Journal of Mass Spectrometry最新文献

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Spatially Resolved Metabolomics Reveals Metabolic Heterogeneity Among Pulmonary Fibrosis 空间分解代谢组学揭示肺纤维化的代谢异质性
IF 1.9 3区 化学
Journal of Mass Spectrometry Pub Date : 2025-04-22 DOI: 10.1002/jms.5138
Shengxi Li, Cong Li, Wei Sun, Yinghao Cao, Xianmei Qi, Jiawei Zhang, Yanjiang Xing, Jinyu Zhou, Lin Wang
{"title":"Spatially Resolved Metabolomics Reveals Metabolic Heterogeneity Among Pulmonary Fibrosis","authors":"Shengxi Li,&nbsp;Cong Li,&nbsp;Wei Sun,&nbsp;Yinghao Cao,&nbsp;Xianmei Qi,&nbsp;Jiawei Zhang,&nbsp;Yanjiang Xing,&nbsp;Jinyu Zhou,&nbsp;Lin Wang","doi":"10.1002/jms.5138","DOIUrl":"https://doi.org/10.1002/jms.5138","url":null,"abstract":"<div>\u0000 \u0000 <p>Pulmonary fibrosis (PF) is a chronic and progressive lung disease with fatal consequences. The study of PF is challenging due to the complex mechanism involved, the need to understand the heterogeneity and spatial organization within lung tissues. In this study, we investigate the metabolic heterogeneity between two forms of lung fibrosis: idiopathic pulmonary fibrosis (IPF) and silicosis, using advanced spatially-resolved metabolomics techniques. Employing high-resolution mass spectrometry imaging, we spatially mapped and identified over 260 metabolites in lung tissue sections from mouse models of IPF and silicosis. Histological analysis confirmed fibrosis in both models, with distinct pathological features: alveolar destruction and collagen deposition in IPF, and nodule formation in silicosis. Metabolomic analysis revealed significant differences between IPF and silicosis in key metabolic pathways, including phospholipid metabolism, purine/pyrimidine metabolism, and the TCA cycle. Notably, phosphocholine was elevated in silicosis but reduced in IPF, while carnitine levels decreased in both conditions. Additionally, glycolytic activity was increased in both models, but TCA cycle intermediates showed opposing trends. These findings highlight the spatial metabolic heterogeneity of PF and suggest potential metabolic targets for therapeutic intervention. Further investigation into the regulatory mechanisms behind these metabolic shifts may open new avenues for fibrosis treatment.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861540","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}
引用次数: 0
Sulfuric/Sulfurous Acids Induce Self-Protection of Phospholipids Against Air–Water Interfacial Ozonolysis 硫酸/硫酸诱导磷脂对空气-水界面臭氧分解的自我保护
IF 1.9 3区 化学
Journal of Mass Spectrometry Pub Date : 2025-04-21 DOI: 10.1002/jms.5139
Hong Zhang, Yuqing Niu, Jiaqi Xing, Jing He, Yuexin Zhang, Lina Qiao, Panpan Bai, Xiangnan Zhang, Jie Jiang
{"title":"Sulfuric/Sulfurous Acids Induce Self-Protection of Phospholipids Against Air–Water Interfacial Ozonolysis","authors":"Hong Zhang,&nbsp;Yuqing Niu,&nbsp;Jiaqi Xing,&nbsp;Jing He,&nbsp;Yuexin Zhang,&nbsp;Lina Qiao,&nbsp;Panpan Bai,&nbsp;Xiangnan Zhang,&nbsp;Jie Jiang","doi":"10.1002/jms.5139","DOIUrl":"https://doi.org/10.1002/jms.5139","url":null,"abstract":"<div>\u0000 \u0000 <p>Sulfides are ubiquity in atmosphere and can convert to be H<sub>2</sub>SO<sub>3</sub>/H<sub>2</sub>SO<sub>4</sub>, which could affect the inflammatory responses induced by ozone. However, the mixing effect and mechanism of H<sub>2</sub>SO<sub>3</sub>/H<sub>2</sub>SO<sub>4</sub> and ozone at molecular-level on the lung surface is still indefinable. Herein, using 1-palmitoyl-2-oleoyl-<i>sn</i>-glycero-3-phosphatidylglycerol (POPG) monolayer as a model, effects of H<sub>2</sub>SO<sub>4</sub>/H<sub>2</sub>SO<sub>3</sub> on interfacial ozonolysis of phospholipids were explored. Both H<sub>2</sub>SO<sub>4</sub> and H<sub>2</sub>SO<sub>3</sub> could decrease ozonolysis efficiencies of POPG and showed a remarkable concentration dependence. The main components of H<sub>2</sub>SO<sub>4</sub> and H<sub>2</sub>SO<sub>3</sub> in investigated system and their effects on POPG ozonolysis were separately explored, and the mechanism was proposed. The observed decrease of ozonolysis efficiencies resulted from POPG hydrolysis induced by H<sup>+</sup> and reactive activity of HSO<sub>3</sub><sup>−</sup> and SO<sub>3</sub><sup>2−</sup> towards ozone. The hydrolysis of POPG could provide oleic acids, which further lowered the ozonolysis efficiency. In addition, the efficiency of POPG ozonolysis in H<sub>2</sub>SO<sub>3</sub> case was lower than that in H<sub>2</sub>SO<sub>4</sub> case, and the self-sacrificing oxidation of HSO<sub>3</sub><sup>−</sup> and SO<sub>3</sub><sup>2−</sup> by ozone was responsible for this process. Considering extra phospholipids in epithelial lining fluid of lung, the short-term or low concentration exposure of H<sub>2</sub>SO<sub>4</sub>/H<sub>2</sub>SO<sub>3</sub> was thought to trigger the self-protection of lung. However, the long-term or high concentration exposure would lead to irreversible damage.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856800","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}
引用次数: 0
Multi-Omic Evaluation of PLK1 Inhibitor—Onvansertib—In Colorectal Cancer Spheroids PLK1抑制剂onvansertib在结直肠癌球状体中的多组学评价
IF 1.9 3区 化学
Journal of Mass Spectrometry Pub Date : 2025-04-08 DOI: 10.1002/jms.5137
Brian D. Fries, Emily R. Sekera, Joseph H. Holbrook, Amanda B. Hummon
{"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}
引用次数: 0
Collision Cross Section Measurements in Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) Based on the Flipping-Filtering Method 基于翻转过滤法的傅立叶变换离子回旋共振质谱(FT-ICR MS)碰撞截面测量法
IF 1.9 3区 化学
Journal of Mass Spectrometry Pub Date : 2025-04-08 DOI: 10.1002/jms.5136
Dayu Li, Zhiwei Wang, Yanying Fan, Wei Xu
{"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}
引用次数: 0
Comparison of Dip-it-DART-Orbitrap-MS With Nitrogen Plasma to HPLC/Orbitrap-MS in Profiling Aromatic Glycoconjugation in White Grapes 氮等离子体浸泡- dart -Orbitrap-MS与HPLC/Orbitrap-MS分析白葡萄芳香糖缀合的比较
IF 1.9 3区 化学
Journal of Mass Spectrometry Pub Date : 2025-04-08 DOI: 10.1002/jms.5130
Mariusz Dziadas, Henryk Jeleń
{"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 N<sub>2</sub>-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 N<sub>2</sub>-DART-Orbitrap-MS method are comparable to those obtained by HPLC/Orbitrap-MS method. This new analytical approach, N<sub>2</sub>-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}
引用次数: 0
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 全自动和完全验证的高通量LC-MS/MS分析方法用于分析口服液中的多种滥用药物,采用新颖的样品制备和色谱条件
IF 1.9 3区 化学
Journal of Mass Spectrometry Pub Date : 2025-04-08 DOI: 10.1002/jms.5132
Joakim Tan, Alexia Rylski, Anders Bergqvist, Niclas Nikolai Stephanson
{"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><sup>2</sup> ≥ 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 <sup>13</sup>C-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}
引用次数: 0
Prediction of Fragmentation Pathway of Natural Products, Antibiotics, and Pesticides by ChemFrag 利用ChemFrag预测天然产物、抗生素和农药的碎片化途径
IF 1.9 3区 化学
Journal of Mass Spectrometry Pub Date : 2025-04-07 DOI: 10.1002/jms.5129
Jördis-Ann Schüler, Annemarie E. Kramell, Antonia Schmidt, Pauline D. Walesch, René Csuk
{"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><sup><span>n</span></sup> <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><sup><span>n</span></sup> <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><sup><span>n</span></sup> <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><sup><span>n</span></sup> <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}
引用次数: 0
Overcoming Analytical Challenges in Proximity Labeling Proteomics 克服接近标记蛋白质组学的分析挑战
IF 1.9 3区 化学
Journal of Mass Spectrometry Pub Date : 2025-04-07 DOI: 10.1002/jms.5134
Haorong Li, Wan Nur Atiqah Binti Mazli, Ling Hao
{"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}
引用次数: 0
Identification of Mitapivat's In Vivo Metabolites in the Rat Model by Quadrupole-Time-of-Flight (Q-TOF) Mass Spectrometry 四极杆飞行时间(Q-TOF)质谱法鉴定米他伐特在大鼠体内的代谢物
IF 1.9 3区 化学
Journal of Mass Spectrometry Pub Date : 2025-04-07 DOI: 10.1002/jms.5126
Saurabh Pandurang Bodake, Anjali Mukesh, Akshay Bandgar, Kannan Shajkumar, Shrutika Wankhade, Anandhu Kunnath Shaji, Swapnil Jayant Dengale
{"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}
引用次数: 0
Development of High-Throughput Quantitative Imaging Mass Spectrometry for Analysis of Drug Distribution in Tissues 高通量定量成像质谱分析组织中药物分布的研究进展
IF 1.9 3区 化学
Journal of Mass Spectrometry Pub Date : 2025-04-07 DOI: 10.1002/jms.5135
Yukari Tanaka
{"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}
引用次数: 0
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