Journal of the American Society for Mass Spectrometry最新文献

{"title":"Noncontact Detection of Absorbed Dinitrotoluene Using Laser Electrospray Mass Spectrometry.","authors":"Ning Ding, Robert J Levis","doi":"10.1021/jasms.5c00046","DOIUrl":"https://doi.org/10.1021/jasms.5c00046","url":null,"abstract":"<p><p>Noncontact detection of the explosive signature molecule 2,4-dinitrotoluene (DNT) from both metal and sand substrates using laser electrospray mass spectrometry (LEMS) is investigated. The measurement of DNT mass spectral signal intensity as a function of laser vaporization energy reveals that the optimal laser pulse energy for metal (0.4 mJ) is lower than that for dielectric substrates (1.2 mJ). The effects of laser spot area and laser power density on the LEMS analysis of DNT were studied at fixed laser pulse energies. The LEMS signal intensity of DNT is modeled as the product of laser spot area and laser power density. The model shows that both parameters contribute to the measured signal intensity, in agreement with experimental data. Furthermore, investigations of the DNT signal intensity as a function of nine different sampling tube positions were conducted to improve the capture efficiency of laser-vaporized analytes. The limit of detection (LoD) for DNT using LEMS is 15 ng through noncontact detection using a Venturi pump remote sampling system.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LC-ESI(±)-LTQ MSⁿ-Based Metabolomic Profiling of Coffee: Fragmentation Pathways for Identification of Major Polar Compounds.","authors":"Marcos Valério Vieira Lyrio, Danieli Grancieri Debona, Amanda Eiriz Feu, Nayara Araujo Dos Santos, Arlan da Silva Gonçalves, Ricardo Machado Kuster, Eustáquio Vinícius Ribeiro de Castro, Wanderson Romão","doi":"10.1021/jasms.4c00418","DOIUrl":"https://doi.org/10.1021/jasms.4c00418","url":null,"abstract":"<p><p>Coffee is characterized by a complex chemical matrix that significantly influences its organoleptic properties and market value. This complexity is driven by factors such as botanical species, geographical origin, cultivation conditions, and post-harvest processing methods. Metabolomic studies aim to elucidate how these factors impact the biosynthesis of metabolites that contribute to the sensory qualities of high-quality coffee. Among various analytical techniques, liquid chromatography-mass spectrometry (LC-MS) is particularly effective for separating, identifying, and quantifying these compounds. Most metabolomic studies employ high-resolution mass spectrometry (HRMS) for its superior mass accuracy (<1 ppm), whereas the interpretation of low-resolution data requires additional effort, often relying on literature references and proposed fragmentation mechanisms. In this study, we applied LC-ESI(±)LTQ MSⁿ to comprehensively profile coffee metabolites, identifying 60 compounds, including polar compounds and their isomers such as chlorogenic acids, carbohydrates, amino acids, alkaloids, glycosylated diterpenes, and flavonoids. Fragmentation mechanisms were proposed and discussed. The results demonstrate the effectiveness of LC-ESI(±)LTQ MSⁿ in a detailed metabolomic analysis, providing a robust platform for future research in coffee metabolomics.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Chemical Reactivity of Wildfire-Derived Dissolved Organic Molecules: Glutathione Binding through Kendrick Mass Defect Analysis.","authors":"Hannah M Hamontree, Patrick G Hatcher","doi":"10.1021/jasms.5c00077","DOIUrl":"https://doi.org/10.1021/jasms.5c00077","url":null,"abstract":"<p><p>The emerging risks to organisms of pyrogenic-derived dissolved organic matter (PyDOM) from forest fires are of concern due to its toxic and mutagenic potential (e.g., pro-oxidative responses in fauna through the depletion of glutathione, a nitrogen- and sulfur-containing tripeptide found in cells). This study simulates this phenomenon in a laboratory setting by identifying bonding between reduced l-glutathione and organic molecules in leachates from environmentally weathered biomass samples (charred and uncharred) using Kendrick Mass Defect (KMD) analysis from formula lists obtained from negative-mode electrospray ionization-Fourier transform-ion cyclotron resonance-mass spectrometry ((-)ESI-FT-ICR-MS). These formula lists reveal a 10-fold increase in nitrogen- and sulfur-containing molecular formulas in the charred biomass samples compared with the unreacted charred biomass when subjected to reaction with glutathione. KMD analysis attributed the bonding of glutathione to the biomass leachates accounting for approximately 25% of the new nitrogen- and sulfur-containing molecular formulas as either addition-type or condensation/elimination-type reactions. KMD sheds light on a different fraction of chemically reactive wildfire-produced organic compounds that may be of interest for subsequent toxicological studies.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Pharmaceutical Transformation Products by High-Field Asymmetric Waveform Ion Mobility and Infrared Ion Spectroscopy Coupled to Mass Spectrometry.","authors":"César A G Dantas, Pedro H M Garcia, Thiago C Correra","doi":"10.1021/jasms.5c00039","DOIUrl":"https://doi.org/10.1021/jasms.5c00039","url":null,"abstract":"<p><p>The identification of drug degradation products is crucial for pharmaceutical development and quality control, as drug transformation products can significantly affect therapeutic efficacy and patient safety. Traditional analytical methods, such as high-performance liquid chromatography (HPLC) and <i>tandem</i> mass spectrometry (MS/MS), often require reference standards for accurate identification and may be unsuitable for resolving isomeric and isobaric degradation products. This study explores the use of high-field asymmetric waveform ion mobility spectrometry (FAIMS) and infrared multiple photon dissociation (IRMPD) spectroscopy coupled with mass spectrometry (MS) as an effective alternative for identifying drug degradation products without the need for previous chromatographic stages or the use of reference standards. Cyclophosphamide, a widely used DNA-alkylating agent in cancer and autoimmune therapies, is employed as a model system for this study. FAIMS enabled the separation of species based on their differential mobility, while IRMPD provided distinctive spectral data, allowing precise reference-standard-free structural elucidation. This integrated approach offers a robust solution for the identification of complex degradation products, advancing stability studies, formulation development, and quality control in pharmaceutical analysis.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Mass Spectrometric Study of the Role of Water in the Paternò-Büchi (PB) Reaction between 2-Acetylpyridine and Unsaturated Fatty Acids.","authors":"Danna Hu, T-Y Lui, Xiangfeng Chen, T-W Dominic Chan","doi":"10.1021/jasms.5c00075","DOIUrl":"https://doi.org/10.1021/jasms.5c00075","url":null,"abstract":"<p><p>Localizing the double-bond positions in unsaturated fatty acid isomers is of great importance for understanding the reaction pathways in the occurrence and development of some metabolic diseases. The Paternò-Büchi (PB) reaction using 2-acetylpyridine as the charge-tagging PB reagent in combination with tandem mass spectrometry (MS/MS) has been developed as an effective method for determining the positions of C═C bonds in unsaturated fatty acids. Recently, it was found that the presence of water in the reaction solution could greatly enhance the yield of the PB reaction. To optimize the reaction conditions, the water content of the reaction mixture was systematically varied in the reaction between 2-acetylpyridine and oleic acid using a binary acetonitrile/water solvent system. It was observed that increasing water content could increase the yield of the PB reaction. However, this effect was complicated by the Norrish type II reactions and the low water solubility of oleic acid, and the yield of PB product was found to be maximized at 30% water in a water/acetonitrile binary system. At higher water content conditions, the reaction products were dominated by the isomeric products derived from the Norrish type II-A reaction. This enhanced side reaction was tentatively attributed to the increasing production of hydroxyl radicals through the photolysis of water molecules under 254 nm UV illumination. Since there was no evidence for the direct involvement of water molecules in the photocyclization of carbonyl and olefin functionalities, the exact role of water in facilitating the PB reaction was evaluated based on the existing concepts of 'on-water' and 'in-water'. For the reaction system used in this study, our results favor the 'in-water' model, in which aggregates of oleic acid might be formed at elevated water content. Aggregates have a higher concentration of oleic acid or provide microscopic heterogeneous surfaces for promoting the PB reaction by bringing both reaction species together more efficiently. Our preliminary attempt to accelerate the PB reaction under water-free conditions using a suspension of 50 μm C-18 powders was found to be promising. Higher yield of the PB reaction product without elevating the undesirable Norrish type II reaction product was observed.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Prediction of Septic Shock in Emergency Department Using Serum Metabolites.","authors":"Yu Hong, Li-Hua Li, Ting-Hao Kuo, Yi-Tzu Lee, Cheng-Chih Hsu","doi":"10.1021/jasms.5c00009","DOIUrl":"https://doi.org/10.1021/jasms.5c00009","url":null,"abstract":"<p><p>Early recognition of septic shock is crucial for improving clinical management and patient outcomes, especially in the emergency department (ED). This study conducted serum metabolomic profiling on ED patients diagnosed with septic shock (n = 32) and those without septic shock (n = 92) using a high-resolution mass spectrometer. By implementing a supervised machine learning algorithm, a prediction model based on a panel of metabolites achieved an accuracy of 87.8%. Notably, when employed on a low-resolution instrument, the model maintained its predictive performance with an accuracy of 84.2%. These results demonstrate the potential of metabolite-based algorithms to identify patients at high risk of septic shock. Our proposed workflow aims to optimize risk assessment and streamline clinical management processes in the ED, holding promise as an efficient routine test to promote timely intensive interventions and reduce septic shock mortality.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methane Elimination upon Collision-Activated Dissociation of Selected Product Ions Formed Upon Gas-Phase Reactions of (Isopropenyloxy)trimethylsilane Facilitates the Mass Spectrometric Classification of Specific Oxygen- and/or Nitrogen-Containing Compounds.","authors":"Jaskiran Kaur, Kawthar Z Alzarieni, Judy Kuan Yu Liu, Wanru Li, Ruth O Anyaeche, Hilkka I Kenttämaa","doi":"10.1021/jasms.4c00504","DOIUrl":"10.1021/jasms.4c00504","url":null,"abstract":"<p><p>Unambiguous identification of drug impurities is of the utmost importance for the pharmaceutical sector. Therefore, access to analytical techniques that enable the reliable characterization of drug impurities during and after the drug development process is required. In this study, tandem mass spectrometry combined with gas-phase ion-molecule reactions followed by collision-activated dissociation (CAD) of specific ion-molecule reaction product ions is demonstrated to enable the identification of nucleophilic compounds with at least one H atom on their nucleophilic atom or a H atom on an adjacent heavy atom. Compounds with different oxygen- and/or nitrogen-containing functionalities and their combinations, such as carboxylic acids, phenols, aldehydes, hydroxylamines, amides, anilines, and sulfonamides, were tested. All analytes were protonated via atmospheric pressure chemical ionization (APCI), transferred into a linear quadrupole ion trap, isolated, and allowed to react with (isopropenyloxy)trimethylsilane (ITS). All protonated compounds studied, including the ones mentioned above as well as many others, react with ITS to form an addition product that has eliminated an acetone molecule. Subjecting these product ions to CAD generated diagnostic fragment ions via the loss of <i>methane</i> for most of the compounds with at least one H atom on their nucleophilic atom or a H atom on an adjacent heavy atom. Only three exceptions were identified. Quantum chemical calculations were employed to delineate the likely mechanisms for the formation of the relevant product ions upon ion-molecule reactions and their fragmentation via elimination of methane.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"1068-1076"},"PeriodicalIF":3.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrocyclic Rearrangement Ion Fragmentation of Glutathione Conjugates of Cyclobutane-Containing Covalent BTK Inhibitors.","authors":"Cathy A Muste, Chungang Gu, H George Vandeveer, Simone Sciabola, Martin K Himmelbauer","doi":"10.1021/jasms.4c00275","DOIUrl":"10.1021/jasms.4c00275","url":null,"abstract":"<p><p>Covalent BTK-inhibitor drugs often contain reactive acrylamide warheads designed to irreversibly bind to their protein targets at free thiol cysteines in the kinase active site. This reactivity also makes covalent inhibitors susceptible to conjugation to endogenous tripeptide glutathione (GSH), leading to clearance. During lead optimization efforts for the drug discovery of covalent BTK inhibitor BIIB129, some expected GSH adducts resulted in an unexpected and highly abundant rearrangement fragment ion in LC-MS/MS. By examining more than 30 inhibitors, the rearrangements were found to be dependent on the presence of a cycloalkane linker that connects the warhead to the kinase hinge binder motif of drug molecules. The proposed mechanism includes the formation of a 16-membered macrocyclic intermediate between the γ-glutamic acid residue (Glu) of GSH and a methyl-cyclobutyl cation, resulting in a rearrangement fragment originating from two distant parts of the adduct molecule separated by the warhead conjugated with the cysteine residue in between. Rich sets of chemical analogues available during the lead optimization enabled confirmation of the macrocyclic rearrangement. Proposed macrocyclic rearrangement was verified using GSH derivatives: N-acetylation of the γ-Glu blocked the rearrangement, and esterification of the γ-Glu side chain resulted in an expected shift in the mass of rearranged fragment ion. Proposed rearranged ion structures were supported by MS³ and MS⁴ fragmentations. Comparisons of the ion fragmentation of GSH conjugates between <i>cis</i> and <i>trans</i> matched pairs suggest a concerted mechanism for the cyclobutane linker and a stepwise mechanism for the methylcyclobutane linker, respectively.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"930-941"},"PeriodicalIF":3.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing Unpredicted Aspartic Acid Isomerization Hotspots by Probing Diagnostic Fragmentation Propensities in Top-Down and Middle-Down Mass Spectrometry.","authors":"Blandine Denefeld, Joanna Hajduk, Jure Cerar, Jean-Michel Rondeau, Jérôme Dayer, Manuel Lang, Wolfram Kern, François Griaud","doi":"10.1021/jasms.4c00443","DOIUrl":"10.1021/jasms.4c00443","url":null,"abstract":"<p><p>Isomerization of aspartic acid residues is a relevant degradation pathway of protein biopharmaceuticals as it can impair their biological activity. However, the in silico prediction of isomerization hotspots and their consequences remains ambiguous and misleading. We have previously shown that all ion differential analysis (AiDA) of middle-down spectra can be used to reveal diagnostic terminal and internal fragments with more sensitivity than the conventional fragment ion mass matching methodology. In this study, we use AiDA to characterize the degradation of an antibody fragment at three aspartic acid isomerization sites including a novel DW motif directly with electron-transfer/higher-energy collisional dissociation top-down and middle-down mass spectrometry. We show that AiDA methodology is pivotal to probe diagnostic fragmentation propensities of terminal c and z fragments at the N-terminus and vicinity of isomerization sites in addition to the diagnostic c+57 terminal fragments. Furthermore, AiDA can probe remote structural changes in the loop of an antibody complementarity-determining region induced by isomerization and the succinimide intermediate, revealing interactions between residues in agreement with molecular simulations. This study shows that aspartic acid residues at noncanonical DW and DF motifs can be hotspots for isomerization despite being ranked as false positives in physics-based prediction models. We show that the enzyme-free, fast, and sensitive AiDA methodology can be used as an orthogonal technique to fractionation for online variant characterization.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"969-979"},"PeriodicalIF":3.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multistage Linear Frequency Scanning Mass Analysis Processed by Fractional Fourier Transform.","authors":"Haoqiang Yan, Liangshun Hu, Shi Zhang, Dayu Li, Wei Xu","doi":"10.1021/jasms.5c00012","DOIUrl":"10.1021/jasms.5c00012","url":null,"abstract":"<p><p>The common method of mass analysis in a linear ion trap mass spectrometer is to eject ions with different mass-to-charge ratios (<i>m</i>/<i>z</i>) at different times by resonance excitation. Ions are ejected onto an electron multiplier (EM), generating pulsed signals called the ejection signal. Typically, the ejection signal consisting of multiple pulses is smoothed into a wider Gaussian-like pulse due to the limited bandwidth of the electronic system. For different scan rates and different samples, this bandwidth-limited electronic system and signal smoothing process will differentially increase the peak width and thus decrease the mass resolution. In this study, experiments at different scan rates were performed on a \"Brick\" miniature linear ion trap mass spectrometer. We propose a multistage linear frequency scanning mode that achieves improved mass resolution and extended mass range, in which fractional Fourier transform is applied to process the ejection signals. The proposed signal processing method improves the mass resolution and mitigates the impact of ghost peaks attributed to scattered ion ejection. A peak width of 0.84 Da at a <i>m</i>/<i>z</i> value of 242 and a scan rate of 8000 Da/s was achieved in experiments.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":" ","pages":"1093-1099"},"PeriodicalIF":3.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}