Journal of Mass Spectrometry最新文献

{"title":"Multi-Omic Evaluation of PLK1 Inhibitor—Onvansertib—In Colorectal Cancer Spheroids","authors":"Brian D. Fries,&nbsp;Emily R. Sekera,&nbsp;Joseph H. Holbrook,&nbsp;Amanda B. Hummon","doi":"10.1002/jms.5137","DOIUrl":"https://doi.org/10.1002/jms.5137","url":null,"abstract":"<p>Polo-like kinase 1 (Plk1) is a serine/threonine kinase involved in regulating the cell cycle. It is activated by aurora kinase B along with the cofactors Borealin, INCE, and survivin. Plk1 is involved in the development of resistances to chemotherapeutics such as doxorubicin, Taxol, and gemcitabine. It has been shown that patients with higher levels of Plk1 have lower survival rates. Onvansertib is a competitive ATP inhibitor for Plk1 in clinical trials for the treatment of tumors and has recently entered a trial for the treatment of <i>KRAS</i> mutant colorectal cancers (CRCs). In this study, we conducted an untargeted liquid chromatography–mass spectrometry (LC–MS) proteomics study as well as an untargeted lipidomics analysis of HCT 116 spheroids treated with onvansertib over a 72-h treatment time-course experiment. Mass spectrometry imaging (MSI) showed that onvansertib begins to accumulate most prominently after 12 h of treatment and continues to accumulate through 72 h. Proteomic results displayed alterations to cell cycle control proteins and an increasing abundance of aurora kinase B and Borealin. The proteomics data also showed alterations to many lipid metabolism enzymes. The MSI lipidomics data indicated alterations to phosphatidylcholine lipids, with many lipids increasing in abundance over time or increasing until 12 h of onvansertib treatment and decreasing after that time point. In summary, these results suggest that onvansertib is causing cells within the spheroid to halt at a certain phase of the cell cycle in accordance with previous literature. Our findings suggest the S phase is likely interrupted, with observed alterations in cell cycle control proteins and PC lipid abundance.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jms.5137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793527","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":"Collision Cross Section Measurements in Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) Based on the Flipping-Filtering Method","authors":"Dayu Li,&nbsp;Zhiwei Wang,&nbsp;Yanying Fan,&nbsp;Wei Xu","doi":"10.1002/jms.5136","DOIUrl":"https://doi.org/10.1002/jms.5136","url":null,"abstract":"<div>\u0000 \u0000 <p>The ion collision cross section (CCS) is closely related to the structural and physical conformation of compounds, making it an ideal parameter for constructing databases. In recent years, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) has gained widespread application in CCS measurements thanks to its ultra-high mass resolution and accuracy. Due to the collisions between ions and neutral molecules within the FT-ICR MS cell, the image current decays. Based on this feature, the ion CCS can be precisely calculated by applying corresponding collision models and algorithms. A new time-frequency analysis method is introduced: the flipping-filtering method based on the Levenberg–Marquardt algorithm. Before filtering, the data undergoes flipping and extension, effectively mitigating the issue of signal point waste commonly associated with traditional filtering techniques. This approach ensures a smooth and uninterrupted envelope of the image current signal while significantly enhancing the accuracy of decay factor and ion CCS measurements. Compared to the linewidth correction method and the line shape fitting method, this method exhibits superior noise resistance and resolution capabilities, serving as a valuable adjunct to ion CCS measurement techniques.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793452","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 Dip-it-DART-Orbitrap-MS With Nitrogen Plasma to HPLC/Orbitrap-MS in Profiling Aromatic Glycoconjugation in White Grapes","authors":"Mariusz Dziadas,&nbsp;Henryk Jeleń","doi":"10.1002/jms.5130","DOIUrl":"https://doi.org/10.1002/jms.5130","url":null,"abstract":"<div>\u0000 \u0000 <p>Direct analysis of aromatic glycosidic precursors in plants has posed an analytical challenge for decades. Traditional techniques, such as SPE-GC/MS, primarily provided information on volatile aglycones released through hydrolysis. However, the application of high-resolution mass spectrometry combined with liquid chromatography has enabled the direct analysis of intact glycosides without the need for derivatization or hydrolysis. Advances in soft ionization methods, such as DART, offer a novel approach to exploring the hidden aromatic potential in grapes without chromatographic separation. In this work, we present a novel and rapid method for screening aromatic glycosidic precursors in white grapes using high-resolution mass spectrometry (Orbitrap) combined with the soft ionization DART method with nitrogen plasma. Optimization of N₂-DART ionization parameters, including grid voltage, gas temperature, and Dip-it sampler speed, performed on selected synthetic glycosidic precursors, allowed the establishment of characteristic ionization patterns and evaluation of 15 groups of glycosidic precursors. The results from the profiling analysis using the N₂-DART-Orbitrap-MS method are comparable to those obtained by HPLC/Orbitrap-MS method. This new analytical approach, N₂-DART-Orbitrap-MS, reduces drastically analysis time by eliminating the need for chromatographic separation when screening glycoside precursors, uses a convenient Dip-it tips for sampling. It also allows for deeper exploration of ionization using nitrogen plasma, applied for the first time in the analysis of glycoside precursors, demonstrating the applicability of this method for the rapid characterization and screening of glycosidically bound aroma compounds in plants.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793426","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":"Automated and Fully Validated High-Throughput LC-MS/MS Assay for Analyzing Multiple Drugs of Abuse in Oral Fluids Using Novel Features in Sample Preparation and Chromatographic Conditions","authors":"Joakim Tan,&nbsp;Alexia Rylski,&nbsp;Anders Bergqvist,&nbsp;Niclas Nikolai Stephanson","doi":"10.1002/jms.5132","DOIUrl":"https://doi.org/10.1002/jms.5132","url":null,"abstract":"<p>Oral fluid sampling offers advantages over other biological matrices, mainly due to its noninvasive procedure avoiding privacy intrusion. The fully automated sample preparation procedure is based on salting-out assisted liquid–liquid extraction (SALLE) combined with high-efficiency LC-MS/MS methods for both screening and confirmation of 37 drugs and incorporates novel features enabling direct injection of acetonitrile extracts into an innovative chromatographic system. The methods' drug panel includes opioids, benzodiazepines, benzodiazepine-like drugs, cannabinoids, and stimulants. A full method validation was performed using OF/buffer from Greiner Bio-ONE International and Quantisal saliva collection devices. The validation included assessments of linearity, sensitivity, precision, accuracy, extraction recovery, matrix effects, process efficiency, stability, and carryover. All compounds demonstrated linearity across the concentration range 1–25 ng/mL, with <i>R</i>² ≥ 0.99. Both methods' limit of detection ranged between 0.001 and 0.03 ng/mL, and the limit of quantification ranged between 0.02 and 0.09 ng/mL. Precision was ≤ 14.8% for screening and ≤ 8.5% for the confirmation method. Accuracy was ± 13.6% for screening and ± 8.7% (except at 0.5 and 1 ng/mL, where it was ± 25.3% and ± 17.6%, respectively) for the confirmation method. Extraction recoveries ranged from 40.0% to 95.1%, except for hydromorphone (27.4%) and morphine (34.4%). Although matrix effects were observed for a large number of compounds to varying degrees, they were largely compensated for by the use of deuterium- and ¹³C-labeled internal standards (IS). IS-corrected overall process efficiency ranged from 100.7% to 119.1% with precision (CV%) ≤ 10.8% for all compounds. Spiked calibrators and QC samples in OF were stable in autosampler for up to 72 h and in the freezer for 3 days. Methanol working solutions were stable for 6 months. No significant carryover was observed. The methods have been successfully implemented in the routine analysis of approximately &gt; 1000 samples per month since March 2024.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jms.5132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793526","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":"Prediction of Fragmentation Pathway of Natural Products, Antibiotics, and Pesticides by ChemFrag","authors":"Jördis-Ann Schüler,&nbsp;Annemarie E. Kramell,&nbsp;Antonia Schmidt,&nbsp;Pauline D. Walesch,&nbsp;René Csuk","doi":"10.1002/jms.5129","DOIUrl":"https://doi.org/10.1002/jms.5129","url":null,"abstract":"<p><span>Because the manual interpretation of ESI-MS</span>^{<span>n</span>} <span>fragmentation spectra is time-consuming and usually requires expert knowledge, automated annotation is often sought. The fragmentation software</span> <span>ChemFrag</span> <span>enables the annotation of MS</span>^{<span>n</span>} <span>spectra by combining a rule-based fragmentation and a semiempirical quantum chemical approach. In this study, the rule set was extended by 31 cleavage rules and 12 rearrangement rules and used for the interpretation of ESI(+)-MS</span>^{<span>n</span>} <span>spectra of antibiotics, pesticides, and natural products as well as their structural analogs. The fragmentation pathways predicted by</span> <span>ChemFrag</span> <span>for compounds such as 17<i>β</i>-estradiol were confirmed by a comparison with pathways published in other studies. In addition, the annotations were compared with those of the programs</span> <span>MetFrag</span> <span>and</span> <span>CFM-ID</span><span>, for example, with regard to the number and intensity of annotated fragment ions. Our experiments show that</span> <span>ChemFrag</span> <span>provides reliable and in some cases chemically more realistic annotations for the fragment ions of the investigated compounds. Thus,</span> <span>ChemFrag</span> <span>is a helpful addition to the established in silico methods for the interpretation of ESI(+)-MS</span>^{<span>n</span>} <span>spectra.</span></p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jms.5129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793645","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":"Overcoming Analytical Challenges in Proximity Labeling Proteomics","authors":"Haorong Li,&nbsp;Wan Nur Atiqah Binti Mazli,&nbsp;Ling Hao","doi":"10.1002/jms.5134","DOIUrl":"https://doi.org/10.1002/jms.5134","url":null,"abstract":"<p>Proximity labeling (PL) proteomics has emerged as a powerful tool to capture both stable and transient protein interactions and subcellular networks. Despite the wide biological applications, PL still faces technical challenges in robustness, reproducibility, specificity, and sensitivity. Here, we discuss major analytical challenges in PL proteomics and highlight how the field is advancing to address these challenges by refining study design, tackling interferences, overcoming variation, developing novel tools, and establishing more robust platforms. We also provide our perspectives on best practices and the need for more robust, scalable, and quantitative PL technologies.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jms.5134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793648","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":"Identification of Mitapivat's In Vivo Metabolites in the Rat Model by Quadrupole-Time-of-Flight (Q-TOF) Mass Spectrometry","authors":"Saurabh Pandurang Bodake,&nbsp;Anjali Mukesh,&nbsp;Akshay Bandgar,&nbsp;Kannan Shajkumar,&nbsp;Shrutika Wankhade,&nbsp;Anandhu Kunnath Shaji,&nbsp;Swapnil Jayant Dengale","doi":"10.1002/jms.5126","DOIUrl":"https://doi.org/10.1002/jms.5126","url":null,"abstract":"<div>\u0000 \u0000 <p>Mitapivat is a novel, first-in-class, allosteric activator of pyruvate kinase enzyme. It has been approved by the US FDA in February 2022 for disease modifying treatment of haemolytic anaemia in adults. In the current study, the in vivo metabolites of mitapivat in the rat model were identified using quadrupole-time-of-flight mass spectrometry. A total 20 metabolites were identified, out of which nine metabolites were found to be novel and reported first time in the literature. The study also further refined the chemical structures of some of the reported metabolites. Oxidation, N-dealkylation, oxidation followed by dehydrogenation, and hydrolysis were the major Phase I metabolic pathways of mitapivat. The chief Phase II metabolism pathway was glucuronide conjugation of oxidised and amide hydrolysed metabolites of mitapivat.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793646","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 High-Throughput Quantitative Imaging Mass Spectrometry for Analysis of Drug Distribution in Tissues","authors":"Yukari Tanaka","doi":"10.1002/jms.5135","DOIUrl":"https://doi.org/10.1002/jms.5135","url":null,"abstract":"<div>\u0000 \u0000 <p>Matrix-assisted laser desorption/ionization–imaging mass spectrometry (MALDI–IMS) is applied in drug discovery and development. A high-throughput quantitative MALDI–IMS methodology was developed to confirm whether epertinib is superior to lapatinib in penetrating brain metastases using intraventricular injection mouse models (IVMs) of human EGFR2 (HER2)-positive breast or T790M–EGFR-positive lung cancer cells. A simple calibration curve was prepared for each compound via spotting standard solutions without using blank tissue sections or blank tissues onto the same glass slide as the epertinib or lapatinib brain section samples. Quantitative MALDI–IMS was performed via coating a glass slide with a MALDI matrix solution containing each internal standard solution. The samples of calibration curve and brain section were analyzed using a linear ion trap mass spectrometer with a MALDI ion source. Epertinib and lapatinib responses were strongly linear, with a wide dynamic range and low variation (relative standard deviation [RSD] &lt; 20%) among the individual concentrations. Epertinib and lapatinib were sufficiently extracted from brain sections after oral administration in a breast cancer IVM. The quantitative MALDI–IMS results revealed that the epertinib concentrations administered to the brain sections in the lung cancer IVM were similar to those measured using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Quantitative MALDI–IMS, owing to its high reproducibility and throughput, is useful for selecting drug candidates in the early stages of discovery and development, enabling efficient and rapid screening of candidate compounds as well as an understanding of the mechanisms of drug efficacy, toxicity, and pharmacokinetics/pharmacodynamics.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793647","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":"Analysis of Amine Drugs Dissolved in Methanol by High-Resolution Accurate Mass Gas Chromatography Mass Spectrometry, GC-Orbitrap","authors":"Chee-Leong Kee,&nbsp;Xiaowei Ge,&nbsp;Min-Yong Low,&nbsp;Laura A. Ciolino","doi":"10.1002/jms.5127","DOIUrl":"https://doi.org/10.1002/jms.5127","url":null,"abstract":"<div>\u0000 \u0000 <p>The fragmentation pathways for amines dissolved in methanol (CH₃OH) or deuterated methanol (CD₃OD) have been investigated by high-resolution accurate mass gas chromatography mass spectrometry (HRAM-GCMS) or GC-Orbitrap. Primary and secondary amines used in this study were 1,3-dimethylamylamine (1,3-DMAA) and ephedrine hydrochloride (Eph), respectively. For isotopic labeling experiment, <i>1S</i>, 2<i>R</i> (+) ephedrine-D₃ hydrochloride (D₃-Eph) was used. Under splitless injection mode at an inlet temperature of 250°C, formaldehyde and its deuterated form were generated from CH₃OH and CD₃OD, respectively. This was evidenced by the oxonium ions generated from each solvent. When 1,3-DMAA was dissolved in CH₃OH or CD₃OD, distinct separation between the unreacted amine and condensation product fragments was observed, specifically methylene-imine (M + 12) and deuteromethylene-imine (M + 14) artifacts. More complex condensation patterns for Eph and D₃-Eph were observed, attributed to the labile hydrogen/deuterium exchange and gradual deuteration from CH₃OH to CD₃OD. The fragmentation pathways were supported by the presence of oxazolidine intermediates before forming smaller condensation product fragments. Despite their close retention time and mass, the HRAM data distinguished the isobaric unreacted amine and condensation product fragments produced by Eph and D₃-Eph in the coeluting region.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762032","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":"Determination of the Metabolic Mechanism of the Principal Components From Moringa oleifera (Lam) Seed by MALDI-IMS","authors":"Tao Wang,&nbsp;Jinglin Wang,&nbsp;Saifei Yang,&nbsp;Jinchao Wei,&nbsp;Yuanyuan Sun,&nbsp;Rui Chen","doi":"10.1002/jms.5125","DOIUrl":"https://doi.org/10.1002/jms.5125","url":null,"abstract":"<div>\u0000 \u0000 <p>In this study, the components of <i>Moringa oleifera</i> (Lam) seed were extracted using an ultrasonic-assisted extraction technique with 70% methanol solution as the solvent. The antioxidant properties of the extract were evaluated through its scavenging abilities against DPPH^. and ABTS. The antiproliferative effects of this extract on breast cancer MDA-MB-231, colon cancer SW480, leukemia HL-60, liver cancer SMMC-7721, and lung cancer A549 were assessed using the MTS assay. The distribution of MA, D-trehalose, and rbGlu in the heart, kidney, liver, and spleen of mice in various intervals was visually investigated using MALDI-IMS. In particular, the metabolic pathways of rbGlu were further elucidated. The result shows that rbGlu is metabolized to rbot-Glu in mice within 1 h. This approach further substantiates the use of MALDI-MSI technique in situ for studying the pharmacological mechanisms of bioactive component in natural products.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762031","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}