Journal of the American Society for Mass Spectrometry最新文献

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Calibration of the Mass Spectrometer of China’s Chang’E-7 Lunar Soil Water Molecule Analyzer 中国嫦娥7号月球土壤水分子分析仪质谱仪的标定
IF 2.9 2区 化学
Journal of the American Society for Mass Spectrometry Pub Date : 2026-09-02 Epub Date: 2026-08-14 DOI: 10.1021/jasms.6c00327
Meiru Guo, Detian Li, Zhengyi Ren, Wenze Tao, Gang Li, Dongxue Xi, Juncheng Mao, Yin Zhou, Jianhong Zhuang, Jian Geng, Jingyao Yang, Dongzheng Mu, Xiaoxia Ma, Hongxiang Chen, Jingjing Wang, Fei Wang, Derong Zhou, Wentao Li
{"title":"Calibration of the Mass Spectrometer of China’s Chang’E-7 Lunar Soil Water Molecule Analyzer","authors":"Meiru Guo,&nbsp;Detian Li,&nbsp;Zhengyi Ren,&nbsp;Wenze Tao,&nbsp;Gang Li,&nbsp;Dongxue Xi,&nbsp;Juncheng Mao,&nbsp;Yin Zhou,&nbsp;Jianhong Zhuang,&nbsp;Jian Geng,&nbsp;Jingyao Yang,&nbsp;Dongzheng Mu,&nbsp;Xiaoxia Ma,&nbsp;Hongxiang Chen,&nbsp;Jingjing Wang,&nbsp;Fei Wang,&nbsp;Derong Zhou,&nbsp;Wentao Li","doi":"10.1021/jasms.6c00327","DOIUrl":"https://doi.org/10.1021/jasms.6c00327","url":null,"abstract":"<p>The existence of water ice at the lunar south pole hasbecome amajor topic in contemporary deep-space exploration. China’sChang’e-7 lunar mission is scheduled for launch in 2026. Oneof its primary scientific objectives is to conduct an in situ investigationof water ice within a permanently shadowed crater at the lunar southpole. The candidate landing site is located near the Shackleton crater.During the exploration, lunar regolith samples will be drilled toa depth of approximately 1 m within the permanently shadowed craterat the lunar south pole and transferred to a furnace to be heatedto 200 °C. The H<sub>2</sub>O and other volatile components releasedduring heating will be introduced into the LSWMA, Lunar Soil WaterMolecule Analyzer, which will measure the composition and amount ofgases released from the lunar regolith. We developed the LSWMA andestablished a ground-based mass spectrometer calibration device capableof calibrating gas–liquid mixtures. The flight model of themass spectrometer was calibrated using CO<sub>2</sub> and H<sub>2</sub>O under different temperatures and inlet pressures. The sensitivityof CO<sub>2</sub>, <em>S</em>*(<em>I</em>/<em>p</em>)<sub>CO<sub>2</sub></sub>, and the sensitivity of H<sub>2</sub>O, <em>S</em>*(<em>I</em>/<em>p</em>)<sub>H<sub>2</sub>O</sub>, were obtained under different pressuresand temperatures, and the relative sensitivity of CO<sub>2</sub> toH<sub>2</sub>O, <em>S</em><sub><em>r</em></sub>, wasthen calculated. Under molecular-flow inlet conditions, the mass spectrometer’srelative sensitivity remains constant. Based on this principle, thesensitivity of H<sub>2</sub>O can be extrapolated from the sensitivityof CO<sub>2</sub> under on-orbit conditions. Ultimately, this allowsfor the accurate inversion of the partial pressure of H<sub>2</sub>O gas in the tubing assembly and the H<sub>2</sub>O content of thelunar soil.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 9","pages":"2238–2246"},"PeriodicalIF":2.9,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148870440","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}
引用次数: 0
Impact of Salt and Urine Matrices on Electrokinetic Stacking Coupled to Paper Spray Mass Spectrometry 盐和尿基质对纸喷雾质谱联用电动力学堆积的影响
IF 2.9 2区 化学
Journal of the American Society for Mass Spectrometry Pub Date : 2026-09-02 Epub Date: 2026-08-13 DOI: 10.1021/jasms.6c00238
Jamison R. Polley, Varadaraju V. Dyavegowda, Lahiru Wedasingha, Merlin L. Bruening, Nicholas E. Manicke
{"title":"Impact of Salt and Urine Matrices on Electrokinetic Stacking Coupled to Paper Spray Mass Spectrometry","authors":"Jamison R. Polley,&nbsp;Varadaraju V. Dyavegowda,&nbsp;Lahiru Wedasingha,&nbsp;Merlin L. Bruening,&nbsp;Nicholas E. Manicke","doi":"10.1021/jasms.6c00238","DOIUrl":"https://doi.org/10.1021/jasms.6c00238","url":null,"abstract":"<p>Relative to liquid chromatography coupled to electrosprayionization(ESI), paper spray ionization (PSI) can more rapidly ionize analytesfrom complex matrices with less sample preparation and less expensiveinstrumentation. However, matrix effects can lead to ion suppressionand poorer sensitivity. To overcome these problems, we combined on-paperfaradaic ion concentration polarization (f-ICP), a form of electrokineticstacking, with PSI to preconcentrate analytes directly on the spraysubstrate prior to ionization. Electrokinetic stacking also enablesdesalting because of the separation of analyte molecules from smallions like sodium. 3D-printed cartridges containing chemically modifiedPTFE papers were utilized with a high voltage isolated power supplyto perform on-paper stacking from the same device as paper spray.In this study, ion suppression was compared for paper spray with andwithout electrokinetic stacking in the presence of five salts andartificial urine at varying concentrations. The signal enhancementachieved for f-ICP/PSI relative to normal PSI was also quantified.Finally, the effect of salt type and concentration on stacking timewas assessed. Increasing salt concentrations generally results inlonger stacking times and increased currents, indicative of increasingquantities of charge being desalted. In the presence of single salt-containingmatrices, f-ICP/PSI frequently decreased ion suppression and gavea signal enhancement of 2 to &gt;200× for small molecule drugscomparedto unstacked paper spray (uPSI). In artificial urine, a more complexmatrix with various salts and metabolites, f-ICP/PSI did not reliablydecrease matrix effects due to creatinine and other matrix componentscostacking with the analytes. Nevertheless, f-ICP/PSI still resultedin signal enhancements of 8 to &gt;50× relative to uPSI due toanalytepreconcentration from electrokinetic stacking. Overall, this researchdemonstrated that f-ICP/PSI results in significant sensitivity improvementsrelative to uPSI.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 9","pages":"2201–2214"},"PeriodicalIF":2.9,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148870321","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}
引用次数: 0
An Explanation for the 32 and 54 Da Losses Seen in N-Linked Glycan Permethylation Reactions 对n -链聚糖过甲基化反应中32和54 Da损失的解释
IF 2.9 2区 化学
Journal of the American Society for Mass Spectrometry Pub Date : 2026-09-02 Epub Date: 2026-08-13 DOI: 10.1021/jasms.6c00173
Lisa M. Parsons, John F. Cipollo
{"title":"An Explanation for the 32 and 54 Da Losses Seen in N-Linked Glycan Permethylation Reactions","authors":"Lisa M. Parsons,&nbsp;John F. Cipollo","doi":"10.1021/jasms.6c00173","DOIUrl":"https://doi.org/10.1021/jasms.6c00173","url":null,"abstract":"<p>Permethylation is a widely used derivatization techniquefor massspectrometry-based glycan analysis, applicable to both research anddrug product characterization. It stabilizes sialic acids, improvesglycan ionization, and is commonly used to analyze PNGase F-released <em>N</em>-linked glycans for distribution and composition profiling,yielding semiquantitative or quantitative data. We occasionally observedpeaks 32 and 54 Da below expected ion masses, anomalies which areunreported in the literature. Investigation revealed these lossesstem from slower-than-expected spontaneous exchange of C-1 aminesfor water in nascent glycosylamines following PNGase F release. Here,we report the origin of these mass losses, propose a mechanistic explanation,and suggest mitigation strategies.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 9","pages":"2251–2255"},"PeriodicalIF":2.9,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877859","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}
引用次数: 0
Screen for Tissue-Specific Markers of Drug-Induced Phospholipidosis Using Mass Spectrometry Imaging 使用质谱成像筛选药物性磷脂病的组织特异性标记物。
IF 2.9 2区 化学
Journal of the American Society for Mass Spectrometry Pub Date : 2026-08-05 Epub Date: 2026-06-27 DOI: 10.1021/jasms.6c00010
Christoph Hoffmann, Vladimir Lekić, Michael Becker, Manfred Claassen
{"title":"Screen for Tissue-Specific Markers of Drug-Induced Phospholipidosis Using Mass Spectrometry Imaging","authors":"Christoph Hoffmann,&nbsp;Vladimir Lekić,&nbsp;Michael Becker,&nbsp;Manfred Claassen","doi":"10.1021/jasms.6c00010","DOIUrl":"10.1021/jasms.6c00010","url":null,"abstract":"<p>Drug-induced phospholipidosis is a common side effectof the pharmacologicaltreatment. Although mostly reversible, it can lead to deleteriousconsequences, including inflammation and fibrosis. While it can bereadily detected in tissue biopsies or cell cultures, biomarkers thatcan be measured noninvasively remain scarce. We used a panel of fourcompounds known to induce phospholipidosis to investigate three primarytarget tissues as potential new biomarkers. Using mass spectrometryimaging, followed by analysis with prediction models and feature-wisestatistical analysis, we identified over 150 mass/charge featurescorrelated with DIPL in general or in specific tissues, many of whichyielded database hits in the LipidMaps DB in molecule classes linkedto DIPL before. Our data set provides a foundation for annotatingreliable biomarkers in blood and urine.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1783–1791"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337321","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}
引用次数: 0
Molecular Framework Modification in Mass Spectrometry: Atom Exchange, Insertion, and Deletion 质谱中的分子框架修饰:原子交换、插入和删除。
IF 2.9 2区 化学
Journal of the American Society for Mass Spectrometry Pub Date : 2026-08-05 Epub Date: 2026-06-26 DOI: 10.1021/jasms.6c00171
Myles Q. Edwards, Dylan T. Holden, R. Graham Cooks
{"title":"Molecular Framework Modification in Mass Spectrometry: Atom Exchange, Insertion, and Deletion","authors":"Myles Q. Edwards,&nbsp;Dylan T. Holden,&nbsp;R. Graham Cooks","doi":"10.1021/jasms.6c00171","DOIUrl":"10.1021/jasms.6c00171","url":null,"abstract":"<p>The ionization and activation of molecules, as performedusingmass spectrometry (MS), have long been known to induce unimolecularrearrangements in gas-phase ions and, in some cases, reorganizationof the underlying skeletal framework. Here, we explore skeletal rearrangementsoccurring from the electrospray ionization process, including atomexchange, insertion, and deletion, within pre-existing ring systems.The Baeyer–Villiger oxidation, the Beckmann rearrangement,and the Favorskii rearrangement are longstanding organic reactionsthat are here explored in MS, alongside a unique sulfur-for-oxygenexchange reaction within a 2,4,6-triphenylpyrylium scaffold. MS<sup>n</sup> and high-resolution MS are used to examine four representativetransformations of molecular frameworks. Reactions across the fourtypes 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 authenticstandards or by characteristic fragmentation behavior. Beyond demonstratingframework modifications in electrospray droplets, these results pointto an expanded suite of reactions for reactive MS derivatization,as well as the development of future strategies for late-stage functionalization.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1981–1989"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337341","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}
引用次数: 0
An m/z- and Intensity-Based HRMS Clustering Algorithm Targeted toward Single-Cell Metabolomics 针对单细胞代谢组学的基于m/z和强度的HRMS聚类算法
IF 2.9 2区 化学
Journal of the American Society for Mass Spectrometry Pub Date : 2026-08-05 Epub Date: 2026-07-10 DOI: 10.1021/jasms.6c00150
Dirk Wevers, Laura Koldenhof, Laura Castaneda, Anouschka van der Zeeuw, Hellen Fass, Thomas Hankemeier, Charlie Clark, Ahmed Ali
{"title":"An m/z- and Intensity-Based HRMS Clustering Algorithm Targeted toward Single-Cell Metabolomics","authors":"Dirk Wevers,&nbsp;Laura Koldenhof,&nbsp;Laura Castaneda,&nbsp;Anouschka van der Zeeuw,&nbsp;Hellen Fass,&nbsp;Thomas Hankemeier,&nbsp;Charlie Clark,&nbsp;Ahmed Ali","doi":"10.1021/jasms.6c00150","DOIUrl":"10.1021/jasms.6c00150","url":null,"abstract":"<p>Single-cell(SC) metabolomics holds great potential in the developmentof novel diagnostic tools and mechanistic insights into cell biology.Using high-resolution mass spectrometry (HRMS), the masses of a singlecell’s constituents can be determined with an accuracy highenough to derive their respective elemental compositions. Using amolecule’s mass and its MS fragmentation pattern, in many casesa molecular structure can be assigned or looked up in databases. Dueto the small measurement cell volume of an Orbitrap HRMS instrument,samples need to be scanned multiple times, which necessitates across-scanclustering per sample, and across-sample alignment of <em>m</em>/<em>z</em> values. However, existing HRMS data processingsoftware is not designed to process SC HRMS data, as it typicallyrequires liquid chromatography retention times or reference spectrafor <em>m</em>/<em>z</em> clustering and alignment.Herein, a novel, robust SC HRMS <em>m</em>/<em>z</em> clustering and alignment algorithm is presented and compared withtwo commercially available and industry standard algorithms used bySciex MarkerView and Thermo FreeStyle. Furthermore, output is comparedwith clustering results from DBSCAN and MaldiQuant binning. Our algorithm,Global Clustering unTargeted Analysis (GCTA), enforces a strict maximumon the cluster size, thereby reducing the chance of peak aggregation.Furthermore, by design, GCTA enables noise filtering based on intensityand number of peaks. Across-scan clustering and across-sample alignmentwere contrasted for accuracy in finding peaks identified by commercialsoftware output and peaks with known <em>m</em>/<em>z</em> values corresponding to standards and HMDB and LipidMaps databasehits. Comparisons are made based on data recorded for quality controlsamples containing standard mixes as well as SC HRMS data recordedfor two different cell lines. This work shows that the presented algorithmis comparable in accuracy with respect to MarkerView and FreeStyle,reliably identifies compounds, is less prone to peak splitting thanMaldiQuant binning while providing similar levels of error in clusteringpeaks, and successfully filters noise. Furthermore, it is shown tobe competitive with DBSCAN, MaldiQuant binning and MarkerView whencompared to theoretical <em>m</em>/<em>z</em> valuesbased on database hits. GCTA encompasses both <em>m</em>/<em>z</em> clustering and reference-free alignment, which makes itpivotal to further development of untargeted SC HRMS metabolomics.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1942–1951"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148417738","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}
引用次数: 0
A Derivatization-Based Charge Localization Strategy for Suppressing in-Source Dehydration in LC-ESI(+)-MS Analysis of Natural Polyether Compounds 基于衍生化的电荷定位策略抑制天然聚醚化合物LC-ESI(+)-MS分析中的源内脱水
IF 2.9 2区 化学
Journal of the American Society for Mass Spectrometry Pub Date : 2026-08-05 Epub Date: 2026-07-14 DOI: 10.1021/jasms.6c00029
Shimba Kawasue, Yuki Komatsu, Kyoko Kuniyoshi, Masashi Uema, Naomasa Oshiro
{"title":"A Derivatization-Based Charge Localization Strategy for Suppressing in-Source Dehydration in LC-ESI(+)-MS Analysis of Natural Polyether Compounds","authors":"Shimba Kawasue,&nbsp;Yuki Komatsu,&nbsp;Kyoko Kuniyoshi,&nbsp;Masashi Uema,&nbsp;Naomasa Oshiro","doi":"10.1021/jasms.6c00029","DOIUrl":"10.1021/jasms.6c00029","url":null,"abstract":"<p>In electrospray ionization (ESI), analytes containingmultiplehydroxyl or ether structures often produce multiple competing precursorions, reducing sensitivity and complicating precursor selection. Okadaicacids (OAs) exhibited pronounced Na<sup>+</sup>/K<sup>+</sup> adductionalong with sequential dehydration. In contrast, azaspiracids, whichpossess a secondary amine capable of forming a stable protonated species,predominantly generate [M + H]<sup>+</sup> ions. This contrast indicatesthat the absence of a strong charge-localization site is the dominantcontributing factor under ESI conditions to ion dispersion in OAs.To address this issue, we chemically introduced a charge-localizinggroup via IPPAH derivatization. The resulting OAs–IPPAH derivativesexhibited substantial precursor-ion convergence in ESI(+), with upto 95% of the total ion abundance as a single [M + H]<sup>+</sup> ion.Peak intensities increased by 2.6–4.7. These findings providethe first demonstration that chemical control of charge localizationcan suppress in-source dehydration and metal adduct formation.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1724–1728"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434582","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}
引用次数: 0
Complementary UV-MALDI and IR-MALDESI Imaging Expand Metabolomic Coverage in the 6-OHDA Rat Model of Parkinson’s Disease 互补UV-MALDI和IR-MALDESI成像扩大6-OHDA大鼠帕金森病模型的代谢组学覆盖
IF 2.9 2区 化学
Journal of the American Society for Mass Spectrometry Pub Date : 2026-08-05 Epub Date: 2026-07-17 DOI: 10.1021/jasms.5c00424
Mary F. Wang, Reza Shariatgorji, Anna Nilsson, Ibrahim Kaya, Per Svenningsson, Per E. Andrén, David C. Muddiman
{"title":"Complementary UV-MALDI and IR-MALDESI Imaging Expand Metabolomic Coverage in the 6-OHDA Rat Model of Parkinson’s Disease","authors":"Mary F. Wang,&nbsp;Reza Shariatgorji,&nbsp;Anna Nilsson,&nbsp;Ibrahim Kaya,&nbsp;Per Svenningsson,&nbsp;Per E. Andrén,&nbsp;David C. Muddiman","doi":"10.1021/jasms.5c00424","DOIUrl":"10.1021/jasms.5c00424","url":null,"abstract":"<p>In this study, we demonstrate the complementary strengthsof FMP-10(4-(Anthracen-9-yl)-2-fluoro-1-methylpyridin-1-ium iodide) on-tissuederivatization with UV-MALDI MSI and IR-MALDESI MSI without derivatizationfor small molecule analysis. These MSI approaches were applied tothe striatum of rats administered 6-OHDA to induce dopaminergic neurodegeneration,modeling Parkinson’s disease. UV-MALDI MSI with FMP-10 derivatizationenhanced the detection of dopaminergic and serotonergic metabolites,revealing clear lesion-related effects. IR-MALDESI MSI, in turn, expandedthe molecular coverage by detecting several hundred additional smallmolecules, including neurotransmitters, amino acids, and lipids. Thecomplementary application of these ionization strategies broadenedmetabolomic coverage, highlighting their potential for broader disease-relatedstudies.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1744–1753"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468161","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}
引用次数: 0
Strategies for the Identification of Cyclic Peptide Drugs and Their Impurities 环肽类药物及其杂质的鉴定策略。
IF 2.9 2区 化学
Journal of the American Society for Mass Spectrometry Pub Date : 2026-08-05 Epub Date: 2026-07-16 DOI: 10.1021/jasms.6c00023
Zhen Long, Wei Zhang, Xiang Zhu, Xi Luo
{"title":"Strategies for the Identification of Cyclic Peptide Drugs and Their Impurities","authors":"Zhen Long,&nbsp;Wei Zhang,&nbsp;Xiang Zhu,&nbsp;Xi Luo","doi":"10.1021/jasms.6c00023","DOIUrl":"10.1021/jasms.6c00023","url":null,"abstract":"<p>Cyclic peptide drugspose significant analytical challenges dueto their constrained architectures and multiple intramolecular linkages,which complicate fragmentation behavior and hinder structural identification.In this study, electron-transfer/higher-energy collision dissociation(EThcD) was systematically optimized to analyze three clinically relevantclasses of cyclic peptides: disulfide-bridged, ester- and disulfide-bridged,and macrolactam-bridged peptides. Compared with higher-energy collisionaldissociation (HCD) and electron transfer dissociation without supplementalactivation (ETnoD), EThcD significantly increased the abundance ofboth c/z and b/y fragment ions, providing an improved sequence coverage.Distinct diagnostic fragmentation behaviors were observed. Disulfide-bridgedcyclic peptides exhibited dominant M33 neutral losses associated withHS• elimination. Ester- and disulfide-bridged peptides generatedboth M–33 and M–46 fragments, corresponding to HS•and CH<sub>2</sub>S losses. Macrolactam-bridged peptides showed characteristicM–28 neutral losses consistent with CO elimination. These neutrallosses serve as diagnostic markers for rapid classification and impurityidentification. Targeted MS<sup>3</sup> experiments further supportedthe proposed formation mechanisms of these product ions. An EThcDMS<sup>2</sup>–CID MS<sup>3</sup> strategy was also evaluatedto investigate fragmentation mechanisms. However, for sequence determination,EThcD MS<sup>2</sup> spectra provided more regular c/z ion seriesand reduced spectral complexity, enabling straightforward analysisusing commercial software. Applying optimized EThcD conditions andestablished fragmentation rules, impurities in atosiban and carbetocinwere characterized, leading to the identification of three impuritiesin atosiban and two in carbetocin. This approach demonstrates theeffectiveness of EThcD for structural elucidation and impurity profilingof cyclic peptide therapeutics.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1792–1803"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468200","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}
引用次数: 0
Immobilized Metal Affinity Beads for Recombinant Protein Analysis by Desorption Electrospray Ionization Mass Spectrometry 固定化金属亲和珠用于重组蛋白的解吸电喷雾质谱分析。
IF 2.9 2区 化学
Journal of the American Society for Mass Spectrometry Pub Date : 2026-08-05 Epub Date: 2026-07-17 DOI: 10.1021/jasms.6c00155
Christopher James Taylor, Sumana Parvin, Fazeleh Shafiepour, Frederick Stull, Andre R. Venter
{"title":"Immobilized Metal Affinity Beads for Recombinant Protein Analysis by Desorption Electrospray Ionization Mass Spectrometry","authors":"Christopher James Taylor,&nbsp;Sumana Parvin,&nbsp;Fazeleh Shafiepour,&nbsp;Frederick Stull,&nbsp;Andre R. Venter","doi":"10.1021/jasms.6c00155","DOIUrl":"10.1021/jasms.6c00155","url":null,"abstract":"<p>We address the limitations of the low binding capacityof smoothmetal affinity surfaces (below 1.661 femtomoles per mm<sup>2</sup>) and the well-documented low sensitivity of DESI-MS toward largerproteins by increasing the specific surface area of the sampling substrate,thereby providing a greater binding capacity per unit area of thedesorption footprint. This was achieved using Ni-NTA-functionalizedmagnetic beads adhered to a flat surface. Close packing of the sphericalbeads provides a greater surface area, yielding an increased proteinbinding capacity as high as 4.028 nmol per mm<sup>2</sup> of sampledsurface. The magnetic properties of these beads allow for simplifiedworkflows and efficient protein recovery directly from cell lysateprior to mass spectrometric analysis. The approach is demonstratedby purifying known concentrations of His-labeled S-adenosylhomocysteinenucleosidase and lactate oxidase. The known enzymatic reactions foreach protein are shown directly from the captured proteins adsorbedon the beads by DESI-MS. Acidifying the desorption solvent disruptsinteractions between chelated nickel and histidine, allowing for therelease of the protein and its analysis by DESI-MS.</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"37 8","pages":"1964–1970"},"PeriodicalIF":2.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468218","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}
引用次数: 0
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