International Journal of Mass Spectrometry最新文献

{"title":"Single amino acid variation identification in high resolution tandem mass spectrometry data in bottom up proteomics","authors":"Kishankumar Bhimani ,&nbsp;Arina Peresadina ,&nbsp;Karina Burmak ,&nbsp;Kartik Joshi ,&nbsp;Attila Kertesz-Farkas","doi":"10.1016/j.ijms.2025.117532","DOIUrl":"10.1016/j.ijms.2025.117532","url":null,"abstract":"<div><div>Database-searching based precursor ion identification in tandem mass spectrometry data analysis is limited to the search space. Once a single amino acid variation (SAAV) or a modification is not included to the search space, then its observed spectra will not be annotated correctly. Several methods have been developed to identify and localize post-translational modifications (PTMs); however, few methods have been introduced to identify peptide sequences with amino acid mutations. Here, we present our approach to detect SAAVs, called SeVa (standing for <u>Se</u>quence <u>Va</u>riation). SeVa is based on the High-Resolution Exact P-Value (HR-XPV) method (doi:10.1002/pmic.202300145), which builds an exact empirical null distribution by implicitly scoring the spectra against all possible amino acid sequences in high-resolution fragmentation settings. SeVa extracts the amino acid sequence from HR-XPV, which produces the highest score. The SeVa peptides identified are subjected to a homology search against a proteome database containing shuffled decoy protein sequences. This step increases the sensitivity of the results and the decoy identifications can be used to estimate the FDR. We tested SeVa with two experimental datasets related to immunopeptidomics (PXD017407) and cancer (PDC000224), and our method identified 781 and 15,764 peptide sequences with mutations at 1.68% and 0.52% of FDRs.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"519 ","pages":"Article 117532"},"PeriodicalIF":1.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a laser desorption ionization – ion mobility – mass spectrometry method to accelerate the cyclic peptides stereochemistry determination workflow","authors":"Jia-Xuan Yan,&nbsp;Wendy Zhong","doi":"10.1016/j.ijms.2025.117533","DOIUrl":"10.1016/j.ijms.2025.117533","url":null,"abstract":"<div><div>Cyclic peptides are a class of compounds with significant therapeutic potential. The increase in number of stereocenters resulting in exponential surge of stereoisomers poses an immense challenge on the stereochemical analysis of these molecules. Current stereochemistry control strategies for synthetic peptides requires chiral LC method development using synthetic markers. However, the synthesis of all possible stereoisomers as well as chiral LC method development to separate all of them is extremely costly and time consuming. Alternatively, cyclic peptides can be hydrolyzed into single amino acids (AA), further derivatized by chiral reagents for LC-MS analysis, and compared to AA standards subjected to identical derivatization protocols. This LC-MS based methodologies could determine chirality for all possible stereoisomers within short time (less than 1hr) avoiding the need to synthesize large number of cyclic peptide stereoisomers. While examining literature reported LC-MS methodologies, we sought opportunities to further reduce the analysis time required for comprehensive determinations of the stereochemistry of cyclic peptides via advanced MS platforms. Here-in we report a new laser desorption/ionization-ion mobility-mass spectrometry (LDI-IM-MS) method for the rapid determination of amino acid stereochemistry in cyclic peptides. Chiral derivatization reagents, <span>l</span>-FDLA (Nα-(2,4-dinitro-5-fluorophenyl)-<span>l</span>-leucinamide) and <span>d</span>-FDLA were used to derivatize the amino acids into diastereomer pairs. The diastereomers were differentiated using LDI-IM-MS on a Bruker timsTOF flex platform, with key ion mobility parameters optimized and experimental CCS (collision cross section) values calculated. Enhanced sample preparation workflow including solid phase extraction (SPE) and CuCl₂ doping exhibited better ion mobility differentiation for selected samples. This approach was successfully applied to the analysis of polymyxin B, a natural product cyclic peptide, providing comprehensive stereochemical determination of all constituent amino acids within 1 min. The new workflow not only accelerates the stereochemical analysis of cyclic peptides but also holds promise for broader applications in pharmaceuticals including chiral quality control and monitoring of peptide stability.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"519 ","pages":"Article 117533"},"PeriodicalIF":1.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the results of the aberration approach for the calculation of electrostatic TOF mass analyzers with simulation in SIMION","authors":"Daniil D. Odintsov ,&nbsp;Sergey S. Poteshin","doi":"10.1016/j.ijms.2025.117526","DOIUrl":"10.1016/j.ijms.2025.117526","url":null,"abstract":"<div><div>In the last few years, high-resolution time-of-flight mass analyzers (TOF-MA) have been intensively developed. Their development requires tools that provide very accurate calculation of ion trajectories in electric fields, since an error on the scale of hundreds of picoseconds at millisecond flight times (10⁻¹⁰ %) already leads to noticeable distortions of the result. The main apparatus for calculating such systems is the aberration theory, but it has a limitation in the accuracy of calculations, since it is based on expansion in a series, and taking into account the next order of expansion significantly complicates the formulas. In this regard, using the example of calculating ion trajectories for TOF-MA with sector electrostatic fields, a comparison of the results, obtained using the aberration theory was carried out with the results of modeling in Simion. Results of the comparison indicate the possibility of applicability of the program for calculating multi-turn mass analyzers (MT-MA). Using the developed program, MT-MA with a resolution of 470,000 was calculated.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"519 ","pages":"Article 117526"},"PeriodicalIF":1.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GC-MS unveils monosaccharide D-Allose in Terminalia arjuna bark extract acting against biofilm regulatory proteins (SrtA and SarA) of Staphylococcus aureus: A drug discovery approach","authors":"Shraavani Konatam,&nbsp;Dijendra Nath Roy","doi":"10.1016/j.ijms.2025.117527","DOIUrl":"10.1016/j.ijms.2025.117527","url":null,"abstract":"<div><div>The rising prevalence of biofilm-related infections and foodborne diseases, particularly those caused by <em>Staphylococcus aureus</em>, presents significant challenges to conventional treatment strategies due to the increasing phenomenon of antibiotic resistance caused by biofilm. In response, this study employed GC-MS analysis of the methanolic and n-hexane extracts of <em>Terminalia arjuna</em> bark, a traditional medicinal plant, and identified a diverse array of bioactive compounds. All 79 compounds identified from GC-MS data were examined to determine the best binding score with SrtA and SarA, two key proteins involved in the development of biofilms and the pathogenicity of <em>Staphylococcus aureus.</em> Among 79 compounds, D-Allose, a monosaccharide, demonstrated the best binding affinity with SrtA (−6.304 kcal/mol) by involving five hydrogen bonds and SarA (−5.101 kcal/mol) by involving three hydrogen bonds, compared to other compounds among 158 interactions. Molecular dynamics and simulations were performed for 100 ns to analyze the interaction parameters with SrtA and SarA. Corresponding MM-GBSA binding energy values were −33.66 kcal/mol (D-Allose with SrtA), −18.09 kcal/mol (D-Allose with SarA). The fact that D-Allose has zero violations of Lipinski's Rule of Five further exemplifies its suitability as a medication candidate. These interactions suggest that D-Allose may interfere with bacterial adhesion, quorum sensing, and the synthesis of the biofilm matrix by interacting with SrtA and SarA. To the best of our knowledge, this is the first study to elucidate the potential mechanism by which D-Allose exerts its antibiofilm activity. Future research on in vitro and <em>in vivo</em> studies should focus on experimental validation to establish D-Allose as a promising monosaccharide candidate for combating biofilm-related antibiotic-resistant <em>Staphylococcus aureus</em> infections.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117527"},"PeriodicalIF":1.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-dimensional tandem mass spectrometry in a linear quadrupole ion trap using consecutive product ion sweeps","authors":"Eric T. Dziekonski","doi":"10.1016/j.ijms.2025.117524","DOIUrl":"10.1016/j.ijms.2025.117524","url":null,"abstract":"<div><div>Two-dimensional tandem mass spectrometry (2D-MS/MS) is a powerful analysis technique which can quickly produce a map of all precursor-product ion relationships within a sample, from a single ion injection event, and is greatly suited to low-cost instrumentation like ion traps. The ability to record this type of information in an unsupervised and unbiased manner makes this technique highly amenable to artificial intelligence-based workflows which can statistically examine the datasets to perform structural elucidation, generate more confident peak assignments, and/or discover new chemistries. Previous implementations of the 2D-MS/MS scan function kept the RF voltage applied to the trap constant and scanned an auxiliary frequency to eject and detect the product ions. A direct consequence of this is that ions of higher precursor and product <em>m/z</em> would have a lower observed mass resolution and sensitivity, leading to more potential candidates for peak identification algorithms and higher uncertainty in the reported results. Herein, we describe a new approach to 2D-MS/MS analysis in a linear quadrupole ion trap which utilizes consecutive, traditional, RF amplitude ramps to resonantly eject ions from the trap near the boundary of the Mathieu stability diagram. Relative to its predecessors, the technique does require more time to acquire, however, it necessitates fewer instrument modifications and has more robust calibration procedures. More importantly though, its use produces higher sensitivity spectra with constant 2D peak resolutions (3 Da FWHM @ 125 kDa/s), which can be predicted based on the set product ion scan rate and resonant ejection point. Additional discussion is aimed at methods by which the scan might be improved, or optimized, for higher speed workflows utilizing sample arrays. This work paves the path towards isotopically resolved 2D-MS/MS spectra, which would greatly enhance the power of the technique.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117524"},"PeriodicalIF":1.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structures of species formed by sequential methane activation by Ta+: Infrared multiple photon dissociation spectroscopy and ab Initio calculations","authors":"P.B. Armentrout ,&nbsp;Bastiaan Poetsma ,&nbsp;David H. Loertscher ,&nbsp;Satish Kumar ,&nbsp;Joost M. Bakker","doi":"10.1016/j.ijms.2025.117525","DOIUrl":"10.1016/j.ijms.2025.117525","url":null,"abstract":"<div><div>Products resulting from the sequential activation of four and five methane molecules by atomic tantalum cations were characterized by gas-phase infrared multiple photon dissociation spectroscopy and density functional theory (DFT) calculations. Tantalum cations were generated using a laser ablation source and reacted with methane in a linear radiofrequency ion trap before mass analysis and spectroscopic interrogation in a Fourier transform ion cyclotron resonance mass spectrometer coupled to the free-electron laser for intracavity experiments (FELICE) beamline. Product ions were irradiated using infrared light over the 300−2000 cm⁻¹ spectral range. Comparisons between the experimental and DFT-calculated spectra enabled structural determination of the products formed. The observed products are (CH₃)₂TaC₂H₂⁺ and (CH₃)₃Ta(C₂H₃)⁺. Formation of these products provides evidence for efficient C−H bond activation and subsequent C−C coupling on the atomic tantalum cation.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117525"},"PeriodicalIF":1.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145060030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A thermal perspective on MALDI ionization: A long journey from fundamental mechanisms to a practical solution for carbohydrate analysis","authors":"I-Chung Lu","doi":"10.1016/j.ijms.2025.117516","DOIUrl":"10.1016/j.ijms.2025.117516","url":null,"abstract":"<div><div>Matrix-assisted laser desorption/ionization (MALDI) is a vital analytical tool, but the fundamental ionization mechanism has long been debated. This perspective summarizes over a decade of research to introduce a comprehensive thermal framework, culminating in the quantitative thermally induced proton transfer (TIPT) model for MALDI. Validated by numerous experiments without fitting parameters, we identify that laser-induced temperature is the dominant factor in the primary ionization of protonated ions. The principle was subsequently applied to resolve the longstanding challenges of carbohydrate analysis. To overcome the characteristically low sensitivity of carbohydrates, the rapidly freeze-drying droplet (RFDD) sample preparation method was developed by preserving homogeneously distributed, preformed sodium adducts. RFDD increases ion intensity by over two orders of magnitude, eliminates the \"sweet spot\" effect, and enables reliable quantitative analysis. This journey from fundamental mechanistic inquiry to a practical, innovative technology powerfully illustrates how basic science drives analytical advancements.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117516"},"PeriodicalIF":1.7,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extended m/z range of coaxial linear ion trap/time-of-flight mass spectrometry using dynamic electric field ejection","authors":"Yixue Cao ,&nbsp;Xuesong Zhang ,&nbsp;Jilong Wang ,&nbsp;Chenxin Wu ,&nbsp;Lei Hua ,&nbsp;Ping Chen ,&nbsp;Haiyang Li","doi":"10.1016/j.ijms.2025.117517","DOIUrl":"10.1016/j.ijms.2025.117517","url":null,"abstract":"<div><div>Linear ion trap/time-of-flight mass spectrometry (LIT/TOFMS) to perform ion accumulation in a separate LIT prior to mass analysis is a more generally accepted method to improve duty cycle. However, a long distance between the accumulation region and the TOF pusher led to time-of-flight dispersion of the injected ions with different <em>m/z</em>, thereby limiting the detectable mass range in a single scan. This paper studies the characteristic behaviors of ion ejection from a segmented LIT through SIMION simulation. A novel dynamic electric field ejection strategy is proposed to broaden the ejection mass range of LIT. By linearly scanning the voltages on the segmented LIT and the ion gate, the axial potential distribution is dynamically adjusted to gradually shift the ion accumulation region toward the TOF pusher. As a result, the ejection distance between the accumulation region and the TOF pusher was slowly shortened, reducing time dispersion among different <em>m/z</em> ions. The simulation results demonstrate that this method significantly improves mass range of the coaxial dual LIT/TOFMS, achieving near 100 % injection efficiency for <em>m/z</em> 130–2000 with a mass window ratio <em>(m/z)</em>_<em>max</em><em>/(m/z)</em>_<em>min</em> of 15. This technology provides a solution for broadening the mass range of LIT-based hybrid instruments.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117517"},"PeriodicalIF":1.7,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next generation MasSpec pen technology: Innovations in instrumentation and medical device development for intraoperative use","authors":"Charles A. Wolfe ,&nbsp;Sydney Povilaitis ,&nbsp;Michael F. Keating ,&nbsp;Ashley E. Montgomery ,&nbsp;Bryan M. Burt ,&nbsp;Amir A. Jazaeri ,&nbsp;Livia S. Eberlin","doi":"10.1016/j.ijms.2025.117515","DOIUrl":"10.1016/j.ijms.2025.117515","url":null,"abstract":"<div><div>The chemical specificity and sensitivity of mass spectrometry techniques are being increasingly explored to enhance intraoperative decision making. Several mass spectrometry technologies have been developed to rapidly detect changes in tissue metabolism, generating “molecular fingerprints” that enable rapid tissue identification in surgical procedures. Among these, our team has developed the MasSpec Pen as a liquid-extraction based device integrated to an interface and mass spectrometer for direct and rapid molecular analysis of tissues <em>in vivo</em> and <em>ex vivo</em>. Since its first report and clinical testing in intraoperative studies, we have made several improvements to the MasSpec Pen technology to improve its analytical and procedural functionality for medical use. Here, we describe the latest advances in MasSpec Pen technology including the development of a new interface with a dual heated path vacuum chamber that improves solvent vaporization, data quality, and enables integration with different mass spectrometers. We also describe the development of new MasSpec Pen devices made with 3D printing technology for use in laparoscopy and bronchoscopy procedures. Examples of molecular data obtained with these systems are provided in the direct analysis of human tissues.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117515"},"PeriodicalIF":1.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyrolysis and thermal extraction of polymeric materials with suction-driven, real-time ionization sources and rapid polarity switching, high resolution mass spectrometry","authors":"G. Asher Newsome ,&nbsp;Katja S. Diaz-Granados ,&nbsp;Karen Sam ,&nbsp;Joshua D. Caldwell ,&nbsp;Erin R. Birdsall","doi":"10.1016/j.ijms.2025.117514","DOIUrl":"10.1016/j.ijms.2025.117514","url":null,"abstract":"<div><div>Real-time sampling systems are assembled for analysis of pyrolyzed material using in-line ionization and high resolution mass spectrometry. Two commercial models of Pyroprobe pyrolyzer with either a wand-mounted coil or a drop-in sample chamber are reconfigured from the standard gas chromatograph interface. Either a flow cell containing a platinum coil or a drop-in pyrolysis chamber is connected to a heated transfer line that conducts pyrolysates directly to a photoionization or dielectric barrier discharge source. The ion source is mounted to the front of an Orbitrap system, drawing analyte through from the pyrolyzer using instrument vacuum and/or supplementary pumping. The mass spectrometer scans in rapidly-alternating polarity so that positive and negative mode analyses are acquired in a single run. Pyrolyzed samples of tens of micrograms of polymeric materials yielded robust and resolved signal, especially from halogenated ions in negative mode that otherwise did not produce enough electron impact ionization signal for identification. The photoionization source in particular was easily purged of lingering pyrolysate by temporarily increasing the supplemental flow rate, rapidly returning signal to baseline levels after an analytical run. Elimination of carryover allowed replicate analyses to be collected at a rate of every 2 min without an autosampler. Slow-ramp thermal extraction analyses was performed on the same system as flash pyrolysis without any change in hardware.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"518 ","pages":"Article 117514"},"PeriodicalIF":1.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}