Journal of Mass Spectrometry最新文献

{"title":"Characterization of PEGylation sites in Neulasta and a biosimilar candidate with a combined fragmentation strategy in mass spectrometry analysis","authors":"Navin Rauniyar,&nbsp;Alyssa J. Togle,&nbsp;Rachel A. Ronci,&nbsp;Diego Reyes,&nbsp;Xuemei Han","doi":"10.1002/jms.5017","DOIUrl":"10.1002/jms.5017","url":null,"abstract":"<p>In the development of biosimilar products to Neulasta, it is essential to determine the intact molecular mass and confirm precise PEGylation sites. In this study, we applied a combination of techniques, including post-column addition of triethylamine in reversed-phase liquid chromatography–mass spectrometry (RPLC-MS) to determine the intact molecular mass, and in-source fragmentation (ISF) and higher-energy collision dissociation–tandem mass spectrometry (HCD-MS/MS) to identify the PEGylation site. Our results show that both the pegfilgrastim biosimilar candidate and Neulasta lots are mono-PEGylated at the N-terminal end. Furthermore, we show that the combined ISF and HCD-MS/MS method can be used for identifying the PEGylation sites in the diPEGylated variant of pegfilgrastim. The diPEGylated variant has modification sites at the N-terminal end and a lysine at position 35 in the protein sequence.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184632","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":"Crowd control of ions in the Astral analyzer","authors":"Hamish Stewart,&nbsp;Dmitry Grinfeld,&nbsp;Johannes Petzoldt,&nbsp;Bernd Hagedorn,&nbsp;Michael Skoblin,&nbsp;Alexander Makarov,&nbsp;Christian Hock","doi":"10.1002/jms.5006","DOIUrl":"10.1002/jms.5006","url":null,"abstract":"<p>Space charge effects are the Achilles' heel of all high-resolution ion optical devices. In time-of-flight mass analyzers, these may manifest as reduction of resolving power, mass measurement shift, peak coalescence, and/or transmission losses, while highly sensitive modern ion sources and injection devices ensure that such limits are easily exceeded. Space charge effects have been investigated, by experiment and simulation study, for the astral multi-reflection analyzer, incorporating ion focusing via a pair of converging ion mirrors, and fed by a pulsed extraction ion trap. Major factors were identified as the resonant effect between ~10³ ions of similar m/z in-flight and the expansion of trapped packets of ~10^4–5 ions prior to extraction. Optimum operation and compensated ion mirror calibration strategies were then generated and described based on these findings.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158335","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":"Simplified processing and rapid quantification of buprenorphine, norbuprenorphine, and their conjugated metabolites in human plasma using UPLC–MS/MS: Assessment of buprenorphine exposure during opioid use disorder treatment","authors":"Wenchen Zhao,&nbsp;Osama Y. Alshogran,&nbsp;Hongfei Zhang,&nbsp;Anand Joshi,&nbsp;Elizabeth E. Krans,&nbsp;Steve Caritis,&nbsp;Imam H. Shaik,&nbsp;Raman Venkataramanan","doi":"10.1002/jms.5015","DOIUrl":"10.1002/jms.5015","url":null,"abstract":"<p>Opioid use disorder (OUD) is a chronic neurobehavioral ailment and is prevalent in pregnancy. OUD is commonly treated with methadone or buprenorphine (BUP). Pregnancy is known to alter the pharmacokinetics of drugs and may lead to changes in drug exposure and response. A simple, specific, and sensitive analytical method for measuring the parent drug and its metabolites is valuable for assessing the impact of pregnancy on drug exposure. A new liquid chromatography–tandem mass spectrometric method that utilized a simple protein precipitation procedure for sample preparation and four deuterated internal standards for quantification was developed and validated for BUP and its major metabolites (norbuprenorphine [NBUP], buprenorphine-glucuronide [BUP-G], and norbuprenorphine-glucuronide [NBUP-G]) in human plasma. The standard curve was linear over the concentration range of 0.05–100 ng/mL for BUP and NBUP, and 0.1–200 ng/mL for BUP-G and NBUP-G. Intra- and inter-day bias and precision were within ±15% of nominal values for all the analytes. Quality controls assessed at four levels showed high recovery consistently for all the analytes with minimal matrix effect. Adequate analyte stability was observed at various laboratory conditions tested. Overall, the developed method is simple, sensitive, accurate and reproducible, and was successfully applied for the quantification of BUP and its metabolites in plasma samples collected from pregnant women in a clinical study assessing BUP exposure during OUD treatment.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158336","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 (qMSI): A tutorial","authors":"Russell R. Kibbe,&nbsp;David C. Muddiman","doi":"10.1002/jms.5009","DOIUrl":"10.1002/jms.5009","url":null,"abstract":"<p>Mass spectrometry imaging (MSI) is an analytical technique that enables the simultaneous detection of hundreds to thousands of chemical species while retaining their spatial information; usually, MSI is applied to biological tissues. Combining these elements can create ion images, which allows for the identification and localization of multiple chemical species within the sample. Being able to produce molecular images of biological tissues has already impacted the study of health and disease; however, the next logical step is being able to combine MSI with quantitative mass spectrometry methods to both quantify and determine the localization of disease progression or drug action. In this tutorial, we will detail the main factors to consider when designing a qMSI experiment and highlight the methods that have been developed to overcome these added complexities, specifically for those newer to the field of MSI.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jms.5009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131739","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":"Estimation of thermodynamic and physicochemical properties of the alkali astatides: On the bond strength of molecular astatine (At2) and the hydration enthalpy of astatide (At−)","authors":"Peter C. Burgers,&nbsp;Lona Zeneyedpour,&nbsp;Theo M. Luider,&nbsp;John L. Holmes","doi":"10.1002/jms.5010","DOIUrl":"10.1002/jms.5010","url":null,"abstract":"<p>The recent accurate and precise determination of the electron affinity (<i>EA</i>) of the astatine atom At⁰ warrants a re-investigation of the estimated thermodynamic properties of At⁰ and astatine containing molecules as this <i>EA</i> was found to be much lower (by 0.4 eV) than previous estimated values. In this contribution we estimate, from available data sources, the following thermodynamic and physicochemical properties of the alkali astatides (MAt, M = Li, Na, K, Rb, Cs): their solid and gaseous heats of formation, lattice and gas-phase binding enthalpies, sublimation energies and melting temperatures. Gas-phase charge-transfer dissociation energies for the alkali astatides (the energy requirement for M⁺At⁻ ➔ M⁰ + At⁰) have been obtained and are compared with those for the other alkali halides. Use of Born-Haber cycles together with the new <i>AE</i> (At⁰) value allows the re-evaluation of Δ<i>H</i>_<i>f</i> (At⁰)_g (=56 ± 5 kJ/mol); it is concluded that (At₂)_g is a weakly bonded species (bond strength &lt;50 kJ/mol), significantly weaker bonded than previously estimated (116 kJ/mol) and much weaker bonded than I₂ (148 kJ/mol), but in agreement with the finding from theory that spin-orbit coupling considerably reduces the bond strength in At₂. The hydration enthalpy (Δ<i>H</i>_<i>aq</i>) of At⁻ is estimated to be −230 ± 2 kJ/mol (using Δ<i>H</i>_<i>aq</i>[H⁺] = −1150.1 kJ/mol), in good agreement with molecular dynamics calculations. Arguments are presented that the largest alkali halide, CsAt, like the smallest, LiF, will be only sparingly soluble in water, following the generalization from hard/soft acid/base principles that “small likes small” and “large likes large.”</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jms.5010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131738","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":"A general, most basic rule for ion dissociation: Protonated molecules","authors":"Adriano Reis,&nbsp;Rodinei Augusti,&nbsp;Marcos N. Eberlin","doi":"10.1002/jms.5003","DOIUrl":"10.1002/jms.5003","url":null,"abstract":"<p>Contrary to the common but potentially misleading belief that when a protonated molecule is excited, it is its most stable protomer that will mandatorily dissociate, we demonstrate herein that, when rationalizing or predicting the chemistry of such ions, we should always search for the most labile protomer. This “most labile protomer” rule, based on the mobile proton model, states therefore that when a protonated molecule is heated, during ionization or by collisions for instance, the loosely bonded proton (H⁺) can acquire enough energy to detach itself from the most basic site of the molecule and then freely “walk through” the molecular framework to eventually find, if available, another protonation site, forming other less stable but more labile protomers, that is, protomers that may display lower dissociation thresholds. To demonstrate the validity of the “most labile protomer” rule as well as the misleading nature of the “most stable protomer” rule, we have selected several illustrative molecules and have collected their ESI(+)-MS/MS. To compare energies of precursors and products, we have also performed PM7 calculations and elaborated potential energy surface diagrams for their possible protomers and dissociation thresholds. We have also applied the “most labile protomer” rule to reinterpret—<i>exclusively</i> via <i>classical charge-induced dissociation cleavages</i>—several dissociation processes proposed for protonated molecules. In an accompanying letter, we have also applied a similar “most labile electromer” rule to ionized molecules.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039505","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":"Spatial neurolipidomics—MALDI mass spectrometry imaging of lipids in brain pathologies","authors":"Durga Jha,&nbsp;Kaj Blennow,&nbsp;Henrik Zetterberg,&nbsp;Jeffrey N. Savas,&nbsp;Jörg Hanrieder","doi":"10.1002/jms.5008","DOIUrl":"10.1002/jms.5008","url":null,"abstract":"<p>Given the complexity of nervous tissues, understanding neurochemical pathophysiology puts high demands on bioanalytical techniques with respect to specificity and sensitivity. Mass spectrometry imaging (MSI) has evolved to become an important, biochemical imaging technology for spatial biology in biological and translational research. The technique facilitates comprehensive, sensitive elucidation of the spatial distribution patterns of drugs, lipids, peptides, and small proteins in situ. Matrix-assisted laser desorption ionization (MALDI)-based MSI is the dominating modality due to its broad applicability and fair compromise of selectivity, sensitivity price, throughput, and ease of use. This is particularly relevant for the analysis of spatial lipid patterns, where no other comparable spatial profiling tools are available. Understanding spatial lipid biology in nervous tissue is therefore a key and emerging application area of MSI research. The aim of this review is to give a concise guide through the MSI workflow for lipid imaging in central nervous system (CNS) tissues and essential parameters to consider while developing and optimizing MSI assays. Further, this review provides a broad overview of key developments and applications of MALDI MSI-based spatial neurolipidomics to map lipid dynamics in neuronal structures, ultimately contributing to a better understanding of neurodegenerative disease pathology.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jms.5008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039508","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":"Integrating density functional theory and chemical ionization mass spectrometry techniques to assess benzophenone derivatives in food packaging: implications for enhancing food quality and safety","authors":"Manjeet Bhatia","doi":"10.1002/jms.5011","DOIUrl":"10.1002/jms.5011","url":null,"abstract":"<p>Benzophenone and related derivatives are widely used as photoinitiators for food packaging to cure inks or lacquers with ultraviolet (UV) light on cardboard and paper. However, there are concerns about the potential health risks of their migration into food. Knowing the physical and chemical properties of benzophenone and its derivatives could play a significant role in their quantification and analysis using chemical ionization mass spectrometry (CI-MS) methods. These parameters are evaluated using B3LYP/6-311++** density functional theory (DFT) implemented on Gaussian code. Ion–molecule chemistry through the selection of reagent ions, reaction energetics and kinetics, thermodynamic stability, and reactivity of molecules deemed to foster VOC identification and quantification via CI-MS techniques. The VOCs under study are expected to undergo exothermic reactions from H₃O⁺, NH₄⁺, NO⁺, and O₂⁺ ions, except endothermic proton transfer from NH₄⁺ to 2-hydroxy-4-methoxybenzophenone and 2,3,4-trihydroxy benzophenone. These compounds possess less proton affinities than NH₃ and are least stable in their protonated forms. The DFT computed properties provide the basis for developing reliable and accurate methods to detect and measure the presence of benzophenone and its derivatives in packaging materials and food products.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039507","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":"Discerning the stability behaviour of mavacamten availing liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy: In silico toxicity and mutagenicity prediction of degradation products","authors":"Vijaya Madhyanapu Golla,&nbsp;Mallika Kalyan,&nbsp;Upasana Gholap,&nbsp;Hara Prasad Padhy,&nbsp;Roshitha K. Ramachandran,&nbsp;Gananadhamu Samanthula","doi":"10.1002/jms.5007","DOIUrl":"10.1002/jms.5007","url":null,"abstract":"<p>The present study aimed to separate, identify, and characterise the degradation products formed when mavacamten is exposed to stress degradation as well as the stability of the drug in various environments and also to understand its degradation chemistry. Prediction of <i>in silico</i> toxicity and mutagenicity was aimed at the observed degradation products. Stress degradation along with stability studies and degradation kinetics were performed on mavacamten, and separation of degradation products was carried out by high-performance liquid chromatography. Tandem mass spectrometry studies were executed to characterise the structures of degradation products using product ion fragments. Orthogonally, nuclear magnetic resonance experiments were conducted to elucidate the structures having ambiguity in characterising them. Deductive Estimation of Risk from Existing Knowledge and Structure Activity Relationship Analysis using Hypotheses software were used to establish <i>in silico</i> toxicity and mutagenic profiles of mavacamten and its degradation products. Two degradation products of mavacamten found in acidic hydrolytic stress conditions were separated, identified, characterised, and proposed as 1-isopropylpyrimidine-2,4,6(1H,3H,5H)-trione and 1-phenylethanamine. Mavacamten was found to be stable under different pH and gastrointestinal conditions. The degradation kinetics of mavacamten under 1 N acidic condition followed zero-order kinetics, and it was degraded completely within 6 h. <i>In silico</i> toxicity and mutagenicity studies revealed that 1-phenylethanamine can be a skin sensitiser. A high-performance liquid chromatography method was developed for the separation of degradation products of mavacamten and characterised by liquid chromatography–tandem mass spectrometry and nuclear magnetic resonance. During the manufacturing and storage of drug product, precautions need to be taken when dealing with acidic solutions as the drug is prone to hydrolysis in acidic conditions. The formation of 1-phenylethanamine under these conditions is to be monitored as it is a skin sensitiser.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of radium-226 separation methods based on chromatographic and extraction resins for its determination by ICP-MS in drinking waters","authors":"Marine Roulier,&nbsp;Pascale Anabelle Baya,&nbsp;Steeve Roberge,&nbsp;Dominic Larivière","doi":"10.1002/jms.5005","DOIUrl":"10.1002/jms.5005","url":null,"abstract":"<p>Over the past century, human activities have contributed to the release of ²²⁶Ra (t_½ = 1,600 y) in the environment, increasing the potential risks for human exposure and thus prompting scientists to monitor it. Inductively coupled plasma mass spectrometry (ICP-MS) is an alternative to alpha-spectrometry for the quantification of ²²⁶Ra. However, the performances of radioanalytical procedures are rarely compared in a rigorous framework, which means that researchers may choose one on subjective factors or guesses.</p><p>This article compares five published methods for the separation and preconcentration of ²²⁶Ra in drinking waters based on chromatographic and extraction resins prior to its analysis by ICP-MS. We evaluated the turnaround time, generated wastes, and final cost of each protocol as the economic aspect can be an important criterion when selecting a method, particularly for sustainable environmental monitoring. Our results showed that ²²⁶Ra was successfully separated and preconcentrated, yielding recoveries ranging between 84% and 105%. Method detection and quantification limits of respectively 2–7 fg L⁻¹ (0.1–0.3 mBq L⁻¹) and 6–24 fg L⁻¹ (0.2–0.9 mBq L⁻¹) were achieved when the separation method was coupled with ICP-MS. The turnaround times ranged between 6 and 21 hours, whereas the cost of the methods varied between 40 and 132 USD.</p><p>This study highlights for the first time that methodologies recently published on the evaluation of ²²⁶Ra levels in drinking water by ICP-MS have comparable figures of merit. Our results offer essential insights into the selection of the most suitable separation method.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jms.5005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139681161","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}