Stable electrospray ionization is crucial for ensuring consistent ion generation in mass spectrometry. Previously, a feedback control system based on spray current and Taylor cone angle was developed to automatically adjust the emitter voltage (Anal. Chem. 2023, 95, 28, 10744–10751). However, the system was susceptible to false signals caused by electrical noise, leakage, and discharge, and was not easy to implement in commercial ion sources. Here, we report a robust feedback system that relies solely on the optical image of the liquid meniscus condition at the emitter tip. A set of geometric parameters, including meniscus area, rectangularity, diameter-to-length ratio, and the degree of apex blurring, is extracted in real time from CCD images to identify the spraying mode and determine the required emitter voltage adjustment. The system maintains the Taylor cone shape within a target range, thereby preserving steady cone-jet operation under variations in flow rate, surface tension, and solvent composition. The feedback system was evaluated under both atmospheric and high-pressure ESI conditions. Under high-pressure operation, the system successfully stabilized the cone-jet mode even for pure water. The feedback-stabilized electrospray minimizes ion signal fluctuation caused by spray instability and may contribute to more reproducible ESI-MS analyses that reflect the true condition of the analyte in solution.
{"title":"Feedback control for electrospray ionization based on the shape of the liquid meniscus at the ESI emitter","authors":"Xiangting Chen , Qiangqiang Xie , Satoshi Ninomiya , Lee Chuin Chen","doi":"10.1016/j.ijms.2025.117567","DOIUrl":"10.1016/j.ijms.2025.117567","url":null,"abstract":"<div><div>Stable electrospray ionization is crucial for ensuring consistent ion generation in mass spectrometry. Previously, a feedback control system based on spray current and Taylor cone angle was developed to automatically adjust the emitter voltage (Anal. Chem. 2023, 95, 28, 10744–10751). However, the system was susceptible to false signals caused by electrical noise, leakage, and discharge, and was not easy to implement in commercial ion sources. Here, we report a robust feedback system that relies solely on the optical image of the liquid meniscus condition at the emitter tip. A set of geometric parameters, including meniscus area, rectangularity, diameter-to-length ratio, and the degree of apex blurring, is extracted in real time from CCD images to identify the spraying mode and determine the required emitter voltage adjustment. The system maintains the Taylor cone shape within a target range, thereby preserving steady cone-jet operation under variations in flow rate, surface tension, and solvent composition. The feedback system was evaluated under both atmospheric and high-pressure ESI conditions. Under high-pressure operation, the system successfully stabilized the cone-jet mode even for pure water. The feedback-stabilized electrospray minimizes ion signal fluctuation caused by spray instability and may contribute to more reproducible ESI-MS analyses that reflect the true condition of the analyte in solution.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"520 ","pages":"Article 117567"},"PeriodicalIF":1.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880441","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}
Pub Date : 2026-02-01Epub Date: 2025-12-24DOI: 10.1016/j.ijms.2025.117565
László Rinyu , Andrea Czébely , Diána Kiss , Sándor Kele , Sándor Czellár , József Molnár , Marianna Túri
Clumped isotope thermometry is a robust technique for reconstructing carbonate formation temperatures; however its analytical precision is highly dependent on instrumental stability. In this study, we address the challenge of achieving long-term Δ47 repeatability using a Thermo Scientific™ 253 Plus 10 kV isotope ratio mass spectrometer (IRMS) coupled to a Kiel IV automated carbonate preparation device. The IRMS is equipped with 1013 Ω resistors on high-gain Faraday cups. To minimize the impact of daily laboratory temperature fluctuations, we developed and implemented a prototype Peltier-based cooling system for the amplifier housing.
The combined approach reduced long-term Δ47 standard deviation from 40 to 45 ppm (occasionally reaching up to 60 ppm under extreme conditions) to around 32 ppm. Validation was performed using international carbonate standards and natural travertine samples with known formation temperatures (10–95 °C), and results were bench-marked against previously published data. These improvements demonstrate a practical pathway towards achieving high-precision clumped isotope measurements under variable environmental conditions, and they provide a reproducible methodology for laboratories operating similar instrumentation in comparable settings.
块状同位素测温是重建碳酸盐地层温度的可靠技术；然而，其分析精度高度依赖于仪器的稳定性。在这项研究中，我们使用Thermo Scientific™253 Plus 10 kV同位素比质谱仪（IRMS）与Kiel IV自动碳酸盐制备装置相结合，解决了实现长期Δ47重复性的挑战。IRMS在高增益法拉第杯上配备了1013个Ω电阻。为了尽量减少日常实验室温度波动的影响，我们为放大器外壳开发并实施了一个基于peltier的原型冷却系统。综合方法将长期Δ47标准偏差从40到45 ppm（在极端条件下偶尔达到60 ppm）降低到32 ppm左右。使用国际碳酸盐标准和已知地层温度（10-95℃）的天然石灰华样品进行验证，并根据先前发表的数据对结果进行基准测试。这些改进表明了在可变环境条件下实现高精度团块同位素测量的可行途径，并为在可比环境下操作类似仪器的实验室提供了可重复的方法。
{"title":"Improving long-term Δ47 repeatability of the Thermo Scientific 253 Plus 10 kV IRMS using a prototype Peltier-based cooling system","authors":"László Rinyu , Andrea Czébely , Diána Kiss , Sándor Kele , Sándor Czellár , József Molnár , Marianna Túri","doi":"10.1016/j.ijms.2025.117565","DOIUrl":"10.1016/j.ijms.2025.117565","url":null,"abstract":"<div><div>Clumped isotope thermometry is a robust technique for reconstructing carbonate formation temperatures; however its analytical precision is highly dependent on instrumental stability. In this study, we address the challenge of achieving long-term Δ<sub>47</sub> repeatability using a Thermo Scientific™ 253 Plus 10 kV isotope ratio mass spectrometer (IRMS) coupled to a Kiel IV automated carbonate preparation device. The IRMS is equipped with 10<sup>13</sup> Ω resistors on high-gain Faraday cups. To minimize the impact of daily laboratory temperature fluctuations, we developed and implemented a prototype Peltier-based cooling system for the amplifier housing.</div><div>The combined approach reduced long-term Δ<sub>47</sub> standard deviation from 40 to 45 ppm (occasionally reaching up to 60 ppm under extreme conditions) to around 32 ppm. Validation was performed using international carbonate standards and natural travertine samples with known formation temperatures (10–95 °C), and results were bench-marked against previously published data. These improvements demonstrate a practical pathway towards achieving high-precision clumped isotope measurements under variable environmental conditions, and they provide a reproducible methodology for laboratories operating similar instrumentation in comparable settings.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"520 ","pages":"Article 117565"},"PeriodicalIF":1.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837276","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}
Pub Date : 2026-02-01Epub Date: 2025-12-24DOI: 10.1016/j.ijms.2025.117566
Justin Mak, Amin Famili, Christopher M. Crittenden
Structures for Lossless Ion Manipulation (SLIM) for high resolution ion mobility (HRIM) mass spectrometry has greatly enhanced resolution of isomers and compounds that challenge chromatography. However, in the current commercial setup consisting of a MOBIE SLIM coupled to an Agilent 6545XT, the upper limit of sensitive ion transmission is near m/z 4000.
We therefore aimed to overcome the truncated mass range because detecting large peptides, intact proteins, nucleic acids, and native complexes, as well as their aggregates, at lower charge states (higher m/z) increases spectral clarity of precursor ions, simplifies deconvolution, and can enrich sequencing coverage. Believing this was a solvable issue stemming from currently uncharacterized ion behavior, we investigated gas setup and DC potentials. Using cesium iodide and trastuzumab emtansine, our studies identified the importance of (1) increasing collision cell pressure, (2) reducing ion funnel source pressure, (3) placing the primary accelerating potential immediately before the ion trap (Trap Desolvation Delta), and (4) optimizing voltages in the Ion Beam Compressor. We also found that argon gas marginally increased signal intensities, suggesting that new hardware and electronics would be needed to further extend high-mass transmission. Taken together, our findings revise the current working theory of ion transmission in hybrid SLIM-MS systems—the primary accelerating potential must be applied immediately prior to the ion trap that accumulates ions for mobility separation instead of after the mobility separation—and serve as a more accurate user guide for higher m/z transmission.
{"title":"A framework for high-mass ion transmission in a hybrid SLIM-QTOF system","authors":"Justin Mak, Amin Famili, Christopher M. Crittenden","doi":"10.1016/j.ijms.2025.117566","DOIUrl":"10.1016/j.ijms.2025.117566","url":null,"abstract":"<div><div>Structures for Lossless Ion Manipulation (SLIM) for high resolution ion mobility (HRIM) mass spectrometry has greatly enhanced resolution of isomers and compounds that challenge chromatography. However, in the current commercial setup consisting of a MOBIE SLIM coupled to an Agilent 6545XT, the upper limit of sensitive ion transmission is near <em>m/z</em> 4000.</div><div>We therefore aimed to overcome the truncated mass range because detecting large peptides, intact proteins, nucleic acids, and native complexes, as well as their aggregates, at lower charge states (higher <em>m/z</em>) increases spectral clarity of precursor ions, simplifies deconvolution, and can enrich sequencing coverage. Believing this was a solvable issue stemming from currently uncharacterized ion behavior, we investigated gas setup and DC potentials. Using cesium iodide and trastuzumab emtansine, our studies identified the importance of (1) increasing collision cell pressure, (2) reducing ion funnel source pressure, (3) placing the primary accelerating potential immediately before the ion trap (Trap Desolvation Delta), and (4) optimizing voltages in the Ion Beam Compressor. We also found that argon gas marginally increased signal intensities, suggesting that new hardware and electronics would be needed to further extend high-mass transmission. Taken together, our findings revise the current working theory of ion transmission in hybrid SLIM-MS systems—the primary accelerating potential must be applied immediately prior to the ion trap that accumulates ions for mobility separation instead of after the mobility separation—and serve as a more accurate user guide for higher <em>m/z</em> transmission.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"520 ","pages":"Article 117566"},"PeriodicalIF":1.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837270","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}
Pub Date : 2026-02-01Epub Date: 2025-12-05DOI: 10.1016/j.ijms.2025.117555
Vitor M. Nilson , Nicole H. Lazzari , Suzan C. Zilli , Mariana R. Gama , Cristane S. Schwalm , Salatiel W. da Silva , Livia Streit , Tânia M. Pizzolato
Contaminants of environmental concern are compounds frequently detected in surface and groundwater due to anthropogenic activity. Among these compounds are atrazine (ATZ, a pesticide), carbamazepine (CBZ, an antiepileptic), and sulfamethoxazole (SMX, an antibiotic). These compounds are frequently detected in both raw and treated water samples, with concentrations ranging from ng L−1 to μg L−1. The degradation of these contaminants can lead to incomplete mineralization, potentially forming sub-products known as transformation products. Both parent compounds and by-products may be of toxicological concern. In the present study, samples resulting from the degradation of ATZ, CBZ, and SMX by combined UV-C irradiation and chlorination were analyzed to investigate the formation of transformation products and their associated toxicity. ATZ and SMX underwent nearly complete degradation (>99 %), whereas CBZ showed limited degradation (28 %). A total of 24 transformation products were identified using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) and a suspect screening approach. In silico quantitative structure–activity relationship analysis was performed to assess the potential risks of the compounds. Developmental toxicity, ready biodegradability, carcinogenicity, and mutagenicity were predicted using VEGA software. The results show that, while CBZ itself is not mutagenic, all transformation products except CBZ-255 are predicted as mutagenic with high reliability. CBZ transformation products are carcinogenic and toxicants with moderate to high reliability, and non-readily biodegradable with moderate to low reliability. All ATZ transformation products were found to be carcinogenic with moderate to low reliability, and toxicant with low reliability.
{"title":"Identification of transformation products by high resolution mass spectrometry wide scope screening, and risk assessment for atrazine, carbamazepine, and sulfamethoxazole aqueous solution, resulting from UV-C/chlorination","authors":"Vitor M. Nilson , Nicole H. Lazzari , Suzan C. Zilli , Mariana R. Gama , Cristane S. Schwalm , Salatiel W. da Silva , Livia Streit , Tânia M. Pizzolato","doi":"10.1016/j.ijms.2025.117555","DOIUrl":"10.1016/j.ijms.2025.117555","url":null,"abstract":"<div><div>Contaminants of environmental concern are compounds frequently detected in surface and groundwater due to anthropogenic activity. Among these compounds are atrazine (ATZ, a pesticide), carbamazepine (CBZ, an antiepileptic), and sulfamethoxazole (SMX, an antibiotic). These compounds are frequently detected in both raw and treated water samples, with concentrations ranging from ng L<sup>−1</sup> to μg L<sup>−1</sup>. The degradation of these contaminants can lead to incomplete mineralization, potentially forming sub-products known as transformation products. Both parent compounds and by-products may be of toxicological concern. In the present study, samples resulting from the degradation of ATZ, CBZ, and SMX by combined UV-C irradiation and chlorination were analyzed to investigate the formation of transformation products and their associated toxicity. ATZ and SMX underwent nearly complete degradation (>99 %), whereas CBZ showed limited degradation (28 %). A total of 24 transformation products were identified using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) and a suspect screening approach. <em>In silico</em> quantitative structure–activity relationship analysis was performed to assess the potential risks of the compounds. Developmental toxicity, ready biodegradability, carcinogenicity, and mutagenicity were predicted using VEGA software. The results show that, while CBZ itself is not mutagenic, all transformation products except CBZ-255 are predicted as mutagenic with high reliability. CBZ transformation products are carcinogenic and toxicants with moderate to high reliability, and non-readily biodegradable with moderate to low reliability. All ATZ transformation products were found to be carcinogenic with moderate to low reliability, and toxicant with low reliability.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"520 ","pages":"Article 117555"},"PeriodicalIF":1.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145748584","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}
Pub Date : 2026-02-01Epub Date: 2025-12-03DOI: 10.1016/j.ijms.2025.117553
Annabel S.J. Eardley-Brunt , Liwen Song , Oxford Acute Myocardial Infarction Study , Oxford Abdominal Aortic Aneurysm Study , Claire Vallance
Construction of large mass spectrometric data sets usually involves some combination of normalisation, scaling, and transformation of individual mass spectra in order to correct for technical (and sometimes biological) variation. Many different approaches to data normalisation have been reported, and there is no particular consensus on the best approach. The present study systematically evaluates a set of 24 normalisation, scaling, and transformation methods, and their 420 possible combinations, in the context of atmospheric solids analysis probe (ASAP) mass spectra of human blood plasma. The plasma samples came from two separate cohorts of patients, enrolled respectively in the Oxford Acute Myocardial Infarction (OxAMI) and Oxford Abdominal Aortic Aneurysm (OxAAA) clinical studies. Within each cohort, patients are classified according to a number of different clinical variables. We have investigated the effect of normalisation, scaling, and transformation method on subsequent clustering of the data into the classes of interest, and on machine-learning based classification of the data into the categories of interest. The choice of method was found to have a substantial effect on data clustering, measured via the clustering ratio , but a much smaller effect on machine-learning based classification, quantified via Cohen’s statistic. New intensity-histogram-based normalisation methods were found to have the greatest effect on clustering, while mean, median, vector, and AUC normalisation yielded the best machine-learning classification performance across multiple algorithms. High clustering ratios do not necessarily correlate with improved supervised classification outcomes, underscoring the need to consider subsequent data analysis methodology carefully when optimising data preprocessing pipelines.
{"title":"Optimising the choice of normalisation method for use in machine-learning classification of human blood plasma ambient ionisation mass spectra","authors":"Annabel S.J. Eardley-Brunt , Liwen Song , Oxford Acute Myocardial Infarction Study , Oxford Abdominal Aortic Aneurysm Study , Claire Vallance","doi":"10.1016/j.ijms.2025.117553","DOIUrl":"10.1016/j.ijms.2025.117553","url":null,"abstract":"<div><div>Construction of large mass spectrometric data sets usually involves some combination of normalisation, scaling, and transformation of individual mass spectra in order to correct for technical (and sometimes biological) variation. Many different approaches to data normalisation have been reported, and there is no particular consensus on the best approach. The present study systematically evaluates a set of 24 normalisation, scaling, and transformation methods, and their 420 possible combinations, in the context of atmospheric solids analysis probe (ASAP) mass spectra of human blood plasma. The plasma samples came from two separate cohorts of patients, enrolled respectively in the Oxford Acute Myocardial Infarction (OxAMI) and Oxford Abdominal Aortic Aneurysm (OxAAA) clinical studies. Within each cohort, patients are classified according to a number of different clinical variables. We have investigated the effect of normalisation, scaling, and transformation method on subsequent clustering of the data into the classes of interest, and on machine-learning based classification of the data into the categories of interest. The choice of method was found to have a substantial effect on data clustering, measured via the clustering ratio <span><math><msub><mrow><mi>C</mi></mrow><mrow><mi>R</mi></mrow></msub></math></span>, but a much smaller effect on machine-learning based classification, quantified via Cohen’s <span><math><mi>κ</mi></math></span> statistic. New intensity-histogram-based normalisation methods were found to have the greatest effect on clustering, while mean, median, vector, and AUC normalisation yielded the best machine-learning classification performance across multiple algorithms. High clustering ratios do not necessarily correlate with improved supervised classification outcomes, underscoring the need to consider subsequent data analysis methodology carefully when optimising data preprocessing pipelines.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"520 ","pages":"Article 117553"},"PeriodicalIF":1.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145692375","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}
Pub Date : 2026-02-01Epub Date: 2025-12-26DOI: 10.1016/j.ijms.2025.117568
Julia Laskin, Zheng Ouyang, Isabelle Fournier, Stephen Blanksby
{"title":"The IJMS Young Scientist Feature: a special article collection featuring perspectives and critical insights from early career mass spectrometrists around the globe","authors":"Julia Laskin, Zheng Ouyang, Isabelle Fournier, Stephen Blanksby","doi":"10.1016/j.ijms.2025.117568","DOIUrl":"10.1016/j.ijms.2025.117568","url":null,"abstract":"","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"520 ","pages":"Article 117568"},"PeriodicalIF":1.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880442","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}
Pub Date : 2026-02-01Epub Date: 2025-12-12DOI: 10.1016/j.ijms.2025.117564
Benny Neumark , Aviv Amirav
Explosives present significant challenges for chemical analysis. Traditional methods like High-Pressure Liquid Chromatography (HPLC) with UV/Vis detection often lack sufficient sensitivity and selectivity for complex matrices. HPLC coupled with Mass Spectrometry (MS) is also limited, as many explosives do not ionize efficiently with electrospray or atmospheric pressure chemical ionization. Gas Chromatography (GC) methods using Electron Capture Detection (ECD) or Mass Spectrometry (MS) with standard Electron Ionization (EI) also fall short. GC-MS with standard EI struggles due to thermal degradation at the injector and the hot metallic surface of the ion source and limited sensitivity. While GC-ECD can achieve lower detection limits, it lacks the selectivity of MS and poses safety risks due to its radioactive source.
GC-MS with Cold Electron Ionization (Cold EI) offers a superior solution. Cold EI incorporates a supersonic molecular beam (SMB) interface, allowing contact-free ionization of vibrationally cold molecules. This enhances molecular ions, improves sensitivity, reduces noise, and expands the range of compounds amenable for GC-MS analysis. The result is faster, more selective, and sensitive analysis that is ideal for the full range of organic explosives.
This study demonstrates the effectiveness of GC-MS with Cold EI for trace explosives analysis in soil. Using 17 explosive compounds listed in EPA Method 8095, we performed a complete method validation. The method's limits of detection were below 10 ng/g for all explosives, well below EPA thresholds for GC-ECD. GC-MS with Cold EI thus represents a significant advancement in mass spectrometry for forensic and environmental chemical analysis.
爆炸物对化学分析提出了重大挑战。传统的紫外/可见高压液相色谱（HPLC）检测方法对复杂的基质往往缺乏足够的灵敏度和选择性。高效液相色谱联用质谱（MS）也有局限性，因为许多炸药不能通过电喷雾或大气压化学电离有效地电离。使用电子捕获检测（ECD）的气相色谱（GC）方法或使用标准电子电离（EI）的质谱（MS）方法也存在不足。使用标准EI的GC-MS由于进样器的热降解和离子源的热金属表面以及有限的灵敏度而挣扎。GC-ECD虽然可以达到较低的检出限，但缺乏MS的选择性，并且由于其放射源存在安全风险。气相色谱-质谱与冷电子电离（冷EI）提供了一个优越的解决方案。Cold EI集成了一个超音速分子束（SMB）界面，允许振动冷分子的无接触电离。这增强了分子离子，提高了灵敏度，降低了噪声，并扩大了适用于GC-MS分析的化合物范围。结果是更快，更有选择性，更敏感的分析，是理想的全范围的有机炸药。本研究验证了冷EI气相色谱-质谱法分析土壤中痕量炸药的有效性。使用EPA方法8095中列出的17种爆炸性化合物进行了完整的方法验证。该方法对所有爆炸物的检测限均低于10 ng/g，远低于EPA对GC-ECD的阈值。GC-MS with Cold EI因此代表了质谱法在法医和环境化学分析方面的重大进步。
{"title":"Overcoming the limitations of explosives analysis by GC-MS with cold EI","authors":"Benny Neumark , Aviv Amirav","doi":"10.1016/j.ijms.2025.117564","DOIUrl":"10.1016/j.ijms.2025.117564","url":null,"abstract":"<div><div>Explosives present significant challenges for chemical analysis. Traditional methods like High-Pressure Liquid Chromatography (HPLC) with UV/Vis detection often lack sufficient sensitivity and selectivity for complex matrices. HPLC coupled with Mass Spectrometry (MS) is also limited, as many explosives do not ionize efficiently with electrospray or atmospheric pressure chemical ionization. Gas Chromatography (GC) methods using Electron Capture Detection (ECD) or Mass Spectrometry (MS) with standard Electron Ionization (EI) also fall short. GC-MS with standard EI struggles due to thermal degradation at the injector and the hot metallic surface of the ion source and limited sensitivity. While GC-ECD can achieve lower detection limits, it lacks the selectivity of MS and poses safety risks due to its radioactive source.</div><div>GC-MS with Cold Electron Ionization (Cold EI) offers a superior solution. Cold EI incorporates a supersonic molecular beam (SMB) interface, allowing contact-free ionization of vibrationally cold molecules. This enhances molecular ions, improves sensitivity, reduces noise, and expands the range of compounds amenable for GC-MS analysis. The result is faster, more selective, and sensitive analysis that is ideal for the full range of organic explosives.</div><div>This study demonstrates the effectiveness of GC-MS with Cold EI for trace explosives analysis in soil. Using 17 explosive compounds listed in EPA Method 8095, we performed a complete method validation. The method's limits of detection were below 10 ng/g for all explosives, well below EPA thresholds for GC-ECD. GC-MS with Cold EI thus represents a significant advancement in mass spectrometry for forensic and environmental chemical analysis.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"520 ","pages":"Article 117564"},"PeriodicalIF":1.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797438","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}
Pub Date : 2026-01-01Epub Date: 2025-09-23DOI: 10.1016/j.ijms.2025.117533
Jia-Xuan Yan, Wendy Zhong
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, l-FDLA (Nα-(2,4-dinitro-5-fluorophenyl)-l-leucinamide) and d-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.
{"title":"Development of a laser desorption ionization – ion mobility – mass spectrometry method to accelerate the cyclic peptides stereochemistry determination workflow","authors":"Jia-Xuan Yan, 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 CuCl<sub>2</sub> 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":"2026-01-01","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}
Pub Date : 2026-01-01Epub Date: 2025-10-31DOI: 10.1016/j.ijms.2025.117546
Jaskiran Kaur , Ruth O. Anyaeche , Landon Wence , Yue Fu , Kawthar Z. Alzarieni , Hilkka Kenttämaa
The levels of potentially mutagenic impurities and metabolites, such as aldehydes and ketones, are highly regulated in active pharmaceutical ingredients and must be below a critical safety threshold. Therefore, the ability to detect and identify previously known as well as unknown aldehydes and ketones in drug products is of utmost importance. However, traditional tandem mass spectrometry methods based on collision-activated dissociation (CAD) usually fail in this task as isomeric protonated analytes often fragment in an identical manner, and CAD can cause isomerization of the ions. In this study, selective gas-phase ion-molecule reactions of trimethoxymethylsilane (TMMS) with protonated oxygen-containing analytes were combined with diagnostic CAD to reliably detect all mono- and polyfunctional analytes with aromatic aldehyde and ketone functionalities in a mixture. Various aliphatic and aromatic oxygen-containing analytes, e.g., aldehydes, ketones, carboxylic acids, esters, alcohols, phenols, and amides, were protonated in a linear quadrupole ion trap mass spectrometer, transferred from the ion source into the ion trap, isolated, and allowed to react with TMMS. All protonated analytes produced a stable TMMS adduct and/or an adduct that had lost a methanol molecule. CAD of the latter product ion produced diagnostic fragment ions that correspond to the elimination of a formaldehyde molecule, an ion formally corresponding to the elimination of an oxygen atom from the original protonated analyte, and an ion with mass-to-charge ratio one unit less than the MW of the protonated analyte. These three fragment ions are diagnostic for protonated mono- and polyfunctional analytes with aromatic aldehyde and ketone functionalities, with the exception of pyrrole-2-carboxaldehyde and 2-quinolinecarboxaldehyde. Quantum chemical calculations were employed to delineate the likely mechanisms for the formation of the relevant product ions upon ion-molecule reactions and for the diagnostic fragmentation of specific product ions. This analysis does not require model compounds as the ion-molecule reactions are highly predictable, as opposed to CAD reactions.
{"title":"Identification of aromatic aldehyde and keto functionalities in protonated polyfunctional analytes via gas-phase ion-molecule reactions followed by collision-activated dissociation in a linear quadrupole ion trap mass spectrometer","authors":"Jaskiran Kaur , Ruth O. Anyaeche , Landon Wence , Yue Fu , Kawthar Z. Alzarieni , Hilkka Kenttämaa","doi":"10.1016/j.ijms.2025.117546","DOIUrl":"10.1016/j.ijms.2025.117546","url":null,"abstract":"<div><div>The levels of potentially mutagenic impurities and metabolites, such as aldehydes and ketones, are highly regulated in active pharmaceutical ingredients and must be below a critical safety threshold. Therefore, the ability to detect and identify previously known as well as unknown aldehydes and ketones in drug products is of utmost importance. However, traditional tandem mass spectrometry methods based on collision-activated dissociation (CAD) usually fail in this task as isomeric protonated analytes often fragment in an identical manner, and CAD can cause isomerization of the ions. In this study, selective gas-phase ion-molecule reactions of trimethoxymethylsilane (TMMS) with protonated oxygen-containing analytes were combined with diagnostic CAD to reliably detect all mono- and polyfunctional analytes with aromatic aldehyde and ketone functionalities in a mixture. Various aliphatic and aromatic oxygen-containing analytes, <em>e.g.,</em> aldehydes, ketones, carboxylic acids, esters, alcohols, phenols, and amides, were protonated in a linear quadrupole ion trap mass spectrometer, transferred from the ion source into the ion trap, isolated, and allowed to react with TMMS. All protonated analytes produced a stable TMMS adduct and/or an adduct that had lost a methanol molecule. CAD of the latter product ion produced diagnostic fragment ions that correspond to the elimination of a formaldehyde molecule, an ion formally corresponding to the elimination of an oxygen atom from the original protonated analyte, and an ion with mass-to-charge ratio one unit less than the MW of the protonated analyte. These three fragment ions are diagnostic for protonated mono- and polyfunctional analytes with aromatic aldehyde and ketone functionalities, with the exception of pyrrole-2-carboxaldehyde and 2-quinolinecarboxaldehyde. Quantum chemical calculations were employed to delineate the likely mechanisms for the formation of the relevant product ions upon ion-molecule reactions and for the diagnostic fragmentation of specific product ions. This analysis does not require model compounds as the ion-molecule reactions are highly predictable, as opposed to CAD reactions.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"519 ","pages":"Article 117546"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517064","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}
Pub Date : 2026-01-01Epub Date: 2025-11-17DOI: 10.1016/j.ijms.2025.117552
Kavyasree Chintalapudi, Jonathan N. Chilaka, Abraham K. Badu-Tawiah
A reactive nano-electrospray ionization (nESI) platform is introduced that is capable of electro-catalytic reaction screening when fitted with non-inert Ir electrode. We hypothesized that the application of electrical potential to the Ir electrode in the presence of water (i.e., anodic discharge) will cause the generation of a transient active species MOx (•OH) at the electrode surface, which can dissociate further to provide a more reactive and hydrated oxide form MOx (OH)y. The electro-catalytic activity of the resultant nascent oxide was investigated by analyzing aldehydes in negative-ion mode mass spectrometry (MS) and detecting the corresponding carboxylic acids. Surface effect on oxidizing the C=O bond was confirmed by comparing with MS signal from non-electrical sonic spray and non-contact nESI experiments. Electronic effects were also investigated via the analysis of seven para-substituted benzaldehydes and results subjected to Hammett analysis, which confirmed electron donating groups to undergo anodic oxidation at a faster rate than electron withdrawing groups. These results have significance in analytical measurements and reaction screening via in-situ synthesized oxides.
{"title":"Reactive nano-electrospray ionization for in-situ oxidation of aldehydes for direct mass spectrometry analysis","authors":"Kavyasree Chintalapudi, Jonathan N. Chilaka, Abraham K. Badu-Tawiah","doi":"10.1016/j.ijms.2025.117552","DOIUrl":"10.1016/j.ijms.2025.117552","url":null,"abstract":"<div><div>A reactive nano-electrospray ionization (<strong>nESI</strong>) platform is introduced that is capable of electro-catalytic reaction screening when fitted with non-inert Ir electrode. We hypothesized that the application of electrical potential to the Ir electrode in the presence of water (i.e., anodic discharge) will cause the generation of a transient active species MO<sub>x</sub> (•OH) at the electrode surface, which can dissociate further to provide a more reactive and hydrated oxide form MO<sub>x</sub> (OH)<sub>y</sub>. The electro-catalytic activity of the resultant nascent oxide was investigated by analyzing aldehydes in negative-ion mode mass spectrometry (<strong>MS</strong>) and detecting the corresponding carboxylic acids. Surface effect on oxidizing the C=O bond was confirmed by comparing with MS signal from non-electrical sonic spray and non-contact nESI experiments. Electronic effects were also investigated via the analysis of seven para-substituted benzaldehydes and results subjected to Hammett analysis, which confirmed electron donating groups to undergo anodic oxidation at a faster rate than electron withdrawing groups. These results have significance in analytical measurements and reaction screening via in-situ synthesized oxides.</div></div>","PeriodicalId":338,"journal":{"name":"International Journal of Mass Spectrometry","volume":"519 ","pages":"Article 117552"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614852","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}
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