Journal of Mass Spectrometry最新文献

{"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}

{"title":"Development and Validation of a Rapid Liquid Chromatography–Tandem Mass Spectrometry Method for the Quantitation of Vitamin K Metabolites in Different Matrices","authors":"Danchen Wang,&nbsp;Yichen Ma,&nbsp;Honglei Li,&nbsp;Xiaoli Ma,&nbsp;Yutong Zou,&nbsp;Songlin Yu,&nbsp;Ling Qiu","doi":"10.1002/jms.5120","DOIUrl":"https://doi.org/10.1002/jms.5120","url":null,"abstract":"<div>\u0000 \u0000 <p>Adequate vitamin K is crucial for optimal health. Although vitamin K detection methods have been established using liquid chromatography–tandem mass spectrometry (LC–MS/MS), some limitations remain. Therefore, we aimed to establish a stable and rapid LC–MS/MS method that can quantify phylloquinone (VK1), menaquinones-4 (MK-4), and menaquinones-7 (MK-7) in serum and cerebrospinal fluid and explore its clinical applications. We developed an LC–MS/MS method with atmospheric pressure chemical ionization to quantify and validate its performance according to Clinical Laboratory and Standard Institution standards (C62-Ed2). Serums from 50 healthy individuals and cerebrospinal fluid from 15 patients were collected for clinical application. Sample preparation involved lipase incubation, protein precipitation with ethanol, and liquid–liquid extraction with hexane/ethyl; optimization was performed for sample preparation and LC separation. Linearity was 50–10 000 pg/mL for VK1, MK-4, and MK-7. The total coefficient of variation (%) for VK1, MK-4, and MK-7 ranged from 8.5% to 10.4%, 8.0% to 10.4%, and 7.0% to 11.1%, respectively. Recovery of VK1, MK-4, and MK-7 was 82.3%–110.6%, 92.3%–110.6%, and 89.5%–117.8%, respectively. VK1 and MK-7 were detected in the serum of all 50 healthy subjects, whereas MK-4 was detected in only 13 (26%) subjects. Approximately 53.3% (8/15) had no detectable vitamin K in their cerebrospinal fluid. The developed method exhibited satisfactory performance and was applicable for detecting VK1, MK-4, and MK-7 in serum and cerebrospinal fluid.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741481","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":"Precursor Resolution via Ion Z-State Manipulation: A Tandem Mass Spectrometry Approach for the Analysis of Mixtures of Multiply-Charged Ions","authors":"Nicolas J. Pizzala,&nbsp;Hsi-Chun Chao,&nbsp;Boukar K. S. Faye,&nbsp;Scott A. McLuckey","doi":"10.1002/jms.5124","DOIUrl":"https://doi.org/10.1002/jms.5124","url":null,"abstract":"<p>Electrospray ionization (ESI) is often the ionization method of choice, particularly for high-mass polar molecules and complexes. However, when analyzing mixtures of analytes, charge state ambiguities and overlap in mass-to-charge (<i>m/z</i>) can arise from species with different masses and charges. While solution-phase conditions can sometimes be optimized to produce relatively low charge states—thereby reducing charge-state ambiguity and <i>m/z</i> overlap—gas-phase methods offer greater control over charge state reduction. For complex mixtures, however, charge state reduction alone often fails to resolve individual components in the mixture. Incorporating a mass-selection step prior to charge state manipulation can simplify the mixture and significantly improve the separation of the components. This general tandem mass spectrometry approach is referred to here as <b>p</b>recursor <b>r</b>esolution via <b>i</b>on <b>z</b>-state <b>m</b>anipulation (<b>PRIZM</b>). Examples of variations of PRIZM experiments date back roughly 25 years and have involved ion/molecule proton transfer reactions, ion/ion proton transfer reactions, ion/ion electron transfer reactions, electron capture reactions, and multiply-charged ion attachment reactions. This tutorial review describes the PRIZM approach and provides illustrative examples using each of the charge state manipulation approaches mentioned above.</p>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jms.5124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741595","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":"Fast Nonlinear Damping Identification Method to Determine Size, Mass, and Charge of Lycopodium clavatum Spores in a Paul Trap","authors":"Shcherbinin D.P.,&nbsp;Rybin V.V.,&nbsp;Semynin M.S.,&nbsp;Slepneva E.E.,&nbsp;Ivanov A.V.,&nbsp;Rudyi S.S.","doi":"10.1002/jms.5123","DOIUrl":"https://doi.org/10.1002/jms.5123","url":null,"abstract":"<div>\u0000 \u0000 <p>In the present work, we have first applied the fast nonlinear damping identification (NDI) method to nondestructively and simultaneously determine the values of mass, size, and charge of biological micro-objects trapped in a quadrupole Paul trap. Here, we used well-studied <i>Lycopodium clavatum</i> individual spores as a test object. For the nondestructive determination of spore parameters, we analyzed their extended orbit trajectory implemented in the nonlinear regime of viscous friction while trapping in a quadrupole Paul trap. The article discusses the prospects of the method proposed for investigating a wide class of biological objects.</p>\u0000 </div>","PeriodicalId":16178,"journal":{"name":"Journal of Mass Spectrometry","volume":"60 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717416","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}