Structural investigation of bacterial lipopolysaccharides by mass spectrometry and tandem mass spectrometry

Mass spectrometric studies are now playing a leading role in the elucidation of lipopolysaccharide (LPS) structures through the characterization of antigenic polysaccharides, core oligosaccharides and lipid A components including LPS genetic modifications. The conventional MS and MS/MS analyses together with CID fragmentation provide additional structural information complementary to the previous analytical experiments, and thus contribute to an integrated strategy for the simultaneous characterization and correct sequencing of the carbohydrate moiety. © 2010 Wiley Periodicals, Inc., Mass Spec Rev 29:606–650, 2010     

Application of capillary electrophoresis mass spectrometry to the characterization of bacterial lipopolysaccharides

Capillary electrophoresis (CE) is a high-resolution technique for the separation of complex biological mixtures and has been widely applied to biological analyses. The coupling of capillary electrophoresis with mass spectrometry (MS) provides a powerful approach for rapid identification of target analytes present at trace levels in biological matrices, and for structural characterization of complex biomolecules. Here we review the analytical potential of combined capillary electrophoresis electrospray mass spectrometry (CE-MS) for the analysis of bacterial lipopolysaccharides (LPS). This hyphened methodology facilitates the determination of closely related LPS glycoform and isoform families by exploiting differences in their unique molecular conformations and ionic charge distributions by electrophoretic separation. On-line CE-MS also provides an additional avenue to improve detection limits, which has been successfully applied to directly probe oligosaccharide LPS glycoform populations of bacteria isolated from infected animal models without the need for further passage.     

Recent trends of capillary electrophoresis‐mass spectrometry in proteomics research

Progress in proteomics research has led to a demand for powerful analytical tools with high separation efficiency and sensitivity for confident identification and quantification of proteins, posttranslational modifications, and protein complexes expressed in cells and tissues. This demand has significantly increased interest in capillary electrophoresis‐mass spectrometry (CE‐MS) in the past few years. This review provides highlights of recent advances in CE‐MS for proteomics research, including a short introduction to top‐down mass spectrometry and native mass spectrometry (native MS), as well as a detailed overview of CE methods. Both the potential and limitations of these methods for the analysis of proteins and peptides in synthetic and biological samples and the challenges of CE methods are discussed, along with perspectives about the future direction of CE‐MS. @ 2019 Wiley Periodicals, Inc. Mass Spec Rev 00:1–16, 2019.     

Top‐down mass spectrometry for the analysis of combinatorial post‐translational modifications

Protein post‐translational modifications (PTMs) are critically important in regulating both protein structure and function, often in a rapid and reversible manner. Due to its sensitivity and vast applicability, mass spectrometry (MS) has become the technique of choice for analyzing PTMs. Whilst the “bottom‐up' analytical approach, in which proteins are proteolyzed generating peptides for analysis by MS, is routinely applied and offers some advantages in terms of ease of analysis and lower limit of detection, “top‐down” MS, describing the analysis of intact proteins, yields unique and highly valuable information on the connectivity and therefore combinatorial effect of multiple PTMs in the same polypeptide chain. In this review, the state of the art in top‐down MS will be discussed, covering the main instrumental platforms and ion activation techniques. Moreover, the way that this approach can be used to gain insights on the combinatorial effect of multiple post‐translational modifications and how this information can assist in studying physiologically relevant systems at the molecular level will also be addressed. © 2012 Wiley Periodicals, Inc., Mass Spec Rev 32:27–42, 2013     

Recent advances in mass spectrometry analysis of phenolic endocrine disruptors and related compounds

This article reviews recent literature on current methodologies based on chromatography coupled to mass spectrometry to analyze phenolic compounds with endocrine‐disrupting capabilities. For this review we chose alkylphenol ethoxylates, bisphenol A, bisphenol F, and their degradation products and halogenated derivatives, which are considered important environmental contaminants. Additionally, some related compounds such as bisphenol diglycidylethers were included. Growing attention has been paid to the mass spectrometric characterization of these compounds and the instrumentation and strategies used for their quantification and confirmation. The current use of gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS) methodologies with different mass spectrometers and ionization and monitoring modes is discussed. Practical aspects with regards to the use of these analytical techniques, such as derivatizing reagents in GC–MS, ion suppression in LC–MS, and the most problematic aspects of quantification, are included in the discussion. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:776–805, 2010     

Time‐of‐flight mass spectrometry: Introduction to the basics

The intention of this tutorial is to introduce into the basic concepts of time‐of‐flight mass spectrometry, beginning with the most simple single‐stage ion source with linear field‐free drift region and continuing with two‐stage ion sources combined with field‐free drift regions and ion reflectors—the so‐called reflectrons. Basic formulas are presented and discussed with the focus on understanding the physical relations of geometric and electric parameters, initial distribution of ionic parameters, ion flight times, and ion flight time incertitude. This tutorial is aimed to help the applicant to identify sources of flight time broadening which limit good mass resolution and sources of ion losses which limit sensitivity; it is aimed to stimulate creativity for new experimental approaches by discussing a choice of instrumental options and to encourage those who toy with the idea to build an own time‐of‐flight mass spectrometer. Large parts of mathematics are shifted into a separate chapter in order not to overburden the text with too many mathematical deviations. Rather, thumb‐rule formulas are supplied for first estimations of geometry and potentials when designing a home‐built instrument, planning experiments, or searching for sources of flight time broadening. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:86–109, 2017.     

Environmental and food applications of LC-tandem mass spectrometry in pesticide-residue analysis: an overview

An overview is given on pesticide-residue determination in environmental and food samples by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). Pesticides comprise a large number of substances that belong to many completely different chemical groups, the only common characteristic is that they are effective against pests. They still constitute a challenge in MS because there is no collective pathway for fragmentation. A brief introduction to the theory of tandem MS permits a discussion of which parameters influence the ionization efficiency when the ions are subjected to different actions. Emphasis is placed on the different tandem MS instruments: triple and ion-trap quadrupoles, and hybrid quadrupole time-of-flight (Q-TOF), including advantages and drawbacks, typical detection limits, and ion signals at low concentrations. The instrumental setup, as well as LC and mass spectrometric experimental conditions, must be carefully selected to increase the performance of the analytical system. The capacity of each instrument to provide useful data for the identification of pesticides, and the possibility to obtain structural information for the identification of target and non-target compounds, are discussed. Finally, sample preparation techniques and examples of applications are debated to reveal the potential of the current state-of-the-art technology, and to further promote the usefulness of tandem MS.     

Fragmentation of toxicologically relevant drugs in negative‐ion liquid chromatography–tandem mass spectrometry

Negative‐ion LC–MS analysis of drugs is applied far less frequently than positive‐ion LC–MS. Data on the interpretation of negative‐ion MS–MS spectra are even more scarce. Therefore, following the recent review on the class‐specific fragmentation of toxicologically relevant compounds in positive‐ion MS–MS, it was decided to perform a similar study in negative‐ion MS–MS. To this end, a set of over 500 negative‐ion MS–MS spectra was collected from three libraries applied in toxicological general unknown screening and systematic toxicological analysis. The compounds involved were classified by chemical and therapeutic class. The MS–MS spectra were manually interpreted and relevant interpretation data were searched for in the scientific literature. The emphasis in the discussion is on class‐specific fragmentation, because discussing fragmentation of all individual compounds would take far too much space. Negative‐ion MS–MS fragmentation is discussed for a wide variety of toxicologically relevant compounds, including dihydropyridine calcium channel blockers, diuretics, barbiturates, anti‐inflammatory drugs, anti‐diabetics, sulfonamide and betalactam antibiotics, and a number of classes of pesticides. © 2012 Wiley Periodicals, Inc. Mass Spec Rev 31:626–665, 2012     

Structural characterization of flavonoid glycosides by multi‐stage mass spectrometry

Flavonoids are secondary plant metabolites of great structural variety and high medicinal significance. The search for new chemical entities and the quality control of flavonoid containing natural products require easy‐to‐use but reliable and robust analytical methodologies. For structural elucidation of flavonoids and their glycosides, nuclear magnetic resonance (NMR) and mass spectroscopy (MS) are the generally used techniques. In phytochemical analyses, however, high amounts of flavonoids are difficult to isolate for NMR, thus low sample volume requiring MS based methods are emerging. This review summarizes and compares currently available methods for structural elucidation of flavonoids by LC–MS and LC–MSⁿ, and focuses on the identification options of unknown flavonoid glycosides in complex samples (e.g., plant extracts) with the emphasis on the differentiation of isomeric compounds. © 2008 Wiley Periodicals, Inc., Mass Spec Rev 29:1–16, 2010     

Controlled band dispersion for quantitative binding determination and analysis with electrospray ionization‐mass spectrometry

This review discusses recent emerging techniques that have been used to couple flow‐injection analysis (FIA) and electrospray ionization‐mass spectrometry (ESI‐MS) for the quantitation of noncovalent binding interactions. Focus is placed predominantly on two such methods. Diffusion‐based measurements, developed by Konermann and co‐workers, uses controlled‐band dispersion prior to ESI‐MS to determine diffusion constants and binding constants based on the temporal variation of ligand signal measured in the mass spectrum (an indirect technique). Dynamic titration, developed by Schug and co‐workers, is a direct method, where a temporal compositional gradient of a guest molecule is induced in the presence of host in solution to monitor the concentration dependence of complex formation as a function of observed complex ion abundance after ESI‐MS. Further discussion places these techniques in the context of a variety of other direct and indirect ESI‐MS‐based binding determination methods, and highlights advantages, disadvantages, and practical considerations for their proper use to investigate a broad range of macromolecular and small‐molecule interaction systems. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:806–829, 2010