biomarker panel for inherited metabolic disorders is a priority to strengthen diagnostic capacity and reduce diagnostic delay. Methods: We developed and validated a rapid LC-MS/MS method for the simultaneous quantification of creatine (Cr), guanidinoacetate (GAA), and creatinine (Crn) in plasma and urine using isotopically labelled internal standards and a standardized sample preparation procedure. Analytical performance, including linearity, precision, accuracy, sensitivity, matrix effects, carryover, inter-sample contamination, stability, and measurement uncertainty, was assessed in accordance with ISO 15189:2022 requirements. Results: The assay showed excellent linearity across the analytical range (r2 > 0.99), with robust intra- and inter-day precision (CV < 10%). Limits of detection (LOD) were 0.05 µmol/L for Cr and 0.03 µmol/L for GAA in urine, and 0.05 µmol/L for Cr and GAA in plasma. The total run time was 1.1 min per sample, supporting high-throughput implementation. Method performance was further supported by satisfactory results in ERNDIM external quality assessment schemes. Preliminary internal reference ranges and expanded measurement uncertainty were calculated from the available anonymized dataset. Conclusions: This rapid LC-MS/MS method enables the measurement of key CDS biomarkers and contributes to expanding the LC-MS/MS biomarker panel for inherited metabolic disorders in Morocco.
    Keywords:  LC-MS/MS; creatine; creatine deficiency syndromes; guanidinoacetate
    DOI:  https://doi.org/10.3390/metabo16060388
  29. J Sci Food Agric. 2026 Jun 22.
    Functional enhancement of fermented dairy-based tarhana with Thymus vulgaris: phytochemical characterisation and in vitro antidiabetic potential.
    Serap Kılıç Altun, Mehmet Emin Aydemir, Kasim Takim, Adem Necip, Mustafa Abdullah Yilmaz.
       BACKGROUND: This study investigated the effects of Thymus vulgaris (TV) enrichment on the phytochemical profile, antioxidant capacity, antimicrobial activity, amino acid composition, and α-glucosidase inhibitory potential of fermented dairy-based tarhana. Tarhana was produced in three formulations (control, 40 g kg-1 (TV4), and 80 g kg-1 (TV8) thyme enrichment) under controlled fermentation and drying conditions.
    RESULTS: The results showed that TV integration significantly increased total phenolic content (TPC) and total flavonoid content (TFC) in a dose-dependent manner, leading to superior DPPH and ABTS radical scavenging activities. Microbiological analysis revealed a selective antimicrobial effect; TV effectively suppressed yeast and mould growth while maintaining the viability of lactic acid bacteria (LAB), ensuring fermentation integrity. Specifically, TV enrichment increased nutrient density, raising total free amino acids from 1821.7 μg g-1 to 2803.6 μg g-1. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identified a robust bioactive profile, including rosmarinic acid, luteolin, and naringenin. The TV8 group exhibited a strong antidiabetic profile, providing approximately 90% inhibition of α-glucosidase. Molecular docking confirmed that TV-derived ligands exhibited high binding affinities in the catalytic pockets of metabolic enzymes, mimicking or exceeding the stability of standard inhibitors.
    CONCLUSION: The results demonstrate that thyme enrichment enhances the functional and bioactive properties of fermented dairy-based tarhana, offering a scientifically supported strategy for developing value-added functional dairy products with potential metabolic health benefits. © 2026 Society of Chemical Industry.
    Keywords:  Thymus vulgaris; antidiabetic activity; molecular docking; phytochemical profiling; tarhana
    DOI:  https://doi.org/10.1002/jsfa.70845
  30. Metabolites. 2026 May 29. pii: 369. [Epub ahead of print]16(6):
    Metabolomics Analysis of Aged Garlic Extract for the Identification of Novel Compounds.
    Masato Nakamoto, Tsubasa Nishimura, Masahiro Ohtani, Toshiaki Matsutomo.
       BACKGROUND/OBJECTIVES: Aged garlic extract (AGE), produced by aging raw garlic in an aqueous ethanol solution for over 10 months, exhibits multiple pharmacological activities, including antioxidant and anti-inflammatory effects. However, because AGE has a complex composition and many constituents remain insufficiently characterized, the chemical basis underlying its broad activities is not fully understood. This study aimed to investigate these previously overlooked compounds in AGE to better understand its chemical complexity.
    METHODS: AGE was fractionated using bioactivity assays to select target fractions for detailed chemical analysis. Metabolomics profiling was performed using liquid chromatography-mass spectrometry (LC-MS). Compounds were tentatively identified through database matching, fragmentation pattern analysis, and comparison with authentic standards.
    RESULTS: Thirteen compounds not previously reported in AGE were tentatively identified. Citric acid was present at high levels. Citrulline and galacturonic acid were detected in AGE but not in raw garlic, suggesting that they are formed during the aging process. Trigonelline was detected and tentatively identified in the AGE sample used in this study. The remaining compounds included choline, 5-oxoproline, malic acid, gluconic acid, adenine, succinic acid, mucic acid, pipecolinic acid, and caffeic acid. These compounds may contribute to the diverse biological activities of AGE.
    CONCLUSIONS: These findings expand the chemical characterization of AGE and provide a foundation for understanding its broad pharmacological activities. They may also support future studies on functional food development and the health benefits of AGE.
    Keywords:  aged garlic extract; garlic; identification; metabolomics analysis
    DOI:  https://doi.org/10.3390/metabo16060369
  31. Plant Foods Hum Nutr. 2026 Jun 20. pii: 80. [Epub ahead of print]81(3):
    Effect of Leaf Extracts of Cornus sanguinea L., C. sericea L., and C. alba L. on Digestive Enzymes and Blood Coagulation In Vitro.
    Tatiana Krol, Ekaterina Sokolova, Vladimir Ossipov, Natalya Gudkova, Dmitry Baleev, Nikolay Sidelnikov.
      Cornus plants have found extensive applications in food and exhibit a versatile and complex pharmacological potential due to their broad spectrum of bioactive compounds. The aim of our study was to investigate and compare the composition of phenolic compounds and the inhibitory activity of leaf extracts of three species of the genus Cornus: C. alba, C. sanguinea, and C. sericea on pancreatic lipase, α-amylase, and blood coagulation in vitro. A total of 42 compounds classified as terpenoids and phenolic compounds were identified using ultra-high pressure liquid chromatography with photodiode array detection coupled to high-resolution mass spectrometry (UPLC-PDA-HRMS). Terpenoids were represented by three iridoids. Phenolic compounds included phenolic acids, galloylglucoses, ellagitannins (monomeric, dimeric, and trimeric), and flavonoids. Differences were observed in the composition of iridoids. Loganic acid was absent from C. sanguinea leaf extracts. However, plant species significantly affected biological properties. Selective inhibition of either amylase or lipase was demonstrated by C. sanguinea and C. sericea extracts. Extracts from C. sanguinea leaves were capable of moderately inhibiting amylase activity (34% inhibition at C = 0.2 mg/ml), while extracts from C. sericea leaves showed an inhibitory effect on lipase (30% inhibition at C = 0.2 mg/ml). Extracts of C. sanguinea and C. sericea leaves indicated significant inhibitory activity in the activated partial thromboplastin time test (50 and 57% increase in clotting time, respectively), especially when compared with the extract from C. alba leaves (17% increase in clotting time).
    Keywords:   Cornus plants; Anticoagulant activity; Ellagitannins; Lipase; Phenolic compounds; UPLC-PDA-HRMS/MS; α-amylase
    DOI:  https://doi.org/10.1007/s11130-026-01531-y
  32. Toxins (Basel). 2026 Jun 05. pii: 255. [Epub ahead of print]18(6):
    Unveiling Hidden Aconitum Alkaloids in a Poisoning-Implicated Tincture by Untargeted Screening and Molecular Networking.
    Qian He, Micong Jin, Jing Zhou, Hongshun Zhang, Chengye Sun.
      Aconitum poisoning is a major public health concern in East Asia, and remains difficult to diagnose when the causative toxins are not covered by routine targeted assays. In a poisoning incident that occurred in 2018, 15 individuals were affected, including five fatalities, after accidentally consuming a medicinal tincture during a shared meal. The comprehensive alkaloid profile of the tincture implicated in the poisoning was achieved through the integration of targeted analysis, molecular networking, and untargeted screening based on ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry, aiming to clarify the causative agents. Targeted quantitative analysis detected nine alkaloids derived from Aconitum plants, confirming the presence of Aconitum ingredients in the medicinal tincture. However, these alkaloids were either present at low concentrations or exhibited low toxicity, and thus were not the principal causative agents of this poisoning incident. Molecular networking revealed additional hidden diester-diterpenoid alkaloids (DDAs) and monoester-diterpenoid alkaloids (MDAs) that were undetected by targeted analysis. Untargeted screening identified 58 Aconitum alkaloids, including 15 DDAs, 17 MDAs, 17 amino-diterpenoid alkaloids (ADAs), 2 C20-diterpenoid alkaloids, and seven unclassified alkaloids. The three most abundant alkaloids were structurally identified as pseudoaconitine, 8-deacetylpseudoaconitine, and 3'-methoxyacoforestinine, and were identified as the main causative agents of this poisoning. To our knowledge, this is the first detection of these alkaloids in Aconitum poisoning in China. These findings demonstrate that integrated targeted and untargeted toxicological analysis can identify undocumented toxins in poisoning events of unknown origin and clarify the chemical etiology of unusual Aconitum poisoning.
    Keywords:  3′-methoxyacoforestinine; 8-deacetylpseudoaconitine; Aconitum alkaloids; Aconitum poisoning; molecular networking; pseudoaconitine; untargeted screening
    DOI:  https://doi.org/10.3390/toxins18060255
  33. ACS Meas Sci Au. 2026 Jun 17. 6(3): 703-714
    Transformation-Aware Molecular Networking for Interpretation of Untargeted LC-HRMS Data.
    Elena Ferri, Cristian Caprari, Maria Angela Vandelli, Rossana Cecchi, Patrizia Verri, Cinzia Citti, Giuseppe Cannazza.
      The rapid emergence of new psychoactive substances (NPS) and their extensive biotransformation challenge the reliability and interpretability of chemical measurements in forensic toxicology. Targeted analytical workflows offer high selectivity but frequently fail when parent compounds are present at low concentrations or are absent from biological matrices, limiting metabolite coverage and evidential interpretation. In this study, an untargeted LC-HRMS measurement and data-analysis framework was evaluated to improve metabolite annotation and structural contextualization in complex forensic samples. Blood and urine collected from a suspected driving under the influence of drugs (DUID) case were analyzed using high-resolution full-scan and data-dependent MS/MS acquisition as a representative test system. Data were processed in Compound Discoverer using a customized workflow combining spectral library matching (mzCloud and in-house spectral database built from HighResNPS.com, containing over 2400 high-resolution spectra of drugs of abuse and NPS), rule-based metabolite prediction (MetID), and transformation-aware molecular networking. The transformation-aware molecular networking strategy integrates MS/MS spectral similarity with predicted phase I and phase II biotransformations, enabling relational organization of parent compounds, metabolites, and structurally related features. Compared to rule-based metabolite prediction alone, this approach increased the number of metabolite-related features associated with detected xenobiotics and supported reconstruction of chemically consistent metabolic families, including cases in which parent compounds were not observed in the measured sample. Taken together, the results show that transformation-aware molecular networking provides an effective means of organizing and interpreting untargeted LC-HRMS data by linking spectral similarity with biotransformation relationships. This framework supports a more contextual interpretation of metabolite-related features in forensic and toxicological investigations involving NPS and other xenobiotics.
    Keywords:  biotransformation pathways; forensic toxicology; metabolite identification; new psychoactive substances; transformation-aware molecular networking; untargeted LC–HRMS
    DOI:  https://doi.org/10.1021/acsmeasuresciau.6c00011
  34. Metabolites. 2026 Jun 02. pii: 386. [Epub ahead of print]16(6):
    Metabolomic Profiling of Extracellular Vesicles from Flower and Leaf Tissues of Hibiscus syriacus.
    Junhe Hu, Shuting Peng, Shichang Zhou, Zhi Zeng, Shuanghui Wang, Zhenzhen Guo, Yong Chen.
      Objectives: Plant extracellular vesicles (EVs) mediate intercellular communication and carry tissue-specific metabolites, yet tissue-resolved EV metabolomics in non-model medicinal plants remains poorly explored. Hibiscus syriacus is a valuable medicinal and ornamental species rich in bioactive compounds, but the metabolic profiles of flower- and leaf-derived EVs are unknown. This study aimed to characterize tissue-specific EV metabolomes of H. syriacus and reveal their functional implications. Methods: EVs were isolated from flowers (MJH) and leaves (MJY) of H. syriacus and verified by TEM and DLS. Untargeted LC-MS/MS metabolomics was applied to profile EV metabolites. Multivariate statistics (PCA, OPLS-DA), differential metabolite screening (VIP > 1, p < 0.05), and KEGG pathway enrichment were performed. Results: MJH- and MJY-EVs exhibited typical EV morphology and high purity. In total, 3338 metabolites were identified, dominated by lipids (29.43%). Clear metabolic separation was observed between MJH- and MJY-EVs. Thirty-nine differential metabolites were identified: 31 upregulated in MJH-EVs (lipids, pentadecanoic acid) and eight in MJY-EVs (nucleotides, secondary metabolites). Glycerophospholipid metabolism was the most enriched pathway in MJH-EVs, while MJY-EVs were linked to energy and defensive metabolism. Conclusions:H. syriacus EVs display strong tissue-specific metabolic signatures. Leaf EVs prioritize lipid metabolism for photosynthetic function and stress tolerance, while flower EVs accumulate secondary and energy-related metabolites for reproduction and defense. These findings advance plant EV biology and support potential applications of H. syriacus EVs in cosmetics and agriculture.
    Keywords:  Hibiscus syriacus; LC-MS/MS; differential metabolites (DMs); extracellular vesicles (EVs); metabolomic profiling; tissue-specific metabolism
    DOI:  https://doi.org/10.3390/metabo16060386
  35. Int J Mol Sci. 2026 Jun 15. pii: 5393. [Epub ahead of print]27(12):
    Searching for Amaranthin-A Multipotential Betacyanin from Natural Sources and In Vitro Cultures.
    Małgorzata Jeziorek.
      Amaranthin is a major red-violet betacyanin of Amaranthaceae and an increasingly relevant natural pigment for food, cosmetic, nutraceutical, and biotechnological applications. This review integrates knowledge from over 100 studies, addressing amaranthin as a chemically defined betalain, distinguishing it from other scientific uses of the term, and evaluates its natural sources, analytical methods, extraction strategies, in vitro production systems, biosynthetic regulation, and biological activity. Cultivated Amaranthus species are among the richest plant sources, with total betacyanins of 46.1-199 mg/100 g fresh weight and amaranthin comprising, on average, 80.9% of the pigment fraction. Reliable identification and quantification rely on high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and ultraviolet-visible (UV-Vis) spectrophotometry. Microwave- and ultrasound-assisted extraction can improve pigment recovery under optimized conditions, although its stability depends strongly on pH, temperature, solvent, time and storage parameters. While plant in vitro cultures, including callus, suspension, and shoot systems, have clarified biosynthetic regulation and offer controlled production platforms, engineered yeast systems have recently expanded production options, with Yarrowia lipolytica reaching 2.97 ± 0.029 g L-1 amaranthin in fed-batch fermentation. Amaranthin-rich extracts and amaranthin-type pigments show antioxidantand anti-inflammatory potential, while antimicrobial and antiviral activities have mainly been reported for mixed betacyanin fractions; direct mechanistic, bioavailability, and in vivo evidence for purified amaranthin remains limited. Standardized analytical protocols, further investigation of stable high-yield sources, physicochemical stability assessment, and structure-activity studies are identified as priorities for advancing future application-oriented research on this multipotential pigment.
    Keywords:  amaranthin; betacyanin; betalain; callus culture; natural pigments; plant biotechnology; plant in vitro culture; suspension culture
    DOI:  https://doi.org/10.3390/ijms27125393
  36. Antioxidants (Basel). 2026 Jun 03. pii: 712. [Epub ahead of print]15(6):
    Enzyme-Assisted Ultrasonic Extraction of Flavonoids from Pinus koraiensis Needle Litterfall: Process Optimization, Component Identification, and In Vitro Bioactivity Evaluation.
    Weiwei Liang, Le Ouyang, Chun Bian, Yuxin Shan, Xiufang Xia.
      Flavonoids from Pinus koraiensis needle (PN) litterfall were efficiently recovered using an enzyme-assisted ultrasonic extraction (EAU) method optimized via response surface methodology (RSM). The optimal conditions (enzyme dosage 1.7%, ethanol concentration 70%, ultrasonic time 21 min, cellulase-pectinase ratio 1:3, liquid-solid ratio 40:1, enzymatic hydrolysis at 42.5 °C for 1 h, ultrasonic extraction at 50 °C and 150 W) yielded a total flavonoid content (TFC) of 17.08 mg rutin/g, which was significantly higher than that obtained via conventional extraction (CE). Scanning electron microscopy (SEM) confirmed that the treatment disrupted the cell wall, promoting flavonoid release. Ultra-performance liquid chromatography coupled with triple-quadrupole time-of-flight mass spectrometry (UPLC-Triple-TOF/MS) identified 60 flavonoids in the purified extract obtained under the optimal EAU conditions (OT group), including quercitrin, tiliroside, taxifolin, and procyanidin B2. Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) showed higher crystallinity but slightly reduced thermal stability for OT flavonoids. Notably, compared with the purified flavonoids obtained by CE (CK1 group), the OT group achieved a higher TFC and exhibited significantly better in vitro antioxidant activity (DPPH IC50 = 71.82 μg/mL; ABTS IC50 = 28.93 μg/mL) and in vitro carbohydrate-digesting-enzyme-inhibitory activity (α-glucosidase (α-GLU) IC50 = 79.52 μg/mL; α-amylase (α-AMY) IC50 = 793.9 μg/mL), with α-AMY inhibition being approximately 8.2-fold higher. These findings suggest that enzyme-assisted ultrasonic extraction is an efficient and reliable method for recovering flavonoids from PN and may provide a theoretical reference for the development and utilization of these flavonoids.
    Keywords:  DPPH radical and ABTS cation radical scavenging activity; Pinus koraiensis needle; enzyme-assisted ultrasonic extraction; flavonoids; response surface methodology; α-amylase- and α-glucosidase-inhibitory activities
    DOI:  https://doi.org/10.3390/antiox15060712
  37. J Am Soc Mass Spectrom. 2026 Jun 26.
    Molecular Framework Modification in Mass Spectrometry: Atom Exchange, Insertion, and Deletion.
    Myles Q Edwards, Dylan T Holden, R Graham Cooks.
      The ionization and activation of molecules, as performed using mass spectrometry (MS), have long been known to induce unimolecular rearrangements in gas-phase ions and, in some cases, reorganization of the underlying skeletal framework. Here, we explore skeletal rearrangements occurring from the electrospray ionization process, including atom exchange, insertion, and deletion, within pre-existing ring systems. The Baeyer-Villiger oxidation, the Beckmann rearrangement, and the Favorskii rearrangement are longstanding organic reactions that are here explored in MS, alongside a unique sulfur-for-oxygen exchange reaction within a 2,4,6-triphenylpyrylium scaffold. MSn and high-resolution MS are used to examine four representative transformations of molecular frameworks. Reactions across the four types emphasize the fact that ESI-MS can be intrinsically reactive. Product assignments in each case are supported by exact-mass measurements, isotopic distribution analysis, and MS/MS comparison with authentic standards or by characteristic fragmentation behavior. Beyond demonstrating framework modifications in electrospray droplets, these results point to an expanded suite of reactions for reactive MS derivatization, as well as the development of future strategies for late-stage functionalization.
    Keywords:  ambient ionization; electrospray ionization; microdroplet reactions; reactive ionization; skeletal rearrangements; tandem mass spectrometry
    DOI:  https://doi.org/10.1021/jasms.6c00171
  38. Sci Rep. 2026 Jun 23.
    Phenolic profiling, synergistic antibacterial and antioxidant potentials of various honey combinations: in vitro and in silico study.
    Nacira Siad, Chahrazed Hamia, Amar Djeridane, Mohamed Benalia, Reguia Mahfoudi, Mohamed Yousfi, Ayomide Victor Atoki, Mustafa Abdullah Yilmaz, Oguz Cakir, Abbas Tarha, Mohammed Messaoudi.
      This study investigated the synergistic interactions within binary combinations of ten Algerian honey samples, focusing on their phytochemical profiles and bioactivities. Ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) profiling identified 22 phenolic compounds, with quinic acid, gallic acid, naringenin, and acacetin predominant across samples. The antioxidant (DPPH, ABTS, FRAP) and antibacterial activities against Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Escherichia coli (E. coli) were evaluated using both in vitro assays and in silico molecular docking. Results revealed significant synergistic effects; specifically, combinations involving Bunium mauritanicum honey (M3) exhibited superior antioxidant capacity, while samples M2, M5, and M8 showed enhanced antibacterial efficacy. Molecular docking confirmed strong interactions between major phenolics and target protein active sites, which yielded favorable binding scores. These findings highlight the enhanced therapeutic as well as nutritional potential of Algerian honey combinations as potent natural sources of synergistic bioactive compounds.
    Keywords:   UHPLC-MS; Antibacterial capacity; Antioxidant activity; Binary combinations; Honey; Molecular docking
    DOI:  https://doi.org/10.1038/s41598-026-57418-0
  39. Int J Mol Sci. 2026 Jun 18. pii: 5535. [Epub ahead of print]27(12):
    Molecular Profiling and Selective Pro-Apoptotic Activity of a Pruning-Derived Lavandula dentata Leaf-Surface Extract in Colorectal Cancer Cells.
    Shiva Pouramin Arabi, Marcello Scivicco, Valentina Parisi, Emanuele Rosa, Nunziatina De Tommasi, Ammar Bader, Vitale Del Vecchio, Nunzio Antonio Cacciola, Lorella Severino.
      Lavandula dentata is a medicinal and aromatic plant rich in specialised secondary metabolites, but the biomedical potential of leaf-surface metabolites recovered from pruning biomass remains poorly investigated. In this study, a pruning-derived leaf-surface extract of L. dentata was obtained by brief acetone immersion followed by n-hexane partitioning. Its chemical profile was investigated by ultra-high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry analysis combined with feature-based molecular networking, which revealed an enrichment in methoxylated flavonoids and pentacyclic triterpenes, including oleanane- and ursane-like derivatives. The biological activity of the extract was evaluated in HCT116 colorectal cancer cells, MDA-MB-231 triple-negative breast cancer cells, and HaCaT keratinocytes. After 24 h treatment, the extract selectively reduced HCT116 cell viability in a concentration-dependent manner, with an IC50 of 27.8 ± 1.049 μg/mL, whereas MDA-MB-231 and HaCaT cells were less sensitive. Mechanistic analyses in HCT116 cells showed increased early and late apoptotic populations, mitochondrial membrane depolarisation, and enhanced cleavage of caspase-9, caspase-3, and PARP. These findings indicate that a chemically profiled L. dentata leaf-surface extract selectively impairs colorectal cancer cell survival by activating mitochondria-mediated apoptosis. The study also supports the valorisation of pruning-derived aromatic plant biomass as a source of bioactive natural products with potential biomedical relevance.
    Keywords:  Lavandula dentata; colon cancer cells; leaf-surface extract; methoxylated flavonoids; mitochondria-mediated apoptosis; pruning residues
    DOI:  https://doi.org/10.3390/ijms27125535
  40. Molecules. 2026 Jun 15. pii: 2106. [Epub ahead of print]31(12):
    Bioactivity-Guided Identification of Metabolites from Syzygium polycephalum with Antioxidant and α-Glucosidase Inhibitory Activities.
    Ira Rahmiyani, Saeful Amin, Muhamad Insanu, Irda Fidrianny.
      Syzygium polycephalum (Miq.) Merr. & L.M. Perry is an underexplored species within the Syzygium genus, traditionally consumed for its edible fruit. However, the potential of its non-edible biomass as a source of bioactive metabolites remains poorly investigated. This study evaluated the antioxidant and α-glucosidase inhibitory activities of different parts of S. polycephalum and identified the metabolites associated with these activities using an LC-HRMS-guided approach. The ethanolic leaf extract demonstrated superior phenolic (457.89 ± 12.10 mg GAE/g) and flavonoid (11.08 ± 1.10 mg QE/g) contents with strong antioxidant (DPPH: 683.21 ± 24.54; FRAP: 1338.37 ± 7.04; CUPRAC: 771.91 ± 8.78 mg AEAC/g) and alpha-glucosidase inhibitory activities (52,145.16 ± 801.54 mg AEAGIC/g). LC-HRMS/MS identified four compounds, including chrysin and formononetin. Integrated in silico analyses revealed that chrysin consistently outperformed other metabolites, exhibiting optimal docking scores, favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, and superior dynamic stability and binding affinity in molecular dynamics simulations. Collectively, these results position chrysin as the dominant bioactive driver and establish S. polycephalum leaf as a promising and sustainable source of dual-acting antioxidant and antidiabetic agents.
    Keywords:  LC-HRMS/MS; S. polycephalum; alpha-glucosidase inhibition; antioxidant; bioactive metabolites; molecular docking
    DOI:  https://doi.org/10.3390/molecules31122106
  41. Leg Med (Tokyo). 2026 Jun 23. pii: S1344-6223(26)00128-8. [Epub ahead of print]84 102900
    LC-MS/MS analysis of propofol in postmortem blood: propofol glucuronide as an indicator of exposure.
    Koji Yamaguchi, Ayumi Motomura, Namiko Ishii, Keisuke Okaba, Shizuru Hara, Aiko Ando, Daisuke Yajima.
      Propofol (PRF) is a short-acting intravenous anesthetic widely used for the induction and maintenance of general anesthesia. However, multiple accidental deaths resulting from the non-therapeutic use of PRF have been reported; therefore, PRF is an important target analyte in forensic investigations. In this study, quantitative analytical methods for PRF and propofol glucuronide (PRG) in postmortem blood were developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). For quantification, PRF was derivatized with N-(2-(bromomethyl)benzyl)-N,N-diethylethanaminium bromide (CAXB) to increase LC-MS/MS detection sensitivity. PRF was quantified using selected reaction monitoring (SRM) in positive ion mode. The extract was diluted after the derivatization reaction, and the quantification range was set to 0.1-20 μg/mL, which is suitable for routine quantitative analysis of PRF in postmortem blood samples. PRG was quantified using SRM in positive ion mode. Both analytical methods were validated and applied to authentic postmortem blood samples. The utility of PRG as a complementary marker in SRM-based drug screening was evaluated. Our findings demonstrate that PRG is a valuable indicator of PRF exposure in forensic casework and may help address limitations in the routine detection of PRF.
    Keywords:  CAX-B; Derivatization; Drug screening; LC-MS/MS; Propofol; Propofol glucuronide
    DOI:  https://doi.org/10.1016/j.legalmed.2026.102900
  42. Foods. 2026 Jun 18. pii: 2196. [Epub ahead of print]15(12):
    Mass Spectrometry-Based Lipidomics in Coffee: Linking Lipid Transformation to Flavor Formation and Quality Control.
    Yanbing Wang, Xiaoyuan Wang, Ping Du, Xiaogang Liu.
      Mass spectrometry-based lipidomics has created new opportunities to investigate the role of lipids in coffee quality formation and stability across the production chain. Coffee lipids contribute to flavor precursor formation, aroma release, mouthfeel, and storage behavior, but their molecular remodeling during maturation, processing, roasting, and storage remains insufficiently integrated. This review summarizes recent progress in lipidomics methodologies relevant to coffee research, with emphasis on sample preparation, mass spectrometry platforms, data analysis, and the strengths and limitations of current lipid annotation strategies. It further examines how lipid profiles change during bean maturation, how they differ among coffee species and varieties, and how they are reshaped by postharvest processing, roasting, and storage. However, it is important to note that most of these associations are currently correlational rather than causal; direct evidence linking specific lipid species to particular sensory attributes remains limited. Existing studies suggest that lipid composition, rather than total lipid content alone, is more informative for understanding coffee quality differences and for identifying candidate markers associated with origin, processing method, roasting degree, and storage conditions. In particular, alterations in glycerolipids, glycerophospholipids, fatty acids, diterpenes, and other minor lipid constituents are increasingly associated with lipid oxidation, thermal degradation, and flavor-related transformations in coffee. However, current evidence is still limited by incomplete structural annotation, isomeric ambiguity, platform dependence, and the frequent gap between statistical discrimination and mechanistic validation. Future work integrating high-resolution mass spectrometry, ion mobility, targeted quantification, stable isotope tracing, sensory analysis, and multi-omics approaches will be essential to improve marker reliability and to clarify the functional roles of coffee lipids. Overall, lipidomics provides a promising framework for linking molecular composition with coffee quality control, traceability, and process optimization, although substantial work is still needed to establish mechanistic links to flavor formation.
    Keywords:  aroma formation; coffee; flavor formation; lipidomics; roasting; storage stability
    DOI:  https://doi.org/10.3390/foods15122196
  43. Antioxidants (Basel). 2026 Jun 15. pii: 753. [Epub ahead of print]15(6):
    Ultrasound-Treated Sweet Potato Peel Enhances Nutritional Quality and Antioxidant Potential of Gluten-Free Brownies: A Metabolomics and Cell-Based Approach.
    Pablo Ayuso, Rocío Peñalver, Jhazmin Quizhpe, Pascual García-Pérez, Gema Nieto.
      Agri-food by-products such as sweet potato peel (SP) represent a sustainable and valuable source of bioactive compounds for improving gluten-free (GF) foods. This study evaluated the nutritional and functional impact of incorporating SP at 8% and 16%, either untreated or ultrasound-assisted extraction (UAE)-treated, into GF brownies. An untargeted metabolomics approach combined with chemometrics was applied to characterize phytochemical modulation after in vitro digestion of the brownies, while antioxidant and anti-inflammatory effects were assessed using RAW264.7 macrophages. SP incorporation increased the dietary fiber (reaching a content of 7.86%) and glycosylated flavonoid content in reformulated brownies, leading to a reduction of inflammatory markers in the cellular model. Sensory evaluation showed that SP addition did not significantly affect texture-related attributes or extract-related perception. In contrast, UAE acted as an efficient extraction strategy, enhancing terpenoid-like compounds and total phenolic content (TPC), reaching values of 401.97 mg GAE 100 g-1 after 16% incorporation. Overall, combining SP valorization with UAE represents a promising strategy to develop nutritionally enhanced GF products, providing a foodomics-based framework for next-generation functional bakery products.
    Keywords:  anti-inflammatory; bioactive compounds; foodomics; gluten-free; mixomics
    DOI:  https://doi.org/10.3390/antiox15060753
  44. BMC Pregnancy Childbirth. 2026 Jun 22.
    First-trimester plasma targeted metabolomics for eicosanoids reveals predictive potential and preventive targets for severe preeclampsia: a nested case-control study.
    Yongqiang Ma, Linjie Li, Yiwen Fang, Wei Cai, Jingbo Yang, Liuyang Zhang, Lushu Zuo, Xiulong Niu, Shaobo Chen, Qing Yang, Ying Yu, Cha Han, Hongliang Cong, Xu Zhang, Xin Zhou.
       BACKGROUND: Eicosanoids are a diverse family of oxygenated derivatives of 20-carbon polyunsaturated fatty acids that play crucial roles in maintaining cardiovascular homeostasis. The metabolic profiles of eicosanoids preceding the onset of severe preeclampsia remain incompletely understood. This study aimed to use a targeted metabolomic approach to identify eicosanoid metabolites in first-trimester blood samples and assess their potential to predict severe preeclampsia.
    METHODS: Within a prospective cohort of 5,809 pregnant women, a nested case-control study analyzed 45 participants who later developed severe preeclampsia and 41 controls with uncomplicated pregnancies. Targeted metabolomic analysis was performed using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS). Metabolomic data were examined, and predictive performance of these metabolites was evaluated using receiver operating characteristic curves.
    RESULTS: Among 40 eicosanoids metabolites quantified, 10 metabolites differed statistically between the severe preeclampsia and control groups. Specifically, metabolites in the cyclooxygenase (COX) pathway, such as thromboxane B2 (TXB2), and the 12/15-lipoxygenase (LOX) pathway, such as 14-hydroxy-docosahexaenoic acid (14-HDoHE), were significantly upregulated in the severe preeclampsia group. Conversely, metabolites in the cytochrome P450 (CYP450) pathway, notably 19,20-epoxy-docosapentaenoic acid (19,20-EDP), were significantly downregulated. The 14-HDoHE/19,20-EDP ratio was identified as the most significant predictive marker. Integrating this ratio into the Fetal Medicine Foundation (FMF) screening algorithms significantly improved the area under the curve (AUC) from 0.77 to 0.87 (ΔAUC = 0.10, 95% confidence interval [CI]: 0.03-0.18, P = 0.008). This combined model demonstrated a sensitivity of 0.73 (95% CI: 0.60-0.86) and a specificity of 0.85 (95% CI: 0.75-0.96).
    CONCLUSIONS: Our findings revealed novel prediction models for severe preeclampsia based on first-trimester eicosanoid metabolomics, and provide mechanistic evidence supporting early aspirin use for COX pathway inhibition and suggest that rebalancing the 12/15-LOX and CYP450 pathways may be a potential strategy for preventing severe preeclampsia.
    TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier ChiCTR-EOC-15007644, registered on 03 December 2015.
    Keywords:  Eicosanoids; Polyunsaturated Fatty Acid; Prediction Model; Preeclampsia
    DOI:  https://doi.org/10.1186/s12884-026-09532-0
  45. Molecules. 2026 Jun 13. pii: 2077. [Epub ahead of print]31(12):
    Feature Down-Selection to Improve Supervised Classification by Machine Learning on Mass Spectrometry Imaging Data.
    Braysen Miller, Aleesa E Chua, Madeline Isom, Eden P Go, Emily R Sekera, Amanda B Hummon, Heather Desaire.
      The advancements made in the mass spectrometry imaging (MSI) field have allowed for the generation of very large-scale data sets. These data are often interrogated by machine learning (ML), although storing and handling data sets of this size can be difficult. To aid impacted researchers, we seek to evaluate feature reduction strategies that will minimize the amount of data stored while still maintaining the ability to correctly classify the data. Two different feature selection strategies are tested on six different data sets, leveraging XGBoost as the machine learning algorithm. The study provides evidence that selecting features based on the greatest average abundance across all samples is best suited to scale down the feature set at a more modest trimming level, while selecting features based on statistical analysis via a Student's t-test is better suited for a more aggressive trimming level. These trends were present regardless of training set size or cross-validation strategy. The results from this work provide insight into when these feature filtering steps can be used effectively and when another data reduction strategy, including not restricting the data set, should be considered.
    Keywords:  data analysis; feature selection; lipids; machine learning; mass spectrometry; mass spectrometry imaging; spheroids
    DOI:  https://doi.org/10.3390/molecules31122077
  46. Int J Obstet Anesth. 2026 Jun 17. pii: S0959-289X(26)00375-4. [Epub ahead of print]67 105217
    Epidural-related maternal fever and metabolomic changes: a pilot exploratory study.
    Minyu Zhang, Li Zhang, Dongyan Chen, Xiaodan Chen, Zhiqiang Yu, Jiangang Xu.
       BACKGROUND: The causes of intrapartum fever associated with labor epidural analgesia remain unclear. Metabolomics enables the qualitative and quantitative analysis of small-molecule metabolites in living organisms. We aimed to apply metabolomic analysis in this pilot exploratory study to explore the preliminary pathophysiological mechanisms underlying fever during labor epidural analgesia.
    METHODS: Non-targeted metabolomic analysis was performed on plasma samples from parturients in both groups: the control group included parturients who did not develop fever after labor epidural analgesia, and the fever group included parturients with a body temperature ≥ 37.3 °C after labor epidural analgesia. Principal component analysis and orthogonal partial least squares discriminant analysis were performed on the processed data. Model reliability was assessed using 200 permutation tests, and differential metabolites were screened and identified using ultra-high-performance liquid chromatography-quadrupole Orbitrap mass spectrometry.
    TRIAL REGISTRATION: ChiCTR2500103459; May 29, 2025.
    RESULTS: A total of 79 differential metabolites were identified. Glutamate, glutathione, arginine, and metabolites involved in the ammonia and urea cycles showed significant differences between the two groups of parturients. The top enriched pathways were arginine biosynthesis, glutamate metabolism, linoleic acid metabolism, glycerophospholipid metabolism, and the urea cycle.
    CONCLUSION: This pilot study preliminarily observed metabolite alterations in the blood of parturients who developed fever after labor epidural analgesia. Changes in the arginine metabolic pathway may be associated with the development of fever, warranting further large-scale validation.
    Keywords:  Arginine metabolism; Epidural-related maternal fever; Labor epidural analgesia; Non-targeted metabolomics
    DOI:  https://doi.org/10.1016/j.ijoa.2026.105217
  47. Nat Prod Bioprospect. 2026 Jun 23. pii: 71. [Epub ahead of print]16(1):
    Novel bioactive compounds from marine-derived endosymbiotic Penicillium fungi reported during 2020-2025.
    Sarah A Omran, Mohamed S Elnaggar, Fadia S Youssef, Safaa A El-Moghazy.
      Marine-derived Penicillium fungus gained significant attention in recent years due to their potential as a valuable source of unique natural compounds with a wide range of chemical structures and bioactive capabilities. The primary origins of marine-derived Penicillium fungi are mangroves, sediments, marine shrimps, corals, starfish, algae, and sponges. A total of 390 unique natural compounds were extracted from Penicillium fungi which were found in marine environments. These compounds primarily consist of polyketides, alkaloids, terpenoids, chromone derivatives, anthraquinones, citrinins, steroids, azaphilones, and macrolides. Biological studies demonstrated that these compounds exhibit antimicrobial, anti-inflammatory, cytotoxic, pesticide development, neuroprotective, anti-glioma, anti-proliferative, α-glucosidase inhibitory activities, anti-allergic, photo-protective, anti-angiogenic effect, larvicidal activity, antiviral, anti-diabetic activity, and other activities that could be useful in the development of new drugs. This study shed the light on the recent discovery of bioactive MNPs (marine-derived Penicillium; natural products) derived from Penicillium fungi found in marine environments in the last five years from 2020 to 2025, classified the MNPs based on the sources of the fungi and their specific biological activities. Besides, the results of molecular docking studies recently performed on Penicillium metabolites referring to various biological activities were also compiled in this review. Thus, this review highlighted that Penicillium species obtained from marine organisms act as an everlasting mine of bioactive novel metabolites combating various ailments.
    Keywords:  Anti-inflammatory; Antimicrobial; Cytotoxic; MNPs; Marine-derived Penicillium ; Natural products
    DOI:  https://doi.org/10.1007/s13659-026-00633-z
  48. Metabolites. 2026 Jun 18. pii: 429. [Epub ahead of print]16(6):
    Improving Speed and Efficiency of DESI Imaging with the Xevo MRT Mass Spectrometer for Analyte Mapping.
    Mark Towers, Emmanuelle Claude, Lisa Towers, Helen Yates, Joanne Ballantyne.
      Background: Recent technology improvements have enabled desorption electrospray ionisation (DESI) mass spectrometry imaging to achieve down to 5 µm (pixel) image resolution. However, operating at this resolution introduces challenges, particularly regarding increased total analysis time and the need for sufficient instrument sensitivity to detect analytes from very small tissue areas. Methods: High mass and image resolution DESI imaging was performed on rat brain tissue using a Xevo™ MRT benchtop mass spectrometer equipped with a multi-reflecting time-of-flight mass analyser and a DESI XS source. Data acquisition was conducted at speeds of up to 100 Hz. Sensitivity was assessed using a dilution series of five Active Pharmaceutical Ingredients (APIs) spotted onto porcine liver tissue. Signal detection limits were evaluated using extracted ion chromatograms (XICs) with signal-to-noise (S/N) calculations against blank samples. Additionally, enhanced duty cycle (EDC) was applied to evaluate improvements in analyte signal intensity across specific mass ranges in both positive and negative ionisation modes. Results: At acquisition speeds of up to 100 Hz, excellent data quality was achieved, with signal intensity remaining suitable for analytical applications. All five tested APIs were detectable at concentrations of 25 pg/mm2. Three of the five compounds were further detected at concentrations as low as 2.5 pg/mm², with signal-to-noise ratios greater than 5. The application of EDC resulted in a significant increase in analyte signal intensity within the targeted mass ranges, particularly for small molecule endogenous metabolites and lipids, in both ionisation modes. Furthermore, the system demonstrated substantially improved spectral quality, achieving mass resolution up to 100,000 FWHM. This enabled the resolution of previously indistinguishable analytes with significantly improved mass accuracy compared to systems operating at approximately 30,000 FWHM. Conclusions: The Xevo™ MRT mass spectrometer with DESI XS source enables high-resolution DESI imaging at speeds up to 100 Hz without compromising data quality or sensitivity. The system demonstrates excellent detection limits for pharmaceutical compounds and improved performance through enhanced duty cycle operation. Overall, the combination of high spatial resolution, increased mass resolution, and improved spectral quality allows for more accurate analyte differentiation, representing a significant advancement over lower-resolution systems.
    Keywords:  DESI; Xevo MRT MS; imaging; lipidomics; metabolites
    DOI:  https://doi.org/10.3390/metabo16060429
  49. Plants (Basel). 2026 Jun 12. pii: 1821. [Epub ahead of print]15(12):
    Chemical Profile and Evaluation of the Growth-Inhibitory, Anti-Inflammatory, and Antioxidant Activity Potential of Polar Extracts of Reseda alba L. (Resedaceae).
    Giuseppe A Malfa, Antonietta Cerulli, Donata Condorelli, Assunta Napolitano, Elena Preite, Nicodemo G Passalacqua, Monica R Loizzo, Sonia Piacente, Rosa Tundis.
      This study provides a comprehensive evaluation of the chemical composition and the biological properties of Reseda alba L., commonly known as white mignonette. Extracts obtained from leaves (L), flowers (F), stems (S), and immature fruits (Fr) by ultrasound-assisted extraction (UAE) were assessed for their antioxidant, anti-inflammatory, and growth-inhibitory activity, and chemically characterized by an analytical approach based on liquid chromatography/electrospray/high-resolution tandem-mass spectrometry (LC-ESI/HRMS/MS). The resulting chromatographic profile revealed 30 major constituents belonging to the flavonoids, glucosinolates, phenolic acids, and polar lipids, as well as hydroxy fatty acid classes. Naringenin-di-C-glucoside, isorhamnetin-O-deoxyhexosyl-hexoside, kaempferol-O-dideoxyhexosyl-hexoside, and isorhamnetin O-dideoxyhexoside are reported here for the first time in the genus Reseda. The Fr extract exhibited the highest anti-inflammatory and radical scavenging properties, likely due to its higher flavonoid content compared to the other extracts. On the other hand, the F extract significantly reduced the viability of colorectal adenocarcinoma (CaCo-2) and hepatocarcinoma (HepG-2) cells. Lactate dehydrogenase (LDH) release assay showed that the treatments with R. alba did not induce the release of the marker enzyme in CaCo-2 and HepG-2 cells, suggesting the involvement of a different cell death pathway. Overall, the bioactivities observed among the different plant organs highlight the beneficial potential of R. alba and provide a rationale for future bioactivity-guided isolation studies.
    Keywords:  LC-ESI/HRMS/MS; LDH; Reseda alba; cancer cells; flowers; immature fruits; leaves; stems
    DOI:  https://doi.org/10.3390/plants15121821
  50. Plants (Basel). 2026 Jun 17. pii: 1887. [Epub ahead of print]15(12):
    Quantitative Lipidomics Reveals Dynamic Lipid Profiles in Cinnamomum camphora Seed Kernels at Different Developmental Stages.
    Han Xie, Yongjie Zheng, Yueting Zhang, Chenglin Luo, Ting Zhang, Wanwen Yu, Xuhui Zhang, Xinliang Liu.
      Cinnamomum camphora seed kernels are a potentially valuable fatty oil resource; however, their lipid composition and dynamic changes during development remain poorly understood. In this study, morphological and anatomical observations combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipidomics were used to investigate lipid accumulation patterns in C. camphora seed kernels across five developmental stages. The results showed that seed development followed a distinctive pattern in which morphological maturation preceded physiological maturity. A total of 627 lipid molecules were identified and classified into 27 subclasses and 5 major classes. Among them, glycerolipids (GLs) and glycerophospholipids (GPs) were the dominant lipid classes, with triacylglycerols (TGs) representing the principal storage lipids. Approximately 84.2% of the detected lipids were unsaturated, indicating a highly unsaturated lipid profile. The fatty acid composition was enriched in medium-chain fatty acids (MCFAs), especially decanoic acid and lauric acid, suggesting that C. camphora seed kernel oil possesses distinctive compositional characteristics compared with conventional fatty oils. In addition, coenzyme Q (CoQ) showed relatively high abundance and dynamic accumulation during seed development. Differential lipid analysis further revealed that lipid remodelling occurred mainly during the early developmental stages and was significantly associated with glycerolipid and glycerophospholipid metabolism. Diacylglycerols (DGs), phosphatidylcholines (PCs), and phosphatidylethanolamines (PEs) decreased during early development, whereas TGs accumulated continuously from the middle stage onwards. Overall, this study provides a systematic characterisation of lipid composition and developmental dynamics in C. camphora seed kernels and offers a theoretical basis for their future utilisation as a novel functional fatty oil resource.
    Keywords:  Cinnamomum camphora; developmental stages; kernels; medium-chain fatty acids; quantitative lipidomics; triacylglycerol (TG)
    DOI:  https://doi.org/10.3390/plants15121887
  51. Front Plant Sci. 2026 ;17 1843809
    Integrated metabolomics, network pharmacology and molecular docking to reveal the effects of drying processes on the antioxidant activity of mulberry (Morus alba L.) leaves.
    Yang Liu, Wendan Chi, Qian Liu.
       Introduction: Mulberry (Morus alba L.) leaves (MLs), a well-known food-medicine homologous substance, possess potent properties against oxidative stress. However, the impact of industrial drying methods on their antioxidant activity is still not completely clear.
    Methods: A comprehensive approach based on UPLC-MS/MS metabolomics, network pharmacology and molecular docking was employed to find the active compounds in MLs treated by different drying methods and their potential antioxidant mechanisms in this study.
    Results and discussion: A total of 1467 metabolites were detected through UPLC-MS/MS analysis, and differential metabolites of MLs were searched by multivariate statistical analysis. Hot-air dried MLs exhibited the highest DPPH and ABTS radical scavenging capacities, as well as the strongest ferric reducing antioxidant power. This enhanced activity might be attributed to the maximal hydrolysis of kaempferol glycosides, leading to the significant accumulation of free kaempferol. Network pharmacology analysis further revealed that the bioactive compounds in MLs exerted their antioxidant effects by targeting key proteins, including AKT1, TNF, ALB, IL-1B, and BCL2. These findings provided valuable insights into how different drying methods influenced the antioxidant property of MLs.
    Keywords:  antioxidant; drying method; integrated metabolomics; molecular docking; mulberry leaves; network pharmacology
    DOI:  https://doi.org/10.3389/fpls.2026.1843809
  52. Front Cardiovasc Med. 2026 ;13 1849138
    Integrative multi-omics analysis identifies a robust 14-metabolite signature and reveals microbiome-metabolite-host interactions in atherosclerosis.
    Leiyang Dai, Xiao Wang, Hui Zhang, Rong Gong, Jianli Pang, Junxi Pan, Qiuyue Xu, Yong Duan.
       Background: Atherosclerosis (AS) is a complex metabolic and inflammatory disease in which interactions between host metabolism and gut microbiota play critical roles. However, robust metabolic biomarkers and their integration with microbial and host factors remain incompletely understood.
    Methods: We performed untargeted metabolomics to characterize metabolic alterations between AS patients and healthy controls (HC). Differential metabolites were identified and subjected to pathway enrichment analysis. Three machine learning models, including random forest (RF), least absolute shrinkage and selection operator (LASSO), and support vector machine (SVM), were applied to identify key metabolite signatures. Gut microbiota composition was analyzed using 16S rRNA sequencing, and correlation analyses were conducted to explore microbiome-metabolite interactions. In addition, inflammatory and senescence-related markers were assessed to evaluate host responses.
    Results: A total of 122 differential metabolites were identified between AS and HC, primarily enriched in amino acid-related pathways, including tryptophan, phenylalanine, and methionine metabolism. Machine learning integration revealed a robust panel of 14 overlapping metabolites with strong discriminative performance. Among them, Trimethylamine N-oxide, 3-Hydroxyhippuric acid, and Cholesteryl sulfate showed the highest diagnostic potential. Despite limited differences in gut microbial composition, several microbiota-derived metabolites and significant correlations between specific genera and metabolites were observed, suggesting functional alterations in the microbiome. Furthermore, senescence markers P16 and P21 were significantly elevated in AS and were associated with key metabolites and microbial taxa, whereas classical inflammatory markers showed no significant differences.
    Conclusion: This study identifies a robust metabolite signature associated with AS and highlights a coordinated microbiome-metabolite-host interaction network. These findings provide new insights into the metabolic mechanisms underlying AS and suggest potential biomarkers and therapeutic targets for disease diagnosis and intervention.
    Keywords:  atherosclerosis; cellular senescence; gut microbiota; machine learning; metabolomics
    DOI:  https://doi.org/10.3389/fcvm.2026.1849138
  53. Metabolites. 2026 May 28. pii: 365. [Epub ahead of print]16(6):
    Untargeted Metabolomics and Metabolite-Gene Network Analysis Predict NF-κB Inhibition in Artemisian B-Treated Triple-Negative Breast Cancer Cells.
    Shujun Shan, Ziyun Hu, Guimin Xue, Ping Yao, Peipei Du, Ruixi Gan, Junsong Wang.
      Background: Triple-negative breast cancer (TNBC) remains a formidable clinical challenge due to the scarcity of targeted therapies and profound metabolic heterogeneity. Although Artemisian B, a dimeric sesquiterpene lactone derived from Artemisia argyi, exhibits potent antiproliferative activity, its comprehensive metabolic footprint and the translation of these perturbations into downstream signaling regulation remain poorly characterized. Methods: To address this gap, we employed an integrative analytical framework combining untargeted metabolomics, topology-guided metabolite-gene network mapping, and parallel experimental validation in MDA-MB-231 cells. This workflow systematically profiled cellular phenotypes, global metabolic reprogramming, and key signaling nodes, enabling the prioritization of high-confidence mechanistic links between metabolic alterations and signal transduction. Results: Artemisian B dose-dependently suppressed TNBC cell viability (IC50 = 12.12 μM) and triggered mitochondrial apoptosis, characterized by Bax upregulation, Bcl-2 downregulation, and caspase-9/3 activation. Untargeted metabolomics identified 129 significantly altered metabolites, reflecting extensive dysregulation across lipid peroxidation, bioenergetics, and nucleotide metabolism. Topological analysis of the metabolite-gene network identified the NF-κB pathway as a highly interconnected hub within this perturbed landscape. Parallel experimental validation corroborated this prediction, demonstrating that Artemisian B consistently suppressed the phosphorylation of IKKα/β, IκBα, and p65, while markedly attenuating p65 nuclear translocation. Conclusions: Artemisian B induces TNBC apoptosis through extensive metabolic reprogramming coupled with concurrent inhibition of NF-κB signaling. By seamlessly integrating untargeted metabolomics with network topology, our framework not only successfully bridges metabolic perturbations with signaling outcomes but also establishes a versatile, dual-perspective strategy applicable to both biochemical reaction networks and signal transduction pathways. This approach provides a robust predictive paradigm for decoding the multi-target pharmacological mechanisms of natural products.
    Keywords:  NF-κB signaling; apoptosis; artemisian B; metabolic reprogramming; metabolite–gene network topology; triple-negative breast cancer; untargeted metabolomics
    DOI:  https://doi.org/10.3390/metabo16060365
  54. J AOAC Int. 2026 Jun 26. pii: qsag059. [Epub ahead of print]
    Single-Laboratory Validation of Simultaneous Determination of Aflatoxins in Nutraceuticals following immune-affinity Column Cleanup and Liquid Chromatography Tandem Mass Spectrometry Analysis.
    Saravanan J, Santhosh Kumar J Urumarudappa, Vijay Bommuluri, Ashutosh Kumar Mittal, Peter Chang, Gary Swanson.
       BACKGROUND: Aflatoxins B1, B2, G1, and G2 are highly carcinogenic mycotoxins frequently detected in nutraceutical products. Due to their toxicological significance and the complex composition of nutraceutical matrices, sensitive and validated analytical methods are required to ensure regulatory compliance, product safety, and routine surveillance.
    OBJECTIVE: This study aimed to develop and perform single-laboratory validation of a reliable and sensitive method for the simultaneous determination of aflatoxins B1, B2, G1, and G2 in nutraceutical products, in accordance with AOAC Appendix F.
    METHOD: Samples were extracted using an organic solvent system and purified through aflatoxin-specific immunoaffinity columns to reduce matrix interference. Quantitative analysis was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Method validation evaluated linearity, limits of detection (LOD) and quantitation (LOQ), precision (repeatability and intermediate precision), and accuracy across three representative nutraceutical matrices.
    RESULTS: The method showed linearity for all analytes, with coefficients of determination (R2) between 0.9984 and 0.9989. The LOD and LOQ values ranged from 0.1268 to 0.6170 µg/kg and from 0.2733 to 1.1290 µg/kg, respectively. Precision studies demonstrated acceptable repeatability and intermediate precision, with relative standard deviations ≤20%. Accuracy assessment across beverage and protein-based nutraceutical products yielded recoveries between 88% and 119% at multiple fortification levels, meeting AOAC performance requirements for mycotoxin analysis.
    CONCLUSIONS: The validated LC-MS/MS method is sensitive, accurate, and precise for the determination of aflatoxins B1, B2, G1, and G2 in complex nutraceutical products. The method is fit for purpose of routine quality control, regulatory testing, and surveillance of aflatoxins in nutraceutical matrices.
    HIGHLIGHTS: Optimized sample extraction and immunoaffinity cleanup enabled sensitive LC-MS/MS determination of aflatoxins B1, B2, G1, and G2. The method was validated for linearity, LOD, LOQ, sensitivity, precision, and accuracy, and was found to be suitable for routine aflatoxin estimation in nutraceutical products.
    Keywords:  Aflatoxins; LC-MS/MS; immune-affinity cleanup; method development; quantification
    DOI:  https://doi.org/10.1093/jaoacint/qsag059
  55. Plant Commun. 2026 Jun 26. pii: S2590-3462(26)00284-1. [Epub ahead of print] 101976
    DeepMASS v2: An enhanced deep learning platform for large-scale discovery and structural annotation of unknown plant metabolites.
    Siyu Jiang, Qiong Yang, Ziyao Xiong, Kairong Li, Qinliang Dai, Meifeng Su, Yaqing Lyu, Yanchun Peng, Ran Du, Jianbin Yan, Hongchao Ji.
      Structural elucidation of unknown metabolites remains a fundamental bottleneck in plant metabolomics, where the vast chemical diversity of plant secondary metabolites far exceeds the coverage of existing spectral libraries. Here, we present DeepMASS v2, a substantially enhanced platform for LC-MS/MS-based compound annotation designed to address this challenge at scale. DeepMASS v2 leverages a semantic representation model trained on millions of spectra from GNPS, NIST, and in-house resources. By integrating Spec2Vec-based embeddings with Hierarchical Navigable Small World (HNSW) graph retrieval and a unified chemical space defined by molecular fingerprints, DeepMASS v2 identifies structurally related neighbors for unknown spectra and ranks candidate structures based on spatial proximity to these predicted chemical contexts. Benchmarking using CASMI datasets and a curated natural product collection demonstrates that DeepMASS v2 outperforms state-of-the-art in silico annotation tools including SIRIUS, CFM-ID, MetFrag, and MS-Finder. Importantly, DeepMASS v2 maintains strong performance for metabolites absent from spectral libraries, highlighting its capability for genuine unknown discovery. Application of DeepMASS v2 to large-scale plant datasets further reveals its power to expand the accessible metabolome space. Delivered as an intuitive web platform, DeepMASS v2 provides the community with a scalable, interpretable, and high-throughput solution for structural annotation, enabling more comprehensive characterization of plant chemical diversity and accelerating natural product discovery in molecular plant science. The web server of DeepMASS v2 can be accessed through http://deepmass.cn.
    Keywords:  LC–MS/MS; deep learning; metabolite annotation; metabolomics; natural products; plant secondary metabolites
    DOI:  https://doi.org/10.1016/j.xplc.2026.101976
  56. Toxics. 2026 Jun 06. pii: 494. [Epub ahead of print]14(6):
    Plasma or Serum? A Pilot Evaluation of Matrix Selection for Integrated Metabolomics and Exposomics of Clinical Samples.
    Xiaowen Ji, Julian Edwards, Miaomiao Wang, Juan C Irwin, Binya Liu, Amanda M Gutierrez, Lin Li, Jeannette C Lager, Camran R Nezhat, David K Stevenson, Tomiko T Oskotsky, Marina Sirota, Dimitri Abrahamsson, Linda C Giudice, Tracey J Woodruff, Joshua F Robinson, June-Soo Park.
      Serum and plasma are the most widely used matrices in metabolomics and human biomonitoring studies; however, the optimal matrix for integrated non-targeted analysis (NTA) workflows combining metabolomics and exposomics has not been systematically evaluated. This pilot study applied parallel NTA workflows to paired serum and plasma samples from five individuals to characterize matrix-dependent differences and provide an empirical basis for matrix selection in integrated studies. Three analytical methods were employed: one metabolomic method (Method 1) using Hydrophilic Interaction Liquid Chromatography (HILIC) and Reversed-Phase Liquid Chromatography (RPLC) columns and one exposomics (Method 2) method using an RPLC column, each analyzed in both electrospray ionization (ESI) positive and negative modes. Overall, serum and plasma showed broad similarity, with substantial overlap in detected features and strong linear correlations between paired samples (R2 = 0.70-0.87). However, PCA revealed systematic differences between the two matrices along PC1 and PC2, likely attributable to matrix effects arising from coagulation-related compositional changes in serum. For metabolomics, glycerophospholipids, sphingolipids, and acylcarnitines were consistently enriched in serum, attributable to platelet activation and phospholipase release during blood coagulation, consistent with prior reports. In contrast, oxidized fatty acid species were predominantly elevated in plasma, warranting caution in oxylipin-focused studies using serum. For exogenous chemical profiling, the two matrices performed comparably, with 32 out of 36 annotated features showing no significant matrix-dependent differences (p > 0.05), including PFAS, pharmaceuticals, and diverse xenobiotics. These findings support the interchangeability of serum and plasma for broad exposomics studies. Overall, while both matrices provided broadly comparable global coverage, plasma may represent a more appropriate matrix for integrated NTA workflows, as it better preserves in vivo metabolite composition and minimizes coagulation-induced confounding, though validation in larger cohorts is needed.
    Keywords:  exposomics; matrix selection; metabolomics; non-targeted analysis; plasma; serum
    DOI:  https://doi.org/10.3390/toxics14060494
  57. Anal Chem. 2026 Jun 22.
    Integrated Multiomics Enabled by Sequential Extraction for Comprehensive Molecular Profiling of Small Extracellular Vesicles.
    Andrew J Perciaccante, Holden T Rogers, Yanlong Zhu, Aditi Barnwal, David Inman, Man-Di Wang, Song Jin, Suzanne M Ponik, Ying Ge.
      Small extracellular vesicles (sEVs) are membrane-bound particles whose protein, lipid, and metabolite cargo reflects the molecular state of their cells of origin, making them attractive targets for biomarker discovery and therapeutic development. However, comprehensive characterization of sEVs remains challenging due to the extremely limited material available. Here, we present an integrated mass spectrometry-based multiomics platform for simultaneous characterization of lipids, metabolites, and proteins from a single sEV sample enabled by sequential extraction, maximizing sample utilization. To enhance molecular coverage and analytical depth, the platform combines iterative tandem mass spectrometry for improved small-molecule fragmentation and nanoflow proteomics with data-independent acquisition. We achieved deep and reproducible multiomic characterization of proteins, lipids, and metabolites using 10 million sEVs. We further demonstrated the compatibility of our multiomics platform with sEVs isolated from plasma by ultracentrifugation, size exclusion chromatography with ultrafiltration, and polymer precipitation, revealing purification-dependent differences in molecular profiles associated with trade-offs in yield and purity of sEVs. By enabling integrated multiomics from the same sample, this strategy addresses a key challenge in low-input sEV analysis and establishes a robust analytical foundation for synergistic biomarker discovery and therapeutic applications.
    DOI:  https://doi.org/10.1021/acs.analchem.6c01280
  58. Curr Issues Mol Biol. 2026 Jun 05. pii: 596. [Epub ahead of print]48(6):
    Time-Resolved Secondary Metabolite Profiling of Seeded and Seedless Ougan at Commercial Harvest Maturity.
    Quan Zhao, Peian Zhang, Yang Song, Fayong Li, Yingyao Liu, Jun Chen, Dongfeng Liu.
      Ougan (Citrus suavissima Hort. et Tanaka) is valued for its distinctive sweet-bitter flavor and nutritional properties; however, tissue-resolved metabolic differences between two cultivar forms (seeded and seedless) of Ougan (C. suavissima) remains poorly understood. In this study, a comprehensive UPLC-MS/MS-based metabolomic analysis was conducted on peel (SP and NP), pulp (SF and NF), segment membrane (SM and NM) and seed tissues (SS, from seeded fruit only) of seeded and seedless Ougan fruits. A total of 1333 metabolites were annotated, with flavonoids (48.53%) and phenolics (12.25%) representing the predominant compound classes. Tissues specificity was the primary determinant of metabolic variation, with peel and segment membrane tissue showing relatively high abundance (fold change ≥ 2, |Log2FC| ≥ 1) of phenylpropanoid- and flavonoid-derived metabolites. Comparative analysis between seeded and seedless tissues revealed significant modulation of phenylpropanoid biosynthesis, flavonoid biosynthesis, phenylalanine metabolism, and related secondary metabolite pathways. Seeded tissues showed a higher relative abundance of selected flavonol glycosides (6-hydroxykaempferol-3,6-O-diglucoside), hydroxycinnamic acid derivatives, and santhocyanin-related compounds, whereas seedless tissues showed higher relative abundance of selected flavanones and malonylated flavonoid glycosides. Seeds were characterized by high limonin content, consistent with limonoid-associated bitterness chemistry. Overall, our findings provide a tissue-resolved metabolomic framework for understanding quality-associated secondary metabolite variation in mature Ougan fruit.
    Keywords:  Ougan; UPLC-MS/MS; flavonoids; fruit quality; metabolomics; secondary metabolites
    DOI:  https://doi.org/10.3390/cimb48060596
  59. Molecules. 2026 Jun 18. pii: 2143. [Epub ahead of print]31(12):
    DESI-MSI-Based Multi-Organ Distribution Mapping of Psilocin in Zebrafish.
    Mengxuan Dong, Yi Zhang, Manzhu Cao, Tong Shi, Liqin Li, Xingxing Zong, Chen Wang.
      Psilocybin, a psychedelic drug with reported anxiolytic and antidepressant potential, is rapidly metabolized to its active metabolite psilocin. However, a lack of adequate toxicity studies and tissue distribution studies currently restricts its development and application. This study combined behavioral assays in zebrafish with desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to systematically evaluate the acute neurotoxicity of psilocybin and characterize the in vivo spatial distribution of its active metabolite, psilocin. The novel tank test was used to evaluate zebrafish following a 4 h exposure to psilocybin at three different doses (20, 40, and 80 μM; n = 6 per group). Statistical analysis of the data was performed using ANOVA. Behavioral analyses revealed that exposure to psilocybin induced pronounced neurobehavioral alterations, including hyperactivity and disrupted swimming patterns, as evidenced by significant increases in the number of zone transitions and shuttle frequency. We established a DESI-MSI-based method for quantitative mapping and visualization of psilocin in zebrafish tissues. Methodological validation indicated that a linear relationship between ion intensity, spotted amount (R2 = 0.9947), and reproducibility (RSD < 15%) is suitable for quantitative analysis of psilocin in zebrafish tissues. Spatial distribution maps showed that following continuous exposure for 4 h, psilocin was widely distributed across multiple tissues, such as the eye, brain, heart, liver, and kidney, with marked accumulation in the brain and the periportal regions of the liver. Relative psilocin signal intensity revealed a dose-dependent increase in tissue drug levels. The dose-dependent increase in both behavioral hyperactivity and brain psilocin levels points to a consistent relationship, in line with a central site of action. Collectively, these findings demonstrate that DESI-MSI provides a visual and efficient strategy for studying drug distribution in biological tissues from exposed animals. The neurobehavioral toxicity phenotypes and distinct tissue distribution patterns of psilocin uncovered in this study offer critical insights into the biological effects and potential risks of this psychoactive substance.
    Keywords:  DESI-MSI; neurotoxicity; psilocin; psilocybin; spatial distribution; zebrafish
    DOI:  https://doi.org/10.3390/molecules31122143
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