Journal of Mass Spectrometry最新文献

{"title":"GC/MS Investigation of the Reaction Products of Nitrogen Mustards and N,N-Dialkylaminoethyl-2-Chlorides With Phenol","authors":"K. G. Harsha,&nbsp;M. Nikita Singh,&nbsp;A. Veeresham,&nbsp;V. V. S. Lakshmi,&nbsp;V. Jayathirtha Rao,&nbsp;K. Srinivas,&nbsp;T. Jagadeshwar Reddy,&nbsp;S. Prabhakar","doi":"10.1002/jms.5153","DOIUrl":"https://doi.org/10.1002/jms.5153","url":null,"abstract":"<div>\u0000 \u0000 <p>The Chemical Weapons Convention (CWC)–scheduled chemicals that contain chlorine atom (e.g., mustards, aminoethyl-2-chlorides, and phosphorylchlorides) are highly reactive in environmental matrices, especially when they are in contact with phenols, for example, in the decontamination process. In such a case, these scheduled chemicals are converted to corresponding phenyl ethers/esters, which are referred to as the reaction products. The detection and identification of any reaction products of CWC chemicals are crucial markers for verification processes, and they provide a clue to the alleged use or presence of the parent CWC scheduled chemicals. In this study, a series of reaction products of nitrogen mustards (HN1, HN2, and HN3) with phenol (<b>1</b>–<b>3</b>) and N,N-dialkylaminoethyl-2-chlorides with phenol (<b>4</b>–<b>13</b>) were synthesized using respective aminoethyl-2-bromides as intermediates and subsequently analyzed the products, phenyl ethers (<b>1</b>–<b>13</b>) by GC-EIMS and GC-CIMS. The GC/EI spectra of <b>1</b>–<b>13</b> exhibited M⁺· ions and distinctive structure indicative fragment ions. The selective fragmentation of the alkyl groups attached to nitrogen facilitated the discrimination of possible isomeric compounds. The primary fragmentation of <b>1</b>–<b>13</b> was C-C bond cleavage (α-carbon with respect to the nitrogen) gave rise to [M-C₇H₇O]⁺ ion as the base peak. GC/CI (methane) spectra included abundant [M + H]⁺ ion, reagent-specific adduct ions, and a few structure-indicative fragment ions. The GC retention index (GC/RI) values of <b>1</b>–<b>13</b> were calculated using a hydrocarbon mixture, and these values were higher than those of the corresponding reported GC/RI values of nitrogen mustards/N,N-dialkylaminoethyl-2-chlorides. The GC/MS and GC/RI data provide critical insights for the unambiguous identification of the targeted reaction products, which are essential for effective verification under the CWC and help in the participation of official proficiency tests conducted by the Organization for the Prohibition of Chemical Weapons.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 8","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558229","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 Method for Determining PFAS in Bovine Meat and Tuna Fish by UHPLC-HRMS Orbitrap","authors":"Andrea Roviaro,&nbsp;Aurora Scarduzio,&nbsp;Sara Savini,&nbsp;Anna Sannino","doi":"10.1002/jms.5151","DOIUrl":"https://doi.org/10.1002/jms.5151","url":null,"abstract":"<div>\u0000 \u0000 <p>Per- and polyfluoroalkyl substance (PFAS) can be present in foodstuff, including preserved foods like canned meats, due to their ubiquity and difficult degradation.</p>\u0000 <p>In this work, an analytical method for the quantification of 20 PFAS in canned bovine meat and tuna fish in olive oil was developed, optimized and validated. The analytical approach was based on a QuEChERS extraction, purification with dSPE followed by Solid Phase Extraction (SPE) protocol with subsequent quantification of the extracted analytes by isotope dilution using ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry with an Orbitrap analyzer (UHPLC-HRMS). The validation procedure allowed to ascertaining good analytical performances in terms of sensitivity, accuracy and robustness. The values obtained for recovery percentages (range: 80%–120%) were in accordance with the guidelines used for the determination of PFAS in food, LOQs achieved were low enough to ensure compliance with Commission Regulation (EU) 2022/2388 amending Regulation (EC) 1881/2006 as regards maximum levels of perfluoroalkyl substances in certain foodstuffs which was repealed very recently by the Commission Regulation (EU) 2023/915. With the developed method 10 samples from the local markets (n. five canned beef and n. five tuna in olive oil) were analyzed.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503127","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":"Characterization of the Trimethylsilyl Derivatives of 6-Amino-3-methyl-1,4-diphenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile and Its Analogs by Electron Ionization Gas Chromatography/Mass Spectrometry","authors":"Quan-Long Pu,&nbsp;Yufang Zheng,&nbsp;Edward P. Erisman,&nbsp;Edward White V,&nbsp;Jeremiah W. Woodcock,&nbsp;William E. Wallace","doi":"10.1002/jms.5150","DOIUrl":"https://doi.org/10.1002/jms.5150","url":null,"abstract":"<div>\u0000 \u0000 <p>Pyranopyrazoles, especially pyrano[2,3-c]pyrazoles, have broad applications as pharmaceutical ingredients and biodegradable agrochemicals, with new compounds and synthesis methods continually emerging. Gas chromatography/mass spectrometry (GC/MS) has difficulty obtaining useful mass spectra under typical measurement conditions due to thermal degradation of the analyte. However, the analysis of the trimethylsilyl (TMS) derivatives of 6-amino-3-methyl-1,4-diphenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile and 19 closely related analogs provided characteristic ions by which the mass spectral fragmentation pathways could be determined. Nuclear magnetic resonance (NMR) tests showed that the pyran ring cleaved during the TMS derivatization of the compounds with the TMS group connected to oxygen. The fragmentation mechanism involved an alpha cleavage reaction, with the loss of a C₃HN₂ radical to form a stable characteristic cation [M-65]⁺. The mass spectra of positional isomers (o-, m-, and p-) of substituent X (X = Cl, Br, F, CH₃, or OCH₃) on the 4-phenyl group were compared, revealing that the <i>ortho</i> compound has a unique fragment ion peak m/z 261. Lastly, two isomeric di-TMS derivatives were observed: one with both TMS groups connected to nitrogen of the 6-amino substituent (N,N-di-TMS) and the second on the oxygen where the pyran ring was cleaved (N,O-di-TMS). Their mass spectra have apparent differences involving different cleavage pathways.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503126","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":"Investigation on Chiral Amino Acids Enantiomeric Excess With Cyclodextrin Inclusion Complex Ions Assisted Differential Ion Mobility Separation Mass Spectrometry","authors":"Simin Zhang,&nbsp;Xiangfeng Chen,&nbsp;T.-Y. Lui,&nbsp;Danna Hu,&nbsp;T.-W. Dominic Chan","doi":"10.1002/jms.5155","DOIUrl":"https://doi.org/10.1002/jms.5155","url":null,"abstract":"<div>\u0000 \u0000 <p>Development of a rapid, inexpensive, and specific method for chiral amino acids (AAs) identification and separation is challenging owing to their similar properties. In this work, a chiral AAs separation method was developed by analyzing the AAs-cyclodextrin (CD) host–guest complex in the CaptiveSpray-DMS-MS system. Compared with β- and γ-CDs, <i>α</i>-CD was revealed to provide the best differentiation performance. The optimized conditions enabled the analysis of six pairs of respective AA-<i>α</i>-CD complexes within several minutes. Ionograms obtained using this strategy effectively determined the enantiomeric ratio of chiral AAs, as illustrated by the strong linearity (<i>R</i>² = 0.996) between peak abundance ratios and molar ratios of L-serine and D-serine. This method does not require the use of metal ions, and the single peak shape in ionograms of chiral AA-α-CD complex ions simplifies data interpretation.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482366","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":"Quantitative Mass Spectrometry Imaging by Targeted-DESI-MSI in MRM Mode Provides Higher Sensitivity and Specificity for Fast Quantification of Chloroquine Drug in Mice Kidney","authors":"Md. Muedur Rahman,&nbsp;Mst. Sayela Afroz,&nbsp;Md. Al Mamun,&nbsp;Ariful Islam,&nbsp;Takumi Sakamoto,&nbsp;Shuhei Aramaki,&nbsp;Tomohito Sato,&nbsp;Thanai Paxton,&nbsp;Yutaka Takahashi,&nbsp;Tomoaki Kahyo,&nbsp;Mitsutoshi Setou","doi":"10.1002/jms.5148","DOIUrl":"https://doi.org/10.1002/jms.5148","url":null,"abstract":"<div>\u0000 \u0000 <p>Quantitative mass spectrometry imaging (QMSI) is being applied for spatial quantification of drugs and metabolites using mass spectrometry imaging (MSI) tools. DESI-MSI is ideally suited to QMSI as a soft and ambient ionization technique. However, some challenging issues of QMSI include extraction efficiency, matrix effect, sensitivity, and specificity, which need to be addressed. Here, we applied targeted DESI-MSI in multiple reaction monitoring (MRM) mode for QMSI of chloroquine, an antimalarial drug, as a model in mice kidneys and carefully addressed those challenging issues. A triple quadrupole mass spectrometer coupled with a DESI source was used to quantify the chloroquine (transition <i>m/z</i> 320.2 → 247.1) drug. A deuterated internal standard chloroquine-d₅ (transition <i>m/z</i> 325.2 → 147.1), was used to normalize the data from pixel to pixel. A mimetic in-tissue model was employed to constract a calibration curve demonstrating good linearity (y = 0.0041x, <i>R</i>^<i>2</i> = 0.9953) and precision (RSD &lt; 15%). The calibration curve was validated by back-calculation, with results falling within acceptable ranges (accuracy error&lt; ±15%). Finally, the dosed (30 mg/kg) chloroquine was quantified in three spatial regions (cortex, medulla, and pelvis) in the mice kidneys. The highest concentrations of chloroquine in the pelvis (399.85 and 436.28 ng/mg of kidney tissue at 30 and 60 min intervals) region is consistent with the previous report that a portion of the drug is eliminated from the kidney as unchanged forms. This study provides valuable insights into using DESI-MSI in MRM mode for the QMSI of drugs in biological tissues and will have implications for future research on pharmacology and toxicology.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299687","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":"Extend m/z Range of External Ion Injection Into Ion Trap/TOFMS: SIMION Analysis","authors":"Yixue Cao,&nbsp;Ping Chen,&nbsp;Xuesong Zhang,&nbsp;Yuanyuan Xie,&nbsp;Lichuan Zhang,&nbsp;Chenxin Wu,&nbsp;Lei Hua,&nbsp;Haiyang Li","doi":"10.1002/jms.5152","DOIUrl":"https://doi.org/10.1002/jms.5152","url":null,"abstract":"<div>\u0000 \u0000 <p>Ion trap usually serves as a TOF pusher region in ion trap time-of-flight mass spectrometer (IT/TOF), achieving benefits of high duty cycle, MS/MS capability, and high mass resolution. While a short ion trap rod length improves TOF resolution, it limits the mass range in coaxial IT/TOF. Through a computational study based on SIMION simulations, this work systematically investigates the influence of geometric parameters (trap rod length) and voltage parameters (bias DC voltage, end-cap electrode voltage) on the mass range of coaxial IT-TOF systems. By optimizing length of trap rod, over 90% injection efficiency was achieved within a <i>m/z</i> 400–1400 without sacrificing mass resolution. By implementing DC bias voltage adjustments for low-m/z ions and step voltage optimization on end-cap electrodes for high-<i>m/z</i> ions, the simulated mass range is extended to <i>m/z</i> 200–1400 with minimal mass discrimination. All above these findings are derived solely from simulation analysis.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 7","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299688","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":"“Touch&Play” Wood Typification by the MasSpec Pen","authors":"Adriano Reis,&nbsp;Caroline Pais Carvalho,&nbsp;Iasmim Lopes de Lima,&nbsp;Felipe R. P. Mansoldo,&nbsp;Alane Beatriz Vermelho,&nbsp;Rosineide Costa Simas,&nbsp;Livia S. Eberlin,&nbsp;Marcos N. Eberlin","doi":"10.1002/jms.5133","DOIUrl":"https://doi.org/10.1002/jms.5133","url":null,"abstract":"<p>We have investigated the ability of a MasSpec Pen (MSPen) “three-in-one” (extraction, transfer, and ionization) device coupled to a mass spectrometer to provide instantaneous chemical profiles that could promptly characterize wood samples from the mahogany (<i>Meliaceae)</i> family. For that, we selected a set of five representative wood species, that is, Brazilian mahogany (<i>Swietenia macrophylla</i>, also known as Honduran mahogany), two African mahoganies (<i>Khaya ivorensis and Khaya senegalensis</i>), and two “nongenuine” (“fake”) mahogany woods: cedar (<i>Cedrela odorata</i>) and andiroba (<i>Carapa guianensis</i>). By simply touching the superficially polished wood surface and after 3 s of automatic extraction, profiles of highly characteristic markers that effectively discriminated all five mahoganies were detected. The superficial surface of a wood Brazilian mahogany sample as compared with internal wood accessed via deep sanding showed minor profile changes mainly by shifts in the relative abundances of the wood markers, indicating that aging only marginally changes MSPen wood signatures. The direct “touch&amp;play” analysis offered by MSPen was therefore found to provide nondestructive, fast, sample-preparation-free, and reliable typification of woods. This “spatially free” device also allows broad screening because multiple points on the whole surface of any small or large-size intricate wood sample can be rapidly analyzed, demonstrating its high potential for forensic investigations, particularly for endangered species such as the Brazilian mahogany.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 6","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jms.5133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Qualitative and Comparative Analysis of Chemical Constituents in Epimedii Folium From Four Species Based on UPLC-ZenoTOF-MS/MS","authors":"Jia Xue,&nbsp;Zhichen Cai,&nbsp;Dongyang Yi,&nbsp;Haijie Chen,&nbsp;Yongyi Zhou,&nbsp;Jingjing Shi,&nbsp;Cuihua Chen,&nbsp;Lisi Zou,&nbsp;Wei Yang,&nbsp;Xunhong Liu,&nbsp;Jianming Cheng","doi":"10.1002/jms.5146","DOIUrl":"https://doi.org/10.1002/jms.5146","url":null,"abstract":"<div>\u0000 \u0000 <p>Epimedii Folium (EF) is frequently used in clinical as traditional Chinese medicine with a long history in China. The Pharmacopoeia of the People's Republic of China (2020 Version) contains four species of the plants of the genus Epimedium as its medicinal sources, namely, <i>Epimedium brevicornu</i> Maxim (EBM), <i>E. sagittatum</i> (Sieb. et Zucc) Maxim (ESM), <i>E. pubescens</i> Maxim (EPM), and <i>E. koreanum</i> Nakai (EKN). However, the available studies on a comprehensive analysis of the chemical constituents in the above four species are much scarce. The objective of this study is to establish a method which uses ultra-high performance liquid chromatography coupled with time-of-flight tandem mass spectrometry (UPLC-ZenoTOF-MS/MS) to identify and characterize the chemical constituents in samples from different species. At the same time, multivariate statistical analysis is applied to screen the differential chemical constituents among different species. A total of <b>116</b> constituents were identified from different species of EF; and the possible cleavage pathways of various types of constituents were preliminarily inferred based on the fragmentation behavior of the main constituents. Besides, 23 differential characteristic constituents were screened based on variable importance in projection (VIP) value and <i>p</i>-value, of which nine constituents were common differential constituents. The intrinsic quality of EF was thoroughly assessed in this work using metabolomic analysis based on UPLC-ZenoTOF-MS/MS, which provides basic information for the identification of different varieties of EF, and serves as an experimental foundation for the sensible use of EF from various variations in therapeutic practice.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 6","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140727","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 Simultaneous Analytical Method of Three Polypeptide Toxins α-Amanitin, β-Amanitin and Phalloidin in Poisonous Mushrooms and Human Serum Using UHPLC–MS/MS","authors":"Hang-Ji Ok,&nbsp;Eun-Young Park,&nbsp;Yongho Shin,&nbsp;Jeong-Han Kim,&nbsp;Min-Ho Song,&nbsp;Ji-Ho Lee","doi":"10.1002/jms.5145","DOIUrl":"https://doi.org/10.1002/jms.5145","url":null,"abstract":"<p>Accidental ingestion of toxic mushrooms remains a global public health concern because of the presence of highly potent peptide toxins such as α-amanitin, β-amanitin, and phalloidin. These compounds exhibit strong hepatotoxicity and can lead to acute liver failure and death. However, their rapid detection in biological and food matrices remains analytically challenging. Existing methods often require extensive sample preparation and are not suitable for urgent diagnostic applications. This study presents the development and validation of a rapid and sensitive analytical method for the simultaneous quantitation of α-amanitin, β-amanitin, and phalloidin in poisonous mushrooms and human serum. Among several preparation strategies evaluated, a method following direct extraction with 1% formic acid in methanol was selected for its speed, simplicity, and effectiveness in minimizing matrix interference. The method demonstrated excellent linearity (<i>r</i>² ≥ 0.99), low quantitation limits (10–50 ng/mL), and satisfactory recovery (72%–117%) and precision (RSD ≤ 19%) in both food and biological matrices. When applied to field-collected <i>Amanita virosa</i>, α-amanitin and β-amanitin were detected at 39 and 145 mg/kg, respectively, whereas no toxins were found in <i>Amanita volvata</i>. These findings demonstrate that the established method enables rapid and reliable detection of lethal peptide toxins with minimal sample preparation. The protocol is suitable for forensic investigations, clinical toxicology, and food safety monitoring. Its applicability in emergency settings underscores its potential as a practical tool for improving public health responses to mushroom poisoning incidents.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 6","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jms.5145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surface and Subsurface Mass Spectrometric Analysis of Dexamethasone in Solid Pharmaceutical Dosage Forms","authors":"Matjaž Finšgar","doi":"10.1002/jms.5147","DOIUrl":"https://doi.org/10.1002/jms.5147","url":null,"abstract":"<p>This study presents an in-depth mass spectrometric investigation of dexamethasone (DEX) distribution within pharmaceutical tablets using time-of-flight secondary ion mass spectrometry (ToF-SIMS) combined with gas cluster ion beam (GCIB) sputtering. Fragmentation mechanism of DEX was identified, which enabled the determination of three-dimensional chemical imaging of the active ingredient in both surface and subsurface regions. The data reveal that a 4-mg DEX formulation exhibits a continuous and extended distribution of the drug into the tablet matrix, while a 0.5-mg formulation shows DEX localized in distinct, isolated domains. Topographical features and the overall composition of the surface were confirmed by complementary analyses employing atomic force microscopy (AFM) and x-ray photoelectron spectroscopy (XPS). These results demonstrate how molecule distribution patterns can be linked to formulation heterogeneity using advanced mass spectrometric techniques, opening new possibilities for pharmaceutical manufacturing quality control and optimization.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 6","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jms.5147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}