Biological Mass Spectrometry (J Mass Spectrom)

Publications in this journal

• Article: Identification of reducing and nonreducing neutral carbohydrates by laser-enhanced in-source decay (LEISD) MALDI MS.

  Hongmei Yang, Zong-Jun Li, Debin Wan, Wenhui Lian, Shuying Liu
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  ABSTRACT: In this work, laser-enhanced in-source decay (LEISD) technique of matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FT-ICR-MS) was used to distinguish reducing and nonreducing carbohydrates. Interestingly, easier cleavage of (1 → 2)-linked glycosidic bonds for nonreducing carbohydrates containing D-fructofuranosyl units was observed in MALDI-FT-ICR-MS, which was in agreement with the result of theoretical calculation by the software package Gaussian 09. Importantly, no cross-ring cleavage of fructofuranosyl residues was detected in the LEISD spectra of nonreducing carbohydrates. LEISD method therefore offers an attractive alternative for fast and efficient differentiation of reducing and nonreducing carbohydrates, and the positions of nonreducing monosaccharide residues in a carbohydrate chain could be easily speculated. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 05/2013; 48(5):539-543.
• Article: Identification tree based on fragmentation rules for structure elucidation of organophosphorus esters by electrospray mass spectrometry.

  Adrián Schwarzenberg, Farid Ichou, Richard B Cole, Xavier Machuron-Mandard, Christophe Junot, Denis Lesage, Jean-Claude Tabet
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  ABSTRACT: Organophosphorus compounds have played important roles as pesticides, chemical warfare agents and extractors of radioactive material. Structural elucidation of phosphonates poses a particular challenge because their initial forms can be hydrolyzed, thus, degradation products may predominate in samples acquired in the field. The analysis of non-volatile organophosphorus compounds and their degradation products is possible using electrospray tandem mass spectrometry ESI-MS/MS. Here, we present a generic strategy that allows the unambiguous identification of substituents for two families of organophosphorus compounds: the phosphonates and phosphates. General fragmentation rules were deduced based on the study of decomposition pathways of 55 organophosphorus esters, including examples found in the literature. Multistage MS (MS(n) ) experiments at high resolution in a hybrid mass spectrometer provide accurate mass measurements, whereas collision-induced dissociation experiments in a triple quadrupole give access to small fragment ions. The creation of a specific nomenclature for each possible structure of organophosphorus compound, depending on the alkyl side chain linked to the oxygen, was achieved by applying these fragmentation rules. This led to the creation of an 'identification tree' based upon the unique consecutive decomposition pathways uncovered for each individual compound. Hence, seven structural motifs were created that orient an unequivocal identification using the 'identification tree'. Despite the similar structures of the ensemble of phosphate and phosphonate esters, distinct identifications based upon characteristic neutral losses and diagnostic fragment ions were possible in all cases. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 05/2013; 48(5):576-586.
• Article: A quantitative analysis of histone methylation and acetylation isoforms from their deuteroacetylated derivatives: application to a series of knockout mutants.

  Katherine L Fiedler, Poonam Bheda, Junbiao Dai, Jef D Boeke, Cynthia Wolberger, Robert J Cotter
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  ABSTRACT: The core histones, H2A, H2B, H3 and H4, undergo post-translational modifications (PTMs) including lysine acetylation, methylation and ubiquitylation, arginine methylation and serine phosphorylation. Lysine residues may be mono-, di- and trimethylated, the latter resulting in an addition of mass to the protein that differs from acetylation by only 0.03639 Da, but that can be distinguished either on high-performance mass spectrometers with sufficient mass accuracy and mass resolution or via retention times. Here we describe the use of chemical derivatization to quantify methylated and acetylated histone isoforms by forming deuteroacetylated histone derivatives prior to tryptic digestion and bottom-up liquid chromatography-mass spectrometric analysis. The deuteroacetylation of unmodified or mono-methylated lysine residues produces a chemically identical set of tryptic peptides when comparing the unmodified and modified versions of a protein, making it possible to directly quantify lysine acetylation. In this work, the deuteroacetylation technique is used to examine a single histone H3 peptide with methyl and acetyl modifications at different lysine residues and to quantify the relative abundance of each modification in different deacetylase and methylase knockout yeast strains. This application demonstrates the use of the deuteroacetylation technique to characterize modification 'cross-talk' by correlating different PTMs on the same histone tail. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 05/2013; 48(5):608-615.
• Article: Structure-oriented UHPLC-LTQ Orbitrap-based approach as a dereplication strategy for the identification of isoflavonoids from Amphimas pterocarpoides crude extract.

  Job Tchoumtchoua, Dieudonné Njamen, Jean Claude Mbanya, Alexios-Leandros Skaltsounis, Maria Halabalaki
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  ABSTRACT: Hyphenated techniques and especially ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) are nowadays widely employed in natural products research. However, the complex nature of plant extracts complicates considerably the analysis and the identification of their constituents. Nevertheless, new MS analyzers with increased resolving power and accuracy such as the orbital trap (Orbitrap) could facilitate drastically this process. The objective of this study is the development of a new structure-oriented approach based on fast UHPLC-high-resolution (HR)MS and HRMS/MS methodologies for the identification of isoflavonoids in crude extracts. In addition, aims to assist dereplication procedures, to decrease the laborious isolation steps and orient the focused isolation of compounds of interest. As a proof of concept, the methanol extract of the stem bark of Amphimas pterocarpoides (Leguminosae) was selected. Based on chromatographic (retention time, polarity) and spectrometric features (ultraviolet spectra, accurate m/z, proposed elemental composition, ring double bond equivalent, and relative isotopic abundance) as well as HRMS/MS spectra, several isoflavonoids were identified. In order to verify the proposed structures, 11 isoflavonoids were selectively isolated and unambiguously identified using 1&2D nuclear magnetic resonance techniques. Moreover, the isolated isoflavonoids were studied in HRMS/MS level, employing electrospray ionization and atmospheric pressure chemical ionization sources, in both modes. Useful information regarding their fragmentation patterns was obtained, and characteristic diagnostic ions were defined for the identification of methoxylated isoflavones, dihydroisoflavones and 5-hydroxylated isoflavonoids. Based on the current results, the proposed dereplication strategy was verified and could comprise a novel approach for the analysis of crude extracts in the future not only for isoflavonoids but also for other chemical classes of natural products. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 05/2013; 48(5):561-575.
• Article: Direct detection of chlorpropham on potato skin using desorption electrospray ionization.

  Christian Berchtold, Vivian Müller, Lukas Meier, Stefan Schmid, Renato Zenobi
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  ABSTRACT: Most pesticides, herbicides and other plant treatment agents are applied to the crop surface. Direct mass spectrometric methods, such as desorption electrospray ionization (DESI), offer new ways to analyze plant samples directly and rapidly. A strategy for the development and optimization of a DESI method for the direct determination of chemicals on complex surfaces is described. Chlorpropham (CP) was applied to potato surfaces as an example for a crop protection agent and analyzed using a self-made DESI source. Aspects such as instrument selectivity, sensitivity and reproducibility were investigated. The MS(4) fragmentation pattern of CP was analyzed to achieve the necessary detection selectivity, and is discussed in detail. Similar fragmentation was found in the ESI and DESI mass spectra, indicating that the mechanisms of ESI and DESI are closely related. A DESI method for semi-quantification of CP on potatoes was developed. Detection limits of 6.5 µg/kg were found using MS/MS. The reproducibility, in the range of 12% (signal variation), appears to be sufficient for semi-quantitative measurements. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 05/2013; 48(5):587-593.
• Article: High-throughput determination of Sudan Azo-dyes within powdered chili pepper by paper spray mass spectrometry.

  Domenico Taverna, Leonardo Di Donna, Fabio Mazzotti, Barbara Policicchio, Giovanni Sindona
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  ABSTRACT: A high-throughput mass spectrometric method is presented for the simultaneous detection of Sudan I, II, III, IV and Para-Red azo-dyes in foodstuff. The method is based on the use of paper spray mass spectrometry (MS) and deuterium-labeled internal standards on a triple-quadrupole instrument. A detailed assay of each azo-dye was performed by the isotope dilution method, through the precursor ion scan approach, using deuterium-labeled internal standards. The gas-phase breakdown pattern of each labeled and unlabeled analogue displays the naphthoic moiety as a common fragment. Sudan dyes can be determined above the threshold of 1 ppm. Paper spray allows for a wide range of analytes and samples to be investigated by MS in the open air and without sample preparation and bypassing chromatography. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 05/2013; 48(5):544-547.
• Article: Differentiation of isomeric β-(1-4) hexose disaccharides by positive electrospray tandem mass spectrometry.

  Cátia S R Azenha, Manuel A Coimbra, Ana S P Moreira, P Domingues, M Rosário M Domingues
  Biological Mass Spectrometry 05/2013; 48(5):548-552.
• Article: A validated assay by liquid chromatography-tandem mass spectrometry for the simultaneous quantification of elvitegravir and rilpivirine in HIV positive patients.

  Manel Aouri, Alexandra Calmy, Bernard Hirschel, Amalio Telenti, Thierry Buclin, Matthias Cavassini, Andri Rauch, Laurent A Decosterd
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  ABSTRACT: Because of the large variability in the pharmacokinetics of anti-HIV drugs, therapeutic drug monitoring in patients may contribute to optimize the overall efficacy and safety of antiretroviral therapy. An LC-MS/MS method for the simultaneous assay in plasma of the novel antiretroviral agents rilpivirine (RPV) and elvitegravir (EVG) has been developed to that endeavor. Plasma samples (100 μL) extraction is performed by protein precipitation with acetonitrile, and the supernatant is subsequently diluted 1:1 with 20-mM ammonium acetate/MeOH 50:50. After reverse-phase chromatography, quantification of RPV and EVG, using matrix-matched calibration samples, is performed by electrospray ionization-triple quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. The stable isotopic-labeled compounds RPV-(13) C6 and EVG-D6 were used as internal standards. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effects variability (<6.4%), as well as EVG and RPV short and long-term stability in plasma. Calibration curves were validated over the clinically relevant concentrations ranging from 5 to 2500 ng/ml for RPV and from 50 to 5000 ng/ml for EVG. The method is precise (inter-day CV%: 3-6.3%) and accurate (3.8-7.2%). Plasma samples were found to be stable (<15%) in all considered conditions (RT/48 h, +4°C/48 h, -20°C/3 months and 60°C/1 h). Selected metabolite profiles analysis in patients' samples revealed the presence of EVG glucuronide, that was well separated from parent EVG, allowing to exclude potential interferences through the in-source dissociation of glucuronide to parent drug. This new, rapid and robust LCMS/MS assay for the simultaneous quantification of plasma concentrations of these two major new anti-HIV drugs EVG and RPV offers an efficient analytical tool for clinical pharmacokinetics studies and routine therapeutic drug monitoring service. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 05/2013; 48(5):616-625.
• Article: Protein analysis by desorption electrospray ionization mass spectrometry and related methods.

  K A Douglass, A R Venter
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  ABSTRACT: As a tool for analyzing solid samples Desorption Electrospray Ionization MS (DESI-MS) offers some very attractive features: samples require minimal treatment and can remain at atmosphere during the measurement, which have fueled the growth of the technique. In recent years there have been numerous applications for using DESI to analyze a variety of compounds and surfaces which show DESI analysis of larger protein molecules can still present a challenge, particularly when high sensitivity is required. The droplet pickup model of ion formation has been proposed for protein desorption/ionization whereby the charged primary spray interacts with the sample surface to dissolve and desorb analyte molecules followed by desolvation and charge transfer. In the Special Feature, Professor Andre Venter and Kevin Douglass from Western Michigan University deconstruct the DESI process with a particular focus on large proteins and examine the efficiency of the desorption and ionization processes separately, in order to better understand of how each process contributes to the overall detection efficiency of large protein ions.
  Biological Mass Spectrometry 05/2013; 48(5):i.
• Article: Protein analysis by desorption electrospray ionization mass spectrometry and related methods.

  Kevin Aart Douglass, Andre R Venter
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  ABSTRACT: Desorption electrospray ionization mass spectrometry (DESI-MS) requires little to no sample preparation and has been successfully applied to the study of biologically significant macromolecules such as proteins. However, DESI-MS and other ambient methods that use spray desorption to process samples during ionization appear limited to smaller proteins with molecular masses of 25 kDa or less, and a decreasing instrumental response with increasing protein size has often been reported. It has been proposed that this limit results from the inability of some proteins to easily desorb from the surface during DESI sampling. The present study investigates the apparent mass dependence of the instrumental response observed during the DESI-MS analysis of proteins using spray desorption collection and reflective electrospray ionization. Proteins, as large as 66 kDa, are shown to be quantitatively removed from surfaces by using spray desorption collection. However, incomplete dissolution and the formation of protein-protein and protein-contaminant clusters appear to be responsible for the mass-dependent loss in sensitivity for protein analysis. Alternative ambient mass spectrometry approaches that address some of the problems encountered by spray desorption techniques for protein analysis are also discussed. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 05/2013; 48(5):553-560.
• Article: Comparison of direct mass spectrometry methods for the on-line analysis of volatile compounds in foods.

  Isabelle Déléris, Anne Saint-Eve, Etienne Sémon, Hervé Guillemin, Elisabeth Guichard, Isabelle Souchon, Jean-Luc Le Quéré
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  ABSTRACT: For the on-line monitoring of flavour compound release, atmospheric pressure chemical ionization (APCI) and proton transfer reaction (PTR) combined to mass spectrometry (MS) are the most often used ionization technologies. APCI-MS was questioned for the quantification of volatiles in complex mixtures, but direct comparisons of APCI and PTR techniques applied on the same samples remain scarce. The aim of this work was to compare the potentialities of both techniques for the study of in vitro and in vivo flavour release. Aroma release from flavoured aqueous solutions (in vitro measurements in Teflon bags and glass vials) or flavoured candies (in vivo measurements on six panellists) was studied using APCI- and PTR-MS. Very similar results were obtained with both techniques. Their sensitivities, expressed as limit of detection of 2,5-dimethylpyrazine, were found equivalent at 12 ng/l air. Analyses of Teflon bag headspace revealed a poor repeatability and important ionization competitions with both APCI- and PTR-MS, particularly between an ester and a secondary alcohol. These phenomena were attributed to dependency on moisture content, gas/liquid volume ratio, proton affinities and product ion distribution, together with inherent drawbacks of Teflon bags (adsorption, condensation of water and polar molecules). Concerning the analyses of vial headspace and in vivo analyses, similar results were obtained with both techniques, revealing no competition phenomena. This study highlighted the equivalent performances of APCI-MS and PTR-MS for in vitro and in vivo flavour release investigations and provided useful data on the problematic use of sample bags for headspace analyses. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 05/2013; 48(5):594-607.
• Article: Large mixed complexes involving uracil, cytosine, thymine and/or 1-methyl uracil around Ca(2+) ions: an electrospray ionization/MS study.

  Zins Emilie-Laure
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  ABSTRACT: We investigated the possible formation of mixed Bn B'n' Ca(2+) complexes where B and B' are two different nucleobases. Electrospray ionization (ESI) mass spectrometric experiments from solutions containing two different kinds of nucleobases and calcium ions were carried out to investigate the formation of magic number clusters that may be relevant in a biological point of view. The results presented here clearly show that mixed complexes can be formed and are stable in the gas phase. This represents an important step toward more complex solutions in which several nucleobases are present simultaneously and may compete in the formation of cationized clusters. We believe that thorough investigations on such systems may help understanding biological processes that may effect the tridimensional structure of the DNA macromolecule. The formation of mixed hexamers, decamers, dodecamers and tetradecamers are clearly favored from solution containing uracil (Ura), thymine (Thy) and Ca(2+) , whereas mixed octamers are preferred from 1-methyl uracil (MeU), uracil and Ca(2+) mixtures. Cytosine (Cyto) can form mixed complexes with either uracil or 1-methyl uracil or thymine. On the other hand, the main species formed in these latter cases are mixed tetramers. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 04/2013; 48(4):438-47.
• Article: Migration of non intentionally added substances from adhesives by UPLC-Q-TOF/MS and the role of EVOH to avoid migration in multilayer packaging materials.

  Francesca Isella, Elena Canellas, Osvaldo Bosetti, Cristina Nerin
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  ABSTRACT: Polyurethane adhesives are commonly used to laminate multilayer packaging materials for food. Since these materials are in direct contact with the food, compounds could migrate from adhesive into it. For this reason, it is important to identify all the potential migrants and verify their migration. Ultra-high performance liquid chromatography-quadrupole time-of-flight-mass spectrometry analyses and ChemSpider database are used to identify the potential migrants from polyurethane adhesives, and these techniques were demonstrated to be very powerful and useful tools for this purpose. Migration tests were carried out using Tenax® as food simulant. Nine out of fifteen non-volatile compounds, identified in the cured adhesives, migrated. Most of them were identified as cyclic compounds, adipic based, which is the most commonly used monomer to make the polyester/polyol resins for polyurethane bi-component adhesives. In this work, the use of EvOH layer in several multilayer materials to minimize or avoid migration was evaluated too. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 04/2013; 48(4):430-7.
• Article: Universal proteolysis and MS(n) for N- and O- glycan branching analysis.

  John E Schiel, Nicholas J Smith, Karen W Phinney
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  ABSTRACT: The continually growing list of critical glycosylation-related processes has made analytical methodology for detailed glycan characterization an area of increasing interest. Glycosylation is a post translational modification of unsurpassed complexity due to the variety of compositions and linkages formed by these biopolymers. Structural characterization of glycan isomers has been achieved using ion trap mass spectrometry and MS(n) of released, permethylated glycans. However, N- and O-glycans require different sample preparation strategies; and release of the glycans may be hindered, result in degradation of the glycan, and/or produce limited yields of permethylated product. In the current report, we demonstrate universal proteolysis of both N- and O-linked glycoproteins to individual glycoamino acids. These samples were shown to be directly amenable to permethylation and MS(n) analysis for isomeric structural determination. Universal proteolysis and permethylation provides an identical sample preparation strategy for both classes of glycans that avoids potential pitfalls of commonly used release methods. This methodology should be applicable to all glycoproteins and serve as an alternative to glycan release for MS(n) branching analysis. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
  Biological Mass Spectrometry 04/2013; 48(4):533-8.
• Article: Simultaneous determination of three alkaloids, four ginsenosides and limonin in the plasma of normal and headache rats after oral administration of Wu-Zhu-Yu decoction by a novel ultra fast liquid chromatography-tandem mass spectrometry method: application to a comparative pharmacokinetics and ethological study.

  Huarong Xu, Qing Li, Yidi Yin, Chunxiao Lv, Wanyang Sun, Bosai He, Ran Liu, Xiaohui Chen, Kaishun Bi
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  ABSTRACT: A novel, sensitive and reliable ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method has been developed and validated for simultaneous quantitation of eight main active ingredients (evodiamine, rutaecarpine, dehydroevodiamine, limonin, ginsenoside Rb1 , Rd, Re and Rg1 ) in rat plasma after oral administration of Wu-Zhu-Yu (WZY) decoction, which is a celebrated and widely used Traditional Chinese Medicine formula for the treatment of headache. The analytes and internal standard (IS) were separated on a SHIM-PACK XR-ODS II column, and the detection was performed on a UFLC-MS/MS system with turbo ion spray source. The lower limits of quantification were 1.5, 0.5, 1.0, 2.0, 2.0, 1.0, 0.5 and 0.2 ng ml(-1) for evodiamine, rutaecarpine, dehydroevodiamine, limonin, gensenoside Rb1 , Rd, Re and Rg1 , respectively. Linearity, accuracy, precision and absolute recoveries of the eight analytes were all within satisfaction. The IS-normalized matrix factor was adopted for assessing the matrix effect and accompanied with a satisfactory result. The validated method has been successfully applied to compare pharmacokinetic profiles of the eight active ingredients in rat plasma between normal and headache rats after administration. Exact pharmaceutical effect of WZY decoction on headache was demonstrated by the ethological response of headache rats induced by nitric oxide donor after administration. The results indicated that the absorption of evodiamine, rutaecarpine, gensenoside Rb1 , Re and Rg1 in headache group were significantly higher than those in normal group with similar concentration-time curves while no significant differences existed in limonin and ginsenoside Rd between the two groups. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 04/2013; 48(4):519-32.
• Article: UFLC-MS/MS method for simultaneous determination of six lignans of Schisandra chinensis (Turcz.) Baill. in normal and insomniac rats brain microdialysates and homogenate samples: towards an in-depth study for its sedative-hypnotic activity.

  Binbin Wei, Qing Li, Ronghua Fan, Dan Su, Xiuli Ou, Kelin Chen, Xiaohui Chen, Ying Jia, Kaishun Bi
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  ABSTRACT: Schisandra chinensis (Turcz.) Baill., a traditional Chinese medicine, has been clinically used for the treatment of insomnia for centuries. The insomnia mechanism and the possible active ingredients of S. chinensis remain largely unknown. The objective of this study was to develop a method to detect its components which could pass through the blood brain barrier (BBB) by determining the brain microdialysate and brain tissue homogenate samples and then obtain the pharmacokinetic profile in brain for comprehensive understanding of its hypnotic clinical efficacy. Therefore, an efficient, sensitive and selective ultra fast liquid chromatography/tandem mass spectrometry method for the simultaneous determination of six sedative and hypnotic lignans (schisandrin, schisandrol B, schisantherin A, deoxyshisandrin, γ-schisandrin and gomisin N) of Schisandra chinensis (Turcz.) Baill. in rat brain tissue homogenate and brain microdialysates has been developed and validated. The analysis was performed on a Shim-pack XR-ODS column (75 mm × 3.0 mm, 2.2 µm) using gradient elution with the mobile phase consisting of acetonitrile and 0.1% formic acid water. The method was validated in brain homogenate and microdialysate samples, which all showed good linearity over a wide concentration range (r(2) > 0.99), and the obtained lower limit of quantification was 0.1 ng · ml(-1) for the analytes in brain microdialysate samples. The intra- and inter-day assay variability was less than 15% for all analytes. The study proved the six lignans, as sedative and hypnotic ingredients, could pass through the BBB with brain targeting, distributed mainly in the hypothalamus and possessed complete pharmacokinetics process in brain. The results also indicated that significant difference in pharmacokinetic parameters of the analytes was observed between two groups, while absorptions of these analytes in insomniac group were significantly better than those in normal group. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 04/2013; 48(4):448-58.
• Article: Gas-phase fragmentation of the protonated benzyl ester of proline: intramolecular electrophilic substitution versus hydride transfer.

  Fei Li, Xiaoping Zhang, Huarong Zhang, Kezhi Jiang
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  ABSTRACT: In this study, the gas phase chemistry of the protonated benzyl esters of proline has been investigated by electrospray ionization mass spectrometry and theoretical calculation. Upon collisional activation, the protonated molecules undergo fragmentation reactions via three primary channels: (1) direct decomposition to the benzyl cation (m/z 91), (2) formation of an ion-neutral complex of [benzyl cation + proline](+) , followed by a hydride transfer to generate the protonated 4,5-dihydro-3H-pyrrole-2-carboxylic acid (m/z 114), and (3) electrophilic attack at the amino by the transferring benzyl cation, and the subsequent migration of the activated amino proton leading to the simultaneous loss of (H2 O + CO). Interestingly, no hydrogen/deuterium exchange for the fragment ion m/z 114 occurs in the d-labeling experiments, indicating that the transferring hydride in path-b comes from the methenyl hydrogen rather than the amino hydrogen. For para-substituted benzyl esters, the presence of electron-donating substituents significantly promotes the direct decomposition (path-a), whereas the presence of electron-withdrawing ones distinctively inhibits that channel. For the competing channels of path-b and path-c, the presence of electron-donating substituents favors path-b rather than path-c, whereas the presence of electron-withdrawing ones favors path-c rather than path-b. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 04/2013; 48(4):423-9.
• Article: From the mobile proton to wandering hydride ion: mechanistic aspects of gas-phase ion chemistry.

  Guy Bouchoux
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  ABSTRACT: Structural characterization of molecular species by mass spectrometry supposes the knowledge of the type of ions generated and the mechanism by which they dissociate. In this context, a need for a rationalization of electrospray ionization(+)(-) mass spectra of small molecules has been recently expressed. Similarly, at the other end of the mass scale, efforts are currently made to interpret the major fragmentation processes of protonated and deprotonated peptides and their reduced forms produced in electron capture or electron transfer experiments. Most fragmentation processes of molecular and pseudo-molecular ions produced in the ion source of a mass spectrometer may be described by a combination of several key mechanistic steps: simple bond dissociation, formation of ion-neutral complex intermediates, hydrogen atom, hydride ion or proton migrations and nucleophilic attack. Selected crucial aspects of these elementary reactions, occurring inside positively charged ions, will be recalled and illustrated by examples taken in recent mass spectrometry literature. Emphasis will be given on the protonation process and its consequence in terms of structure and energetic. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 04/2013; 48(4):505-18.
• Article: Testing an alternative search algorithm for compound identification with the 'Wiley Registry of Tandem Mass Spectral Data, MSforID'.

  Herbert Oberacher, Graeme Whitley, Bernd Berger, Wolfgang Weinmann
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  ABSTRACT: A tandem mass spectral database system consists of a library of reference spectra and a search program. State-of-the-art search programs show a high tolerance for variability in compound-specific fragmentation patterns produced by collision-induced decomposition and enable sensitive and specific 'identity search'. In this communication, performance characteristics of two search algorithms combined with the 'Wiley Registry of Tandem Mass Spectral Data, MSforID' (Wiley Registry MSMS, John Wiley and Sons, Hoboken, NJ, USA) were evaluated. The search algorithms tested were the MSMS search algorithm implemented in the NIST MS Search program 2.0g (NIST, Gaithersburg, MD, USA) and the MSforID algorithm (John Wiley and Sons, Hoboken, NJ, USA). Sample spectra were acquired on different instruments and, thus, covered a broad range of possible experimental conditions or were generated in silico. For each algorithm, more than 30 000 matches were performed. Statistical evaluation of the library search results revealed that principally both search algorithms can be combined with the Wiley Registry MSMS to create a reliable identification tool. It appears, however, that a higher degree of spectral similarity is necessary to obtain a correct match with the NIST MS Search program. This characteristic of the NIST MS Search program has a positive effect on specificity as it helps to avoid false positive matches (type I errors), but reduces sensitivity. Thus, particularly with sample spectra acquired on instruments differing in their setup from tandem-in-space type fragmentation, a comparably higher number of false negative matches (type II errors) were observed by searching the Wiley Registry MSMS. Copyright © 2013 John Wiley & Sons, Ltd.
  Biological Mass Spectrometry 04/2013; 48(4):497-504.