Mass Spectrometry Reviews最新文献

Mass spectrometry (MS) has become a powerful technique for clinical applications with high sensitivity and specificity. Different from conventional MS diagnosis in laboratory, point-of-care (POC) analyses in clinics require mass spectrometers and analytical procedures to be friendly for novice users and applicable for on-site clinical diagnosis. The recent decades have seen the progress in the development of miniature mass spectrometers, providing a promising solution for clinical POC applications. In this review, we report recent advances of miniature mass spectrometers and their exploration in clinical applications, mainly including the rapid analysis of illegal drugs, on-site monitoring of therapeutic drugs, and detection of biomarkers. With improved analytical performance, miniature mass spectrometers are also expected to apply to more and more clinical applications. Some promising POC analyses that can be performed by miniature mass spectrometers in the future are discussed. Lastly, we also provide our perspectives on the challenges in technical development of miniature mass spectrometers for clinical POC analysis.

Direct analysis in real time (DART) represents a new generation of ionization techniques that are used to rapidly ionize small molecules under ambient environments. The combination of DART with various mass spectrometry (MS) instruments allows analyzing multiple plant materials, including traditional Chinese herbal medicines (TCHMs), under simple or no sample treatment conditions. This review discussed the DART principles, including devices, ionization mechanisms, and operation parameters. Typical spectra detected by DART-MS were exhibited and discussed. Numerous applications of DART-MS in the fields of plant material and TCHM analysis were reviewed, including compound identification, biomarker discovery, fingerprinting analysis, and quantification analysis. Besides, modifications and improvements of DART-MS, such as hyphenated application with other separation methods, laser-based desorption techniques, and online sampling configuration, were summarized as well.

Epigenetic modifications are closely related to certain disorders of the organism, including the development of tumors. One of the main epigenetic modifications is the methylation of DNA cytosines, 5-methyl-2′-deoxycycytidine. Furthermore, 5-mdC can be oxidized to form three new modifications, 5-(hydroxymethyl)-2′-deoxycytidine, 5-formyl-2′-deoxycytidine, and 5-carboxy-2′-deoxycytidine. The coupling of liquid chromatography with tandem mass spectrometry has been widely used for the total determination of methylated DNA cytosines in samples of biological and clinical interest. These methods are based on the measurement of the free compounds (e.g., urine) or after complete hydrolysis of the DNA (e.g., tissues) followed by a preconcentration, derivatization, and/or clean-up step. This review highlights the main advances in the quantification of modified nucleotides and nucleosides by isotope dilution using isotopically labeled analogs combined with liquid or gas chromatography coupled to mass spectrometry reported in the last 20 years. The different possible sources of labeled compounds are indicated. Special emphasis has been placed on the different types of chromatography commonly used (reverse phase and hydrophilic interaction liquid chromatography) and the derivatization methods developed to enhance chromatographic resolution and ionization efficiency. We have also revised the application of bidimensional chromatography and indicated significant biological and clinical applications of these determinations.

Lysosomal storage disorders (LSDs) are a type of inherited metabolic disorders in which biomolecules, accumulate as a specific substrate in lysosomes due to specific individual enzyme deficiencies. Despite the fact that LSDs are incurable, various approaches, including enzyme replacement therapy, hematopoietic stem cell transplantation, or gene therapy are now available. Therefore, a timely diagnosis is a critical initial step in patient treatment. The-state-of-the-art in LSD diagnostic uses, in the first stage, enzymatic activity determination by fluorimetry or by mass spectrometry (MS) with the aid of dry blood spots, based on different enzymatic substrate structures. Due to its sensitivity, high precision, and ability to screen for an unprecedented number of diseases in a single assay, multiplexed tandem MS-based enzyme activity assays for the screening of LSDs in newborns have recently received a lot of attention. Here, (i) we review the current approaches used for simultaneous enzymatic activity determination of LSDs in dried blood spots using multiplex—LC-MS/MS; (ii) we explore the need for designing novel enzymatic substrates that generate different enzymatic products with distinct molecular masses in multiplexed-MS studies; and (iii) we give examples of the relevance of affinity-MS technique as a basis for reversing undesirable immune-reactivity in enzyme replacement therapy.

The molecular composition of exhaled human breath can reflect various physiological and pathological conditions. Considerable progress has been achieved over the past decade in real-time analysis of exhaled human breath using direct mass spectrometry methods, including selected ion flow tube mass spectrometry, proton transfer reaction mass spectrometry, extractive electrospray ionization mass spectrometry, secondary electrospray ionization mass spectrometry, acetone-assisted negative photoionization mass spectrometry, atmospheric pressure photoionization mass spectrometry, and low-pressure photoionization mass spectrometry. Here, recent developments in direct mass spectrometry analysis of exhaled human breath are reviewed with regard to analytical performance (chemical sensitivity, selectivity, quantitative capabilities) and applications of the developed methods in disease diagnosis, targeted molecular detection, and real-time metabolic monitoring.

We are approaching the third decade since the establishment of the very first proteomics repositories back in the mid-'00s. New experimental approaches and technologies continuously enrich the field while producing vast amounts of mass spectrometry data. Together with initiatives to establish standard terminology and file formats, proteomics is rapidly transforming into a mature component of systems biology. Here we describe the ProteomeXchange consortium repositories. We specifically search, collect and evaluate public human tissue datasets (categorized as "complete" by the repository) submitted in 2015-2022, to both map the existing information and assess the data set reusability. Human tissue data are variably represented in the repositories reviewed, ranging between 10% and 25% of the total data submitted, with cancers being the most represented, followed by neuronal and cardiovascular diseases. About half of the retrieved data sets were found to lack annotations or metadata necessary to directly replicate the analysis. This poses a rough challenge to data reusability and highlights the need to increase awareness of the mage-tab file format for metadata in the community. Overall, proteomics repositories have evolved greatly over the past 7 years, as they have grown in size and become equipped with various powerful applications and tools that enable data searching and analytical tasks. However, to make the most of this potential, priority must be given to finding ways to secure detailed metadata for each submission, which is likely the next major milestone for proteomics repositories.

This article reviews the analytical tool chest used for characterizing alkoxylates and their associated copolymer mixtures. Specific emphasis will be placed upon the use of mass spectrometry-based techniques as rapid characterization tools for optimizing reaction processes in an industrial R&D setting. An initial tutorial will cover the use of matrix-assisted laser desorption/ionization-mass spectrometry and tandem mass spectrometry fragmentation for detailed component analysis (e.g., polyol and isocyanate) of a model polyurethane-based foam. Next, this critical feedback information will be used with the guidance of mass spectrometry to initiate the development of a new, more efficient, tris(pentafluorophenyl)borane (FAB) catalyst-based alkoxylation process for generating the next generation of glycerin-initiated poly(propylene oxide)-co-poly(ethylene oxide) copolymers. Examples will be provided for each step in the FAB-based optimization process that were required to generate the final product. Following this example, two-dimensional liquid chromatography, supercritical fluid chromatography, and ion mobility separations, along with their coupling to mass spectrometry, will be reviewed for their efficiency in characterizing and quantitating the components within these complex polyether polyol mixtures.

Mass spectrometry (MS) has been proven as an excellent tool in ocular drug research allowing analyzes from small samples and low concentrations. This review begins with a short introduction to eye physiology and ocular pharmacokinetics and the relevance of advancing ophthalmic treatments. The second part of the review consists of an introduction to ocular proteomics, with special emphasis on targeted absolute quantitation of membrane transporters and metabolizing enzymes. The third part of the review deals with liquid chromatography-MS (LC-MS) and MS imaging (MSI) methods used in the analysis of drugs and metabolites in ocular samples. The sensitivity and speed of LC-MS make simultaneous quantitation of various drugs and metabolites possible in minute tissue samples, even though ocular sample preparation requires careful handling. The MSI methodology is on the verge of becoming as important as LC-MS in ocular pharmacokinetic studies, since the spatial resolution has reached the level, where cell layers can be separated, and quantitation with isotope-labeled standards has come more reliable. MS will remain in the foreseeable future as the main analytical method that will progress our understanding of ocular pharmacokinetics.

The role of mass spectrometry (MS) has become more important in most application domains in recent years. Pharmaceutical analysis is specific due to its stringent regulation procedures, the need for good laboratory/manufacturing practices, and a large number of routine quality control analyses to be carried out. The role of MS is, therefore, very different throughout the whole drug development cycle. While it dominates within the drug discovery and development phase, in routine quality control, the role of MS is minor and indispensable only for selected applications. Moreover, its role is very different in the case of analysis of small molecule pharmaceuticals and biopharmaceuticals. Our review explains the role of current MS in the analysis of both small-molecule chemical drugs and biopharmaceuticals. Important features of MS-based technologies being implemented, method requirements, and related challenges are discussed. The differences in analytical procedures for small molecule pharmaceuticals and biopharmaceuticals are pointed out. While a single method or a small set of methods is usually sufficient for quality control in the case of small molecule pharmaceuticals and MS is often not indispensable, a large panel of methods including extensive use of MS must be used for quality control of biopharmaceuticals. Finally, expected development and future trends are outlined.

This Tutorial is to provide a summary of parameters useful for successful outcomes of laserspray ionization (LSI) and related methods that employ a laser to ablate a matrix:analyte sample to produce highly charged ions. In these methods the purpose of the laser is to transfer matrix-analyte clusters into the gas phase. Ions are hypothesized to be produced by a thermal process where emitted matrix:analyte gas-phase particles/clusters are charged and loss of matrix from the charged particles leads to release of the analyte ions into the gas phase. The thermal energy responsible for the charge-separation process is relatively low and not necessarily supplied by the laser; a heated inlet tube linking atmospheric pressure with the first vacuum stage of a mass spectrometer is sufficient. The inlet becomes the “ion source”, and inter alia, pressure, temperature, and the matrix, which can be a solid, liquid, or combinations, become critical parameters. Injecting matrix:analyte into a heated inlet tube using laser ablation, a shockwave, or simply tapping, all produce the similar mass spectra. Applications are provided that showcase new opportunities in the field of mass spectrometry.