Mass Spectrometry: Current Research Articles
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On this page considered biochemistry journals:
Mass Spectrometry Reviews - published by
Wiley Interscience -
Journal of Mass Spectrometry - published by
Wiley Interscience -
Current research articles of the mentioned
journals:
Gas phase isomeric differentiation of oleanolic and ursolic acids associated with heptakis-(2,6-di-O-methyl)-[beta]-cyclodextrin by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry
Oleanolic acid (OA) and ursolic acid (UA) are isomeric triterpenoid compounds with similar pharmaceutical properties. Usually, modern chromatographic and electrophoretic methods are widely utilized to differentiate these two compounds. Compared with mass spectrometric (MS) methods, these modern separation methods are both time- and sample-consuming. Herein, we present a new method for structural differentiation of OA and UA by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) with the association of heptakis-(2,6-di-O-methyl)-[beta]-cyclodextrin (DM-[beta]-CD). Exact MS and tandem MS (MS/MS) data showed that there is no perceptible difference between OA and UA, as well as their [beta]-cyclodextrin and [gamma]-cyclodextrin complexes. However, there is a remarkable difference in MS/MS spectra of DM-[beta]-CD complexes of OA and UA. The peak corresponding to the neutral loss of a formic acid and a water molecule could only be observed in the MS/MS spectrum of the complex of DM-[beta]-CD : OA. Molecular modeling calculations were also employed to further investigate the structural differences of DM-[beta]-CD : OA and DM-[beta]-CD : UA complexes. Therefore, by employing DM-[beta]-CD as a reference reagent, OA and UA could be differentiated with purely MS method. Copyright © 2010 John Wiley & Sons, Ltd.
Mass spectrometry of fluorocarbon-labeled glycosphingolipids
A method for generation of novel fluorocarbon derivatives of glycosphingolipids (GSLs) with high affinity for fluorocarbon phases has been developed, and their potential applications to mass spectrometry (MS)-based methodologies for glycosphingolipidomics have been investigated. Sphingolipid ceramide N-deacylase (SCDase) is used to remove the fatty acid from the ceramide moiety, after which a fluorocarbon-rich substituent (F-Tag) is incorporated at the free amine of the sphingoid. In initial trials, a neutral GSL, globotriaosylceramide (Gb3Cer), three purified bovine brain gangliosides, and four fungal glycosylinositol phosphorylceramides (GIPCs) were de-N-acylated, derivatized by prototype F-Tags, and recovered by solid phase extraction on fluorocarbon-derivatized silica (F-SPE). The efficacy of SCDase treatment of GIPCs was here demonstrated for the first time. Compatibility with subsequent per-N,O-methylation was established for the F-tagged Gb3 Cer and purified gangliosides, and extensive mass spectra (MS1 and MS2) consistent with all of the expected products were acquired. The potential use of F-tagged derivatives for a comprehensive MS based profiling application was then demonstrated on a crude ganglioside mixture extracted from bovine brain. Finally, a simple trial in microarray format demonstrated fixation of F-tagged GM1 ganglioside to a fluorous glass surface, with the glycan intact and available for interaction with a fluorescent derivative of cholera toxin B chain. The methods described thus provide a new avenue for rapid GSL recovery or cleanup, potentially compatible with a variety of platforms for mass spectrometric profiling and structure analysis, as well as parallel analysis of functional interactions. Copyright © 2010 John Wiley & Sons, Ltd.
A study of the cesium cation bonding to carboxylate anions by the kinetic method and quantum chemical calculations
Collision-induced dissociation (CID) of the Cs+ heterodimer adducts of the nitrate anion (NO3-) and a variety of substituted benzoates (XBenz-) [(XBenz-)(Cs+)(NO3-)]- produces essentially nitrate and benzoate ions. A plot of the natural logarithm of their intensity ratio, ln[I (NO3-)/I(XBenz-)], versus the calculated cesium cation affinity (DFT B3LYP) of the substituted benzoate ions (equivalent to the enthalpy of heterolytic dissociation of the salt) is reasonably linear. This suggests that the kinetic method can be used as a source of data on the intrinsic interaction between the anionic and the cationic moieties in a salt. Copyright © 2010 John Wiley & Sons, Ltd.
Direct analysis of lipids in mouse brain using electrospray droplet impact/SIMS
Electrospray droplet impact (EDI)/secondary ion mass spectrometry (SIMS) is a new desorption/ionization technique for mass spectrometry in which highly charged water clusters produced from the atmospheric-pressure electrospray are accelerated in vacuum by 10 kV and impact the sample deposited on the metal substrate. EDI/SIMS was shown to enhance intact molecular ion formation dramatically compared to conventional SIMS. EDI/SIMS has been successfully applied to the analysis of mouse brain without any sample preparation. Five types of lipids, i.e. phosphatidylcholine (PC), phosphatidylserine, phosphatidylinositol (PI), galactocerebroside (GC) and sulfatide (ST), were readily detected from mouse brain section. In addition, by EDI/SIMS, six different regions of the mouse brain (cerebral cortex, corpus callosum, striatum, medulla oblongata, cerebellar cortex and cerebellar medulla) were examined. While GCs and STs were found to be rich in white matter, PIs were rich in gray matter. Copyright © 2010 John Wiley & Sons, Ltd.
Hydride transfer reactions via ion-neutral complex: fragmentation of protonated N-benzylpiperidines and protonated N-benzylpiperazines in mass spectrometry
An ion-neutral complex (INC)-mediated hydride transfer reaction was observed in the fragmentation of protonated N-benzylpiperidines and protonated N-benzylpiperazines in electrospray ionization mass spectrometry. Upon protonation at the nitrogen atom, these compounds initially dissociated to an INC consisting of [RC6H4CH2]+ (R = substituent) and piperidine or piperazine. Although this INC was unstable, it did exist and was supported by both experiments and density functional theory (DFT) calculations. In the subsequent fragmentation, hydride transfer from the neutral partner to the cation species competed with the direct separation. The distribution of the two corresponding product ions was found to depend on the stabilization energy of this INC, and it was also approved by the study of substituent effects. For monosubstituted N-benzylpiperidines, strong electron-donating substituents favored the formation of [RC6H4CH2]+, whereas strong electron-withdrawing substituents favored the competing hydride transfer reaction leading to a loss of toluene. The logarithmic values of the abundance ratios of the two ions were well correlated with the nature of the substituents, or rather, the stabilization energy of this INC. Copyright © 2010 John Wiley & Sons, Ltd.
Molecular dynamics simulations of MALDI: laser fluence and pulse width dependence of plume characteristics and consequences for matrix and analyte ionization
Molecular dynamics simulations of matrix-assisted laser desorption/ionization were carried out to investigate laser pulse width and fluence effects on primary and secondary ionization process. At the same fluence, short (35 or 350 ps) pulses lead to much higher initial pressures and ion concentrations than longer ones (3 ns), but these differences do not persist because the system relaxes toward local thermal equilibrium on a nanosecond timescale. Higher fluences accentuate the initial disparities, but downstream differences are not substantial. Axial velocities of ions and neutrals are found to span a wide range, and be fluence dependent. Total ion yield is only weakly dependent on pulse width, and consistent with experimental estimates. Secondary reactions of matrix cations with analyte neutrals are efficient even though analyte ions are ablated in clusters of matrix. Copyright © 2010 John Wiley & Sons, Ltd.
Quantification, confirmation and screening capability of UHPLC coupled to triple quadrupole and hybrid quadrupole time-of-flight mass spectrometry in pesticide residue analysis
The potential of three mass spectrometry (MS) analyzers (triple quadrupole, QqQ; time of flight, TOF; and quadrupole time of flight, QTOF) has been investigated and compared for quantification, confirmation and screening purposes in pesticide residue analysis of fruit and vegetable samples. For this purpose, analytical methodology for multiresidue determination of 11 pesticides, taken as a model, has been developed and validated in nine food matrices for the three mass analyzers coupled to ultra high pressure liquid chromatography. In all cases, limits of quantification around 0.01 mg/kg were reached, fulfilling the most restrictive case of baby-food analysis. Regarding absolute sensitivity, the lower limits of detection were obtained, as expected, for QqQ (100 fg), whereas slightly higher limits (300 fg) were obtained for both TOF and QTOF. Confirmative capacity of each analyzer was studied for each analyte based on the identification points (IPs) criterion, useful for a comprehensive comparison. QTOF mass analyzer showed the highest confirmatory capacity, although QqQ normally led to sufficient number of IPs, even at lower concentration levels. The potential of TOF MS was also investigated for screening purposes. To this aim, around 50 commercial fruits and vegetables samples were analyzed, searching for more than 400 pesticides. TOF MS proved to be an attractive analytical tool for rapid detection and reliable identification of a large number of pesticides thanks to the full spectrum acquisition at accurate mass with satisfactory sensitivity. This process is readily boosted when combined with specialized software packages, together with theoretical exact mass databases. Several pesticides (e.g. carbendazim in citrus and indoxacarb in grape) were detected in the samples. Further unequivocal confirmation of the identity was performed using reference standards and/or QTOF MS/MS experiments. Copyright © 2010 John Wiley & Sons, Ltd.
Structural identification of hindered amine light stabilisers in coil coatings using electrospray ionisation tandem mass spectrometry
Hindered amine light stabilisers (HALS) are the most effective antioxidants currently available for polymer systems in post-production, in-service applications, yet the mechanism of their action is still not fully understood. Structural characterisation of HALS in polymer matrices, particularly the identification of structural modifications brought about by oxidative conditions, is critical to aid mechanistic understanding of the prophylactic effects of these molecules. In this work, electrospray ionisation tandem mass spectrometry (ESI-MS/MS) was applied to the analysis of a suite of commercially available 2,2,6,6-tetramethylpiperidine-based HALS. Fragmentation mechanisms for the [M + H]+ ions are proposed, which provide a rationale for the product ions observed in the MS/MS and MS3 mass spectra of N-H, N-CH3, N-C(O)CH3 and N-OR containing HALS (where R is an alkyl substituent). A common product ion at m/z 123 was identified for the group of antioxidants containing N-H, N-CH3 or N-C(O)CH3 functionality, and this product ion was employed in precursor ion scans on a triple quadrupole mass spectrometer to identify the HALS species present in a crude extract from of a polyester-based coil coating. Using MS/MS, two degradation products were unambiguously identified. This technique provides a simple and selective approach to monitoring HALS structures within complex matrices. Copyright © 2010 John Wiley & Sons, Ltd.
Qualitative screening for volatile organic compounds in human blood using solid-phase microextraction and gas chromatography-mass spectrometry
A fast and simple screening procedure using solid-phase microextraction and gas chromatography-mass spectrometry (SPME-GC-MS) in full-scan mode for the determination of volatile organic compounds (VOC) is presented. The development of a fast and simple screening technique for the simultaneous determination of various volatiles is of great importance, because of their widespread use, frequent occurrence in forensic toxicological questions and the fact that there is often no hint on involved substances at the crime scene. To simulate a screening procedure, eight VOC with different chemical characteristics were chosen (isoflurane, halothane, hexane, chloroform, benzene, isooctane, toluene and xylene). To achieve maximum sensitivity, variables that influence the SPME process, such as type of fiber, extraction and desorption temperature and time, agitation and additives were optimized by preliminary studies and by means of a central composite design. The limits of detection and recoveries ranged from 2.9 µg/l (xylene) to 37.1 µg/l (isoflurane) and 7.9% (chloroform) to 61.5% (benzene), respectively. This procedure can be used to answer various forensic and toxicological questions. The short time taken for the whole analytical procedure may make its eventual adoption for routine analysis attractive. Copyright © 2010 John Wiley & Sons, Ltd.
Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: An update for the period 2005-2006
This review is the fourth update of the original review, published in 1999, on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2006. The review covers fundamental studies, fragmentation of carbohydrate ions, method developments, and applications of the technique to the analysis of different types of carbohydrate. Specific compound classes that are covered include carbohydrate polymers from plants, N- and O-linked glycans from glycoproteins, glycated proteins, glycolipids from bacteria, glycosides, and various other natural products. There is a short section on the use of MALDI-TOF mass spectrometry for the study of enzymes involved in glycan processing, a section on industrial processes, particularly the development of biopharmaceuticals and a section on the use of MALDI-MS to monitor products of chemical synthesis of carbohydrates. Large carbohydrate-protein complexes and glycodendrimers are highlighted in this final section. © 2010 Wiley Periodicals, Inc. Mass Spec Rev
Identification of carbonylation sites in apomyoglobin after exposure to 4-hydroxy-2-nonenal by solid-phase enrichment and liquid chromatography-electrospray ionization tandem mass spectrometry
Identification of protein carbonylation because of covalent attachment of a lipid peroxidation end-product was performed by combining proteolytic digestion followed by solid-phase hydrazide enrichment and liquid chromatography (LC)-electrospray ionization (ESI) tandem mass spectrometry (MS/MS) using both collision-induced dissociation (CID) and electron capture dissociation (ECD). To evaluate this approach, we selected apomyoglobin and 4-hydroxy-2-nonenal (4-HNE) as a model protein and a representative end-product of lipid peroxidation, respectively. Although the characteristic elimination of 4-HNE (156 Da) in CID was found to serve as a signature tag for the modified peptides, generation of nearly complete fragment ion series because of efficient peptide backbone cleavage (in most cases over 75%) and the capability to retain the labile 4-HNE moiety of the tryptic peptides significantly aided the elucidation of primary structural information and assignment of exact carbonylation sites in the protein, when ECD was employed. We have concluded that solid-phase enrichment with both CID- and ECD-MS/MS are advantageous during an in-depth interrogation and unequivocal localization of 4-HNE-induced carbonylation of apomyoglobin that occurs via Michael addition to its histidine residues. Copyright © 2010 John Wiley & Sons, Ltd.
Pneumatically assisted desorption/ionization: 1. Some thoughts on the possible ionization mechanism(s)
We have observed that spraying solvent droplets on a zopiclone tablet produced MH+ ions also in the absence of any electrical field and without the addition of organic acids to the sprayed solvent. The choice of a drug tablet as test bench has been done for the signal stability, higher than that observed when the drug is directly placed on a stainless steel surface. This behavior indicates that the formation of MH+ ions is mainly due to pneumatical effects and the results are discussed with respect to those obtained by other research groups. Different mechanisms contributing to MH+ production under these conditions are proposed and discussed. The local heating of the solvent thin layer present on the surface has been calculated and the small temperature increase (and the consequent small decrease of pKa value) suggests that this effect can play only a minor role. However, different solvents have been employed for studying this aspect and, quite surprisingly, the best results have been obtained with acetonitrile (ACN). Experiments performed by spraying CD3CN showed again the formation of MH+ and not MD+, and this excludes the role of ACN as protonating medium. A further thought was stimulated by the behavior observed by varying the sheath gas (N2) flow, showing that the MH+ ion intensity increases by increasing the flow. Side effects related to the highest kinetic energy of the spraying droplets can be considered, but an active role of N2 in the MH+ formation could be taken into account, by considering the possible ionization of N2 by collisional phenomena. The N2+[bull] ions could undergo a charge-exchange reaction with analyte molecules leading to a short-lived odd electron ion which behaves as protonating media for neutral molecules. The above-described mechanism does not require either the presence of electrical fields nor the addition of organic acid to the sprayer solvent and can give a rationale for what was observed when only pneumatical conditions are employed. Copyright © 2010 John Wiley & Sons, Ltd.
Applications of mass spectrometry to the study of siRNA
RNA interference (RNAi) has quickly become a well-established laboratory tool for regulating gene expression and is currently being explored for its therapeutic potential. The design and use of double-stranded RNA oligonucleotides as therapeutics to trigger the RNAi mechanism and a greater effort to understand the RNAi pathway itself is driving the development of analytical techniques that can characterize these oligonucleotides. Electrospray (ESI) and MALDI have been used routinely to analyze oligonucleotides and their ability to provide mass and sequence information has made them ideal for this application. Reviewed here is the work done to date on the use of ESI and MALDI for the study of RNAi oligonucleotides as well as the strategies and issues associated with siRNA analysis by mass spectrometry. While there is not a large body of literature on the specific application of mass spectrometry to RNAi, the work done in this area is a good demonstration of the range of experiments that can be conducted and the value that ESI and MALDI can provide to the RNAi field. © 2010 Wiley Periodicals, Inc. Mass Spec Rev
Characterization and de novo sequencing of snow crab tropomyosin enzymatic peptides by both electrospary ionization and matrix-assisted laser desorption ionization QqToF tandem mass spectrometry
The protein tropomyosin (TM) is a known major allergen present in shellfish causing frequent food allergies. TM is also an occupational allergen generated in the working environment of snow crab (Chionoecetes opilio) processing plants. The TM protein was purified from both claw and leg meats of snow crab and analyzed by electrospray ionization and matrix-assisted laser desorption/ionization (MALDI) using hybrid quadruple time-of-flight tandem mass spectrometry (QqToF-MS). The native polypeptide molecular weight of TM was determined to be 32 733 Da. The protein was further characterized using the 'bottom-up' MS approach. A peptide mass fingerprinting was obtained by two different enzymatic digestions and de novo sequencing of the most abundant peptides performed. Any post-translational modifications were identified by searching their calculated and predicted molecular weights in precursor ion spectra. The immunological reactivity of snow crab extract was evaluated using specific antibodies and allergenic reactivity assessed with serum of allergic patients. Subsequently, a signature peptide for TM was identified and evaluated in terms of identity and homology using the basic local alignment search tool (BLAST). The identification of a signature peptide for the allergen TM using MALDI-QqToF-MS will be critical for the sensitive and specific quantification of this highly allergenic protein in the work place. Copyright © 2010 John Wiley & Sons, Ltd.
The carbon versus mass diagram to visualize and exploit FTICR-MS data of natural organic matter
A two-dimensional diagram is proposed, in which the carbon number of each formula is plotted against its nominal mass, to visualize large sets of molecular formula data that can be derived from data generated by ultrahigh-resolution Fourier transform ion cyclotron resonance-MS. In such a carbon versus mass (CvM) diagram, each formula (CcHhOo) is unambiguously described by c, its (nominal) mass and the parameter i = c + o. Calculations of chemically allowable formulas illustrate that organic molecules occupy only certain spaces in such a diagram. The extension of these spaces increases with molecular mass in x-direction (hydrogenation) and y-direction (oxygenation). The data sets of molecules determined in natural organic matter(NOM) occupy only a certain range of the allowable space. The intensity of the mass spectrometric signals can be included as the third dimension into a CvM diagram. Separate CvM diagrams can be plotted for NOM molecules that include different heteroatoms. The benefits of the CvM diagram are illustrated by application onto data sets of fulvic acids from riverine and marine origin, of secondary organic aerosol, including organosulfates and organonitrates, as well as of ozonation of fulvic acids. The CvM diagram is a useful tool to visualize the elemental regularities in NOM isolates as well as the differences between isolates. It may also be applicable to large sets of molecular formula data generated in other disciplines such as petroleum biogeochemistry or metabolomics. Copyright © 2010 John Wiley & Sons, Ltd.
The assay of pterostilbene in spiked matrices by liquid chromatography tandem mass spectrometry and isotope dilution method
Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is an active component found in several plant species, exhibiting important pharmacological properties. A new and reliable method of assaying this phyto compound in various matrices is presented; the assay is based on (1) the selectivity of liquid chromatography (LC) hyphenated with electrospray ionisation (ESI), (2) the specificity of a two-step mass spectrometric analysis (MS/MS) and (3) the accuracy of the isotope dilution method. The labelled analogue may be conveniently synthesised in a few steps. The sensitivity of the method is confirmed by the very low limit of detection (LOD) and limit of quantitation (LOQ) values achieved in the assay of pterostilbene in two distinct fortified matrices, and is further supported by the observed accuracy values. Copyright © 2010 John Wiley & Sons, Ltd.
Modelling mass analyzer performance with fields determined using the boundary element method
Computer modelling is widely used in the design of mass analysers to evaluate proposed designs and determine the effects of manufacturing imperfections. For quadrupole mass filters and ion traps, the models require accurate values of the electric field throughout the regions of the analyser in which ions travel. Most published results using models to predict mass analyser behaviour use electric fields computed with finite element (FE) or finite difference (FD) method. However, the boundary element method (BEM) is capable of achieving the same, or higher, accuracy with both computation times and memory requirements that are at least an order of magnitude less than those required by FE and FD methods. In this paper, electric field evaluation is performed using the BEM formulated in a manner described by previous workers; modifications to their method are described, which lead to higher accuracy field values. Simultaneous equation solution techniques are incorporated, which avoid solutions that are physically not realistic. The performance of linear quadrupole mass spectrometers with hyperbolic, circular and planar section electrodes has been determined using fields computed using these methods and compared with previous results obtained by alternative field computation techniques and with experiment. Behaviour of an ion trap mass spectrometer with circular symmetry has also been investigated. The results demonstrate that in each case using the BEM to determine the fields produces the observed behaviour. Copyright © 2010 John Wiley & Sons, Ltd.
Biomedical application of MALDI mass spectrometry for small-molecule analysis
Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) is an emerging analytical tool for the analysis of molecules with molar masses below 1,000 Da; that is, small molecules. This technique offers rapid analysis, high sensitivity, low sample consumption, a relative high tolerance towards salts and buffers, and the possibility to store sample on the target plate. The successful application of the technique is, however, hampered by low molecular weight (LMW) matrix-derived interference signals and by poor reproducibility of signal intensities during quantitative analyses. In this review, we focus on the biomedical application of MALDI-MS for the analysis of small molecules and discuss its favorable properties and its challenges as well as strategies to improve the performance of the technique. Furthermore, practical aspects and applications are presented. © 2010 Wiley Periodicals, Inc. Mass Spec Rev
Developments in molecular SIMS depth profiling and 3D imaging of biological systems using polyatomic primary ions
In principle mass spectral imaging has enormous potential for discovery applications in biology. The chemical specificity of mass spectrometry combined with spatial analysis capabilities of liquid metal cluster beams and the high yields of polyatomic ion beams should present unprecedented ability to spatially locate molecular chemistry in the 100 nm range. However, although metal cluster ion beams have greatly increased yields in the m/z range up to 1000, they still have to be operated under the static limit and even in most favorable cases maximum yields for molecular species from 1 µm pixels are frequently below 20 counts. However, some very impressive molecular imaging analysis has been accomplished under these conditions. Nevertheless although molecular ions of lipids have been detected and correlation with biology is obtained, signal levels are such that lateral resolution must be sacrificed to provide a sufficient signal to image. To obtain useful spatial resolution detection below 1 µm is almost impossible. Too few ions are generated! The review shows that the application of polyatomic primary ions with their low damage cross-sections offers hope of a new approach to molecular SIMS imaging by accessing voxels rather than pixels to thereby increase the dynamic signal range in 2D imaging and to extend the analysis to depth profiling and 3D imaging. Recent data on cells and tissue analysis suggest that there is, in consequence, the prospect that a wider chemistry might be accessible within a sub-micron area and as a function of depth. However, these advances are compromised by the pulsed nature of current ToF-SIMS instruments. The duty cycle is very low and results in excessive analysis times, and maximum mass resolution is incompatible with maximum spatial resolution. New instrumental directions are described that enable a dc primary beam to be used that promises to be able to take full advantage of all the capabilities of the polyatomic ion beam. Some new data are presented that suggest that the aspirations for these new instruments will be realized. However, although prospects are good, the review highlights the continuing challenges presented by the low ionization efficiency and the complications that arise from matrix effects. © 2010 Wiley Periodicals, Inc. Mass Spec Rev
Glycoprotein analysis using protein microarrays and mass spectrometry
Protein glycosylation plays an important role in a multitude of biological processes such as cell-cell recognition, growth, differentiation, and cell death. It has been shown that specific glycosylation changes are key in disease progression and can have diagnostic value for a variety of disease types such as cancer and inflammation. The complexity of carbohydrate structures and their derivatives makes their study a real challenge. Improving the isolation, separation, and characterization of carbohydrates and their glycoproteins is a subject of increasing scientific interest. With the development of new stationary phases and molecules that have affinity properties for glycoproteins, the isolation and separation of these compounds have advanced significantly. In addition to detection with mass spectrometry, the microarray platform has become an essential tool to characterize glycan structure and to study glycosylation-related biological interactions, by using probes as a means to interrogate the spotted or captured glycosylated molecules on the arrays. Furthermore, the high-throughput and reproducible nature of microarray platforms have been highlighted by its extensive applications in the field of biomarker validation, where a large number of samples must be analyzed multiple times. This review covers a brief survey of the other experimental methodologies that are currently being developed and used to study glycosylation and emphasizes methodologies that involve the use of microarray platforms. This review describes recent advances in several options of microarray platforms used in glycoprotein analysis, including glycoprotein arrays, glycan arrays, lectin arrays, and antibody/lectin arrays. The translational use of these arrays in applications related to characterization of cells and biomarker discovery is also included. © 2010 Wiley Periodicals, Inc. Mass Spec Rev
Evidence for site-specific intra-ionic hydrogen/deuterium exchange in the low-energy collision-induced dissociation product ion spectra of protonated small molecules generated by electrospray ionisation
The experimental investigation of site-specific intra-ionic hydrogen/deuterium (H/D) exchange in the low-energy collision-induced dissociation (CID) product ion spectra of protonated small molecules generated by electrospray ionisation (ESI) is presented. The observation of intra-ionic H/D exchange in such ions under low-energy CID conditions has hitherto been rarely reported. The data suggest that the intra-ionic H/D exchange takes place in a site-specific manner between the ionising deuteron, localised at either a tertiary amine or a tertiary amine-N-oxide, and a [gamma]-hydrogen relative to the nitrogen atom. Nuclear magnetic resonance (NMR) spectroscopy measurements showed that no H/D exchange takes place in solution, indicating that the reaction occurs in the gas phase. The compounds analysed in this study suggested that electron-withdrawing groups bonded to the carbon atom bearing the [gamma]-hydrogen can preclude exchange. The effect of the electron-withdrawing group appears dependent upon its electronegativity, with lower [chi] value groups still allowing exchange to take place. However, the limited dataset available in this study prevented robust conclusions being drawn regarding the effect of the electron-withdrawing group. The observation of site-specific intra-ionic H/D exchange has application in the area of structural elucidation, where it could be used to introduce an isotopic label into the carbon skeleton of a molecule containing specific structural features. This could increase the throughput, and minimise the cost, of such studies due to the obviation of the need to produce a deuterium-labelled analogue by synthetic means. Copyright © 2010 John Wiley & Sons, Ltd.
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
Mass spectrometry of the photolysis of sulfonylurea herbicides in prairie waters
This review of mass spectrometry of sulfonylurea herbicides includes a focus on studies relevant to Canadian Prairie waters. Emphasis is given to data gaps in the literature for the rates of photolysis of selected sulfonylurea herbicides in different water matrices. Specifically, results are evaluated for positive ion electrospray tandem mass spectrometry with liquid chromatography separation for the study of the photolysis of chlorsulfuron, tribenuron-methyl, thifensulfuron-methyl, metsulfuron-methyl, and ethametsulfuron-methyl. LC-MS/MS is shown to be the method of choice for the quantification of sulfonylurea herbicides with instrumental detection limits ranging from 1.3 to 7.2 pg (on-column). Tandem mass spectrometry coupled with the use of authentic standards likewise has proven to be well suited for the identification of transformation products. To date, however, the power of time-of-flight MS and ultrahigh resolution MS has not been exploited fully for the identification of unknown photolysis products. Dissipation of the herbicides under natural sunlight fit pseudo-first-order kinetics with half-life values ranging from 4.4 to 99 days. For simulated sunlight, radiation wavelengths shorter than 400 nm are required to induce significant photolytic reactions. The correlation between field dissipation studies and laboratory photolysis experiments suggests that photolysis is a major pathway for the dissipation of some sulfonylurea herbicides in natural Prairie waters. © 2009 Wiley Periodicals, Inc. Mass Spec Rev
The role of mass spectrometry-based metabolomics in medical countermeasures against radiation
Radiation metabolomics can be defined as the global profiling of biological fluids to uncover latent, endogenous small molecules whose concentrations change in a dose-response manner following exposure to ionizing radiation. In response to the potential threat of nuclear or radiological terrorism, the Center for High-Throughput Minimally Invasive Radiation Biodosimetry was established to develop field-deployable biodosimeters based, in part, on rapid analysis by mass spectrometry of readily and easily obtainable biofluids. In this review, we briefly summarize radiation biology and key events related to actual and potential nuclear disasters, discuss the important contributions the field of mass spectrometry has made to the field of radiation metabolomics, and summarize current discovery efforts to use mass spectrometry-based metabolomics to identify dose-responsive urinary constituents, and ultimately to build and deploy a noninvasive high-throughput biodosimeter. © 2009 Wiley Periodicals, Inc. Mass Spec Rev
Nuclear applications of inorganic mass spectrometry
There are several basic characteristics of mass spectrometry that are not always fully appreciated by the science community. These characteristics include the distinction between relative and absolute isotope abundances, and the influence of isotope fractionation on the accuracy of isotopic measurements. These characteristics can be illustrated in the field of nuclear physics with reference to the measurement of nuclear parameters, which involve the use of enriched isotopes, and to test models of s-, r-, and p-process nucleosynthesis. The power of isotope-dilution mass spectrometry (IDMS) to measure trace elements in primitive meteorites to produce accurate Solar System abundances has been essential to the development of nuclear astrophysics. The variety of mass spectrometric instrumentation used to measure the isotopic composition of elements has sometimes been accompanied by a lack of implementation of basic mass spectrometric protocols which are applicable to all instruments. These metrological protocols are especially important in atomic weight determinations, but must also be carefully observed in cases where the anomalies might be very small, such as in studies of the daughter products of extinct radionuclides to decipher events in the early history of the Solar System. There are occasions in which misleading conclusions have been drawn from isotopic data derived from mass spectrometers where such protocols have been ignored. It is important to choose the mass spectrometer instrument most appropriate to the proposed experiment. The importance of the integrative nature of mass spectrometric measurements has been demonstrated by experiments in which long, double beta decay and geochronological decay half-lives have been measured as an alternative to costly radioactive-counting experiments. This characteristic is also illustrated in the measurement of spontaneous fission yields, which have accumulated over long periods of time. Mass spectrometry is also a valuable tool in the determination of neutron capture cross-section measurements and the application of such determinations in Planetary Science. © 2009 Wiley Periodicals, Inc. Mass Spec Rev
Advances in protein turnover analysis at the global level and biological insights
The concept of a dynamic state of body constituents, a precursor of the modern term of proteome dynamics, was conceived over a century ago. But, not until recently can we examine the dynamics of individual "constituents" for example, proteins at a truly global level. The path of advancement in our understanding of protein turnover at the global level is marked by the introduction of some key technological innovations. These methods include the isotopic tracer technique in the 1930s, the two-dimensional gel electrophoresis technique in the 1970s, the sector mass spectrometer that could analyze isotopomers of peptides in the early 1990s, the 2D gel/MALDI-TOF proteomics technology in the late 1990s, the booming liquid chromatography/mass spectrometry proteomics technology in this decade, and the recently emerging protein-tagging approaches that offer single-cell resolution for protein turnover measurements. The long-standing inquiry raised in the 1950s about the existence of a dynamic state in different organisms at different physiological conditions can now be answered with an individual "constituent" resolution on a truly global scale. Now it appears that protein degradation is not necessarily an end to the protein function. Rather, it can be the start of a new function because protein degradation clears the way for the action of other proteins. Protein turnover participates in a multi-layer complex regulatory network and shares equal importance with gene transcription and protein translation. The advances in technologies for protein turnover analysis and the improved understanding of the biological role of protein turnover will likely help to solve some long-standing biomedical problems such as the tuberculosis disease that at the present day still affects one-third of the world population. © 2009 Wiley Periodicals, Inc. Mass Spec Rev
Environmental analysis by inductively coupled plasma mass spectrometry
This article reviews the numerous ways in which inductively coupled plasma mass spectrometry has been used for the analysis of environmental samples since it was commercially introduced in 1983. Its multielemental isotopic capability, high sensitivity and wide linear dynamic range makes it ideally suited for environmental analysis. Provided that some care is taken during sample preparation and that appropriate calibration strategies are used to circumvent non-spectroscopic interferences, the technique is readily applicable to the analysis of a wide variety of environmental samples (natural waters, soils, rocks, sediments, vegetation, etc.), using quadrupole, time-of-flight or double-focusing sector-field mass spectrometers. In cases where spectroscopic interferences arising from the sample matrix cannot be resolved, then separation methods can be implemented either on- or off-line, which can simultaneously allow analyte preconcentration, thus further decreasing the already low detection limits that are achievable. In most cases, the blank, prepared by following the same steps as for the sample but without the sample, limits the ultimate detection limits that can be reached. © 2009 Wiley Periodicals, Inc. Mass Spec Rev
Application of mass spectrometry in the analysis of polybrominated diphenyl ethers
This review summarized the applications of mass spectrometric techniques for the analysis of the important flame retardants polybrominated diphenyl ethers (PBDEs) to understand the environmental sources, fate and toxicity of PBDEs that were briefly discussed to give a general idea for the need of analytical methodologies. Specific performance of various mass spectrometers hyphenated with, for example, gas chromatograph, liquid chromatograph, and inductively coupled plasma (GC/MS, LC/MS, and ICP/MS, respectively) for the analysis of PBDEs was compared with an objective to present the information on the evolution of MS techniques for determining PBDEs in environmental and human samples. GC/electron capture negative ionization quadrupole MS (GC/NCI qMS), GC/high resolution MS (GC/HRMS) and GC ion trap MS (GC/ITMS) are most commonly used MS techniques for the determination of PBDEs. New analytical technologies such as fast tandem GC/MS and LC/MS become available to improve analyses of higher PBDEs. The development and application of the tandem MS techniques have helped to understand environmental fate and transformations of PBDEs of which abiotic and biotic degradation of decaBDE is thought to be one major source of Br1-9BDEs present in the environment in addition to direct loading from commercial mixtures. MS-based proteomics will offer an insight into the molecular mechanisms of toxicity and potential developmental and neurotoxicity of PBDEs. © 2009 Wiley Periodicals, Inc. Mass Spec Rev
Liquid chromatography-tandem mass spectrometry applications in endocrinology
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been recognized as a primary methodology for the accurate analysis of endogenous steroid hormones in biological samples. This review focuses on the use of LC-MS/MS in clinical laboratories to assist with the diagnosis of diverse groups of endocrine and metabolic diseases. Described analytical methods use on-line and off-line sample preparation and analytical derivatization to enhance analytical sensitivity, specificity, and clinical utility. Advantages of LC-MS/MS as an analytical technique include high specificity, possibility to simultaneously measure multiple analytes, and the ability to assess the specificity of the analysis in every sample. All described analytical methods were extensively validated, utilized in routine diagnostic practice, and were applied in a number of clinical and epidemiological studies, including a study of the steroidogenesis in ovarian follicles. © 2009 Wiley Periodicals, Inc. Mass Spec Rev
Mass spectrometry combined with oxidative labeling for exploring protein structure and folding
This review discusses various mass spectrometry (MS)-based approaches for exploring structural aspects of proteins in solution. Electrospray ionization (ESI)-MS, in particular, has found fascinating applications in this area. For example, when used in conjunction with solution-phase hydrogen/deuterium exchange (HDX), ESI-MS is a highly sensitive tool for probing conformational dynamics. The main focus of this article is a technique that is complementary to HDX, that is, the covalent labeling of proteins by hydroxyl radicals. The reactivity of individual amino acid side chains with .OH is strongly affected by their degree of solvent exposure. Thus, analysis of the oxidative labeling pattern by peptide mapping and tandem mass spectrometry provides detailed structural information. A convenient method for .OH production is the photolysis of H2O2 by a pulsed UV laser, resulting in oxidative labeling on the microsecond time scale. Selected examples demonstrate the use of this technique for structural studies on membrane proteins, and the combination with rapid mixing devices for characterizing the properties of short-lived protein (un)folding intermediates. © 2009 Wiley Periodicals, Inc. Mass Spec Rev
The analysis of dioxins and related compounds
The analysis of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, polychlorinated biphenyls, and other related compounds requires complex sample preparation and analytical procedures using highly sensitive and selective state-of-the-art instrumentation to meet very stringent data quality objectives. The analytical procedures (extraction, sample preparation), instrumentation (chromatographic separation and detection by mass spectrometry) and screening techniques for the determination of dioxins, furans, dioxin-like polychlorinated biphenyls and related compounds with a focus on new approaches and alternate techniques to standard regulatory methods are reviewed. © 2009 Wiley Periodicals, Inc. Mass Spec Rev
Advances on the compositional analysis of glycosphingolipids combining thin-layer chromatography with mass spectrometry
Glycosphingolipids (GSLs), composed of a hydrophilic carbohydrate chain and a lipophilic ceramide anchor, play pivotal roles in countless biological processes, including infectious diseases and the development of cancer. Knowledge of the number and sequence of monosaccharides and their anomeric configuration and linkage type, which make up the principal items of the glyco code of biologically active carbohydrate chains, is essential for exploring the function of GSLs. As part of the investigation of the vertebrate glycome, GSL analysis is undergoing rapid expansion owing to the application of novel biochemical and biophysical technologies. Mass spectrometry (MS) takes part in the network of collaborations to further unravel structural and functional aspects within the fascinating world of GSLs with the ultimate aim to better define their role in human health and disease. However, a single-method analytical MS technique without supporting tools is limited yielding only partial structural information. Because of its superior resolving power, robustness, and easy handling, high-performance thin-layer chromatography (TLC) is widely used as an invaluable tool in GSL analysis. The intention of this review is to give an insight into current advances obtained by coupling supplementary techniques such as TLC and mass spectrometry. A retrospective view of the development of this concept and the recent improvements by merging (1) TLC separation of GSLs, (2) their detection with oligosaccharide-specific proteins, and (3) in situ MS analysis of protein-detected GSLs directly on the TLC plate, are provided. The procedure works on a nanogram scale and was successfully applied to the identification of cancer-associated GSLs in several types of human tumors. The combination of these two supplementary techniques opens new doors by delivering specific structural information of trace quantities of GSLs with only limited investment in sample preparation. © 2009 Wiley Periodicals, Inc. Mass Spec Rev
A review of current applications of mass spectrometry for neuroproteomics in epilepsy
The brain is unquestionably the most fascinating organ, and the hippocampus is crucial in memory storage and retrieval and plays an important role in stress response. In temporal lobe epilepsy (TLE), the seizure origin typically involves the hippocampal formation. Despite tremendous progress, current knowledge falls short of being able to explain its function. An emerging approach toward an improved understanding of the complex molecular mechanisms that underlie functions of the brain and hippocampus is neuroproteomics. Mass spectrometry has been widely used to analyze biological samples, and has evolved into an indispensable tool for proteomics research. In this review, we present a general overview of the application of mass spectrometry in proteomics, summarize neuroproteomics and systems biology-based discovery of protein biomarkers for epilepsy, discuss the methodology needed to explore the epileptic hippocampus proteome, and also focus on applications of ingenuity pathway analysis (IPA) in disease research. This neuroproteomics survey presents a framework for large-scale protein research in epilepsy that can be applied for immediate epileptic biomarker discovery and the far-reaching systems biology understanding of the protein regulatory networks. Ultimately, knowledge attained through neuroproteomics could lead to clinical diagnostics and therapeutics to lessen the burden of epilepsy on society. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:197-246, 2010
Metabolomic applications of HILIC-LC-MS
Hydrophilic interaction liquid chromatography (HILIC), although not a new technique, has enjoyed a recent renaissance with the introduction of robust and reproducible stationary phases. It is consequently finding application in metabolomics studies, which have traditionally relied on the stability of reversed phases (RPs), since the biofluids analyzed are predominantly aqueous and thus contain many polar analytes. HILIC's retention of those polar compounds and use of solvents readily compatible with mass spectrometry have seen its increasing adoption in studies of complex aqueous metabolomes. This review describes the stationary phases and their features, surveys HILIC-LC-MS's role in metabolomics experiments, discusses approaches to data extraction and analysis including multivariate analysis, and reviews the literature on HILIC-MS applications in metabolomics. © 2009 Wiley Periodicals, Inc., Mass Spec Rev
Calcium isotope analysis by mass spectrometry
The variations in the isotopic composition of calcium caused by fractionation in heterogeneous systems and by nuclear reactions can provide insight into numerous biological, geological, and cosmic processes, and therefore isotopic analysis finds a wide spectrum of applications in cosmo- and geochemistry, paleoclimatic, nutritional, and biomedical studies. The measurement of calcium isotopic abundances in natural samples has challenged the analysts for more than three decades. Practically all Ca isotopes suffer from significant isobaric interferences, whereas low-abundant isotopes can be particularly affected by neighboring major isotopes. The extent of natural variations of stable isotopes appears to be relatively limited, and highly precise techniques are required to resolve isotopic effects. Isotope fractionation during sample preparation and measurements and instrumental mass bias can significantly exceed small isotope abundance variations in samples, which have to be investigated. Not surprisingly, a TIMS procedure developed by Russell et al. (Russell et al., . Geochim Cosmochim Acta 42: 1075-1090) for Ca isotope measurements was considered as revolutionary for isotopic measurements in general, and that approach is used nowadays (with small modifications) for practically all isotopic systems and with different mass spectrometric techniques. Nevertheless, despite several decades of calcium research and corresponding development of mass spectrometers, the available precision and accuracy is still not always sufficient to achieve the challenging goals. The present article discusses figures of merits of presently used analytical methods and instrumentation, and attempts to critically assess their limitations. In Sections 2 and 3, mass spectrometric methods applied to precise stable isotope analysis and to the determination of 41Ca are described. Section 4 contains a short summary of selected applications, and includes tracer experiments and the potential use of biological isotope fractionation in medical studies, paleoclimatic and paleoceanographic, and other terrestrial as well as extraterrestrial investigations. © 2009 Wiley Periodicals, Inc., Mass Spec Rev
Microchip technology in mass spectrometry
Microfabrication of analytical devices is currently of growing interest and many microfabricated instruments have also entered the field of mass spectrometry (MS). Various (atmospheric pressure) ion sources as well as mass analyzers have been developed exploiting microfabrication techniques. The most common approach thus far has been the miniaturization of the electrospray ion source and its integration with various separation and sampling units. Other ionization techniques, mainly atmospheric pressure chemical ionization and photoionization, have also been subject to miniaturization, though they have not attracted as much attention. Likewise, all common types of mass analyzers have been realized by microfabrication and, in most cases, successfully applied to MS analysis in conjunction with on-chip ionization. This review summarizes the latest achievements in the field of microfabricated ion sources and mass analyzers. Representative applications are reviewed focusing on the development of fully microfabricated systems where ion sources or analyzers are integrated with microfluidic separation devices or microfabricated pums and detectors, respectively. Also the main microfabrication methods, with their possibilities and constraints, are briefly discussed together with the most commonly used materials. © 2009 Wiley Periodicals, Inc., Mass Spec Rev
ICP-MS-Based strategies for protein quantification
In the post-genomics era, proteomics has become a central branch in life sciences. An understanding of biological functions will not only rely on protein identification, but also on protein quantification in a living organism. Most of the existing methods for quantitative proteomics are based on isotope labeling combined with molecular mass spectrometry. Recently, a remarkable progress that utilizes inductively coupled plasma-mass spectrometry (ICP-MS) as an attractive complement to electrospray MS and MALDI MS for protein quantification, especially for absolute quantification, has been achieved. This review will selectively discuss the recent advances of ICP-MS-based technique, which will be expected to further mature and to become one of the key methods in quantitative proteomics. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:326-348, 2010
Cluster secondary ion mass spectrometry of polymers and related materials
Cluster secondary ion mass spectrometry (cluster SIMS) has played a critical role in the characterization of polymeric materials over the last decade, allowing for the ability to obtain spatially resolved surface and in-depth molecular information from many polymer systems. With the advent of new molecular sources such as , , , and , there are considerable increases in secondary ion signal as compared to more conventional atomic beams (Ar+, Cs+, or Ga+). In addition, compositional depth profiling in organic and polymeric systems is now feasible, without the rapid signal decay that is typically observed under atomic bombardment. The premise behind the success of cluster SIMS is that compared to atomic beams, polyatomic beams tend to cause surface-localized damage with rapid sputter removal rates, resulting in a system at equilibrium, where the damage created is rapidly removed before it can accumulate. Though this may be partly true, there are actually much more complex chemistries occurring under polyatomic bombardment of organic and polymeric materials, which need to be considered and discussed to better understand and define the important parameters for successful depth profiling. The following presents a review of the current literature on polymer analysis using cluster beams. This review will focus on the surface and in-depth characterization of polymer samples with cluster sources, but will also discuss the characterization of other relevant organic materials, and basic polymer radiation chemistry. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:247-293, 2010
In vivo monitoring of the transfer kinetics of trace elements in animal brains with hyphenated inductively coupled plasma mass spectrometry techniques
The roles of metal ions to sustain normal function and to cause dysfunction of neurological systems have been confirmed by various studies. However, because of the lack of adequate analytical method to monitor the transfer kinetics of metal ions in the brain of a living animal, research on the physiopathological roles of metal ions in the CNS remains in its early stages and more analytical efforts are still needed. To explicitly model the possible links between metal ions and physiopathological alterations, it is essential to develop in vivo monitoring techniques that can bridge the gap between metalloneurochemistry and neurophysiopathology. Although inductively coupled plasma mass spectrometry (ICP-MS) is a very powerful technique for multiple trace element analyses, when dealing with chemically complex microdialysis samples, the detection capability is largely limited by instrumental sensitivity, selectivity, and contamination that arise from the experimental procedure. As a result, in recent years several high efficient and clean on-line sample pretreatment systems have been developed and combined with microdialysis and ICP-MS for the continuous and in vivo determination of the concentration-time profiles of metal ions in the extracellular space of rat brain. This article reviews the research relevant to the development of analytical techniques for the in vivo determination of dynamic variation in the concentration levels of metal ions in a living animal. © 2009 Wiley Periodicals, Inc. Mass Spec Rev
Proteomics of the photoneuroendocrine circadian system of the brain
The photoneuroendocrine circadian system of the brain consists of (a) specialized photoreceptors in the retina, (b) a circadian generator located in the forebrain that contains "clock genes," (c) specialized nuclei in the forebrain involved in neuroendocrine secretion, and (d) the pineal gland. The circadian generator is a nucleus, called the suprachiasmatic nucleus (SCN). The neurons of this nucleus contain "clock genes," the transcription of which exhibits a circadian rhythm. Most circadian rhythms are generated by the neurons of this nucleus and, via neuronal and humoral connections, the SCN controls circadian activity of the brain and peripheral tissues. The endogenous oscillator of the SCN is each day entrained to the length of the daily photoperiod by light that reach the retina, and specialized photoreceptors transmit impulses to the SCN via the optic nerves. Mass screening for day/night variations in gene expression in the circadian system as well as in the whole brain and peripheral tissues have, during the last decade, been performed. However, studies of circadian changes in the proteome have been less investigated. In this survey, the anatomy and function of the circadian-generating system in mammals is described, and recent proteomic studies that investigate day/night changes in the retina, SCN, and pineal gland are reviewed. Further circadian changes controlled by the SCN in gene and protein expression in the liver are discussed. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:313-325, 2010
The ion funnel: Theory, implementations, and applications
The electrodynamic ion funnel has enabled the manipulation and focusing of ions in a pressure regime (0.1-30 Torr) that has challenged traditional approaches, and provided the basis for much greater mass spectrometer ion transmission efficiencies. The initial ion funnel implementations aimed to efficiently capture ions in the expanding gas jet of an electrospray ionization interface and radially focus them for efficient transfer through a conductance limiting orifice. We review the improvements in fundamental understanding of ion motion in ion funnels, the evolution in its implementations that have brought the ion funnel to its current state of refinement, as well as applications of the ion funnel for purposes such as ion trapping, ion cooling, low pressure electrospray, and ion mobility spectrometry. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:294-312, 2010
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
The Sod2 mutant mouse as a model for oxidative stress: A functional proteomics perspective
Oxidative stress has been implicated in the pathogenesis of numerous human diseases and disorders, but the mechanistic basis often remains enigmatic. The Sod2 mutant mouse, which is sensitized to mitochondrial stress, is an ideal mutant model for studying the role of oxidative stress in a diverse range of complications arising from mitochondrial dysfunction and diminished antioxidant defense. To fully appreciate the widespread molecular consequences under increased oxidative stress, a systems approach utilizing proteomics is able to provide a global overview of the complex biological changes, which a targeted single biomolecular approach cannot address fully. This review focuses on the applications of mass spectrometry and functional proteomics in the Sod2 mouse. The combinatorial approach provides novel insights into the interplay of chemistry and biology, free radicals and proteins, thereby augmenting our understanding of how redox perturbations influence protein dynamics. Ultimately, this knowledge can lead to the development of free radical-targeted therapies. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 29:179-196, 2010
