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Drug Metabolism and Disposition: the... Oct 2023Mass spectrometric imaging is a nontargeted, tag-free, high-throughput, and highly responsive analytical approach. The highly accurate molecular visualization detection... (Review)
Review
Mass spectrometric imaging is a nontargeted, tag-free, high-throughput, and highly responsive analytical approach. The highly accurate molecular visualization detection technology enables qualitative and quantitative analyses of biologic tissues or cells scanned by mass spectrometry in situ, extracting known and unknown multiple compounds, and simultaneously assessing relative contents of targeting molecules by monitoring their molecular ions and pinpointing the spatial locations of those molecules distributed. Five mass spectrometric imaging techniques and their characteristics are introduced in the review, including matrix-assisted laser desorption ionization mass spectrometry, secondary ion mass spectrometry, desorption electrospray ionization mass spectrometry, laser ablation electrospray ionization mass spectrometry, and laser ablation inductively coupled plasma mass spectrometry. The mass spectrometry-based techniques provide the possibility for spatial metabolomics with the capability of high throughput and precision detection. The approaches have been widely employed to spatially image not only metabolome of endogenous amino acids, peptides, proteins, neurotransmitters, and lipids but also the disposition of exogenous chemicals, such as pharmaceutical agents, environmental pollutants, toxicants, natural products, and heavy metals. The techniques also provide us with spatial distribution imaging of analytes in single cells, tissue microregions, organs, and whole animals. SIGNIFICANCE STATEMENT: The review article includes an overview of five commonly used mass spectrometers for spatial imaging and describes the advantages and disadvantages of each. Examples of the technology applications cover drug disposition, diseases, and omics. Technical aspects of relative and absolute quantification by mass spectrometric imaging and challenges for future new applications are discussed as well. The reviewed knowledge may benefit the development of new drugs and provide a better understanding of biochemical processes related to physiology and diseases.
Topics: Animals; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Proteins; Metabolomics; Molecular Imaging
PubMed: 37295949
DOI: 10.1124/dmd.122.001069 -
Talanta Nov 2023Mass spectrometry imaging (MSI) is a novel molecular imaging technology that collects molecular information from the surface of samples in situ. The spatial distribution... (Review)
Review
Mass spectrometry imaging (MSI) is a novel molecular imaging technology that collects molecular information from the surface of samples in situ. The spatial distribution and relative content of various compounds can be visualized simultaneously with high spatial resolution. The prominent advantages of MSI promote the active development of ionization technology and its broader applications in diverse fields. This article first gives a brief introduction to the vital parts of the processes during MSI. On this basis, provides a comprehensive overview of the most relevant MS-based imaging techniques from their mechanisms, pros and cons, and applications. In addition, a critical issue in MSI, matrix effects is also discussed. Then, the representative applications of MSI in biological, forensic, and environmental fields in the past 5 years have been summarized, with a focus on various types of analytes (e.g., proteins, lipids, polymers, etc.) Finally, the challenges and further perspectives of MSI are proposed and concluded.
Topics: Mass Spectrometry; Proteins; Molecular Imaging; Forensic Medicine; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 37271004
DOI: 10.1016/j.talanta.2023.124721 -
Drug Discovery Today Nov 2023Affinity selection mass spectrometry (AS-MS) has gained momentum in drug discovery. This review summarizes how this technology has slowly risen as a new paradigm in hit... (Review)
Review
Affinity selection mass spectrometry (AS-MS) has gained momentum in drug discovery. This review summarizes how this technology has slowly risen as a new paradigm in hit identification and its potential synergy with DNA encoded library technology. It presents an overview of the recent results on challenging targets and perspectives on new areas of research, such as RNA targeting with small molecules. The versatility of the approach is illustrated and strategic drivers discussed in terms of the experience of a small-medium CRO and a big pharma organization.
Topics: Small Molecule Libraries; Drug Discovery; Mass Spectrometry; DNA; Technology
PubMed: 37660985
DOI: 10.1016/j.drudis.2023.103760 -
Current Opinion in Chemical Biology Oct 2023Elucidating protein-protein interaction (PPI) networks and their structural features within cells is central to understanding fundamental biology and associations of... (Review)
Review
Elucidating protein-protein interaction (PPI) networks and their structural features within cells is central to understanding fundamental biology and associations of cell phenotypes with human pathologies. Owing to technological advancements during the last decade, cross-linking mass spectrometry (XL-MS) has become an enabling technology for delineating interaction landscapes of proteomes as they exist in living systems. XL-MS is unique due to its capability to simultaneously capture PPIs from native environments and uncover interaction contacts though identification of cross-linked peptides, thereby permitting the determination of both identity and connectivity of PPIs in cells. In combination with high resolution structural tools such as cryo-electron microscopy and AI-assisted prediction, XL-MS has contributed significantly to elucidating architectures of large protein assemblies. This review highlights the latest developments in XL-MS technologies and their applications in proteome-wide analysis to advance structural systems biology.
Topics: Humans; Systems Biology; Cryoelectron Microscopy; Peptides; Mass Spectrometry; Proteome; Cross-Linking Reagents
PubMed: 37406423
DOI: 10.1016/j.cbpa.2023.102357 -
Molecular & Cellular Proteomics : MCP Sep 2023Data-independent acquisition (DIA) mass spectrometry-based proteomics generates reproducible proteome data. The complex processing of the DIA data has led to the...
Data-independent acquisition (DIA) mass spectrometry-based proteomics generates reproducible proteome data. The complex processing of the DIA data has led to the development of multiple data analysis tools. In this study, we assessed the performance of five tools (OpenSWATH, EncyclopeDIA, Skyline, DIA-NN, and Spectronaut) using six DIA datasets obtained from TripleTOF, Orbitrap, and TimsTOF Pro instruments. By comparing identification and quantification metrics and examining shared and unique cross-tool identifications, we evaluated both library-based and library-free approaches. Our findings indicate that library-free approaches outperformed library-based methods when the spectral library had limited comprehensiveness. However, our results also suggest that constructing a comprehensive library still offers benefits for most DIA analyses. This study provides comprehensive guidance for DIA data analysis tools, benefiting both experienced and novice users of DIA-mass spectrometry technology.
Topics: Mass Spectrometry; Proteomics; Proteome; Gene Library; Data Analysis
PubMed: 37481071
DOI: 10.1016/j.mcpro.2023.100623 -
Accounts of Chemical Research Sep 2023Mass spectrometry (MS) is one of the most widely used technologies in the chemical sciences. With applications spanning the monitoring of reaction products, the... (Review)
Review
Mass spectrometry (MS) is one of the most widely used technologies in the chemical sciences. With applications spanning the monitoring of reaction products, the identification of disease biomarkers, and the measurement of thermodynamic parameters and aspects of structural biology, MS is well established as a universal analytical tool applicable to small compounds as well as large molecular complexes. Regardless of the application, the generation of gas-phase ions from neutral compounds is a key step in any MS experiment. However, this ionization step was for many years limited to high-energy approaches that required gas-phase analytes and thus it was restricted to volatile samples. Over the last few decades, new methodologies have been developed to address this limitation and facilitate ionization of biological molecules. Electrospray ionization (ESI) is the most broadly used of these methods, as it facilitates the ionization of intact polar compounds from solution. Twenty years ago, our group reported a new ionization method that uses a charged solvent spray to impact a surface, generating ions from rather than just and doing so directly in the ambient environment with no vacuum requirements and little to no sample preparation. This method was termed desorption electrospray ionization (DESI), and it initiated a new field that would come to be known as ambient mass spectrometry. The simplicity and wide applicability of the DESI technology—and the tens of ambient ionization methods developed subsequently—revolutionized the MS analysis of complex materials for their organic components, especially for applications. This Account describes the history of DESI, starting with the development of the technique from early electrosonic spray ionization (ESSI) experimental observations as well as the studies leading to the understanding of its mechanism as a “droplet pick-up” phenomenon involving sequential events (, thin film formation, solid–liquid extraction, secondary droplet generation, and ESI-like ionization from these droplets). We also overview the developments and applications of the technology that have been demonstrated by our group during the last two decades. In particular, we describe (i) the use of DESI for tissue imaging, one of its more significant applications to date, and its extension to intraoperative clinical diagnosis; (ii) the integration of the technology with portable instrumentation for analysis, especially when coupled with tandem mass spectrometry (MS/MS); (iii) the use of DESI microdroplets as microvessels to accelerate organic reactions by orders of magnitude compared to those in bulk solution; and (iv) the combination of all these capabilities for automated high-throughput experiments aimed at accelerating drug discovery.
Topics: Drug Discovery; Pentaerythritol Tetranitrate; Solvents; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 37671799
DOI: 10.1021/acs.accounts.3c00382 -
International Journal of Molecular... Feb 2024Lipids represent a large group of biomolecules that are responsible for various functions in organisms. Diseases such as diabetes, chronic inflammation, neurological... (Review)
Review
Lipids represent a large group of biomolecules that are responsible for various functions in organisms. Diseases such as diabetes, chronic inflammation, neurological disorders, or neurodegenerative and cardiovascular diseases can be caused by lipid imbalance. Due to the different stereochemical properties and composition of fatty acyl groups of molecules in most lipid classes, quantification of lipids and development of lipidomic analytical techniques are problematic. Identification of different lipid species from complex matrices is difficult, and therefore individual analytical steps, which include extraction, separation, and detection of lipids, must be chosen properly. This review critically documents recent strategies for lipid analysis from sample pretreatment to instrumental analysis and data interpretation published in the last five years (2019 to 2023). The advantages and disadvantages of various extraction methods are covered. The instrumental analysis step comprises methods for lipid identification and quantification. Mass spectrometry (MS) is the most used technique in lipid analysis, which can be performed by direct infusion MS approach or in combination with suitable separation techniques such as liquid chromatography or gas chromatography. Special attention is also given to the correct evaluation and interpretation of the data obtained from the lipid analyses. Only accurate, precise, robust and reliable analytical strategies are able to bring complex and useful lipidomic information, which may contribute to clarification of some diseases at the molecular level, and may be used as putative biomarkers and/or therapeutic targets.
Topics: Lipids; Gas Chromatography-Mass Spectrometry; Mass Spectrometry; Chromatography, Liquid; Lipidomics
PubMed: 38396926
DOI: 10.3390/ijms25042249 -
Journal of Forensic Sciences Sep 2023The need to detect fentanyl and its analogs in the field is an important capability to help prevent unintentional exposure or overdose on these substances, which may... (Review)
Review
The need to detect fentanyl and its analogs in the field is an important capability to help prevent unintentional exposure or overdose on these substances, which may result in death. Many portable methods historically used in the field by first responders and other field users to detect and identify other chemical substances, such as hazardous materials, have been applied to the detection and identification of these synthetic opioids. This paper describes field portable spectroscopic methods used for the detection and identification of fentanyl and its analogs. The methods described are automated colorimetric tests including lateral flow assays; vibrational spectroscopy (mid-infrared and Raman); gas chromatography-mass spectrometry; ion mobility spectrometry, and high-pressure mass spectrometry. In each case the background and key details of these technologies are outlined, followed by a discussion of the application of the technology in the field. Attention is paid to the analysis of complex mixtures and limits of detection, including the required spectral databases and algorithms used to interrogate these types of samples. There is also an emphasis on providing actionable information to the (likely) non-scientist operators of these instruments in the field.
Topics: Humans; Fentanyl; Analgesics, Opioid; Mass Spectrometry; Gas Chromatography-Mass Spectrometry; Drug Overdose
PubMed: 37565563
DOI: 10.1111/1556-4029.15355 -
Clinica Chimica Acta; International... Mar 2024Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has attracted significant attention in clinical practice owing to its numerous advantages. However, the... (Review)
Review
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has attracted significant attention in clinical practice owing to its numerous advantages. However, the widespread adoption of this technique is hindered by certain limitations, such as inappropriate analyte selection, low levels of automation, and a lack of specific reference intervals and quality control programs. This review comprehensively summarizes the current challenges associated with LC-MS/MS and proposes potential resolutions. The principle of utility should guide the selection of biomarkers, prioritizing their practical value over sheer quantity. To achieve full-process automation, methodological innovation is crucial for developing high-throughput equipment. Establishing reference intervals for mass spectrometry-based assays across multiple centers and diverse populations is essential for accurate result interpretation. Additionally, the development of commercial quality control materials assumes pivotal importance in ensuring assay reliability and reproducibility. Harmonization and standardization efforts should focus on the development of reference methods and materials for the clinical use of LC-MS/MS. In the future, commercial assay kits and laboratory-developed tests (LDTs) are expected to coexist in clinical laboratories, each offering distinct advantages. The collaborative efforts of diverse professionals is vital for addressing the challenges associated with the clinical application of LC-MS/MS. The anticipated advancements include simplification, increased automation, intelligence, and the standardization of LC-MS/MS, ultimately facilitating its seamless integration into clinical routines for both technicians and clinicians.
Topics: Humans; Chromatography, Liquid; Tandem Mass Spectrometry; Reproducibility of Results; Laboratories, Clinical; Liquid Chromatography-Mass Spectrometry
PubMed: 38280490
DOI: 10.1016/j.cca.2024.117797 -
Current Opinion in Structural Biology Oct 2023Cross-linking mass spectrometry (XL-MS) can provide a wealth of information on endogenous protein-protein interaction (PPI) networks and protein binding interfaces.... (Review)
Review
Cross-linking mass spectrometry (XL-MS) can provide a wealth of information on endogenous protein-protein interaction (PPI) networks and protein binding interfaces. These features make XL-MS an attractive tool to support the development of PPI-targeting drugs. Though not yet widely used, applications of XL-MS to drug characterization are beginning to emerge. Here, we compare XL-MS to established structural proteomics methods in drug research, discuss the current state and remaining challenges of XL-MS technology, and provide a perspective on the future role XL-MS can play in drug development, with a particular emphasis on PPI modulators.
Topics: Mass Spectrometry; Protein Binding; Protein Interaction Maps; Cross-Linking Reagents
PubMed: 37423038
DOI: 10.1016/j.sbi.2023.102648