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Ion Activation Methods for Top‐Down Proteomics ABSTRACT Mass spectrometry (MS) has emerged as a premier method used to characterize the sequences of proteins. Top-down proteomics aims to capture the multiple sources of structural diversity reflected in proteins, such as those that arise from alternative RNA splicing events or the addition of post-translational modifications. Tandem MS (i.e., MS/MS) represents a critical component of a top-down proteomics experiment, as the resulting fragmentation patterns unveil various structural features associated with protein function. This review spotlights recent developments and applications of ion activation methods used to decipher the structural properties of intact proteins, including collisional activation and those based on the use of electrons and photons. The analysis of fragment ions generated by these MS/MS methods are also discussed, along with an outlook on future developments in the field related to instrumentation and burgeoning approaches to top-down proteomics, such as single-cell methods.

(MS Reviews) Ion Activation Methods for Top‐Down Proteomics: ABSTRACT




Mass spectrometry (MS) has emerged as a premier method used to characterize the sequences of proteins. Top-down proteomics aims to capture the multiple sources of structural diversity reflected… #MassSpectromRev #MassSpecRSS

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The Development of the Digital Ion Trap ABSTRACT The digital ion trap (DIT) is an ion trap in which the periodic trapping field is driven by digital signals—typically with a rectangular waveform—generated by fast-switching circuits. This paper reviews the research history of rectangular wave-driven quadrupole fields, as well as the invention and development of DITs. It summarizes studies on ion motion stability and secular frequency in both 3D and 2D configurations of DITs and discusses differences in the stability diagrams of DITs arising from different definitions of the a and q parameters. Additionally, this review outlines the performance advantages of the digital driving method in mass analysis and lists the novel analytical functions that have been realized using DIT technology. Finally, it presents the latest developments in commercial DIT instruments.

(MS Reviews) The Development of the Digital Ion Trap: ABSTRACT




The digital ion trap (DIT) is an ion trap in which the periodic trapping field is driven by digital signals—typically with a rectangular waveform—generated by fast-switching circuits. This paper reviews… #MassSpectromRev #MassSpecRSS

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The TriVersa NanoMate: Automation of Nano Electrospray Analyses The evolution of nano-electrospray ionization technology began in the mid-1980s. At that time, no commercial vendors supplied the requisite electrospray emitters, which featured internal diameters of...

The TriVersa NanoMate: Automation of Nano Electrospray Analyses #MassSpectromRev analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/...

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The TriVersa NanoMate: Automation of Nano Electrospray Analyses ABSTRACT The evolution of nano-electrospray ionization technology began in the mid-1980s. At that time, no commercial vendors supplied the requisite electrospray emitters, which featured internal diameters of just a few microns. Tips were manually fabricated by pulling heated glass capillaries to create micron and sub-micron inside diameter tips. High voltage was applied to a sample solution within the capillary body, and when placed close to a counter electrode of the atmospheric pressure ionization (API) mass spectrometer formed a sufficiently high electric field to produce an electrospray plume. Nano electrospray offered key advantages, including enhanced sensitivity and minimized matrix effects for chemical analysis due to better ionization efficiency and reduced contamination due to the lower mass transfer into the mass spectrometer orifice. By the late 1990s, Advion scientists utilized the Cornell Nanofabrication Facility equipment to create an array of nano-electrospray emitters etched in a silicon wafer. Key to the success of this planar emitter array was the inclusion of a dielectric layer that enabled the formation of an electric field estimated to be equivalent to that of a pulled glass capillary emitter with dimensions near one micron, but with a 28 micron outside diameter emitter. This “ESI Chip” was commercialized along with a robot named NanoMate to enable automated, reproducible, and robust nano electrospray of 96 consecutive samples from the chip-based array of micro-fabricated emitters. This paper explores the development and commercialization story of the NanoMate and its use to expand scientific knowledge in the field of protein non-covalent interactions, protein structure, lipidomics, drug metabolism, and a host of other applications.

(MS Reviews) The TriVersa NanoMate: Automation of Nano Electrospray Analyses: ABSTRACT




The evolution of nano-electrospray ionization technology began in the mid-1980s. At that time, no commercial vendors supplied the requisite electrospray emitters, which featured… #MassSpectromRev #MassSpecRSS

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Proteomics of Nitrotyrosine: Integrating Mass Spectrometry and Immunodetection in Redox‐Driven Pathology Nitrooxidative stress, driven by excess reactive nitrogen species like peroxynitrite, contributes to the pathogenesis of many chronic diseases. Among its molecular footprints, 3-nitrotyrosine (3NT) h...

Proteomics of Nitrotyrosine: Integrating Mass Spectrometry and Immunodetection in Redox‐Driven Pathology #MassSpectromRev analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/...

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ISSUE INFORMATION ‐ ToC Mass Spectrometry Reviews, Volume 45, Issue 2, Page 149-151, March/April 2026.

(MS Reviews) ISSUE INFORMATION ‐ ToC: Mass Spectrometry Reviews, Volume 45, Issue 2, Page 149-151, March/April 2026. #MassSpectromRev #MassSpecRSS

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Proteomics of Nitrotyrosine: Integrating Mass Spectrometry and Immunodetection in Redox‐Driven Pathology ABSTRACT Nitrooxidative stress, driven by excess reactive nitrogen species like peroxynitrite, contributes to the pathogenesis of many chronic diseases. Among its molecular footprints, 3-nitrotyrosine (3NT) has emerged as a biologically relevant marker of protein nitration. Its accumulation reflects oxidative damage and altered protein function, positioning it as a promising biomarker. Proteomics has advanced our understanding of nitrooxidative stress and its clinical implications. The integration of high-resolution MS with immunoaffinity and structural modeling enables precise mapping of nitration sites and functional interpretation. However, limitations such as low stoichiometry, ion suppression, and antibody cross-reactivity still constrain the field. Emerging computational predictors and miniaturized platforms offer promising avenues for expanding the clinical utility of 3NT. Future efforts should focus on standardizing workflows, validating site-specific modifications, and translating proteomic insights into diagnostic and therapeutic strategies. This review outlines the biochemical mechanisms of 3NT formation, emphasizing peroxynitrite-dependent and heme peroxidase-mediated pathways. Proteomic strategies for detecting and quantifying nitrated proteins are discussed, including mass spectrometry workflows, enrichment techniques, and immunodetection. Challenges in site-specific identification, antibody specificity, and ionization-induced fragmentation are addressed. Disease-specific patterns of 3NT accumulation in neurodegenerative, cardiovascular, and oncologic contexts are highlighted, along with in silico prediction of nitration sites. Despite significant methodological advances, key limitations such as low nitration stoichiometry, antibody cross-reactivity, and ionization-dependent artifacts continue to challenge confident site-specific analysis of 3-nitrotyrosine. Future progress will depend on improved enrichment strategies, standardized mass spectrometry workflows, and the integration of computational prediction tools with experimental validation. Addressing these gaps will be essential for translating nitrotyrosine profiling into robust mechanistic and clinical applications.

(MS Reviews) Proteomics of Nitrotyrosine: Integrating Mass Spectrometry and Immunodetection in Redox‐Driven Pathology: ABSTRACT




Nitrooxidative stress, driven by excess reactive nitrogen species like peroxynitrite, contributes to the pathogenesis of many chronic… #MassSpectromRev #MassSpecRSS

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The Finnish Mass Spectrometry Regional Issue Mass Spectrometry Reviews, Volume 45, Issue 1, Page 3-3, January/February 2026.

(MS Reviews) The Finnish Mass Spectrometry Regional Issue: Mass Spectrometry Reviews, Volume 45, Issue 1, Page 3-3, January/February 2026. #MassSpectromRev #MassSpecRSS

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ISSUE INFORMATION ‐ ToC Mass Spectrometry Reviews, Volume 45, Issue 1, Page 1-2, January/February 2026.

(MS Reviews) ISSUE INFORMATION ‐ ToC: Mass Spectrometry Reviews, Volume 45, Issue 1, Page 1-2, January/February 2026. #MassSpectromRev #MassSpecRSS

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Human Capital Is the Most Valuable Mass Spectrometry Reviews, EarlyView.

(MS Reviews) Human Capital Is the Most Valuable: Mass Spectrometry Reviews, EarlyView. #MassSpectromRev #MassSpecRSS

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Data‐Independent Acquisition Mass Spectrometry in Tumor Classification and Cancer Biomarker Research Cancer treatment is far from optimal also because current classification systems do not reflect the complex molecular status of the tumor and its phenotype in sufficient detail. To construct molecula...

Data‐Independent Acquisition Mass Spectrometry in Tumor Classification and Cancer Biomarker Research #MassSpectromRev analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/...

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Human Capital Is the Most Valuable Click on the article title to read more.

Human Capital Is the Most Valuable - Zenobi #MassSpectromRev analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/...

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Data‐Independent Acquisition Mass Spectrometry in Tumor Classification and Cancer Biomarker Research Abstract Cancer treatment is far from optimal also because current classification systems do not reflect the complex molecular status of the tumor and its phenotype in sufficient detail. To construct molecular tumor classifiers, omics tools provide complex molecular data reflecting many aspects from genotype to phenotype. However, the true molecular effectors in the cells are proteins which often serve as potent cancer biomarkers and therapy targets. This review summarizes the method aspects that allowed the data-independent acquisition (DIA) mass spectrometry (MS) to outperform the traditional, data-dependent acquisition (DDA) approach in recent years. DIA-MS studies have already recapitulated molecular classification of colorectal and breast cancer, provided data improving molecular classification of prostate and other cancers, and led to validated diagnostic, prognostic, predictive biomarkers and therapy targets for common solid tumors. Tissue-specific spectral libraries are important for a deep characterization of tissue proteomes. Further perspectives of current cancer proteomics lie in the fields of single-cell and spatial proteomics and their integration with clinical data. The importance of functional and clinical validation is highlighted to allow stratified and/or personalized targeted therapy.

(MS Reviews) Data‐Independent Acquisition Mass Spectrometry in Tumor Classification and Cancer Biomarker Research: Abstract




Cancer treatment is far from optimal also because current classification systems do not reflect the complex molecular status of the tumor and… #MassSpectromRev #MassSpecRSS

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Recent Advances in On‐Tissue Chemical Derivatization Strategies for Enhancing MALDI‐MSI ABSTRACT Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has rapidly advanced in biomedical research, enabling label-free, untargeted spatial detection of metabolites, lipids, proteins, and glycans in tissue sections. However, challenges such as low ionization efficiency and chemical instability limit the detection of certain molecules. To address these issues, on-tissue chemical derivatization (OTCD) has been widely applied as an effective strategy to enhance imaging capabilities. This review systematically summarizes the development of derivatization reagents targeting different reactive functional groups and their applications in MALDI-MSI, including strategies for the derivatization of amines, carbonyls, carboxyls, double bonds, hydroxyls, thiols, and platinum-based drugs. Particular attention is given to how these derivatization reagents enhance the detection range and biological relevance by increasing molecular weight, improving ionization efficiency, and reducing background noise interference. Additionally, we explore the application of OTCD in various biological samples and discuss challenges related to experimental workflows, derivatization efficiency, and tissue integrity. This review provides important theoretical support for the advancement of MSI technology and highlights its broad potential applications in biomedical research.

(MS Reviews) Recent Advances in On‐Tissue Chemical Derivatization Strategies for Enhancing MALDI‐MSI: ABSTRACT




Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has rapidly advanced in biomedical research, enabling label-free,… #MassSpectromRev #MassSpecRSS

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Recent Advances in On‐Tissue Chemical Derivatization Strategies for Enhancing MALDI‐MSI Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has rapidly advanced in biomedical research, enabling label-free, untargeted spatial detection of metabolites, lipids...

Recent Advances in On‐Tissue Chemical Derivatization Strategies for Enhancing MALDI‐MSI #MassSpectromRev analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/...

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Mass Spectrometry‐Based Applications in Tannin Analytics: From Qualitative and Quantitative Analyses to Biological Activity ABSTRACT Tannins are widespread specialized plant metabolites that contribute significantly to the polyphenol content of plant-based diets. Their effects on human and animal health vary depending on their structure, with potential benefits including antioxidative, antimicrobial, anthelmintic, and anticarcinogenic properties. Understanding tannin composition and quantity in plant products is essential, as their bioactivities are influenced by their functional groups. Mass spectrometry-based techniques excel in tannin analysis, offering both qualitative and quantitative insights. Combining ultrahigh-performance liquid chromatography with electrospray ionization and high-resolution and triple quadrupole mass analyzers is optimal for comprehensive tannin profiling. Such an approach enables precise analysis and helps predict tannin bioactivities. This review highlights the mass spectrometric analysis of proanthocyanidins and hydrolysable tannins, addressing ionization techniques, interpretation of multiply charged ions, characteristic fragmentations, and reaction monitoring. Applications related to tannin bioactivities are also briefly discussed, demonstrating the utility of mass spectrometry in tannin analysis in complex sample matrices.

(MS Reviews) Mass Spectrometry‐Based Applications in Tannin Analytics: From Qualitative and Quantitative Analyses to Biological Activity: ABSTRACT




Tannins are widespread specialized plant metabolites that contribute significantly to the polyphenol content of… #MassSpectromRev #MassSpecRSS

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Mass Spectrometry‐Based Applications in Tannin Analytics: From Qualitative and Quantitative Analyses to Biological Activity Tannins are widespread specialized plant metabolites that contribute significantly to the polyphenol content of plant-based diets. Their effects on human and animal health vary depending on their str...

Mass Spectrometry‐Based Applications in Tannin Analytics: From Qualitative and Quantitative Analyses to Biological Activity #MassSpectromRev analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/...

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A Special Issue of Mass Spectrometry Reviews to Honor Professor Renato Zenobi: A Lifetime of Mentorship and Innovation in Mass Spectrometry Mass Spectrometry Reviews, EarlyView.

(MS Reviews) A Special Issue of Mass Spectrometry Reviews to Honor Professor Renato Zenobi: A Lifetime of Mentorship and Innovation in Mass Spectrometry: Mass Spectrometry Reviews, EarlyView. #MassSpectromRev #MassSpecRSS

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Advances in Fragmentation Techniques for Glycomics and Glycoproteomics ABSTRACT Glycosylation, the enzymatic addition of carbohydrate moieties to proteins, is essential for immune recognition, protein folding, and disease progression. The structural complexity of glycans and the heterogeneity of glycosylation sites present significant challenges towards accurate identification and quantification, necessitating advanced methodologies for comprehensive characterization. Tandem MS (MS/MS) has emerged as the primary analytical platform for glycomics and glycoproteomics. This review highlights the recent developments in fragmentation techniques, ranging from well-established techniques such as CID/HCD and ETD, to newer and more advanced techniques such as electron-based methods (EThcD), photodissociation strategies (UVPD, IRMPD), and hybrid approaches (sceHCD, EThcD-sceHCD, HCD-pd-ETD), each providing distinct advantages towards glycan structure elucidation and glycosite mapping. This review also discusses emerging computational strategies, especially deep learning for automated interpretation of complex glycomics and glycoproteomics data.

(MS Reviews) Advances in Fragmentation Techniques for Glycomics and Glycoproteomics: ABSTRACT




Glycosylation, the enzymatic addition of carbohydrate moieties to proteins, is essential for immune recognition, protein folding, and disease progression. The structural… #MassSpectromRev #MassSpecRSS

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Advances in Fragmentation Techniques for Glycomics and Glycoproteomics Glycosylation, the enzymatic addition of carbohydrate moieties to proteins, is essential for immune recognition, protein folding, and disease progression. The structural complexity of glycans and the...

Advances in Fragmentation Techniques for Glycomics and Glycoproteomics #MassSpectromRev analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/...

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Reminiscence on Renato Zenobi by Pablo Sinues Mass Spectrometry Reviews, EarlyView.

(MS Reviews) Reminiscence on Renato Zenobi by Pablo Sinues: Mass Spectrometry Reviews, EarlyView. #MassSpectromRev #MassSpecRSS

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Reminiscence on Renato Zenobi by Alfredo Ibáñez Mass Spectrometry Reviews, EarlyView.

(MS Reviews) Reminiscence on Renato Zenobi by Alfredo Ibáñez: Mass Spectrometry Reviews, EarlyView. #MassSpectromRev #MassSpecRSS

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Chemical Ionization Mass Spectrometry: Fundamental Principles, Diverse Applications, and the Latest Technological Frontiers The review examines the evolution of chemical ionization mass spectrometry (CI-MS), a technique developed in 1966 by Field and Munson. CI is a soft-ionization method that produces more intense molecu...

Chemical Ionization Mass Spectrometry: Fundamental Principles, Diverse Applications, and the Latest Technological Frontiers #MassSpectromRev analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/...

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Reminiscence on Renato Zenobi Click on the article title to read more.

Reminiscence on Renato Zenobi - Manicke #MassSpectromRev analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/...

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Chemical Ionization Mass Spectrometry: Fundamental Principles, Diverse Applications, and the Latest Technological Frontiers ABSTRACT The review examines the evolution of chemical ionization mass spectrometry (CI-MS), a technique developed in 1966 by Field and Munson. CI is a soft-ionization method that produces more intense molecular ions with less fragmentation than electron ionization (EI). CI-MS is widely utilized across various fields, including atmospheric chemistry, environmental science, and biomedical research. The article highlights different CI-MS types, such as proton transfer reaction mass spectrometry (PTR-MS), which is renowned for its ability to analyze volatile organic compounds in real-time; negative ion CI-MS, which provides insights into anions; selected ion flow tube mass spectrometry (SIFT-MS), and ion-drift chemical ionization mass spectrometry (ID-CIMS), techniques that allow for the direct analysis of trace gases with high sensitivity and specificity. The article discusses advancements in chromatography with CI-MS, particularly atmospheric pressure chemical ionization (APCI) and liquid electron ionization (LEI) interface. The ongoing exchange of data between fundamental ion/molecule studies and specific applications has significantly boosted the growth of CI-MS in recent decades. In recent years, no extensive review has been published on CI-MS. This article provides an overview of CI-MS technique, its applications, and its evolution over the years, highlighting its importance in advancing scientific research and understanding the chemistry of various environments.

(MS Reviews) Chemical Ionization Mass Spectrometry: Fundamental Principles, Diverse Applications, and the Latest Technological Frontiers: ABSTRACT




The review examines the evolution of chemical ionization mass spectrometry (CI-MS), a technique developed in 1966 by… #MassSpectromRev #MassSpecRSS

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Reminiscence on Renato Zenobi Mass Spectrometry Reviews, EarlyView.

(MS Reviews) Reminiscence on Renato Zenobi: Mass Spectrometry Reviews, EarlyView. #MassSpectromRev #MassSpecRSS

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Advances in the Mechanistic Understanding of Matrix‐Assisted Laser Desorption/Ionization In‐Source Decay Mass Spectrometry for Peptides and Proteins: Electron Transfer Reaction as the Initiating Step of Fragmentation ABSTRACT Because matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD) induces selective cleavage on the peptide backbone, this technique allows reliable identification of peptides and proteins. In the last 15 years, several new matrices have been developed that more efficiently induce MALDI-ISD, opening new research avenues. Fragmentation of peptides by MALDI-ISD can be divided into two categories: reducing and oxidizing matrices induce selective cleavage of N–Cα and Cα–C bonds, respectively. Regarding the dissociation mechanism, MALDI-ISD was believed, until recently, to be initiated by “hydrogen atom” transfer between an analyte peptide and the matrix. Based on this hypothesis, the origin of the hydrogen atoms would be the aniline group of the matrix in MALDI with a reducing matrix and the amide nitrogen of the peptide backbone in MALDI-ISD with an oxidizing matrix. MALDI-ISD involves homolytic cleavage of N–H bonds, though the N–H bond is generally stronger than O–H and C–H bonds. Notably, mass spectrometry experiments cannot distinguish between “hydrogen atom transfer” and “electron transfer and subsequent proton transfer.” Recent well-designed experiments and quantum chemistry calculations have strongly suggested that electron transfer between the peptide and matrix is likely to be the initial step of the MALDI-ISD process. Reducing and oxidizing matrices for MALDI-ISD induce fragmentation through peptide radical anions and cations, respectively. The generated fragment ions and radicals subsequently undergo reactions within the MALDI plume, leading to the formation of stable even-electron ions that are detectable in the mass spectrum. As a result, MALDI-ISD fragments are observed as both positively and negatively charged ions, despite MALDI-ISD entailing the fragmentation of peptide radical anions and cations. The proposed mechanism offers a robust framework for understanding the MALDI-ISD process. A more comprehensive understanding of this process is essential to fully harness the potential of the MALDI-ISD technique and would pave the way for further development of methodologies advancing the field of analytical chemistry based on finding new matrices.

(MS Reviews) Advances in the Mechanistic Understanding of Matrix‐Assisted Laser Desorption/Ionization In‐Source Decay Mass Spectrometry for Peptides and Proteins: Electron Transfer Reaction as the Initiating Step of Fragmentation: ABSTRACT




Because matrix-assisted… #MassSpectromRev #MassSpecRSS

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Advances in the Mechanistic Understanding of Matrix‐Assisted Laser Desorption/Ionization In‐Source Decay Mass Spectrometry for Peptides and Proteins: Electron Transfer Reaction as the Initiating Step ... Because matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD) induces selective cleavage on the peptide backbone, this technique allows reliable identification of peptides and prote....

Advances in the Mechanistic Understanding of Matrix‐Assisted Laser Desorption/Ionization In‐Source Decay Mass Spectrometry for Peptides and Proteins: Electron Transfer Reaction as the Initiating Step of Fragmentation #MassSpectromRev analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/...

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Analytical Approaches to Address Challenges in the Analysis of Cannabinoids in Vascular Matrices Using Mass Spectrometry Phytocannabinoids are bioactive metabolites derived from the Cannabis sativa plant. They have garnered attention due to their recreational uses and therapeutic potential. Although various analytical ....

Analytical Approaches to Address Challenges in the Analysis of Cannabinoids in Vascular Matrices Using Mass Spectrometry #MassSpectromRev analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/...

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Analytical Approaches to Address Challenges in the Analysis of Cannabinoids in Vascular Matrices Using Mass Spectrometry ABSTRACT Phytocannabinoids are bioactive metabolites derived from the Cannabis sativa plant. They have garnered attention due to their recreational uses and therapeutic potential. Although various analytical strategies have been employed for their analysis, mass spectrometry (MS) coupled to chromatographic separation is superior due to its sensitivity and selectivity. Various MS-based strategies, namely Gas chromatography (GC-MS) and liquid chromatography - MS (LC-MS) are reviewed with focus on the analysis of phytocannabinoids in vascular matrices. These include plasma, serum, whole blood, and dried blood spots (DBS). Applications, advantages and challenges associated with each MS strategy in vascular matrices are evaluated and critically discussed. In addition, the review outlines the challenges in DBS spot analysis, such as hematocrit bias, versus plasma/serum and whole blood processing, which involves protein removal, extraction and cleanup steps.

(MS Reviews) Analytical Approaches to Address Challenges in the Analysis of Cannabinoids in Vascular Matrices Using Mass Spectrometry: ABSTRACT




Phytocannabinoids are bioactive metabolites derived from the Cannabis sativa plant. They have garnered attention due to… #MassSpectromRev #MassSpecRSS

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