Science.gov

Sample records for mass spectrometry studies

  1. Study of odor recorder using Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Miura, Tomohiro; Nakamoto, Takamichi; Moriizumi, Toyosaka

    It is necessary to determine the recipe of a target odor with sufficient accuracy to realize an odor recorder for recording and reproducing it. We studied the recipe measurement method of a target odor using a mass spectrometry. It was confirmed that the linear superposition was valid when the binary mixture of the apple-flavor components such as isobutyric acid and ethyl valerate was measured. The superposition of a mass spectrum pattern may enable the recipe determination of a multi-component odor easily. In this research, we succeeded in the recipe determinations of orange flavor made up of 14 component odors when its typical recipe, the equalized, the citral-enhanced and the citronellol-enhanced ones were measured.

  2. Mass spectrometry.

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Johanson, G. A.

    1972-01-01

    Review of the current state of mass spectrometry, indicating its unique importance for advanced scientific research. Mass spectrometry applications in computer techniques, gas chromatography, ion cyclotron resonance, molecular fragmentation and ionization, and isotope labeling are covered. Details are given on mass spectrometry applications in bio-organic chemistry and biomedical research. As the subjects of these applications are indicated alkaloids, carbohydrates, lipids, terpenes, quinones, nucleic acid components, peptides, antibiotics, and human and animal metabolisms. Particular attention is given to the mass spectra of organo-inorganic compounds, inorganic mass spectrometry, surface phenomena such as secondary ion and electron emission, and elemental and isotope analysis. Further topics include mass spectrometry in organic geochemistry, applications in geochronology and cosmochemistry, and organic mass spectrometry.

  3. Mass spectrometry.

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Johanson, G. A.

    1972-01-01

    Review of the current state of mass spectrometry, indicating its unique importance for advanced scientific research. Mass spectrometry applications in computer techniques, gas chromatography, ion cyclotron resonance, molecular fragmentation and ionization, and isotope labeling are covered. Details are given on mass spectrometry applications in bio-organic chemistry and biomedical research. As the subjects of these applications are indicated alkaloids, carbohydrates, lipids, terpenes, quinones, nucleic acid components, peptides, antibiotics, and human and animal metabolisms. Particular attention is given to the mass spectra of organo-inorganic compounds, inorganic mass spectrometry, surface phenomena such as secondary ion and electron emission, and elemental and isotope analysis. Further topics include mass spectrometry in organic geochemistry, applications in geochronology and cosmochemistry, and organic mass spectrometry.

  4. Chip-mass spectrometry for glycomic studies.

    PubMed

    Bindila, Laura; Peter-Katalinić, Jasna

    2009-01-01

    The introduction of micro- and nanochip front end technologies for electrospray mass spectrometry addressed a major challenge in carbohydrate analysis: high sensitivity structural determination and heterogeneity assessment in high dynamic range mixtures of biological origin. Chip-enhanced electrospray ionization was demonstrated to provide reproducible performance irrespective of the type of carbohydrate, while the amenability of chip systems for coupling with different mass spectrometers greatly advance the chip/MS technique as a versatile key tool in glycomic studies. A more accurate representation of the glycan repertoire to include novel biologically-relevant information was achieved in different biological sources, asserting this technique as a valuable tool in glycan biomarker discovery and monitoring. Additionally, the integration of various analytical functions onto chip devices and direct hyphenation to MS proved its potential for glycan analysis during the recent years, whereby a new analytical tool is on the verge of maturation: lab-on-chip MS glycomics. The achievements until early beginning of 2007 on the implementation of chip- and functional integrated chip/MS in systems glycobiology studies are reviewed here. (c) 2009 Wiley Periodicals, Inc.

  5. High-accuracy mass spectrometry for fundamental studies.

    PubMed

    Kluge, H-Jürgen

    2010-01-01

    Mass spectrometry for fundamental studies in metrology and atomic, nuclear and particle physics requires extreme sensitivity and efficiency as well as ultimate resolving power and accuracy. An overview will be given on the global status of high-accuracy mass spectrometry for fundamental physics and metrology. Three quite different examples of modern mass spectrometric experiments in physics are presented: (i) the retardation spectrometer KATRIN at the Forschungszentrum Karlsruhe, employing electrostatic filtering in combination with magnetic-adiabatic collimation-the biggest mass spectrometer for determining the smallest mass, i.e. the mass of the electron anti-neutrino, (ii) the Experimental Cooler-Storage Ring at GSI-a mass spectrometer of medium size, relative to other accelerators, for determining medium-heavy masses and (iii) the Penning trap facility, SHIPTRAP, at GSI-the smallest mass spectrometer for determining the heaviest masses, those of super-heavy elements. Finally, a short view into the future will address the GSI project HITRAP at GSI for fundamental studies with highly-charged ions.

  6. [New mass spectrometry techniques applied to the study of venoms].

    PubMed

    Auvin-Guette, C

    2002-08-01

    Mass spectrometry is a technique for the analysis and very sensitive identification of molecules. It allows one to determine the mass of the studied product, whether pure or in a mixture, and provides some information on its molecular structure. In the particular case of peptides, this method can, under certain conditions, also provide information on the amino acid sequence. There are two complementary methods in mass spectrometry for the study of the biological molecules: i) ionisation by laser desorption assisted by matrix (MALDI) coupled to a mass analyser of the time of flight type (TOF), which is very effective for the direct study of a mixture of products and ii) ionisation by electronebulisation (ESI) coupled to mass analysers of the quadripolar type and time of flight (Qq-TOF), which allows the interfacing between high phase liquid chromatography and mass spectrometry. These two complementary techniques were already used to draw up toxin charts of snake and spider venoms. The purpose is to be able to characterise species based on an actual peptide print of poisonous gland secretions.

  7. Kinetic Studies of Reactions in Solution Using Fast Mass Spectrometry

    DTIC Science & Technology

    2013-08-13

    of Reactions in Solution Using Fast Mass Spectrometry Sb. GRANT NUMBER FA9550-10-1-0235 Sc. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Sd . PROJECT...salt and detergent in electrokinetic separations using a spinning disk. We also applied this technique, we believe with great success, to study...chromatography to MS Salts and detergents used in the mobile phase for electro- kinetic separations suppress ionization efficiencies and con

  8. Vaporization Studies of Olivine via Knudsen Effusion Mass Spectrometry

    NASA Technical Reports Server (NTRS)

    Costa, G. C. C.; Jacobson, N. S.

    2014-01-01

    Olivine is the major mineral in the Earth's upper mantle occurring predominantly in igneous rocks and has been identified in meteorites, asteroids, the Moon and Mars. Among many other important applications in planetary and materials sciences, the thermodynamic properties of vapor species from olivine are crucial as input parameters in computational modelling of the atmospheres of hot, rocky exoplanets (lava planets). There are several weight loss studies of olivine vaporization in the literature and one Knudsen Effusion Mass Spectrometry (KEMS) study. In this study, we examine a forsterite-rich olivine (93% forsterite and 7% fayalite, Fo93Fa7) with KEMS to further understand its vaporization and thermodynamic properties.

  9. Application of accelerator mass spectrometry in aluminum metabolism studies

    NASA Astrophysics Data System (ADS)

    Meirav, O.; Sutton, R. A. L.; Fink, D.; Middleton, R.; Klein, J.; Walker, V. R.; Halabe, A.; Vetterli, D.; Johnson, R. R.

    1990-12-01

    The recent recognition that aluminum causes toxicity in uremie patients and may be associated with Alzheimer's disease has stimulated many studies of its biochemical effects. However, such studies were hampered by the lack of a suitable tracer. In a novel experiment, we have applied the new technique of accelerator mass spectrometry to investigate aluminum kinetics in rats, using as a marker the long-lived isotope 26Al. We present the first aluminum kinetic model for a biological system. The results clearly demonstrate the advantage this technique holds for isotope tracer studies in animals as well as in humans.

  10. THE APPLICATION OF MASS SPECTROMETRY TO THE STUDY OF MICROORGANISMS

    EPA Science Inventory

    The purpose of this research project is to use state-of-the-art mass spectrometric techniques, such as electrospray ionization (ESI) and matrix assisted laser desorption ionization (MALDI) mass spectrometry (MS), to provide "protein mass fingerprinting" and protein sequencing i...

  11. THE APPLICATION OF MASS SPECTROMETRY TO THE STUDY OF MICROORGANISMS

    EPA Science Inventory

    The purpose of this research project is to use state-of-the-art mass spectrometric techniques, such as electrospray ionization (ESI) and matrix assisted laser desorption ionization (MALDI) mass spectrometry (MS), to provide "protein mass fingerprinting" and protein sequencing i...

  12. MASS SPECTROMETRY

    DOEpatents

    Nier, A.O.C.

    1959-08-25

    A voltage switching apparatus is described for use with a mass spectrometer in the concentratron analysis of several components of a gas mixture. The system automatically varies the voltage on the accelerating electrode of the mass spectrometer through a program of voltages which corresponds to the particular gas components under analysis. Automatic operation may be discontinued at any time to permit the operator to manually select any desired predetermined accelerating voltage. Further, the system may be manually adjusted to vary the accelerating voltage over a wide range.

  13. Mass spectrometry methods to study protein-metabolite interactions.

    PubMed

    Guo, Hongbo; Peng, Hui; Emili, Andrew

    2017-09-21

    To ​​​​understand and manipulate biochemical processes and signaling pathways, the knowledge of endogenous protein-metabolite interactions would be extremely helpful. Recent developments in precision mass spectrometry, high-throughput proteomics and sensitive metabolomic profiling are beginning to converge on a possible solution, heralding a new era of global metabolome-proteome 'interactome' studies that promise to change biomedical research and drug discovery. Areas covered: Here, we review innovative mass spectrometry-based methods and recent pioneering studies aimed at elucidating the physical associations of small molecule ligands with cellular proteins. The technologies covered belong to two main categories: tag-based and tag-free methods. We emphasize the latter in this review, and outline promising experimental workflows and key data analysis considerations involved. Expert opinion: Recent ground-breaking advances in chemical-proteomics technology and allied computational methods now make the global detection of protein-ligand engagement an increasingly attractive research problem. Despite ongoing challenges, rapid progress in the field is expected these coming next few years, leading to a refreshed systems biology research paradigm and much needed new opportunities for improving sparse drug discovery pipelines.

  14. MASS SPECTROMETRY

    DOEpatents

    Friedman, L.

    1962-01-01

    method is described for operating a mass spectrometer to improve its resolution qualities and to extend its period of use substantially between cleanings. In this method, a small amount of a beta emitting gas such as hydrogen titride or carbon-14 methane is added to the sample being supplied to the spectrometer for investigation. The additive establishes leakage paths on the surface of the non-conducting film accumulating within the vacuum chamber of the spectrometer, thereby reducing the effect of an accumulated static charge on the electrostatic and magnetic fields established within the instrument. (AEC)

  15. Advanced Mass Spectrometry Technologies for the Study of Microbial Pathogenesis

    PubMed Central

    Moore, Jessica L.; Caprioli, Richard M.; Skaar, Eric P.

    2014-01-01

    Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) has been successfully applied to the field of microbial pathogenesis with promising results, principally in diagnostic microbiology to rapidly identify bacteria based on the molecular profiles of small cell populations. Direct profiling of molecules from serum and tissue samples by MALDI MS providesa means to study the pathogen-host interaction and to discover potential markers of infection. Systematic molecular profiling across tissue sections represents a new imaging modality, enabling regiospecific molecular measurements to be made in situ, in both two- and three-dimensional analyses. Herein, we briefly summarize work that employs MALDI MS to study the pathogenesis of microbial infection. PMID:24997399

  16. Apparatus for studying premixed laminar flames using mass spectrometry and fiber-optic spectrometry

    NASA Astrophysics Data System (ADS)

    Olsson, Jim O.; Andersson, Lars L.; Lenner, Magnus; Simonson, Margaret

    1990-03-01

    An integrated flat-flame/ microprobe sampling quadrupole mass spectrometer system, complemented by optical spectrometry based on optical fibers, is presented. The short microprobe sampling line (total 25 cm) is directly connected to an open ion source closely flanked by two nude cryopumps (900 l/s) yielding a background pressure of 10-9 Torr and a sampling pressure of about 10-5 Torr. Due to this improved microprobe system, mass spectrometry can be used for analysis of stable species (including fuel, O2, H2O, CO2, CO, and Ar) with less disturbance of the sample than with a conventional microprobe with a back pressure of about 1 Torr. Optical spectrometry is used for the study of emission from important radical species (such as C2, CH, and OH). The system is proposed as a complement to more conventional flat-flame/MBMS systems in which the sampling cone can effect the experimental system. Details are provided concerning the configuration of the whole system ranging from gas delivery to data evaluation. Test data are presented for a 16% methanol/68% oxygen/16% argon flame studied at a pressure of 40 Torr, to elucidate the special features of this system.

  17. Metallothionein dimers studied by nano-spray mass spectrometry.

    PubMed

    Hathout, Yetrib; Reynolds, Kristy J; Szilagyi, Zoltan; Fenselau, Catherine

    2002-01-15

    Both transient and stable dimers of metallothionein have been characterized, based on earlier studies using NMR, circular dichroism and size-exclusion chromatography. Here additional characterization is provided by nanospray mass spectrometry. Rapid redistribution of metal ions between monomeric Cd7- and Zn7-metallothionein 2a is monitored by nanospray. An experiment in which theses two forms of the monomeric protein are separated by a dialysis membrane, which will pass metal ions but not proteins, confirms that a transient dimer must form for metal ions to be redistributed. On the other hand, size-exclusion chromatography of reconstituted Zn7- or Cd7-metallothionein revealed the presence of monomeric and dimeric species. These dimers do not equilibrate readily to form monomers and they are shown to be covalent.

  18. Applying mass spectrometry to study non-covalent biomolecule complexes.

    PubMed

    Chen, Fan; Gülbakan, Basri; Weidmann, Simon; Fagerer, Stephan R; Ibáñez, Alfredo J; Zenobi, Renato

    2016-01-01

    Non-covalent interactions are essential for the structural organization of biomacromolecules and play an important role in molecular recognition processes, such as the interactions between proteins, glycans, lipids, DNA, and RNA. Mass spectrometry (MS) is a powerful tool for studying of non-covalent interactions, due to the low sample consumption, high sensitivity, and label-free nature. Nowadays, native-ESI MS is heavily used in studies of non-covalent interactions and to understand the architecture of biomolecular complexes. However, MALDI-MS is also becoming increasingly useful. It is challenging to detect the intact complex without fragmentation when analyzing non-covalent interactions with MALDI-MS. There are two methodological approaches to do so. In the first approach, different experimental and instrumental parameters are fine-tuned in order to find conditions under which the complex is stable, such as applying non-acidic matrices and collecting first-shot spectra. In the second approach, the interacting species are "artificially" stabilized by chemical crosslinking. Both approaches are capable of studying non-covalently bound biomolecules even in quite challenging systems, such as membrane protein complexes. Herein, we review and compare native-ESI and MALDI MS for the study of non-covalent interactions. © 2015 Wiley Periodicals, Inc.

  19. Pyrolysis and mass spectrometry studies of meteoritic organic matter.

    PubMed

    Sephton, M A

    2012-01-01

    Meteorites are fragments of extraterrestrial materials that fall to the Earth's surface. The carbon-rich meteorites are derived from ancient asteroids that have remained relatively unprocessed since the formation of the Solar System 4.56 billion years ago. They contain a variety of extraterrestrial organic molecules that are a record of chemical evolution in the early Solar System and subsequent aqueous and thermal processes on their parent bodies. The major organic component (>70%) is a macromolecular material that resists straightforward solvent extraction. In response to its intractable nature, the most common means of investigating this exotic material involves a combination of thermal decomposition (pyrolysis) and mass spectrometry. Recently the approach has also been used to explore controversial claims of organic matter in meteorites from Mars. This review summarizes the pyrolysis data obtained from meteorites and outlines key interpretations.

  20. Dating Studies of Elephant Tusks Using Accelerator Mass Spectrometry

    SciTech Connect

    Sideras-Haddad, E; Brown, T A

    2002-10-03

    A new method for determining the year of birth, the year of death, and hence, the age at death, of post-bomb and recently deceased elephants has been developed. The technique is based on Accelerator Mass Spectrometry radiocarbon analyses of small-sized samples extracted from along the length of a ge-line of an elephant tusk. The measured radiocarbon concentrations in the samples from a tusk can be compared to the {sup 14}C atmospheric bomb-pulse curve to derive the growth years of the initial and final samples from the tusk. Initial data from the application of this method to two tusks will be presented. Potentially, the method may play a significant role in wildlife management practices of African national parks. Additionally, the method may contribute to the underpinnings of efforts to define new international trade regulations, which could, in effect, decrease poaching and the killing of very young animals.

  1. "Magic" Ionization Mass Spectrometry.

    PubMed

    Trimpin, Sarah

    2016-01-01

    The systematic study of the temperature and pressure dependence of matrix-assisted ionization (MAI) led us to the discovery of the seemingly impossible, initially explained by some reviewers as either sleight of hand or the misinterpretation by an overzealous young scientist of results reported many years before and having little utility. The “magic” that we were attempting to report was that with matrix assistance, molecules, at least as large as bovine serum albumin (66 kDa), are lifted into the gas phase as multiply charged ions simply by exposure of the matrix:analyte sample to the vacuum of a mass spectrometer. Applied heat, a laser, or voltages are not necessary to achieve charge states and ion abundances only previously observed with electrospray ionization (ESI). The fundamentals of how solid phase volatile or nonvolatile compounds are converted to gas-phase ions without added energy currently involves speculation providing a great opportunity to rethink mechanistic understanding of ionization processes used in mass spectrometry. Improved understanding of the mechanism(s) of these processes and their connection to ESI and matrix-assisted laser desorption/ionization may provide opportunities to further develop new ionization strategies for traditional and yet unforeseen applications of mass spectrometry. This Critical Insights article covers developments leading to the discovery of a seemingly magic ionization process that is simple to use, fast, sensitive, robust, and can be directly applied to surface characterization using portable or high performance mass spectrometers.

  2. "Magic" Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Trimpin, Sarah

    2016-01-01

    The systematic study of the temperature and pressure dependence of matrix-assisted ionization (MAI) led us to the discovery of the seemingly impossible, initially explained by some reviewers as either sleight of hand or the misinterpretation by an overzealous young scientist of results reported many years before and having little utility. The "magic" that we were attempting to report was that with matrix assistance, molecules, at least as large as bovine serum albumin (66 kDa), are lifted into the gas phase as multiply charged ions simply by exposure of the matrix:analyte sample to the vacuum of a mass spectrometer. Applied heat, a laser, or voltages are not necessary to achieve charge states and ion abundances only previously observed with electrospray ionization (ESI). The fundamentals of how solid phase volatile or nonvolatile compounds are converted to gas-phase ions without added energy currently involves speculation providing a great opportunity to rethink mechanistic understanding of ionization processes used in mass spectrometry. Improved understanding of the mechanism(s) of these processes and their connection to ESI and matrix-assisted laser desorption/ionization may provide opportunities to further develop new ionization strategies for traditional and yet unforeseen applications of mass spectrometry. This Critical Insights article covers developments leading to the discovery of a seemingly magic ionization process that is simple to use, fast, sensitive, robust, and can be directly applied to surface characterization using portable or high performance mass spectrometers.

  3. Fourier Transform Mass Spectrometry.

    ERIC Educational Resources Information Center

    Gross, Michael L.; Rempel, Don L.

    1984-01-01

    Discusses the nature of Fourier transform mass spectrometry and its unique combination of high mass resolution, high upper mass limit, and multichannel advantage. Examines its operation, capabilities and limitations, applications (ion storage, ion manipulation, ion chemistry), and future applications and developments. (JN)

  4. Iron-Isotopic Fractionation Studies Using Multiple Collector Inductively Coupled Plasma Mass Spectrometry

    NASA Technical Reports Server (NTRS)

    Anbar, A. D.; Zhang, C.; Barling, J.; Roe, J. E.; Nealson, K. H.

    1999-01-01

    The importance of Fe biogeochemistry has stimulated interest in Fe isotope fractionation. Recent studies using thermal ionization mass spectrometry (TIMS) and a "double spike" demonstrate the existence of biogenic Fe isotope effects. Here, we assess the utility of multiple-collector inductively-coupled plasma mass spectrometry(MC-ICP-MS) with a desolvating sample introduction system for Fe isotope studies, and present data on Fe biominerals produced by a thermophilic bacterium. Additional information is contained in the original extended abstract.

  5. 'Moringa oleifera: study of phenolics and glucosinolates by mass spectrometry'.

    PubMed

    Maldini, Mariateresa; Maksoud, Salwa A; Natella, Fausta; Montoro, Paola; Petretto, Giacomo Luigi; Foddai, Marzia; De Nicola, Gina Rosalinda; Chessa, Mario; Pintore, Giorgio

    2014-09-01

    Moringa oleifera is a medicinal plant and an excellent dietary source of micronutrients (vitamins and minerals) and health-promoting phytochemicals (phenolic compounds, glucosinolates and isothiocyanates). Glucosinolates and isothiocyanates are known to possess anti-carcinogenic and antioxidant effects and have attracted great interest from both toxicological and pharmacological points of view, as they are able to induce phase 2 detoxification enzymes and to inhibit phase 1 activation enzymes. Phenolic compounds possess antioxidant properties and may exert a preventative effect in regards to the development of chronic degenerative diseases. The aim of this work was to assess the profile and the level of bioactive compounds in all parts of M. oleifera seedlings, by using different MS approaches. First, flow injection electrospray ionization mass spectrometry (FI-ESI-MS) fingerprinting techniques and chemometrics (PCA) were used to achieve the characterization of the different plant's organs in terms of profile of phenolic compounds and glucosinolates. Second, LC-MS and LC-MS/MS qualitative and quantitative methods were used for the identification and/or determination of phenolics and glucosinolates in M. oleifera. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Mass spectrometry in environmental toxicology.

    PubMed

    Groh, Ksenia J; Suter, Marc J-F

    2014-01-01

    In environmental toxicology, mass spectrometry can be applied to evaluate both exposure to chemicals as well as their effects in organisms. Various ultra-trace techniques are employed today to measure pollutants in different environmental compartments. Increasingly, effect-directed analysis is being applied to focus chemical monitoring on sites of ecotoxicological concern. Mass spectrometry is also very instrumental for studying the interactions of chemicals with organisms on the molecular and cellular level, providing new insights into mechanisms of toxicity. In the future, diverse mass spectrometry-based techniques are expected to become even more widely used in this field, contributing to the refinement of currently used environmental risk assessment strategies.

  7. Direct infusion mass spectrometry or liquid chromatography mass spectrometry for human metabonomics? A serum metabonomic study of kidney cancer.

    PubMed

    Lin, Lin; Yu, Quan; Yan, Xiaomei; Hang, Wei; Zheng, Jiaxin; Xing, Jinchun; Huang, Benli

    2010-11-01

    Serum samples from kidney cancer patients and healthy controls were analyzed by both direct infusion mass spectrometry (DIMS) and liquid chromatography-mass spectrometry (LC-MS) with a high resolution ESI-Q-TOFMS. The classification and biomarker discovery capacities of the two methods were compared, and MS/MS experiments were carried out to identify potential biomarkers. DIMS had comparable classification and prediction capabilities to LC-MS but consumed only ~5% of the analysis time. With regard to biomarker discovery, twenty-three variables were found as potential biomarkers by DIMS, and 48 variables were obtained by LC-MS. DIMS is recommended to be a fast diagnostic method for kidney cancer, while LC-MS is necessary when comprehensive screening of biomarkers is required.

  8. Mass Spectrometry for the Masses

    ERIC Educational Resources Information Center

    Persinger, Jared D.; Hoops, Geoffrey, C.; Samide, Michael J.

    2004-01-01

    A simple, qualitative experiment is developed for implementation, where the gas chromatography-mass spectrometry (GC-MS) plays an important role, into the laboratory curriculum of a chemistry course designed for nonscience majors. This laboratory experiment is well suited for the students as it helps them to determine the validity of their…

  9. Mass Spectrometry for the Masses

    ERIC Educational Resources Information Center

    Persinger, Jared D.; Hoops, Geoffrey, C.; Samide, Michael J.

    2004-01-01

    A simple, qualitative experiment is developed for implementation, where the gas chromatography-mass spectrometry (GC-MS) plays an important role, into the laboratory curriculum of a chemistry course designed for nonscience majors. This laboratory experiment is well suited for the students as it helps them to determine the validity of their…

  10. Forensic Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Hoffmann, William D.; Jackson, Glen P.

    2015-07-01

    Developments in forensic mass spectrometry tend to follow, rather than lead, the developments in other disciplines. Examples of techniques having forensic potential born independently of forensic applications include ambient ionization, imaging mass spectrometry, isotope ratio mass spectrometry, portable mass spectrometers, and hyphenated chromatography-mass spectrometry instruments, to name a few. Forensic science has the potential to benefit enormously from developments that are funded by other means, if only the infrastructure and personnel existed to adopt, validate, and implement the new technologies into casework. Perhaps one unique area in which forensic science is at the cutting edge is in the area of chemometrics and the determination of likelihood ratios for the evaluation of the weight of evidence. Such statistical techniques have been developed most extensively for ignitable-liquid residue analyses and isotope ratio analysis. This review attempts to capture the trends, motivating forces, and likely impact of developing areas of forensic mass spectrometry, with the caveat that none of this research is likely to have any real impact in the forensic community unless: (a) The instruments developed are turned into robust black boxes with red and green lights for positives and negatives, respectively, or (b) there are PhD graduates in the workforce who can help adopt these sophisticated techniques.

  11. Forensic Mass Spectrometry.

    PubMed

    Hoffmann, William D; Jackson, Glen P

    2015-01-01

    Developments in forensic mass spectrometry tend to follow, rather than lead, the developments in other disciplines. Examples of techniques having forensic potential born independently of forensic applications include ambient ionization, imaging mass spectrometry, isotope ratio mass spectrometry, portable mass spectrometers, and hyphenated chromatography-mass spectrometry instruments, to name a few. Forensic science has the potential to benefit enormously from developments that are funded by other means, if only the infrastructure and personnel existed to adopt, validate, and implement the new technologies into casework. Perhaps one unique area in which forensic science is at the cutting edge is in the area of chemometrics and the determination of likelihood ratios for the evaluation of the weight of evidence. Such statistical techniques have been developed most extensively for ignitable-liquid residue analyses and isotope ratio analysis. This review attempts to capture the trends, motivating forces, and likely impact of developing areas of forensic mass spectrometry, with the caveat that none of this research is likely to have any real impact in the forensic community unless: (a) The instruments developed are turned into robust black boxes with red and green lights for positives and negatives, respectively, or (b) there are PhD graduates in the workforce who can help adopt these sophisticated techniques.

  12. Morphine brain pharmacokinetics at very low concentrations studied with accelerator mass spectrometry and liquid chromatography-tandem mass spectrometry.

    PubMed

    Sadiq, Muhammad Waqas; Salehpour, Mehran; Forsgard, Niklas; Possnert, Göran; Hammarlund-Udenaes, Margareta

    2011-02-01

    Morphine has been predicted to show nonlinear blood-brain barrier transport at lower concentrations. In this study, we investigated the possibility of separating active influx of morphine from its efflux by using very low morphine concentrations and compared accelerator mass spectrometry (AMS) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a method for analyzing microdialysis samples. A 10-min bolus infusion of morphine, followed by a constant-rate infusion, was given to male rats (n = 6) to achieve high (250 ng/ml), medium (50 ng/ml), and low (10 ng/ml) steady-state plasma concentrations. An additional rat received infusions to achieve low (10 ng/ml), very low (2 ng/ml), and ultralow (0.4 ng/ml) concentrations. Unbound morphine concentrations from brain extracellular fluid and blood were sampled by microdialysis and analyzed by LC-MS/MS and AMS. The average partition coefficient for unbound drug (K(p,uu)) values for the low and medium steady-state levels were 0.22 ± 0.08 and 0.21 ± 0.05, respectively, when measured by AMS [not significant (NS); p = 0.5]. For the medium and high steady-state levels, K(p,uu) values were 0.24 ± 0.05 and 0.26 ± 0.05, respectively, when measured by LC-MS/MS (NS; p = 0.2). For the low, very low, and ultralow steady-state levels, K(p,uu) values were 0.16 ± 0.01, 0.16 ± 0.02, and 0.18 ± 0.03, respectively, when measured by AMS. The medium-concentration K(p,uu) values were, on average, 16% lower when measured by AMS than by LC-MS/MS. There were no significant changes in K(p,uu) over a 625-fold concentration range (0.4-250 ng/ml). It was not possible to separate active uptake transport from active efflux using these low concentrations. The two analytical methods provided indistinguishable results for plasma concentrations but differed by up to 38% for microdialysis samples; however, this difference did not affect our conclusions.

  13. Ambient ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Lebedev, A. T.

    2015-07-01

    Ambient ionization mass spectrometry emerged as a new scientific discipline only about ten years ago. A considerable body of information has been reported since that time. Keeping the sensitivity, performance and informativity of classical mass spectrometry methods, the new approach made it possible to eliminate laborious sample preparation procedures and triggered the development of miniaturized instruments to work directly in the field. The review concerns the theoretical foundations and design of ambient ionization methods. Their advantages and drawbacks, as well as prospects for application in chemistry, biology, medicine, environmetal analysis, etc., are discussed. The bibliography includes 194 references.

  14. Mass spectrometry. [in organic chemistry

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Shackleton, C. H. L.; Howe, I.; Chizhov, O. S.

    1978-01-01

    A review of mass spectrometry in organic chemistry is given, dealing with advances in instrumentation and computer techniques, selected topics in gas-phase ion chemistry, and applications in such fields as biomedicine, natural-product studies, and environmental pollution analysis. Innovative techniques and instrumentation are discussed, along with chromatographic-mass spectrometric on-line computer techniques, mass spectral interpretation and management techniques, and such topics in gas-phase ion chemistry as electron-impact ionization and decomposition, photoionization, field ionization and desorption, high-pressure mass spectrometry, ion cyclotron resonance, and isomerization reactions of organic ions. Applications of mass spectrometry are examined with respect to bio-oligomers and their constituents, biomedically important substances, microbiology, environmental organic analysis, and organic geochemistry.

  15. Mass spectrometry. [in organic chemistry

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Shackleton, C. H. L.; Howe, I.; Chizhov, O. S.

    1978-01-01

    A review of mass spectrometry in organic chemistry is given, dealing with advances in instrumentation and computer techniques, selected topics in gas-phase ion chemistry, and applications in such fields as biomedicine, natural-product studies, and environmental pollution analysis. Innovative techniques and instrumentation are discussed, along with chromatographic-mass spectrometric on-line computer techniques, mass spectral interpretation and management techniques, and such topics in gas-phase ion chemistry as electron-impact ionization and decomposition, photoionization, field ionization and desorption, high-pressure mass spectrometry, ion cyclotron resonance, and isomerization reactions of organic ions. Applications of mass spectrometry are examined with respect to bio-oligomers and their constituents, biomedically important substances, microbiology, environmental organic analysis, and organic geochemistry.

  16. Analytical mass spectrometry

    SciTech Connect

    Not Available

    1990-01-01

    This 43rd Annual Summer Symposium on Analytical Chemistry was held July 24--27, 1990 at Oak Ridge, TN and contained sessions on the following topics: Fundamentals of Analytical Mass Spectrometry (MS), MS in the National Laboratories, Lasers and Fourier Transform Methods, Future of MS, New Ionization and LC/MS Methods, and an extra session. (WET)

  17. Analytical mass spectrometry. Abstracts

    SciTech Connect

    Not Available

    1990-12-31

    This 43rd Annual Summer Symposium on Analytical Chemistry was held July 24--27, 1990 at Oak Ridge, TN and contained sessions on the following topics: Fundamentals of Analytical Mass Spectrometry (MS), MS in the National Laboratories, Lasers and Fourier Transform Methods, Future of MS, New Ionization and LC/MS Methods, and an extra session. (WET)

  18. Mass spectrometry study of N-alkylbenzenesulfonamides with potential antagonist activity to potassium channels.

    PubMed

    Martins, Carina C; Bassetto, Carlos A Zanutto; Santos, Jandyson M; Eberlin, Marcos N; Magalhães, Alvicler; Varanda, Wamberto; Gonzalez, Eduardo R Perez

    2016-02-01

    Herein, we report the synthesis and mass spectrometry studies of several N-alkylbenzenesulfonamides structurally related to sulfanilic acid. The compounds were synthesized using a modified Schotten-Baumann reaction coupled with Meisenheimer arylation. Sequential mass spectrometry by negative mode electrospray ionization (ESI(-)-MS/MS) showed the formation of sulfoxylate anion (m/z 65) observed in the mass spectrum of p-chloro-N-alkylbenzenesulfonamides. Investigation of the unexpected loss of two water molecules, as observed by electron ionization mass spectrometry (EI-MS) analysis of p-(N-alkyl)lactam sulfonamides, led to the proposal of corresponding fragmentation pathways. These compounds showed loss of neutral iminosulfane dioxide molecule (M-79) with formation of ions observed at m/z 344 and 377. These ions were formed by rearrangement on ESI(+)-MS/MS analysis. Some of the molecules showed antagonistic activity against Kv3.1 voltage-gated potassium channels.

  19. Interlaboratory study to evaluate the robustness of capillary electrophoresis-mass spectrometry for peptide mapping.

    PubMed

    Wenz, Christian; Barbas, Coral; López-Gonzálvez, Ángeles; Garcia, Antonia; Benavente, Fernando; Sanz-Nebot, Victoria; Blanc, Tim; Freckleton, Gordon; Britz-McKibbin, Philip; Shanmuganathan, Meera; de l'Escaille, Francois; Far, Johann; Haselberg, Rob; Huang, Sean; Huhn, Carolin; Pattky, Martin; Michels, David; Mou, Si; Yang, Feng; Neusuess, Christian; Tromsdorf, Nora; Baidoo, Edward E K; Keasling, Jay D; Park, SungAe Suhr

    2015-07-06

    A collaborative study on the robustness and portability of a capillary electrophoresis-mass spectrometry method for peptide mapping was performed by an international team, consisting of 13 independent laboratories from academia and industry. All participants used the same batch of samples, reagents and coated capillaries to run their assays, whereas they utilized the capillary electrophoresis-mass spectrometry equipment available in their laboratories. The equipment used varied in model, type and instrument manufacturer. Furthermore, different types of sheath-flow capillary electrophoresis-mass spectrometry interfaces were used. Migration time, peak height and peak area of ten representative target peptides of trypsin-digested bovine serum albumin were determined by every laboratory on two consecutive days. The data were critically evaluated to identify outliers and final values for means, repeatability (precision within a laboratory) and reproducibility (precision between laboratories) were established. For relative migration time the repeatability was between 0.05 and 0.18% RSD and the reproducibility between 0.14 and 1.3% RSD. For relative peak area repeatability and reproducibility values obtained were 3-12 and 9-29% RSD, respectively. These results demonstrate that capillary electrophoresis-mass spectrometry is robust enough to allow a method transfer across multiple laboratories and should promote a more widespread use of peptide mapping and other capillary electrophoresis-mass spectrometry applications in biopharmaceutical analysis and related fields.

  20. Human mass balance study of the novel anticancer agent ixabepilone using accelerator mass spectrometry

    PubMed Central

    Garner, R. C.; Cohen, M. B.; Galbraith, S.; Duncan, G. F.; Griffin, T.; Beijnen, J. H.; Schellens, J. H. M.

    2007-01-01

    Summary Ixabepilone (BMS-247550) is a semi-synthetic, microtubule stabilizing epothilone B analogue which is more potent than taxanes and has displayed activity in taxane-resistant patients. The human plasma pharmacokinetics of ixabepilone have been described. However, the excretory pathways and contribution of metabolism to ixabepilone elimination have not been determined. To investigate the elimination pathways of ixabepilone we initiated a mass balance study in cancer patients. Due to autoradiolysis, ixabepilone proved to be very unstable when labeled with conventional [14C]-levels (100 μCi in a typical human radio-tracer study). This necessitated the use of much lower levels of [14C]-labeling and an ultra-sensitive detection method, Accelerator Mass Spectrometry (AMS). Eight patients with advanced cancer (3 males, 5 females; median age 54.5 y; performance status 0–2) received an intravenous dose of 70 mg, 80 nCi of [14C]ixabepilone over 3 h. Plasma, urine and faeces were collected up to 7 days after administration and total radioactivity (TRA) was determined using AMS. Ixabepilone in plasma and urine was quantitated using a validated LC-MS/MS method. Mean recovery of ixabepilone-derived radioactivity was 77.3% of dose. Fecal excretion was 52.2% and urinary excretion was 25.1%. Only a minor part of TRA is accounted for by unchanged ixabepilone in both plasma and urine, which indicates that metabolism is a major elimination mechanism for this drug. Future studies should focus on structural elucidation of ixabepilone metabolites and characterization of their activities. PMID:17347871

  1. Mass Spectral Studies of 1-(2-Chloroethoxy)-2-[(2-chloroethyl)thio] Ethane and Related Compounds Using Gas ChromatographyMass Spectrometry and Gas ChromatographyTriple-Quadrupole Mass Spectrometry

    DTIC Science & Technology

    2016-02-01

    Capillary Column Gas Chromatography/Tandem Mass Spectrometry Verification of Chemical Warfare Agents. Rapid Commun . Mass Spectrom. 1992, 6, 717...Applications; American Chemical Society : Washington, DC, 2001. 23. Gross, J.H. Mass Spectrometry; Springer-Verlag: Berlin, 2002. 24. Madsen, J.Ø.; Nolde, C... MASS SPECTRAL STUDIES OF 1-(2-CHLOROETHOXY)-2-[(2-CHLOROETHYL)THIO] ETHANE AND RELATED COMPOUNDS USING GAS

  2. Mass spectrometry with accelerators.

    PubMed

    Litherland, A E; Zhao, X-L; Kieser, W E

    2011-01-01

    As one in a series of articles on Canadian contributions to mass spectrometry, this review begins with an outline of the history of accelerator mass spectrometry (AMS), noting roles played by researchers at three Canadian AMS laboratories. After a description of the unique features of AMS, three examples, (14)C, (10)Be, and (129)I are given to illustrate the methods. The capabilities of mass spectrometry have been extended by the addition of atomic isobar selection, molecular isobar attenuation, further ion acceleration, followed by ion detection and ion identification at essentially zero dark current or ion flux. This has been accomplished by exploiting the techniques and accelerators of atomic and nuclear physics. In 1939, the first principles of AMS were established using a cyclotron. In 1977 the selection of isobars in the ion source was established when it was shown that the (14)N(-) ion was very unstable, or extremely difficult to create, making a tandem electrostatic accelerator highly suitable for assisting the mass spectrometric measurement of the rare long-lived radioactive isotope (14)C in the environment. This observation, together with the large attenuation of the molecular isobars (13)CH(-) and (12)CH 2(-) during tandem acceleration and the observed very low background contamination from the ion source, was found to facilitate the mass spectrometry of (14)C to at least a level of (14)C/C ~ 6 × 10(-16), the equivalent of a radiocarbon age of 60,000 years. Tandem Accelerator Mass Spectrometry, or AMS, has now made possible the accurate radiocarbon dating of milligram-sized carbon samples by ion counting as well as dating and tracing with many other long-lived radioactive isotopes such as (10)Be, (26)Al, (36)Cl, and (129)I. The difficulty of obtaining large anion currents with low electron affinities and the difficulties of isobar separation, especially for the heavier mass ions, has prompted the use of molecular anions and the search for alternative

  3. Desorption in Mass Spectrometry.

    PubMed

    Usmanov, Dilshadbek Tursunbayevich; Ninomiya, Satoshi; Chen, Lee Chuin; Saha, Subhrakanti; Mandal, Mridul Kanti; Sakai, Yuji; Takaishi, Rio; Habib, Ahsan; Hiraoka, Kenzo; Yoshimura, Kentaro; Takeda, Sen; Wada, Hiroshi; Nonami, Hiroshi

    2017-01-01

    In mass spectrometry, analytes must be released in the gas phase. There are two representative methods for the gasification of the condensed samples, i.e., ablation and desorption. While ablation is based on the explosion induced by the energy accumulated in the condensed matrix, desorption is a single molecular process taking place on the surface. In this paper, desorption methods for mass spectrometry developed in our laboratory: flash heating/rapid cooling, Leidenfrost phenomenon-assisted thermal desorption (LPTD), solid/solid friction, liquid/solid friction, electrospray droplet impact (EDI) ionization/desorption, and probe electrospray ionization (PESI), will be described. All the methods are concerned with the surface and interface phenomena. The concept of how to desorb less-volatility compounds from the surface will be discussed.

  4. Desorption in Mass Spectrometry

    PubMed Central

    Usmanov, Dilshadbek Tursunbayevich; Ninomiya, Satoshi; Chen, Lee Chuin; Saha, Subhrakanti; Mandal, Mridul Kanti; Sakai, Yuji; Takaishi, Rio; Habib, Ahsan; Hiraoka, Kenzo; Yoshimura, Kentaro; Takeda, Sen; Wada, Hiroshi; Nonami, Hiroshi

    2017-01-01

    In mass spectrometry, analytes must be released in the gas phase. There are two representative methods for the gasification of the condensed samples, i.e., ablation and desorption. While ablation is based on the explosion induced by the energy accumulated in the condensed matrix, desorption is a single molecular process taking place on the surface. In this paper, desorption methods for mass spectrometry developed in our laboratory: flash heating/rapid cooling, Leidenfrost phenomenon-assisted thermal desorption (LPTD), solid/solid friction, liquid/solid friction, electrospray droplet impact (EDI) ionization/desorption, and probe electrospray ionization (PESI), will be described. All the methods are concerned with the surface and interface phenomena. The concept of how to desorb less-volatility compounds from the surface will be discussed. PMID:28337398

  5. Biological Cluster Mass Spectrometry

    PubMed Central

    Winograd, Nicholas; Garrison, Barbara J.

    2010-01-01

    This article reviews the new physics and new applications of secondary ion mass spectrometry using cluster ion probes. These probes, particularly C60, exhibit enhanced molecular desorption with improved sensitivity owing to the unique nature of the energy-deposition process. In addition, these projectiles are capable of eroding molecular solids while retaining the molecular specificity of mass spectrometry. When the beams are microfocused to a spot on the sample, bioimaging experiments in two and three dimensions are feasible. We describe emerging theoretical models that allow the energy-deposition process to be understood on an atomic and molecular basis. Moreover, experiments on model systems are described that allow protocols for imaging on biological materials to be implemented. Finally, we present recent applications of imaging to biological tissue and single cells to illustrate the future directions of this methodology. PMID:20055679

  6. MASS SPECTROMETRY IN ENVIRONMENTAL SCIENCES

    EPA Science Inventory

    This review covers applications of mass spectrometry to the environmental sciences. From the early applications of mass spectrometry to environmental research in the 1960s and 1970s, mass spectrometry has played an important role in aiding our understanding of environmental poll...

  7. MASS SPECTROMETRY IN ENVIRONMENTAL SCIENCES

    EPA Science Inventory

    This review covers applications of mass spectrometry to the environmental sciences. From the early applications of mass spectrometry to environmental research in the 1960s and 1970s, mass spectrometry has played an important role in aiding our understanding of environmental poll...

  8. Hybrid instruments for mass spectrometry/mass spectrometry

    SciTech Connect

    Glish, G.L.; McLuckey, S.A.

    1986-01-01

    In order to refine further the technique of mass spectrometry/mass spectrometry efforts are being made to combine the desirable features of sector based tandem instruments with those of triple quadrupole mass spectrometers. This has resulted in the construction of tandem mass spectrometers which incorporate both sector type analyzers and quadrupole mass filters. These so-called hybrid instruments, designed specifically for mass spectrometry/mass spectrometry applications, are appearing in a variety of geometries each with unique features. This review describes the hybrid instruments reported to data and discusses general considerations for evaluating hybrid instruments with regard to application. 100 references.

  9. Accelerator mass spectrometry.

    PubMed

    Hellborg, Ragnar; Skog, Göran

    2008-01-01

    In this overview the technique of accelerator mass spectrometry (AMS) and its use are described. AMS is a highly sensitive method of counting atoms. It is used to detect very low concentrations of natural isotopic abundances (typically in the range between 10(-12) and 10(-16)) of both radionuclides and stable nuclides. The main advantages of AMS compared to conventional radiometric methods are the use of smaller samples (mg and even sub-mg size) and shorter measuring times (less than 1 hr). The equipment used for AMS is almost exclusively based on the electrostatic tandem accelerator, although some of the newest systems are based on a slightly different principle. Dedicated accelerators as well as older "nuclear physics machines" can be found in the 80 or so AMS laboratories in existence today. The most widely used isotope studied with AMS is 14C. Besides radiocarbon dating this isotope is used in climate studies, biomedicine applications and many other fields. More than 100,000 14C samples are measured per year. Other isotopes studied include 10Be, 26Al, 36Cl, 41Ca, 59Ni, 129I, U, and Pu. Although these measurements are important, the number of samples of these other isotopes measured each year is estimated to be less than 10% of the number of 14C samples. Copyright 2008 Wiley Periodicals, Inc.

  10. HUMAN MASS BALANCE STUDY OF TAS-102 USING 14C ANALYZED BY ACCELERATOR MASS SPECTROMETRY

    PubMed Central

    Lee, James J.; Seraj, Jabed; Yoshida, Kenichiro; Mizuguchi, Hirokazu; Strychor, Sandra; Fiejdasz, Jillian; Faulkner, Tyeler; Parise, Robert A.; Fawcett, Patrick; Pollice, Laura; Mason, Scott; Hague, Jeremy; Croft, Marie; Nugteren, James; Tedder, Charles; Sun, Weijing; Chu, Edward; Beumer, Jan Hendrik

    2016-01-01

    Background TAS-102 is an oral fluoropyrimidine prodrug composed of trifluridine (FTD) and tipiracil hydrochloride (TPI) in a 1:0.5 ratio. FTD is a thymidine analog, and it is degraded by thymidine phosphorylase (TP) to the inactive trifluoromethyluracil (FTY) metabolite. TPI inhibits degradation of FTD by TP, increasing systemic exposure to FTD. Methods Patients with advanced solid tumors (6 M/2 F; median age 58 years; PS 0–1) were enrolled on this study. Patients in group A (N = 4) received 60 mg TAS-102 with 200 nCi [14C]-FTD, while patients in group B (N = 4) received 60 mg TAS-102 with 1000 nCi [14C]-TPI orally. Plasma, blood, urine, feces, and expired air (group A only) were collected up to 168 h, and were analyzed for 14C by accelerator mass spectrometry and analytes by LC-MS/MS. Results FTD: 59.8% of the 14C dose was recovered; 54.8% in urine mostly as FTY and FTD glucuronide isomers. The extractable radioactivity in the pooled plasma consisted of 52.7% FTD and 33.2% FTY. TPI: 76.8% of the 14C dose was recovered; 27.0% in urine mostly as TPI, and 49.7% in feces. The extractable radioactivity in the pooled plasma consisted of 53.1% TPI and 30.9% 6-HMU, the major metabolite of TPI. Conclusion Absorbed 14C-FTD was metabolized and mostly excreted in urine. The majority of 14C-TPI was recovered in feces, and the majority of absorbed TPI was excreted in urine. The current data with the ongoing hepatic and renal dysfunction studies will provide an enhanced understanding of the TAS-102 elimination profile. PMID:26787503

  11. Human mass balance study of TAS-102 using (14)C analyzed by accelerator mass spectrometry.

    PubMed

    Lee, James J; Seraj, Jabed; Yoshida, Kenichiro; Mizuguchi, Hirokazu; Strychor, Sandra; Fiejdasz, Jillian; Faulkner, Tyeler; Parise, Robert A; Fawcett, Patrick; Pollice, Laura; Mason, Scott; Hague, Jeremy; Croft, Marie; Nugteren, James; Tedder, Charles; Sun, Weijing; Chu, Edward; Beumer, Jan Hendrik

    2016-03-01

    TAS-102 is an oral fluoropyrimidine prodrug composed of trifluridine (FTD) and tipiracil hydrochloride (TPI) in a 1:0.5 ratio. FTD is a thymidine analog, and it is degraded by thymidine phosphorylase (TP) to the inactive trifluoromethyluracil (FTY) metabolite. TPI inhibits degradation of FTD by TP, increasing systemic exposure to FTD. Patients with advanced solid tumors (6 M/2 F; median age 58 years; PS 0-1) were enrolled on this study. Patients in group A (N = 4) received 60 mg TAS-102 with 200 nCi [(14)C]-FTD, while patients in group B (N = 4) received 60 mg TAS-102 with 1000 nCi [(14)C]-TPI orally. Plasma, blood, urine, feces, and expired air (group A only) were collected up to 168 h and were analyzed for (14)C by accelerator mass spectrometry and analytes by LC-MS/MS. FTD: 59.8% of the (14)C dose was recovered: 54.8% in urine mostly as FTY and FTD glucuronide isomers. The extractable radioactivity in the pooled plasma consisted of 52.7% FTD and 33.2% FTY. TPI: 76.8% of the (14)C dose was recovered: 27.0% in urine mostly as TPI and 49.7% in feces. The extractable radioactivity in the pooled plasma consisted of 53.1% TPI and 30.9% 6-HMU, the major metabolite of TPI. Absorbed (14)C-FTD was metabolized and mostly excreted in urine. The majority of (14)C-TPI was recovered in feces, and the majority of absorbed TPI was excreted in urine. The current data with the ongoing hepatic and renal dysfunction studies will provide an enhanced understanding of the TAS-102 elimination profile.

  12. Mass Spectrometry Imaging of Biological Tissue: An Approach for Multicenter Studies

    SciTech Connect

    Rompp, Andreas; Both, Jean-Pierre; Brunelle, Alain; Heeren, Ronald M.; Laprevote, Olivier; Prideaux, Brendan; Seyer, Alexandre; Spengler, Bernhard; Stoeckli, Markus; Smith, Donald F.

    2015-03-01

    Mass spectrometry imaging has become a popular tool for probing the chemical complexity of biological surfaces. This led to the development of a wide range of instrumentation and preparation protocols. It is thus desirable to evaluate and compare the data output from different methodologies and mass spectrometers. Here, we present an approach for the comparison of mass spectrometry imaging data from different laboratories (often referred to as multicenter studies). This is exemplified by the analysis of mouse brain sections in five laboratories in Europe and the USA. The instrumentation includes matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF), MALDI-QTOF, MALDIFourier transform ion cyclotron resonance (FTICR), atmospheric-pressure (AP)-MALDI-Orbitrap, and cluster TOF-secondary ion mass spectrometry (SIMS). Experimental parameters such as measurement speed, imaging bin width, and mass spectrometric parameters are discussed. All datasets were converted to the standard data format imzML and displayed in a common open-source software with identical parameters for visualization, which facilitates direct comparison of MS images. The imzML conversion also allowed exchange of fully functional MS imaging datasets between the different laboratories. The experiments ranged from overview measurements of the full mouse brain to detailed analysis of smaller features (depending on spatial resolution settings), but common histological features such as the corpus callosum were visible in all measurements. High spatial resolution measurements of AP-MALDI-Orbitrap and TOF-SIMS showed comparable structures in the low-micrometer range. We discuss general considerations for planning and performing multicenter studies in mass spectrometry imaging. This includes details on the selection, distribution, and preparation of tissue samples as well as on data handling. Such multicenter studies in combination with ongoing activities for reporting guidelines, a common

  13. Single event mass spectrometry

    DOEpatents

    Conzemius, Robert J.

    1990-01-16

    A means and method for single event time of flight mass spectrometry for analysis of specimen materials. The method of the invention includes pulsing an ion source imposing at least one pulsed ion onto the specimen to produce a corresponding emission of at least one electrically charged particle. The emitted particle is then dissociated into a charged ion component and an uncharged neutral component. The ion and neutral components are then detected. The time of flight of the components are recorded and can be used to analyze the predecessor of the components, and therefore the specimen material. When more than one ion particle is emitted from the specimen per single ion impact, the single event time of flight mass spectrometer described here furnis This invention was made with Government support under Contract No. W-7405-ENG82 awarded by the Department of Energy. The Government has certain rights in the invention.

  14. Clinical Application of Ambient Ionization Mass Spectrometry

    PubMed Central

    Li, Li-Hua; Hsieh, Hua-Yi; Hsu, Cheng-Chih

    2017-01-01

    Ambient ionization allows mass spectrometry analysis directly on the sample surface under atmospheric pressure with almost zero sample pretreatment. Since the development of desorption electrospray ionization (DESI) in 2004, many other ambient ionization techniques were developed. Due to their simplicity and low operation cost, rapid and on-site clinical mass spectrometry analysis becomes real. In this review, we will highlight some of the most widely used ambient ionization mass spectrometry approaches and their applications in clinical study. PMID:28337399

  15. Isotope dilution mass spectrometry

    NASA Astrophysics Data System (ADS)

    Heumann, Klaus G.

    1992-09-01

    In the past isotope dilution mass spectrometry (IDMS) has usually been applied using the formation of positive thermal ions of metals. Especially in calibrating other analytical methods and for the certification of standard reference materials this type of IDMS became a routine method. Today, the progress in this field lies in the determination of ultra trace amounts of elements, e.g. of heavy metals in Antarctic ice and in aerosols in remote areas down to the sub-pg g-1 and sub-pg m-3 levels respectively, in the analysis of uranium and thorium at concentrations of a few pg g-1 in sputter targets for the production of micro- electronic devices or in the determination of sub-picogram amounts of230Th in corals for geochemical age determinations and of226Ra in rock samples. During the last few years negative thermal ionization IDMS has become a frequently used method. The determination of very small amounts of selenium and technetium as well as of other transition metals such as vanadium, chromium, molybdenum and tungsten are important examples in this field. Also the measurement of silicon in connection with a re-determination of Avogadro's number and osmium analyses for geological age determinations by the Re/Os method are of special interest. Inductively-coupled plasma mass spectrometry is increasingly being used for multi-element analyses by the isotope dilution technique. Determinations of heavy metals in samples of marine origin are representative examples for this type of multi-element analysis by IDMS. Gas chromatography-mass spectrometry systems have also been successfully applied after chelation of metals (for example Pt determination in clinical samples) or for the determination of volatile element species in the environment, e.g. dimethyl sulfide. However, IDMS--specially at low concentration levels in the environment--seems likely to be one of the most powerful analytical methods for speciation in the future. This has been shown, up to now, for species of

  16. Mass spectrometry and renal calculi

    PubMed Central

    Purcarea, VL; Sisu, I; Sisu, E

    2010-01-01

    The present review represents a concise and complete survey of the literature covering 2004–2009, concerning the mass spectrometric techniques involved in the structural investigation of renal calculi. After a short presentation of the fundamental mass spectrometric techniques (MALDI–TOF, QTOF, MS–MS) as well as hyphenated methods (GC–MS, LC–MS, CE–MS), an extensive study of the urinary proteome analysis as well as the detection and quantification by mass spectrometry of toxins, drugs and metabolites from renal calculi is presented. PMID:20968197

  17. Accelerator mass spectrometry-enabled studies: current status and future prospects

    PubMed Central

    Arjomand, Ali

    2010-01-01

    Accelerator mass spectrometry is a detection platform with exceptional sensitivity compared with other bioanalytical platforms. Accelerator mass spectrometry (AMS) is widely used in archeology for radiocarbon dating applications. Early exploration of the biological and pharmaceutical applications of AMS began in the early 1990s. AMS has since demonstrated unique problem-solving ability in nutrition science, toxicology and pharmacology. AMS has also enabled the development of new applications, such as Phase 0 microdosing. Recent development of AMS-enabled applications has transformed this novelty research instrument to a valuable tool within the pharmaceutical industry. Although there is now greater awareness of AMS technology, recognition and appreciation of the range of AMS-enabled applications is still lacking, including study-design strategies. This review aims to provide further insight into the wide range of AMS-enabled applications. Examples of studies conducted over the past two decades will be presented, as well as prospects for the future of AMS. PMID:20440378

  18. Application of simultaneous thermogravimetric modulated beam mass spectrometry to the study of energetic materials

    SciTech Connect

    Behrens, R. Jr.

    1995-03-01

    Simultaneous thermogravimetric modulated beam mass spectrometry (STMBMS) and time-of-flight velocity (TOF) spectra have been developed to study reactions that occur during the thermal decomposition of liquids and solids. The data obtained with these techniques are the identity of the reaction products and their rates of gas formation as a function of time. Over the past several years, these techniques have been applied to the study of energetic materials that are used in propellants and explosives. In this presentation, the details of the STMBMS and TOF velocity spectra techniques will be reviewed, the advantages of the techniques over more conventional thermal analysis and mass spectrometry measurements will be discussed, and the use of the techniques will be illustrated with results on the thermal decomposition of hexahydro-1,3,5-s-triazine (RDX).

  19. Accelerator mass spectrometry-enabled studies: current status and future prospects.

    PubMed

    Arjomand, Ali

    2010-03-01

    Accelerator mass spectrometry is a detection platform with exceptional sensitivity compared with other bioanalytical platforms. Accelerator mass spectrometry (AMS) is widely used in archeology for radiocarbon dating applications. Early exploration of the biological and pharmaceutical applications of AMS began in the early 1990s. AMS has since demonstrated unique problem-solving ability in nutrition science, toxicology and pharmacology. AMS has also enabled the development of new applications, such as Phase 0 microdosing. Recent development of AMS-enabled applications has transformed this novelty research instrument to a valuable tool within the pharmaceutical industry. Although there is now greater awareness of AMS technology, recognition and appreciation of the range of AMS-enabled applications is still lacking, including study-design strategies. This review aims to provide further insight into the wide range of AMS-enabled applications. Examples of studies conducted over the past two decades will be presented, as well as prospects for the future of AMS.

  20. Studying the chemistry of cationized triacylglycerols using electrospray ionization mass spectrometry and density functional theory computations.

    PubMed

    Grossert, J Stuart; Cubero Herrera, Lisandra; Ramaley, Louis; Melanson, Jeremy E

    2014-08-01

    Analysis of triacylglycerols (TAGs), found as complex mixtures in living organisms, is typically accomplished using liquid chromatography, often coupled to mass spectrometry. TAGs, weak bases not protonated using electrospray ionization, are usually ionized by adduct formation with a cation, including those present in the solvent (e.g., Na(+)). There are relatively few reports on the binding of TAGs with cations or on the mechanisms by which cationized TAGs fragment. This work examines binding efficiencies, determined by mass spectrometry and computations, for the complexation of TAGs to a range of cations (Na(+), Li(+), K(+), Ag(+), NH4(+)). While most cations bind to oxygen, Ag(+) binding to unsaturation in the acid side chains is significant. The importance of dimer formation, [2TAG + M](+) was demonstrated using several different types of mass spectrometers. From breakdown curves, it became apparent that two or three acid side chains must be attached to glycerol for strong cationization. Possible mechanisms for fragmentation of lithiated TAGs were modeled by computations on tripropionylglycerol. Viable pathways were found for losses of neutral acids and lithium salts of acids from different positions on the glycerol moiety. Novel lactone structures were proposed for the loss of a neutral acid from one position of the glycerol moiety. These were studied further using triple-stage mass spectrometry (MS(3)). These lactones can account for all the major product ions in the MS(3) spectra in both this work and the literature, which should allow for new insights into the challenging analytical methods needed for naturally occurring TAGs.

  1. Studying the Chemistry of Cationized Triacylglycerols Using Electrospray Ionization Mass Spectrometry and Density Functional Theory Computations

    NASA Astrophysics Data System (ADS)

    Grossert, J. Stuart; Herrera, Lisandra Cubero; Ramaley, Louis; Melanson, Jeremy E.

    2014-08-01

    Analysis of triacylglycerols (TAGs), found as complex mixtures in living organisms, is typically accomplished using liquid chromatography, often coupled to mass spectrometry. TAGs, weak bases not protonated using electrospray ionization, are usually ionized by adduct formation with a cation, including those present in the solvent (e.g., Na+). There are relatively few reports on the binding of TAGs with cations or on the mechanisms by which cationized TAGs fragment. This work examines binding efficiencies, determined by mass spectrometry and computations, for the complexation of TAGs to a range of cations (Na+, Li+, K+, Ag+, NH4 +). While most cations bind to oxygen, Ag+ binding to unsaturation in the acid side chains is significant. The importance of dimer formation, [2TAG + M]+ was demonstrated using several different types of mass spectrometers. From breakdown curves, it became apparent that two or three acid side chains must be attached to glycerol for strong cationization. Possible mechanisms for fragmentation of lithiated TAGs were modeled by computations on tripropionylglycerol. Viable pathways were found for losses of neutral acids and lithium salts of acids from different positions on the glycerol moiety. Novel lactone structures were proposed for the loss of a neutral acid from one position of the glycerol moiety. These were studied further using triple-stage mass spectrometry (MS3). These lactones can account for all the major product ions in the MS3 spectra in both this work and the literature, which should allow for new insights into the challenging analytical methods needed for naturally occurring TAGs.

  2. The study of radiation induced DNA-protein crosslinks by electrospray ionization mass spectrometry

    SciTech Connect

    Lipton, M.S.; Fuciarelli, A.F.; Springer, D.L.; Edmonds, C.G.

    1995-12-31

    The authors have used peptide-thymine and histone-thymine solutions to model protein-DNA cross-linking chemistry induced in intact chromatin by low dosage of g-irradiation. Induced thymine crosslinking to model peptide systems has been evaluated by on-line liquid chromatography-electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS-MS) with sensitivity comparable or superior to conventional GC-MS determinations. Radiation damage at doses as low as 0.1 Gy can be detected by this method. Additionally, thymine modified H2B can also be examined by ESI-MS and tandem-MS of the intact protein and proteinase digests. Limited information on the sites of thymine crosslinking can be obtained by tandem mass spectrometry on the intact multiply charged molecular species. More detailed information on the sites of thymine-protein crosslinking is obtained by on-line LC-ESI-MS of selective proteolysis products of the modified histones. Further MS-MS experiments on the selective proteolysis products will reveal specific modified amino acids and their sequence location. These methods reveal the nature, extent and site of radiation induced modification of the oligopeptides. Studies are being extended to the examination of the radiation induced covalent interactions between histones and oligonucleotides in higher states of organization. The eventual object is to study DNA-protein crosslinking interactions in model and native genomic nucleosome systems.

  3. Imaging Mass Spectrometry in Neuroscience

    PubMed Central

    2013-01-01

    Imaging mass spectrometry is an emerging technique of great potential for investigating the chemical architecture in biological matrices. Although the potential for studying neurobiological systems is evident, the relevance of the technique for application in neuroscience is still in its infancy. In the present Review, a principal overview of the different approaches, including matrix assisted laser desorption ionization and secondary ion mass spectrometry, is provided with particular focus on their strengths and limitations for studying different neurochemical species in situ and in vitro. The potential of the various approaches is discussed based on both fundamental and biomedical neuroscience research. This Review aims to serve as a general guide to familiarize the neuroscience community and other biomedical researchers with the technique, highlighting its great potential and suitability for comprehensive and specific chemical imaging. PMID:23530951

  4. Two decades of studying non-covalent biomolecular assemblies by means of electrospray ionization mass spectrometry

    PubMed Central

    Hilton, Gillian R.; Benesch, Justin L. P.

    2012-01-01

    Mass spectrometry (MS) is a recognized approach for characterizing proteins and the complexes they assemble into. This application of a long-established physico-chemical tool to the frontiers of structural biology has stemmed from experiments performed in the early 1990s. While initial studies focused on the elucidation of stoichiometry by means of simple mass determination, developments in MS technology and methodology now allow researchers to address questions of shape, inter-subunit connectivity and protein dynamics. Here, we chart the remarkable rise of MS and its application to biomolecular complexes over the last two decades. PMID:22319100

  5. A Study of Heterogeneous Catalysis by Nanoparticle-Embedded Paper-Spray Ionization Mass Spectrometry.

    PubMed

    Banerjee, Shibdas; Basheer, Chanbasha; Zare, Richard N

    2016-10-04

    We have developed nanoparticle-embedded paper-spray mass spectrometry for studying three types of heterogeneously catalyzed reactions: 1) Palladium-nanoparticle-catalyzed Suzuki cross-coupling reactions, 2) palladium- or silver-nanoparticle-catalyzed 4-nitrophenol reduction, and 3) gold-nanoparticle-catalyzed glucose oxidation. These reactions were almost instantaneous on the nanocatalyst-embedded paper, which subsequently transferred the transient intermediates and products to a mass spectrometer for their detection. This in situ method of capturing transient intermediates and products from heterogeneous catalysis is highly promising for investigating the mechanism of catalysis and rapidly screening catalytic activity under ambient conditions.

  6. Mass spectrometry. [review of techniques

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Kimble, B. J.; Derrick, P. J.

    1976-01-01

    Advances in mass spectrometry (MS) and its applications over the past decade are reviewed in depth, with annotated literature references. New instrumentation and techniques surveyed include: modulated-beam MS, chromatographic MS on-line computer techniques, digital computer-compatible quadrupole MS, selected ion monitoring (mass fragmentography), and computer-aided management of MS data and interpretation. Areas of application surveyed include: organic MS and electron impact MS, field ionization kinetics, appearance potentials, translational energy release, studies of metastable species, photoionization, calculations of molecular orbitals, chemical kinetics, field desorption MS, high pressure MS, ion cyclotron resonance, biochemistry, medical/clinical chemistry, pharmacology, and environmental chemistry and pollution studies.

  7. Mass spectrometry. [review of techniques

    NASA Technical Reports Server (NTRS)

    Burlingame, A. L.; Kimble, B. J.; Derrick, P. J.

    1976-01-01

    Advances in mass spectrometry (MS) and its applications over the past decade are reviewed in depth, with annotated literature references. New instrumentation and techniques surveyed include: modulated-beam MS, chromatographic MS on-line computer techniques, digital computer-compatible quadrupole MS, selected ion monitoring (mass fragmentography), and computer-aided management of MS data and interpretation. Areas of application surveyed include: organic MS and electron impact MS, field ionization kinetics, appearance potentials, translational energy release, studies of metastable species, photoionization, calculations of molecular orbitals, chemical kinetics, field desorption MS, high pressure MS, ion cyclotron resonance, biochemistry, medical/clinical chemistry, pharmacology, and environmental chemistry and pollution studies.

  8. Accounting for isotopic clustering in Fourier transform mass spectrometry data analysis for clinical diagnostic studies.

    PubMed

    Kakourou, Alexia; Vach, Werner; Nicolardi, Simone; van der Burgt, Yuri; Mertens, Bart

    2016-10-01

    Mass spectrometry based clinical proteomics has emerged as a powerful tool for high-throughput protein profiling and biomarker discovery. Recent improvements in mass spectrometry technology have boosted the potential of proteomic studies in biomedical research. However, the complexity of the proteomic expression introduces new statistical challenges in summarizing and analyzing the acquired data. Statistical methods for optimally processing proteomic data are currently a growing field of research. In this paper we present simple, yet appropriate methods to preprocess, summarize and analyze high-throughput MALDI-FTICR mass spectrometry data, collected in a case-control fashion, while dealing with the statistical challenges that accompany such data. The known statistical properties of the isotopic distribution of the peptide molecules are used to preprocess the spectra and translate the proteomic expression into a condensed data set. Information on either the intensity level or the shape of the identified isotopic clusters is used to derive summary measures on which diagnostic rules for disease status allocation will be based. Results indicate that both the shape of the identified isotopic clusters and the overall intensity level carry information on the class outcome and can be used to predict the presence or absence of the disease.

  9. Quality by design study of the direct analysis in real time mass spectrometry response.

    PubMed

    Wang, Lu; Chen, Teng; Zeng, Shanshan; Qu, Haibin

    2014-02-01

    A mass spectrometry method has been developed using the Quality by Design (QbD) principle. Direct analysis in real time mass spectrometry (DART-MS) was adopted to analyze a pharmaceutical preparation. A fishbone diagram for DART-MS and the Plackett-Burman design were utilized to evaluate the impact of a number of factors on the method performance. Multivariate regression and Pareto ranking analysis indicated that the temperature, determined distance, and sampler speed were statistically significant (P < 0.05). Furthermore, the Box-Behnken design combined with response surface analysis was then employed to study the relationships between these three factors and the quality of the DART-MS analysis. The analytical design space of DART-MS was thus constructed and its robustness was validated. In this presented approach, method performance was mathematically described as a composite desirability function of the critical quality attributes (CQAs). Two terms of method validation, including analytical repeatability and method robustness, were carried out at an operating work point. Finally, the validated method was successfully applied to the pharmaceutical quality assurance in different manufacturing batches. These results revealed that the QbD concept was practical in DART-MS method development. Meanwhile, the determined quality was controlled by the analytical design space. This presented strategy provided a tutorial to the development of a robust QbD-compliant mass spectrometry method for industrial quality control.

  10. Quality by Design Study of the Direct Analysis in Real Time Mass Spectrometry Response

    NASA Astrophysics Data System (ADS)

    Wang, Lu; Chen, Teng; Zeng, Shanshan; Qu, Haibin

    2013-12-01

    A mass spectrometry method has been developed using the Quality by Design (QbD) principle. Direct analysis in real time mass spectrometry (DART-MS) was adopted to analyze a pharmaceutical preparation. A fishbone diagram for DART-MS and the Plackett-Burman design were utilized to evaluate the impact of a number of factors on the method performance. Multivariate regression and Pareto ranking analysis indicated that the temperature, determined distance, and sampler speed were statistically significant (P < 0.05). Furthermore, the Box-Behnken design combined with response surface analysis was then employed to study the relationships between these three factors and the quality of the DART-MS analysis. The analytical design space of DART-MS was thus constructed and its robustness was validated. In this presented approach, method performance was mathematically described as a composite desirability function of the critical quality attributes (CQAs). Two terms of method validation, including analytical repeatability and method robustness, were carried out at an operating work point. Finally, the validated method was successfully applied to the pharmaceutical quality assurance in different manufacturing batches. These results revealed that the QbD concept was practical in DART-MS method development. Meanwhile, the determined quality was controlled by the analytical design space. This presented strategy provided a tutorial to the development of a robust QbD-compliant mass spectrometry method for industrial quality control.

  11. Studying the stoichiometries of membrane proteins by mass spectrometry: microbial rhodopsins and a potassium ion channel.

    PubMed

    Hoffmann, Jan; Aslimovska, Lubica; Bamann, Christian; Glaubitz, Clemens; Bamberg, Ernst; Brutschy, Bernd

    2010-04-14

    In the present work we demonstrate the advantages of LILBID mass spectrometry in the mass analysis of membrane proteins with emphasis on ion-pumps and channels. Due to their hydrophobic nature, membrane proteins have to be solubilized by detergents. However, these molecules tend to complicate the analysis by mass spectrometry. In LILBID, detergent molecules are readily tolerated which allows for the study of solution phase quaternary structures of membrane proteins. This is shown for the proton-pump bacteriorhodospin and the potassium channel KcsA where in both cases the stoichiometries found by LILBID reflect the known structures from 2D or 3D crystals. With proteorhodopsin we demonstrate a preliminary detergent screening showing different structures in different detergents and the implications for the functionality of this protein. We show that Triton-X 100 prevents the formation of the pentamer of proteorhodopsin. Furthermore, the quaternary structures of proteorhodopsin cloned without the signal peptide and of the cation channel channelrhodopsin-2 were studied. The intrinsic properties of channelrhodopsin-2 allow for mass spectrometric analysis in very high salt concentrations up to 100 mM of NaCl. In summary we demonstrate that LILBID is an alternative mass spectrometric method for the analysis of membrane proteins from solution phase.

  12. International Mass Spectrometry Society (IMSS).

    PubMed

    Cooks, R G; Gelpi, E; Nibbering, N M

    2001-02-01

    This paper gives a brief description of the recently formalized International Mass Spectrometry Society (IMSS). It is presented here in order to increase awareness of the opportunities for collaboration in mass spectrometry in an international context. It also describes the recent 15th International Mass Spectrometry Conference, held August/September 2000, in Barcelona. Each of the authors is associated with the IMSS. The 15th Conference, which covers all of mass spectrometry on a triennial basis, was chaired by Professor Emilio Gelpi of the Instituto de Investigaciones Biomedicas, Barcelona. The outgoing and founding President of the IMSS is Professor Graham Cooks, Purdue University, and the incoming President is Professor Nico Nibbering, University of Amsterdam. Similar material has been provided to the Editors of other journals that cover mass spectrometry.

  13. Application of isochronous mass spectrometry for the study of angular momentum population in projectile fragmentation reactions

    NASA Astrophysics Data System (ADS)

    Tu, X. L.; Kelić-Heil, A.; Litvinov, Yu. A.; Podolyák, Zs.; Zhang, Y. H.; Huang, W. J.; Xu, H. S.; Blaum, K.; Bosch, F.; Chen, R. J.; Chen, X. C.; Fu, C. Y.; Gao, B. S.; Ge, Z.; Hu, Z. G.; Liu, D. W.; Litvinov, S. A.; Ma, X. W.; Mao, R. S.; Mei, B.; Shuai, P.; Sun, B. H.; Sun, Y.; Sun, Z. Y.; Walker, P. M.; Wang, M.; Winckler, N.; Xia, J. W.; Xiao, G. Q.; Xing, Y. M.; Xu, X.; Yamaguchi, T.; Yan, X. L.; Yang, J. C.; Yuan, Y. J.; Zeng, Q.; Zhang, W.; Zhao, H. W.; Zhao, T. C.; Zhou, X. H.

    2017-01-01

    Isochronous mass spectrometry was applied to measure isomeric yield ratios of fragmentation reaction products. This approach is complementary to conventional γ -ray spectroscopy in particular for measuring yield ratios for long-lived isomeric states. Isomeric yield ratios for the high-spin I =19 /2 ℏ states in the mirror nuclei 53Fe and 53Co are measured to study angular momentum population following the projectile fragmentation of 78Kr at energies of ˜480 A MeV on a beryllium target. The 19/2 state isomeric ratios of 53Fe produced from different projectiles in the literature have also been extracted as a function of mass number difference between projectile and fragment (mass loss). The results are compared to abrabla07 model calculations. The isomeric ratios of 53Fe produced using different projectiles suggest that the theory underestimates not only the previously reported dependence on the spin but also the dependence on the mass loss.

  14. Electrochemistry-mass spectrometry for mechanism study of oxygen reduction at water/oil interface

    NASA Astrophysics Data System (ADS)

    Liu, Shu-Juan; Yu, Zheng-Wei; Qiao, Liang; Liu, Bao-Hong

    2017-04-01

    Electrochemistry methods have been widely employed in the development of renewable energy, and involved in various processes, e.g. water splitting and oxygen reduction. Remarkable progress notwithstanding, there are still many challenges in further optimization of catalysts to achieve high performance. For this purpose, an in-depth understanding of reaction mechanism is needed. In this study, an electrochemistry-mass spectrometry method based on a Y-shaped dual-channel microchip as electrochemical cell and ionization device was demonstrated. Combined solutions of aqueous phase and oil phase were introduced into mass spectrometer directly when electrochemical reactions were happening to study the reduction of oxygen by decamethylferrocene or tetrathiafulvalene under the catalysis of a metal-free porphyrin, tetraphenylporphyrin, at water/1,2-dichloroethane interfaces. Monoprotonated and diprotonated tetraphenylporphyrin were detected by mass spectrometer, confirming the previously proposed mechanism of the oxygen reduction reaction. This work offers a new approach to study electrochemical reactions at liquid-liquid interface.

  15. A Mass Spectrometry Study of Isotope Separation in the Laser Plume

    NASA Astrophysics Data System (ADS)

    Suen, Timothy Wu

    Accurate quantification of isotope ratios is critical for both preventing the development of illicit weapons programs in nuclear safeguards and identifying the source of smuggled material in nuclear forensics. While isotope analysis has traditionally been performed by mass spectrometry, the need for in situ measurements has prompted the development of optical techniques, such as laser-induced breakdown spectroscopy (LIBS) and laser ablation molecular isotopic spectrometry (LAMIS). These optical measurements rely on laser ablation for direct solid sampling, but several past studies have suggested that the distribution of isotopes in the ablation plume is not uniform. This study seeks to characterize isotope separation in the laser plume through the use of orthogonal-acceleration time-of-flight mass spectrometry. A silver foil was ablated with a Nd:YAG at 355 nm at an energy of 50 muJ with a spot size of 71 mum, for a fluence of 1.3 J/cm2 and an irradiance of 250 MW/cm2. Flat-plate repellers were used to sample the plume, and a temporal profile of the ions was obtained by varying the time delay on the high-voltage pulse. A spatial profile along the axis of the plume was generated by changing the position of the sample, which yielded snapshots of the isotopic composition with time. In addition, the reflectron time-of-flight system was used as an energy filter in conjunction with the repellers to sample slices of the laser plasma orthogonal to the plume axis. Mass spectrometry of the plume revealed a fast ion distribution and a slow ion distribution. Measurements taken across the entire plume showed the fast 109Ag ions slightly ahead in both space and time, causing the 107Ag fraction to drop to 0.34 at 3 mus, 4 mm from the sample surface. Although measurements centered on the near side of the plume did not show isotope separation, the slow ions on the far side of the plume included much more 109Ag than 107Ag. In addition to examining the isotope content of the ablation

  16. A theoretical and mass spectrometry study of the fragmentation of mycosporine-like amino acids

    NASA Astrophysics Data System (ADS)

    Cardozo, Karina H. M.; Vessecchi, Ricardo; Carvalho, Valdemir M.; Pinto, Ernani; Gates, Paul J.; Colepicolo, Pio; Galembeck, Sérgio E.; Lopes, Norberto P.

    2008-06-01

    In the present study, the mycosporine-like amino acids (MAAs) were isolated from the marine red alga Gracilaria tenuistipitata and analysed by high-resolution accurate-mass sequential mass spectrometry (MSn). In addition to the proposed fragmentation mechanism based on the MSn analysis, it is clearly demonstrated that the elimination of mass 15 is a radical processes taking place at the methoxyl substituent of the double bond. This characteristic loss of a methyl radical was studied by theoretical calculations and the homolytic cleavage of the OC bond is suggested to be dependent on the bond weakening. The protonation site of the MAAs was indicated by analysis of the Fukui functions and the relative Gibbs energies of the several possible protonated forms.

  17. Study of the microbiodegradation of terpenoid resin-based varnishes from easel painting using pyrolysis-gas chromatography-mass spectrometry and gas chromatography-mass spectrometry.

    PubMed

    Doménech-Carbó, María Teresa; Osete-Cortina, Laura; de la Cruz Cañizares, Juana; Bolívar-Galiano, Fernando; Romero-Noguera, Julio; Fernández-Vivas, María Antonia; Martín-Sánchez, Inés

    2006-08-01

    The alterations produced by microbiological attack on terpenoid resin-based varnishes from panel and canvas paintings have been evaluated using pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) and gas chromatography-mass spectrometry (GC-MS). The proposed methods include the on-line derivatisation of drying oils and diterpenoid resins using hexamethyldisilazane during pyrolysis and the application of methyl chloroformate as a derivatisation reagent for triterpenoid resins in GC-MS. Two types of specimens, consisting of model oil medium prepared from linseed oil and model spirit varnishes prepared from colophony and mastic resins dissolved in turpentine, have been used as reference materials. For a series of specimens upon which different genera of bacteria and fungi were inoculated and encouraged to grow, analyses indicated that no mechanisms that commonly occur during the attack of enzymes on drying oils and terpenoid biodegraders were observed to occur in the oil medium and varnishes studied. Thus, the degradation pathways observed in the performed trials usually occur as consequence of natural ageing. Specific trials consisting of the application of biocides to uninoculated colophony varnish resulted in the identification of processes that produce undesirable degradation of the varnish due to interactions between the biocide and the varnish components. Finally, the studied biocides--Biotin, New-Des and Nipagine--generally exhibited good inhibiting effects on the microorganisms studied, although some interesting differences were found between them regarding the application method and type of biocide.

  18. Studies of Alkali Sorption Kinetics for Pressurized Fluidized Bed Combustion by High Pressure Mass Spectrometry

    SciTech Connect

    Wolf, K.J.; Willenborg, W.; Fricke, C.; Prikhodovsky, A.; Hilpert, K.; Singheiser, L.

    2002-09-20

    This work describes the first approach to use High Pressure Mass Spectrometry (HPMS) for the quantification and analysis of alkali species in a gas stream downstream a sorbent bed of different tested alumosilicates.

  19. Study on the photostability of guaiazulene by high-performance liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry.

    PubMed

    Fiori, Jessica; Gotti, Roberto; Albini, Angelo; Cavrini, Vanni

    2008-09-01

    The photostability of guaiazulene (1,4-dimethyl-7-isopropylazulene; GA), a natural azulenic compound used in cosmetic and health-care products, as well as in pharmaceutical preparations, was investigated in solution (methanol, ethanol, acetonitrile), by different techniques: gas chromatography/mass spectrometry (GC/MS) and high-performance liquid chromatography combined with atmospheric pressure chemical ionization mass spectrometry and UV detection (LC/APCI-MS and HPLC/UV). A solar simulator (xenon-arc lamp) was used as UV-A radiation source. The study involved: monitoring compound decomposition, identifying products of photodegradation (PPs), assessing the role of oxygen and evaluating the kinetics of the process. Minor PPs are volatile compounds and were characterized by GC/MS, while oligomeric polyoxygenated compounds, tentatively characterized on the basis of MS and MS/MS spectra, were found to be the main photoproducts. The photodegradation was found to be enhanced by the presence of oxygen; nevertheless, determination of the singlet oxygen quantum yield for GA gave a lower value than that for the reference standard Rose Bengal. The obtained results and the developed stability-indicating methods (GC/MS and LC/MS) are of interest for stability studies and/or quality control purposes of GA as raw material or cosmetic products.

  20. Ion mobility-mass spectrometry.

    PubMed

    Kanu, Abu B; Dwivedi, Prabha; Tam, Maggie; Matz, Laura; Hill, Herbert H

    2008-01-01

    This review article compares and contrasts various types of ion mobility-mass spectrometers available today and describes their advantages for application to a wide range of analytes. Ion mobility spectrometry (IMS), when coupled with mass spectrometry, offers value-added data not possible from mass spectra alone. Separation of isomers, isobars, and conformers; reduction of chemical noise; and measurement of ion size are possible with the addition of ion mobility cells to mass spectrometers. In addition, structurally similar ions and ions of the same charge state can be separated into families of ions which appear along a unique mass-mobility correlation line. This review describes the four methods of ion mobility separation currently used with mass spectrometry. They are (1) drift-time ion mobility spectrometry (DTIMS), (2) aspiration ion mobility spectrometry (AIMS), (3) differential-mobility spectrometry (DMS) which is also called field-asymmetric waveform ion mobility spectrometry (FAIMS) and (4) traveling-wave ion mobility spectrometry (TWIMS). DTIMS provides the highest IMS resolving power and is the only IMS method which can directly measure collision cross-sections. AIMS is a low resolution mobility separation method but can monitor ions in a continuous manner. DMS and FAIMS offer continuous-ion monitoring capability as well as orthogonal ion mobility separation in which high-separation selectivity can be achieved. TWIMS is a novel method of IMS with a low resolving power but has good sensitivity and is well intergrated into a commercial mass spectrometer. One hundred and sixty references on ion mobility-mass spectrometry (IMMS) are provided.

  1. Comparative Study of Three Methods for Affinity Measurements: Capillary Electrophoresis Coupled with UV Detection and Mass Spectrometry, and Direct Infusion Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Mironov, Gleb G.; Logie, Jennifer; Okhonin, Victor; Renaud, Justin B.; Mayer, Paul M.; Berezovski, Maxim V.

    2012-07-01

    We present affinity capillary electrophoresis and mass spectrometry (ACE-MS) as a comprehensive separation technique for label-free solution-based affinity analysis. The application of ACE-MS for measuring affinity constants between eight small molecule drugs [ibuprofen, s-flurbiprofen, diclofenac, phenylbutazone, naproxen, folic acid, resveratrol, and 4,4'-(propane-1,3-diyl) dibenzoic acid] and β-cyclodextrin is described. We couple on-line ACE with MS to combine the separation and kinetic capability of ACE together with the molecular weight and structural elucidation of MS in one system. To understand the full potential of ACE-MS, we compare it with two other methods: Direct infusion mass spectrometry (DIMS) and ACE with UV detection (ACE-UV). After the evaluation, DIMS provides less reliable equilibrium dissociation constants than separation-based ACE-UV and ACE-MS, and cannot be used solely for the study of noncovalent interactions. ACE-MS determines apparent dissociation constants for all reacting small molecules in a mixture, even in cases when drugs overlap with each other during separation. The ability of ACE-MS to interact, separate, and rapidly scan through m/z can facilitate the simultaneous affinity analysis of multiple interacting pairs, potentially leading to the high-throughput screening of drug candidates.

  2. Mass Spectrometry in Studies of Protein Thiol Chemistry and Signaling: Opportunities and Caveats

    PubMed Central

    Devarie Baez, Nelmi O.; Reisz, Julie A.; Furdui, Cristina M.

    2014-01-01

    Mass spectrometry (MS) has become a powerful and widely utilized tool in the investigation of protein thiol chemistry, biochemistry, and biology. Very early biochemical studies of metabolic enzymes have brought to light the broad spectrum of reactivity profiles that distinguish cysteine thiols with functions in catalysis and protein stability from other cysteine residues in proteins. The development of MS methods for the analysis of proteins using electrospray ionization (ESI) or matrix-assisted laser desorption/ionization (MALDI) coupled with the emergence of high-resolution mass analyzers have been instrumental in advancing studies of thiol modifications, both in single proteins and within the cellular context. This article reviews MS instrumentation and methods of analysis employed in investigations of thiols and their reactivity toward a range of small biomolecules. A selected number of studies are detailed to highlight the advantages brought about by the MS technologies along with the caveats associated with these analyses. PMID:25261734

  3. Review: mass spectrometry in Russia.

    PubMed

    Zaikin, Vladimir G; Sysoev, Alexander A

    2013-01-01

    The present review covers the main research in the area of mass spectrometry from the 1990s which was about the same time as the Russian Federation emerged from the collapse of the Soviet Union (USSR). It consists of two main parts-application of mass spectrometry to chemistry and related fields and creation and development of mass spectrometric technique. Both traditional and comparatively new mass spectrometric methods were used to solve various problems in organic chemistry (reactivity of gas-phase ions, structure elucidation and problems of identification, quantitative and trace analysis, differentiation of stereoisomers, derivatization approaches etc.), biochemistry (proteomics and peptidomics, lipidomics), medical chemistry (mainly the search of biomarkers, pharmacology, doping control), environmental, petrochemistry, polymer chemistry, inorganic and physical chemistry, determination of natural isotope ratio etc. Although a lot of talented mass spectrometrists left Russia and moved abroad after the collapse of the Soviet Union, the vitality of the mass spectral community proved to be rather high, which allowed the continuation of new developments in the field of mass spectrometric instrumentation. They are devoted to improvements in traditional magnetic sector mass spectrometers and the development of new ion source types, to analysis and modification of quadrupole, time-of-flight (ToF) and ion cyclotron resonance (ICR) analyzers. The most important achievements are due to the creation of multi-reflecting ToF mass analyzers. Special attention was paid to the construction of compact mass spectrometers, particularly for space exploration, of combined instruments, such as ion mobility spectrometer/mass spectrometer and accelerating mass spectrometers. The comparatively young Russian Mass Spectrometry Society is working hard to consolidate the mass spectrometrists from Russia and foreign countries, to train young professionals on new appliances and regularly

  4. Mass spectrometry analysis of nucleosides and nucleotides.

    PubMed

    Dudley, Ed; Bond, Liz

    2014-01-01

    Mass spectrometry has been widely utilised in the study of nucleobases, nucleosides and nucleotides as components of nucleic acids and as bioactive metabolites in their own right. In this review, the application of mass spectrometry to such analysis is overviewed in relation to various aspects regarding the analytical mass spectrometric and chromatographic techniques applied and also the various applications of such analysis. © 2013 Wiley Periodicals, Inc.

  5. Linear electric field mass spectrometry

    DOEpatents

    McComas, David J.; Nordholt, Jane E.

    1992-01-01

    A mass spectrometer and methods for mass spectrometry. The apparatus is compact and of low weight and has a low power requirement, making it suitable for use on a space satellite and as a portable detector for the presence of substances. High mass resolution measurements are made by timing ions moving through a gridless cylindrically symmetric linear electric field.

  6. Linear electric field mass spectrometry

    DOEpatents

    McComas, D.J.; Nordholt, J.E.

    1992-12-01

    A mass spectrometer and methods for mass spectrometry are described. The apparatus is compact and of low weight and has a low power requirement, making it suitable for use on a space satellite and as a portable detector for the presence of substances. High mass resolution measurements are made by timing ions moving through a gridless cylindrically symmetric linear electric field. 8 figs.

  7. Cluster secondary ion mass spectrometry microscope mode mass spectrometry imaging.

    PubMed

    Kiss, András; Smith, Donald F; Jungmann, Julia H; Heeren, Ron M A

    2013-12-30

    Microscope mode imaging for secondary ion mass spectrometry is a technique with the promise of simultaneous high spatial resolution and high-speed imaging of biomolecules from complex surfaces. Technological developments such as new position-sensitive detectors, in combination with polyatomic primary ion sources, are required to exploit the full potential of microscope mode mass spectrometry imaging, i.e. to efficiently push the limits of ultra-high spatial resolution, sample throughput and sensitivity. In this work, a C60 primary source was combined with a commercial mass microscope for microscope mode secondary ion mass spectrometry imaging. The detector setup is a pixelated detector from the Medipix/Timepix family with high-voltage post-acceleration capabilities. The system's mass spectral and imaging performance is tested with various benchmark samples and thin tissue sections. The high secondary ion yield (with respect to 'traditional' monatomic primary ion sources) of the C60 primary ion source and the increased sensitivity of the high voltage detector setup improve microscope mode secondary ion mass spectrometry imaging. The analysis time and the signal-to-noise ratio are improved compared with other microscope mode imaging systems, all at high spatial resolution. We have demonstrated the unique capabilities of a C60 ion microscope with a Timepix detector for high spatial resolution microscope mode secondary ion mass spectrometry imaging. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Marine environment pollution: The contribution of mass spectrometry to the study of seawater.

    PubMed

    Magi, Emanuele; Di Carro, Marina

    2016-09-09

    The study of marine pollution has been traditionally addressed to persistent chemicals, generally known as priority pollutants; a current trend in environmental analysis is a shift toward "emerging pollutants," defined as newly identified or previously unrecognized contaminants. The present review is focused on the peculiar contribution of mass spectrometry (MS) to the study of pollutants in the seawater compartment. The work is organized in five paragraphs where the most relevant groups of pollutants, both "classical" and "emerging," are presented and discussed, highlighting the relative data obtained by the means of different MS techniques. The hyphenation of MS and separative techniques, together with the development of different ion sources, makes MS and tandem MS the analytical tool of choice for the determination of trace organic contaminants in seawater. © 2016 Wiley Periodicals, Inc. Mass Spec Rev. © 2016 Wiley Periodicals, Inc.

  9. Mass spectrometry of humic substances of different origin including those from Antarctica A comparative study.

    PubMed

    Peña-Méndez, E M; Gajdosová, D; Novotná, K; Prosek, P; Havel, J

    2005-10-31

    Mass spectra of humic acids (HA) from different sampling sites (Antarctica, Brazil, Czech Republic, Mexico and USA) and origin (plant, soil, peat, and coal derived) were obtained by laser desorption/ionization time of flight mass spectrometry (LDI-TOF MS). Optimisation of the experimental conditions are given as the optimal value of the laser energy at approximately 20-30% higher than the threshold. Under these conditions, reproducible mass spectra of HA samples were obtained. In the mass spectra the majority of the peaks are observed in the m/z region 100-1000Da. Mass spectra fingerprints of HA were analyzed and, in spite of the differences in their origin, a number of common features and profiles (patterns of peaks) were observed in most of the samples. Very similar structural groups (patterns) of the peaks are present in the m/z range 717-918Da for HA samples of quite different origins, countries or continents. The tandem LDI-TOF MS and multivariate statistical tools allowed us to extract and elucidate underlying information contained in the mass spectra of the HA samples under study. Applying principal components and cluster analysis, it was, e.g. demonstrated that most of the Antarctica HA samples show distinguishable differences when compared with humic acids from other continents and of different origin.

  10. Fragmentation study of aminoalcohol-diterpenoid alkaloids by electrospray ionization time-of-flight mass spectrometry.

    PubMed

    Liu, Xiuxiu; Tang, Minghai; Wang, Lu; Chao, Ruobing

    2016-01-15

    Aminoalcohol-diterpenoid alkaloids were found to be a group of cardioactive substances in the lateral roots of Aconitum carmichaeli Debx. Studies on the fragmentation behaviors and features of these alkaloids in mass spectrometry would be important for their structural identification and in vivo metabolic research, which has not received much attention thus far. In this study, the fragmentation behaviors of 14 aminoalcohol-diterpenoid alkaloids were investigated by utilizing high-resolution time-of-flight tandem mass spectrometry. By analysis of the obtained MS(2) data, we summarized the fragmentation features of the corresponding alkaloids under different collision energy. The dissociation of functional groups from the skeleton was observed as the main fragmentation way in electrospray ionization (ESI) mode. The order of fragmentation sites was C1/C3 > C16 > C15 > C6 > N, with loss of one or more CH3OH, H2O, C2H4 (substituent on N atom) or CO (at C15 ) groups. The first systematic investigations on the fragmentation of aminoalcohol-diterpenoid alkaloids are described in this paper, setting the stage for an in-depth identification and study of the corresponding components in complex systems. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Electrochemical oxidation and protein adduct formation of aniline: a liquid chromatography/mass spectrometry study.

    PubMed

    Melles, Daniel; Vielhaber, Torsten; Baumann, Anne; Zazzeroni, Raniero; Karst, Uwe

    2012-04-01

    Historically, skin sensitization tests are typically based on in vivo animal tests. However, for substances used in cosmetic products, these tests have to be replaced according to the European Commission regulation no. 1223/2009. Modification of skin proteins by electrophilic chemicals is a key process associated with the induction of skin sensitization. The present study investigates the capabilities of a purely instrumental setup to determine the potential of commonly used non-electrophilic chemicals to cause skin sensitization by the generation of electrophilic species from the parent compound. In this work, the electrophiles were generated by the electrochemical oxidation of aniline, a basic industrial chemical which may also be released from azo dyes in cosmetics. The compound is a known sensitizer and was oxidized in an electrochemical thin-layer cell which was coupled online to electrospray ionization-mass spectrometry. The electrochemical oxidation was performed on a boron-doped diamond working electrode, which is able to generate hydroxyl radicals in aqueous solutions at high potentials. Without any pretreatment, the oxidation products were identified by electrospray ionization/time-of-flight mass spectrometry (ESI-ToF-MS) using their exact masses. A mass voltammogram was generated by plotting the obtained mass spectra against the applied potential. Oligomerization states with up to six monomeric units in different redox states of aniline were observed using this setup. This approach was extended to generate adducts between the oxidation products of aniline and the tripeptide glutathione. Two adducts were identified with this trapping experiment. Protein modification was carried out subsequently: Aniline was oxidized at a constant potential and was allowed to react with β-lactoglobulin A (β-LGA) or human serum albumin (HSA), respectively. The generated adducts were analyzed by liquid chromatography coupled to ESI-ToF-MS. For both β-LGA and HSA, aniline

  12. Neuroscience and Accelerator Mass Spectrometry

    SciTech Connect

    Palmblad, M N; Buchholz, B A; Hillegonds, D J; Vogel, J S

    2004-08-02

    Accelerator mass spectrometry (AMS) is a mass spectrometric method for quantifying rare isotopes. It has had great impact in geochronology and archaeology and is now being applied in biomedicine. AMS measures radioisotopes such as {sup 3}H, {sup 14}C, {sup 26}Al, {sup 36}Cl and {sup 41}Ca, with zepto- or attomole sensitivity and high precision and throughput, enabling safe human pharmacokinetic studies involving: microgram doses, agents having low bioavailability, or toxicology studies where administered doses must be kept low (<1 {micro}g/kg). It is used to study long-term pharmacokinetics, to identify biomolecular interactions, to determine chronic and low-dose effects or molecular targets of neurotoxic substances, to quantify transport across the blood-brain barrier and to resolve molecular turnover rates in the human brain on the timescale of decades. We will here review how AMS is applied in neurotoxicology and neuroscience.

  13. Neuroscience and accelerator mass spectrometry.

    PubMed

    Palmblad, Magnus; Buchholz, Bruce A; Hillegonds, Darren J; Vogel, John S

    2005-02-01

    Accelerator mass spectrometry (AMS) is a mass spectrometric method for quantifying rare isotopes. It has had a great impact in geochronology and archaeology and is now being applied in biomedicine. AMS measures radioisotopes such as 3H, 14C, 26Al, 36Cl and 41Ca, with zepto- or attomole sensitivity and high precision and throughput, allowing safe human pharmacokinetic studies involving microgram doses, agents having low bioavailability or toxicology studies where administered doses must be kept low (<1 microg kg(-1)). It is used to study long-term pharmacokinetics, to identify biomolecular interactions, to determine chronic and low-dose effects or molecular targets of neurotoxic substances, to quantify transport across the blood-brain barrier and to resolve molecular turnover rates in the human brain on the time-scale of decades. We review here how AMS is applied in neurotoxicology and neuroscience.

  14. Detailed Study of Cyanobacterial Microcystins Using High Performance Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Qi, Yulin; Bortoli, Stella; Volmer, Dietrich A.

    2014-07-01

    Microcystins (MC) are a large group of toxic cyclic peptides, produced by cyanobacteria in eutrophic water systems. Identification of MC variants mostly relies on liquid chromatography (LC) combined with collision-induced dissociation (CID) mass spectrometry. Deviations from the essential amino acid complement are a common feature of these natural products, which makes the CID analysis more difficult and not always successful. Here, both CID and electron capture dissociation (ECD) were applied in combination with ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry to study a cyanobacteria strain isolated from the Salto Grande Reservoir in Sao Paulo State, Brazil, without prior LC separation. CID was shown to be an effective dissociation technique for quickly identifying the MC variants, even those that have previously been difficult to characterize by CID. Moreover, ECD provided even more detailed and complementary information, which enabled us to precisely locate metal binding sites of MCs for the first time. This additional information will be important for environmental chemists to study MC accumulation and production in ecosystems.

  15. Study of Simvastatin Self-Association Using Electrospray-Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Vetrova, E. V.; Lekar, A. V.; Filonova, O. V.; Borisenko, S. N.; Maksimenko, E. V.; Borisenko, N. I.

    2015-07-01

    Self-association of simvastatin, which is widely used to treat coronary heart disease, was investigated using electrospray-ionization mass spectrometry. Formation of simvastatin self-associates in various solvents was demonstrated using mass spectrometry. Solvation effects were shown to play a special role in the formation of the self-associates. Self-associates containing from two to fi ve simvastatin molecules were detected in mass spectra of an aqueous MeOH (20%) solution of simvastatin. The formation of simvastatin self-associates could compete with the complexation of supramolecular structures during the synthesis of new generation drugs.

  16. Mass spectral studies on vinylic degradation products of sulfur mustards under gas chromatography/mass spectrometry conditions.

    PubMed

    Sai Sachin, L; Karthikraj, R; Kalyan Kumar, K; Sony, T; Prasada Raju, N; Prabhakar, S

    2015-01-01

    Sulfur mustards are a class of vesicant chemical warfare agents that rapidly degrade in environmental samples. The most feasible degradation products of sulfur mustards are chloroethyl vinylic compounds and divinylic compounds, which are formed by the elimination of one and two HCl molecules from sulfur mustards, respectively. The detection and characterization of these degradation products in environmental samples are an important proof for the verification of sulfur mustard usage. In this study, we synthesized a set of sulfur mustard degradation products, i.e., divinylic compounds (1-7) and chloroethyl vinylic compounds (8-14), and characterized using gas chromatography/mass spectrometry (GC/MS) under electron ionization (EI) and chemical ionization (CI) (methane) conditions. The EI mass spectra of the studied compounds mainly included the fragment ions that resulted from homolytic cleavages with or without hydrogen migrations. The divinylic compounds (1-7) showed [M-SH](+) ions, whereas the chloroethylvinyl compounds (8-14) showed [M-Cl](+) and [M-CH2CH2Cl](+) ions. Methane/CI mass spectra showed [M+H](+) ions and provided molecular weight information. The GC retention index (RI) values were also calculated for the studied compounds. The EI and CI mass spectral data together with RI values are extremely useful for off-site analysis for the verification of the chemical weapons convention and also to participate in official Organization for the Prohibition of Chemical Weapons proficiency tests.

  17. Inductively coupled plasma mass spectrometry for stable isotope metabolic tracer studies of living systems

    SciTech Connect

    Luong, Elise

    1999-05-10

    This dissertation focuses on the development of methods for stable isotope metabolic tracer studies in living systems using inductively coupled plasma single and dual quadrupole mass spectrometers. Sub-nanogram per gram levels of molybdenum (Mo) from human blood plasma are isolated by the use of anion exchange alumina microcolumns. Million-fold more concentrated spectral and matrix interferences such as sodium, chloride, sulfate, phosphate, etc. in the blood constituents are removed from the analyte. The recovery of Mo from the alumina column is 82 ± 5% (n = 5). Isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS) is utilized for the quantitative ultra-trace concentration determination of Mo in bovine and human blood samples. The average Mo concentration in reference bovine serum determined by this method is 10.2 ± 0.4 ng/g, while the certified value is 11.5 ± 1.1 ng/g (95% confidence interval). The Mo concentration of one pool of human blood plasma from two healthy male donors is 0.5 ± 0.1 ng/g. The inductively coupled plasma twin quadrupole mass spectrometer (ICP-TQMS) is used to measure the carbon isotope ratio from non-volatile organic compounds and bio-organic molecules to assess the ability as an alternative analytical method to gas chromatography combustion isotope ratio mass spectrometry (GC-combustion-IRMS). Trytophan, myoglobin, and β-cyclodextrin are chosen for the study, initial observation of spectral interference of 13C+ with 12C 1H+ comes from the incomplete dissociation of myoglobin and/or β-cyclodextrin.

  18. Study of Electrochemical Reactions Using Nanospray Desorption Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Liu, Pengyuan; Lanekoff, Ingela T.; Laskin, Julia; Dewald, Howard D.; Chen, Hao

    2012-07-03

    The combination of electrochemistry (EC) and mass spectrometry (MS) is a powerful analytical tool for studying mechanisms of redox reactions, identification of products and intermediates, and online derivatization/recognition of analytes. This work reports a new coupling interface for EC/MS by employing nanospray desorption electrospray ionization (nano-DESI), a recently developed ambient ionization method. We demonstrate online coupling of nano-DESI-MS with a traditional electrochemical flow cell, in which the electrolyzed solution emanating from the cell is ionized by nano-DESI for MS analysis. Furthermore, we show first coupling of nano-DESI-MS with an interdigitated array (IDA) electrode enabling chemical analysis of electrolyzed samples directly from electrode surfaces. Because of its inherent sensitivity, nano-DESI enables chemical analysis of small volumes and concentrations of sample solution. Specifically, good-quality signal of dopamine and its oxidized form, dopamine ortho-quinone, was obtained using 10 μL of 1 μM solution of dopamine on the IDA. Oxidation of dopamine, reduction of benzodiazepines, and electrochemical derivatization of thiol groups were used to demonstrate the performance of the technique. Our results show the potential of nano-DESI as a novel interface for electrochemical mass spectrometry research.

  19. Optimization of human dendritic cell sample preparation for mass spectrometry-based proteomics studies

    PubMed Central

    Zhang, Ying; Bottinelli, Dario; Lisacek, Frédérique; Luban, Jeremy; De Castillia, Caterina Strambio; Varesio, Emmanuel; Hopfgartner, Gérard

    2016-01-01

    Dendritic cells (DCs) are specialized leukocytes that orchestrate the adaptive immune response. Mass spectrometry based proteomic study of these cells presents technical challenges, especially when the DCs are human in origin due to the paucity of available biological material. Here, to maximize mass spectrometry coverage of the global human DC proteome, different cell disruption methods, lysis conditions, protein precipitation, and protein pellet solubilisation and denaturation methods were compared. Mechanical disruption of DC cell pellets under cryogenic conditions, coupled with the use of RIPA buffer, was shown to be the method of choice based on total protein extraction and on the solubilisation and identification of nuclear proteins. Precipitation by acetone was found to be more efficient than by 10% TCA/acetone, allowing greater than 28% more protein identifications. Although being an effective strategy to eliminate the detergent residue, the acetone-wash step caused a loss of protein identifications. However, this potential drawback was overcome by adding 1% sodium deoxycholate in the dissolution buffer, which enhanced both solubility of the precipitated proteins and digestion efficiency. This in turn resulted in 6-11% more distinct peptides and 14-19% more total proteins identified than using 0.5M triethylammonium bicarbonate alone with the greatest increase (34%) for hydrophobic proteins. PMID:25983236

  20. Degradation study of enniatins by liquid chromatography-triple quadrupole linear ion trap mass spectrometry.

    PubMed

    Serrano, A B; Meca, G; Font, G; Ferrer, E

    2013-12-15

    Enniatins A, A1, B and B1 (ENs) are mycotoxins produced by Fusarium spp. and are normal contaminants of cereals and derivate products. In this study, the stability of ENs was evaluated during food processing by simulation of pasta cooking. Thermal treatments at different incubation times (5, 10 and 15 min) and different pH (4, 7 and 10) were applied in an aqueous system and pasta resembling system (PRS). The concentrations of the targeted mycotoxins were determined using liquid chromatography coupled to tandem mass spectrometry. High percentages of ENs reduction (81-100%) were evidenced in the PRS after the treatments at 5, 10 and 15 min of incubation. In contrast to the PRS, an important reduction of the ENs was obtained in the aqueous system after 15 min of incubation (82-100%). In general, no significant differences were observed between acid, neutral and basic solutions. Finally, several ENs degradation products were identified using the technique of liquid chromatography-triple quadrupole linear ion trap mass spectrometry.

  1. Deamidation in ricin studied by capillary zone electrophoresis- and liquid chromatography-mass spectrometry.

    PubMed

    Bergström, Tomas; Fredriksson, Sten-Åke; Nilsson, Calle; Åstot, Crister

    2015-01-01

    Deamidation in ricin, a toxin present in castor beans from the plant Ricinus communis, was investigated using capillary zone electrophoresis (CZE) and liquid chromatography coupled to high resolution mass spectrometry. Potential sites for deamidation, converting asparagine (Asn) into aspartic or isoaspartic acid (Asp or isoAsp), were identified in silico based on the protein sequence motifs and tertiary structure. In parallel, CZE- and LC-MS-based screening were performed on the digested toxin to detect deamidated peptides. The use of CZE-MS was critical for the separation of small native/deamidated peptide pairs. Selected peptides were subjected to a detailed analysis by tandem mass spectrometry to verify the presence of deamidation and determine its exact position. In the ricin preparation studied, deamidation was confirmed and located to three asparagine residues: Asn54 in the A-chain, and Asn42 and Asn60 in the B-chain. Possible in vitro deamidation occurring during sample preparation was monitored using a synthetic peptide with a known and rapid rate of deamidation. Finally, we showed that the isoelectric diversity previously reported in ricin is related to the level of deamidation.

  2. A Study of the Complexation of Mercury(II) with Dicysteinyl Tetrapeptides by Electrospray Ionization Mass Spectrometry.

    PubMed

    Mazlo, Johanna; Ngu-Schwemlein, Maria

    2016-01-08

    In this study we evaluated a method for the characterization of complexes, formed in different relative ratios of mercury(II) to dicysteinyl tetrapeptide, by electrospray ionization orbitrap mass spectrometry. This strategy is based on previous successful characterization of mercury-dicysteinyl complexes involving tripeptides by utilizing mass spectrometry among other techniques. Mercury(II) chloride and a dicysteinyl tetrapeptide were incubated in a degassed buffered medium at varying stoichiometric ratios. The complexes formed were subsequently analyzed on an electrospray mass spectrometer consisting of a hybrid linear ion- and orbi- trap mass analyzer. The electrospray ionization mass spectrometry (ESI-MS) spectra were acquired in the positive mode and the observed peaks were then analyzed for distinct mercury isotopic distribution patterns and associated monoisotopic peak. This work demonstrates that an accurate stoichiometry of mercury and peptide in the complexes formed under specified electrospray ionization conditions can be determined by using high resolution ESI MS based on distinct mercury isotopic distribution patterns.

  3. Instrumentation for mass spectrometry: 1997

    SciTech Connect

    McLuckey, S.A.

    1997-08-01

    All mass spectrometry experiments involve the manipulation of material, an interface with the mass spectrometer, ionization, ion manipulation/analysis, detection and data collection/reduction. Each of these elements involve instrumentation. The wide range of species now amenable to mass spectrometry and the diverse areas of physical science in which it plays a role have led to a seemingly unlimited array of instrumental combinations. However, only a limited number of mass analyzers, and their combinations, dominate. The dominant analyzers include time-of-flight, Fourier transform ion cyclotron resonance, the Paul trap, the mass filter, and the sector mass spectrometer. Why there are so few (or so many, depending upon one`s point of view) can be understood upon consideration of a set of mass analyzer figures of merit. These include mass resolution, mass accuracy, mass range, dynamic range, abundance sensitivity, precision, efficiency, speed, MS{sup n} capability, compatibility with the ionizer, cost, and size. The most appropriate form of mass spectrometry is determined by the priorities of the particular measurement placed on the various mass analyzer characteristics and the relative strengths of the analyzers in meeting the requirements. Each of the analyzer types has a unique set of figures of merit that makes it optimally suited for particular applications. This paper discusses these figures of merit, provides data illustrating recent developments for each analyzer type, and gives the figures of merit of each type of analyzer as they stand in 1997. 101 refs., 24 figs.

  4. Chemical crosslinking and mass spectrometry studies of the structure and dynamics of membrane proteins and receptors.

    SciTech Connect

    Haskins, William E.; Leavell, Michael D.; Lane, Pamela; Jacobsen, Richard B.; Hong, Joohee; Ayson, Marites J.; Wood, Nichole L.; Schoeniger, Joseph S.; Kruppa, Gary Hermann; Sale, Kenneth L.; Young, Malin M.; Novak, Petr

    2005-03-01

    Membrane proteins make up a diverse and important subset of proteins for which structural information is limited. In this study, chemical cross-linking and mass spectrometry were used to explore the structure of the G-protein-coupled photoreceptor bovine rhodopsin in the dark-state conformation. All experiments were performed in rod outer segment membranes using amino acid 'handles' in the native protein sequence and thus minimizing perturbations to the native protein structure. Cysteine and lysine residues were covalently cross-linked using commercially available reagents with a range of linker arm lengths. Following chemical digestion of cross-linked protein, cross-linked peptides were identified by accurate mass measurement using liquid chromatography-fourier transform mass spectrometry and an automated data analysis pipeline. Assignments were confirmed and, if necessary, resolved, by tandem MS. The relative reactivity of lysine residues participating in cross-links was evaluated by labeling with NHS-esters. A distinct pattern of cross-link formation within the C-terminal domain, and between loop I and the C-terminal domain, emerged. Theoretical distances based on cross-linking were compared to inter-atomic distances determined from the energy-minimized X-ray crystal structure and Monte Carlo conformational search procedures. In general, the observed cross-links can be explained by re-positioning participating side-chains without significantly altering backbone structure. One exception, between C3 16 and K325, requires backbone motion to bring the reactive atoms into sufficient proximity for cross-linking. Evidence from other studies suggests that residues around K325 for a region of high backbone mobility. These findings show that cross-linking studies can provide insight into the structural dynamics of membrane proteins in their native environment.

  5. Mass spectrometry guided structural biology.

    PubMed

    Liko, Idlir; Allison, Timothy M; Hopper, Jonathan Ts; Robinson, Carol V

    2016-10-01

    With the convergence of breakthroughs in structural biology, specifically breaking the resolution barriers in cryo-electron microscopy and with continuing developments in crystallography, novel interfaces with other biophysical methods are emerging. Here we consider how mass spectrometry can inform these techniques by providing unambiguous definition of subunit stoichiometry. Moreover recent developments that increase mass spectral resolution enable molecular details to be ascribed to unassigned density within high-resolution maps of membrane and soluble protein complexes. Importantly we also show how developments in mass spectrometry can define optimal solution conditions to guide downstream structure determination, particularly of challenging biomolecules that refuse to crystallise.

  6. Mass Spectrometry Applications for Toxicology.

    PubMed

    Mbughuni, Michael M; Jannetto, Paul J; Langman, Loralie J

    2016-12-01

    Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used in the Toxicological analysis of drugs, poisons, and metabolites of both. To date, MS applications have permeated all fields of toxicology which include; environmental, clinical, and forensic toxicology. While many different analytical applications are used in these fields, MS and its hyphenated applications such as; gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), inductively coupled plasma ionization MS (ICP-MS), tandem mass spectrometry (MS/MS and MS(n)) have emerged as powerful tools used in toxicology laboratories. This review will focus on these hyphenated MS technologies and their applications for toxicology.

  7. Mass Spectrometry Applications for Toxicology

    PubMed Central

    Mbughuni, Michael M.; Jannetto, Paul J.

    2016-01-01

    Toxicology is a multidisciplinary study of poisons, aimed to correlate the quantitative and qualitative relationships between poisons and their physiological and behavioural effects in living systems. Other key aspects of toxicology focus on elucidation of the mechanisms of action of poisons and development of remedies and treatment plans for associated toxic effects. In these endeavours, Mass spectrometry (MS) has become a powerful analytical technique with a wide range of application used in the Toxicological analysis of drugs, poisons, and metabolites of both. To date, MS applications have permeated all fields of toxicology which include; environmental, clinical, and forensic toxicology. While many different analytical applications are used in these fields, MS and its hyphenated applications such as; gas chromatography MS (GC-MS), liquid chromatography MS (LC-MS), inductively coupled plasma ionization MS (ICP-MS), tandem mass spectrometry (MS/MS and MSn) have emerged as powerful tools used in toxicology laboratories. This review will focus on these hyphenated MS technologies and their applications for toxicology. PMID:28149262

  8. Enhancing sample preparation capabilities for accelerator mass spectrometry radiocarbon and radiocalcium studies

    SciTech Connect

    Taylor, R E

    1991-08-20

    With support provided by the LLNL Accelerator Mass Spectrometry Laboratory, the UCR Radiocarbon Laboratory continued its studies involving sample pretreatment and target preparation for both AMS radiocarbon ({sup 14}C) and radiocalcium ({sup 41}Ca) involving applications to archaeologically -- and paleoanthropologically- related samples. With regard to AMS {sup 14}C-related studies, we have extended the development of a series of procedures which have, as their initial goal, the capability to combust several hundred microgram amounts of a chemically-pretreated organic sample and convert the resultant CO{sub 2} to graphitic carbon which will consistently yield relatively high {sup 13}C{sup {minus}} ion currents and blanks which will yield, on a consistent basis, {sup 14}C count rates at or below 0.20% modern, giving an 2 sigma age limit of >50,000 yr BP.

  9. Enhancing sample preparation capabilities for accelerator mass spectrometry radiocarbon and radiocalcium studies

    SciTech Connect

    Taylor, R.E.

    1991-08-20

    With support provided by the LLNL Accelerator Mass Spectrometry Laboratory, the UCR Radiocarbon Laboratory continued its studies involving sample pretreatment and target preparation for both AMS radiocarbon ({sup 14}C) and radiocalcium ({sup 41}Ca) involving applications to archaeologically -- and paleoanthropologically- related samples. With regard to AMS {sup 14}C-related studies, we have extended the development of a series of procedures which have, as their initial goal, the capability to combust several hundred microgram amounts of a chemically-pretreated organic sample and convert the resultant CO{sub 2} to graphitic carbon which will consistently yield relatively high {sup 13}C{sup {minus}} ion currents and blanks which will yield, on a consistent basis, {sup 14}C count rates at or below 0.20% modern, giving an 2 sigma age limit of >50,000 yr BP.

  10. Microdosing studies using accelerated mass spectrometry as exploratory investigational new drug trials.

    PubMed

    Bae, Soo Kyung; Shon, Ji-Hong

    2011-11-01

    Innovative attempts have been made to overcome nonproductivity and high expenditure in the clinical stages of new drug development. Microdosing studies using subpharmacological doses provide early insight into the body's disposition toward candidate compounds, and are innovative exploratory trials that can promote productivity in drug development. Highly sensitive analytical technology is crucial in microdosing studies that employ qualitative and quantitative assays of target materials in humans. Accelerator mass spectrometry (AMS) has facilitated the adoption of a human microdosing study in the early phase of clinical drug development. Results derived from AMS microdosing studies using labeled compounds can provide various types of information for candidate selection, including pharmacokinetic characteristics and metabolic profiles of candidate compounds. The applicability of microdosing studies is currently expanding into absolute bioavailability and mass balance studies. Although it remains uncertain whether microdosing adequately predicts the pharmacokinetics of therapeutic doses, further development of microdosing studies using AMS may benefit the field of new drug development and could pose a new challenge to researchers. The use of advanced technology in candidate selection will contribute to improved productivity and competitiveness in pharmaceutical research and development. The introduction of microdosing studies using AMS in Korea will present a newly applicable method for innovative clinical trials and contribute to development potential in global competition.

  11. Imaging mass spectrometry in microbiology

    PubMed Central

    Watrous, Jeramie D.; Dorrestein, Pieter C.

    2013-01-01

    Mass spectrometry tools which allow for the 2-D visualization of the distribution of trace metals, metabolites, surface lipids, peptides and proteins directly from biological samples without the need for chemical tagging or antibodies are becoming increasingly useful for microbiology applications. These tools, comprised of different imaging mass spectrometry techniques, are ushering in an exciting new era of discovery by allowing for the generation of chemical hypotheses based on of the spatial mapping of atoms and molecules that can correlate to or transcend observed phenotypes. In this review, we explore the wide range of imaging mass spectrometry techniques available to microbiologists and describe their unique applications to microbiology with respect to the types of microbiology samples to be investigated. PMID:21822293

  12. Mass spectrometry for malaria diagnosis.

    PubMed

    Demirev, Plamen A

    2004-11-01

    A physical method currently being developed for malaria parasite detection and diagnosis in blood is reviewed in this article. The method - direct laser desorption mass spectrometry - is based on the detection of heme (iron protoporphyrin) as a unique qualitative and quantitative molecular biomarker for malaria. In infected erythrocytes, the parasite sequesters heme in a molecular crystal (hemozoin) - a volume of highly concentrated and purified biomarker molecules. Laser desorption mass spectrometry detects only heme from hemozoin in parasite-infected blood, and not heme that is bound to hemoglobin or other proteins in uninfected blood samples. The method requires only a drop of blood with minimal sample preparation. Laser desorption mass spectrometry may become a rapid and high-throughput tool for specific and sensitive pan-malaria detection at levels below 10 parasites/mul of blood.

  13. Symposium on accelerator mass spectrometry

    SciTech Connect

    1981-01-01

    The area of accelerator mass spectrometry has expanded considerably over the past few years and established itself as an independent and interdisciplinary research field. Three years have passed since the first meeting was held at Rochester. A Symposium on Accelerator Mass Spectrometry was held at Argonne on May 11-13, 1981. In attendance were 96 scientists of whom 26 were from outside the United States. The present proceedings document the program and excitement of the field. Papers are arranged according to the original program. A few papers not presented at the meeting have been added to complete the information on the status of accelerator mass spectrometry. Individual papers were prepared separately for the data base.

  14. Study of selected benzyl azides by UV photoelectron spectroscopy and mass spectrometry

    NASA Astrophysics Data System (ADS)

    Pinto, R. M.; Olariu, R. I.; Lameiras, J.; Martins, F. T.; Dias, A. A.; Langley, G. J.; Rodrigues, P.; Maycock, C. D.; Santos, J. P.; Duarte, M. F.; Fernandez, M. T.; Costa, M. L.

    2010-09-01

    Benzyl azide and the three methylbenzyl azides were synthesized and characterized by mass spectrometry (MS) and ultraviolet photoelectron spectroscopy (UVPES). The electron ionization fragmentation mechanisms for benzyl azide and their methyl derivatives were studied by accurate mass measurements and linked scans at constant B/ E. For benzyl azide, in order to clarify the fragmentation mechanism, labelling experiments were performed. From the mass analysis of methylbenzyl azides isomers it was possible to differentiate the isomers ortho, meta and para. The abundance and nature of the ions resulting from the molecular ion fragmentation, for the three distinct isomers of substituted benzyl azides, were rationalized in terms of the electronic properties of the substituent. Concerning the para-isomer, IRC calculations were performed at UHF/6-31G(d) level. The photoionization study of benzyl azide, with He(I) radiation, revealed five bands in the 8-21 eV ionization energies region. From every photoelectron spectrum of methylbenzyl azides isomers it has been identified seven bands, on the same range as the benzyl azide. Interpretation of the photoelectron spectra was accomplished applying Koopmans' theorem to the SCF orbital energies obtained at HF/6-311++G(d, p) level.

  15. Gas-phase reactions of methyl thiocyanate with aliphatic carbanions - A mass spectrometry and computational study.

    PubMed

    Repeć, Barbara; Błaziak, Kacper; Danikiewicz, Witold

    2016-02-15

    Methyl thiocyanate, like other organic thiocyanates, is a molecule with many electrophilic reactive sites and it has many synthetic applications. For better understanding of the intrinsic reactivity of alkyl thiocyanates against nucleophiles it was important to study gas-phase reactions of methyl thiocyanate with carbanions differing by structure and proton affinity values. All experiments were performed using a modified API 365 triple quadrupole mass spectrometer equipped with a TurboIonSpray electrospray ionization (ESI) source. Carbanions were generated in the ESI source by decarboxylation of the respective carboxylic acid anions. Methyl thiocyanate was delivered as a vapor with nitrogen used as a collision gas to the collision cell where the reactions take place. Mass spectra recorded for the gas-phase reactions of five aliphatic carbanions with methyl thiocyanate showed a variety of product ions formed via different reaction mechanisms, depending on the structure and proton affinity of the carbanion. The pathways considered are: SN 2 nucleophilic substitution, cyanophilic reaction, thiophilic reaction and proton transfer, followed in some instances by subsequent transformations. The proposed reaction pathways are supported by density functional theory (DFT) calculations. Our preliminary experiments showed that mass spectrometry together with quantum chemical calculations is a good tool for studying gas-phase reactions of alkyl thiocyanates with carbanions. In the gas phase all four theoretically possible products can be observed and their formation can be rationalized by the results of the modelling of the reaction energy profiles. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Thermodynamic Studies of High Temperature Materials Via Knudsen Cell Mass Spectrometry

    NASA Technical Reports Server (NTRS)

    Jacobson, Nathan S.; Brady, Michael P.

    1997-01-01

    The Knudsen Cell technique is a classic technique from high temperature chemistry for studying condensed phase/vapor equilibria. It is based on a small enclosure, usually about 1 cm in diameter by 1 cm high, with an orifice of well-defined geometry. This forms a molecular beam which is analyzed with mass spectrometry. There are many applications to both fundamental and applied problems with high temperature materials. Specific measurements include vapor pressures and vapor compositions above solids, activities of alloy components, and fundamental gas/solid reactions. The basic system is shown. Our system can accommodate a wide range of samples, temperatures, and attachments, such as gas inlets. It is one of only about ten such systems world-wide.

  17. Synchrotron photoionization mass spectrometry study of intermediates in fuel-rich 1,2-dimethoxyethane flame

    SciTech Connect

    Lin, Z. K.; Han, D. L.; Li, S. F.; Li, Y. Y.; Yuan, T.

    2009-04-21

    Intermediates in a fuel-rich premixed laminar 1,2-dimethoxyethane (DME) flame are studied by molecular beam mass spectrometry combined with tunable synchrotron vacuum ultraviolet photoionization. About 30 intermediate species are identified in the present work, and their mole fraction profiles are evaluated. The experimental results show that the formations of intermediates, both hydrocarbons and oxygenated hydrocarbons, are closely linked to the structure of fuel, which is consistent with the previous reports. Species produced from H atom abstraction and beta scission of DME usually have much higher concentrations than others. The oxygen atoms in DME are considered to act as partitions of the primary intermediates; therefore farther reactions among these primary intermediates are difficult to occur, resulting in absence of most large intermediate species.

  18. Utilization of capillary electrophoresis/mass spectrometry (CE/MSn) for the study of anthocyanin dyes.

    PubMed

    Bednár, Petr; Papousková, Barbora; Müller, Lukás; Barták, Petr; Stávek, Jan; Pavlousek, Pavel; Lemr, Karel

    2005-08-01

    Hyphenation of capillary electrophoresis with electrospray ionization mass spectrometry was utilized for the monitoring of anthocyanins in wine and wine musts. CE/MS was performed in two electrolytes: 1) an acidic one (chloroacetate-ammonium, pH 2) and 2) a basic one with high selectivity towards derivatives containing vicinal hydroxy groups (borate-ammonium, pH 9). The setup of MS was optimized and the fragmentation of common anthocyanins was studied in detail. Attention was also focused on the fragmentation of anthocyanidin skeleton. The anthocyanidins substituted with hydroxy groups fragment via a cascade of neutral losses of water and carbon monoxide. Fragmentation of anthocyanidins containing a methoxy group on their B-ring starts with the cleavage of methane and/or methyl radical. The optimized method was utilized for the monitoring of changes in anthocyanin profile in red wines as well as the process of release of anthocyanins to wine must.

  19. Mass Spectrometry in Pharmacokinetic Studies of a Synthetic Compound for Spinal Cord Injury Treatment.

    PubMed

    Sánchez-Sierra, María; García-Álvarez, Isabel; Fernández-Mayoralas, Alfonso; Moreno-Lillo, Sandra; Barroso García, Gemma; Moral Dardé, Verónica; Doncel-Pérez, Ernesto

    2015-01-01

    The studies of drugs that could constitute a palliative to spinal cord injury (SCI) are a continuous and increasing demand in biomedicine field from developed societies. Recently we described the chemical synthesis and antiglioma activity of synthetic glycosides. A synthetic sulfated glycolipid (here IG20) has shown chemical stability, solubility in polar solvents, and high inhibitory capacity over glioma growth. We have used mass spectrometry (MS) to monitor IG20 (m/z = 550.3) in cells and tissues of the central nervous system (CNS) that are involved in SCI recovery. IG20 was detected by MS in serum and homogenates from CNS tissue of rats, though in the latter a previous deproteinization step was required. The pharmacokinetic parameters of serum clearance at 24 h and half-life at 4 h were determined for synthetic glycoside in the adult rat using MS. A local administration of the drug near of spinal lesion site is proposed.

  20. Synchrotron photoionization mass spectrometry study of intermediates in fuel-rich 1,2-dimethoxyethane flame

    NASA Astrophysics Data System (ADS)

    Lin, Z. K.; Han, D. L.; Li, S. F.; Li, Y. Y.; Yuan, T.

    2009-04-01

    Intermediates in a fuel-rich premixed laminar 1,2-dimethoxyethane (DME) flame are studied by molecular beam mass spectrometry combined with tunable synchrotron vacuum ultraviolet photoionization. About 30 intermediate species are identified in the present work, and their mole fraction profiles are evaluated. The experimental results show that the formations of intermediates, both hydrocarbons and oxygenated hydrocarbons, are closely linked to the structure of fuel, which is consistent with the previous reports. Species produced from H atom abstraction and beta scission of DME usually have much higher concentrations than others. The oxygen atoms in DME are considered to act as partitions of the primary intermediates; therefore farther reactions among these primary intermediates are difficult to occur, resulting in absence of most large intermediate species.

  1. Mass Spectrometry in Pharmacokinetic Studies of a Synthetic Compound for Spinal Cord Injury Treatment

    PubMed Central

    Moreno-Lillo, Sandra

    2015-01-01

    The studies of drugs that could constitute a palliative to spinal cord injury (SCI) are a continuous and increasing demand in biomedicine field from developed societies. Recently we described the chemical synthesis and antiglioma activity of synthetic glycosides. A synthetic sulfated glycolipid (here IG20) has shown chemical stability, solubility in polar solvents, and high inhibitory capacity over glioma growth. We have used mass spectrometry (MS) to monitor IG20 (m/z = 550.3) in cells and tissues of the central nervous system (CNS) that are involved in SCI recovery. IG20 was detected by MS in serum and homogenates from CNS tissue of rats, though in the latter a previous deproteinization step was required. The pharmacokinetic parameters of serum clearance at 24 h and half-life at 4 h were determined for synthetic glycoside in the adult rat using MS. A local administration of the drug near of spinal lesion site is proposed. PMID:26090386

  2. Impact of Pharmaceutical Impurities in Ecstasy Tablets: Gas Chromatography-Mass Spectrometry Study.

    PubMed

    Jalali, Amir; Hatamie, Amir; Saferpour, Tahere; Khajeamiri, Alireza; Safa, Tahere; Buazar, Foad

    2016-01-01

    In this study, a simple and reliable method by gas chromatograph-mass spectrometry (GC-MS) was developed for the fast and regular identification of 3, 4-MDMA impurities in ecstasy tablets. In so doing, 8 samples of impurities were extracted by diethyl ether under alkaline condition and then analyzed by GC-MS. The results revealed high MDMA levels ranging from 37.6% to 57.7%. The GC-MS method showed that unambiguous identification can be achieved for MDMA from 3, 4-methylenedioxyamphetamine (MDA), Amphetamine (AM), methamphetamine (MA) and ketamine (Keta) compounds, respectively. The experimental results indicated the acceptable time window without interfering peaks. It is found that GC-MS was provided a suitable and rapid identification approach for MDMA (Ecstacy) tablets, particularly in the Forensic labs. Consequently, the intense MDMA levels would support the police to develop a simple quantification of impurity in Ecstasy tablets.

  3. Impact of Pharmaceutical Impurities in Ecstasy Tablets: Gas Chromatography-Mass Spectrometry Study

    PubMed Central

    Jalali, Amir; Hatamie, Amir; Saferpour, Tahere; Khajeamiri, Alireza; Safa, Tahere; Buazar, Foad

    2016-01-01

    In this study, a simple and reliable method by gas chromatograph–mass spectrometry (GC–MS) was developed for the fast and regular identification of 3, 4-MDMA impurities in ecstasy tablets. In so doing, 8 samples of impurities were extracted by diethyl ether under alkaline condition and then analyzed by GC–MS. The results revealed high MDMA levels ranging from 37.6% to 57.7%. The GC-MS method showed that unambiguous identification can be achieved for MDMA from 3, 4-methylenedioxyamphetamine (MDA), Amphetamine (AM), methamphetamine (MA) and ketamine (Keta) compounds, respectively. The experimental results indicated the acceptable time window without interfering peaks. It is found that GC-MS was provided a suitable and rapid identification approach for MDMA (Ecstacy) tablets, particularly in the Forensic labs. Consequently, the intense MDMA levels would support the police to develop a simple quantification of impurity in Ecstasy tablets. PMID:27610162

  4. Laser desorption studies of high mass biomolecules in Fourier-transform ion cyclotron resonance mass spectrometry.

    PubMed Central

    Solouki, T; Russell, D H

    1992-01-01

    Matrix-assisted laser desorption ionization is used to obtain Fourier-transform ion cyclotron resonance mass spectra of model peptides (e.g., gramicidin S, angiotensin I, renin substrate, melittin, and bovine insulin). Matrix-assisted laser desorption ionization yields ions having appreciable kinetic energies. Two methods for trapping the high kinetic energy ions are described: (i) the ion signal for [M+H]+ ions is shown to increase with increasing trapping voltages, and (ii) collisional relaxation is used for the detection of [M+H]+ ions of bovine insulin. Images PMID:1378614

  5. Molecular composition of organic aerosols in central Amazonia: an ultra-high-resolution mass spectrometry study

    NASA Astrophysics Data System (ADS)

    Kourtchev, Ivan; Godoi, Ricardo H. M.; Connors, Sarah; Levine, James G.; Archibald, Alex T.; Godoi, Ana F. L.; Paralovo, Sarah L.; Barbosa, Cybelli G. G.; Souza, Rodrigo A. F.; Manzi, Antonio O.; Seco, Roger; Sjostedt, Steve; Park, Jeong-Hoo; Guenther, Alex; Kim, Saewung; Smith, James; Martin, Scot T.; Kalberer, Markus

    2016-09-01

    The Amazon Basin plays key role in atmospheric chemistry, biodiversity and climate change. In this study we applied nanoelectrospray (nanoESI) ultra-high-resolution mass spectrometry (UHRMS) for the analysis of the organic fraction of PM2.5 aerosol samples collected during dry and wet seasons at a site in central Amazonia receiving background air masses, biomass burning and urban pollution. Comprehensive mass spectral data evaluation methods (e.g. Kendrick mass defect, Van Krevelen diagrams, carbon oxidation state and aromaticity equivalent) were used to identify compound classes and mass distributions of the detected species. Nitrogen- and/or sulfur-containing organic species contributed up to 60 % of the total identified number of formulae. A large number of molecular formulae in organic aerosol (OA) were attributed to later-generation nitrogen- and sulfur-containing oxidation products, suggesting that OA composition is affected by biomass burning and other, potentially anthropogenic, sources. Isoprene-derived organosulfate (IEPOX-OS) was found to be the most dominant ion in most of the analysed samples and strongly followed the concentration trends of the gas-phase anthropogenic tracers confirming its mixed anthropogenic-biogenic origin. The presence of oxidised aromatic and nitro-aromatic compounds in the samples suggested a strong influence from biomass burning especially during the dry period. Aerosol samples from the dry period and under enhanced biomass burning conditions contained a large number of molecules with high carbon oxidation state and an increased number of aromatic compounds compared to that from the wet period. The results of this work demonstrate that the studied site is influenced not only by biogenic emissions from the forest but also by biomass burning and potentially other anthropogenic emissions from the neighbouring urban environments.

  6. A single dose mass balance study of the Hedgehog pathway inhibitor vismodegib (GDC-0449) in humans using accelerator mass spectrometry.

    PubMed

    Graham, Richard A; Lum, Bert L; Morrison, Glenn; Chang, Ilsung; Jorga, Karin; Dean, Brian; Shin, Young G; Yue, Qin; Mulder, Teresa; Malhi, Vikram; Xie, Minli; Low, Jennifer A; Hop, Cornelis E C A

    2011-08-01

    Vismodegib (GDC-0449), a small-molecule Hedgehog pathway inhibitor, was well tolerated in patients with solid tumors and showed promising efficacy in advanced basal cell carcinoma in a Phase I trial. The purpose of the study presented here was to determine routes of elimination and the extent of vismodegib metabolism, including assessment and identification of metabolites in plasma, urine, and feces. Six healthy female subjects of nonchildbearing potential were enrolled; each received a single 30-ml oral suspension containing 150 mg of vismodegib with 6.5 μg of [(14)C]vismodegib to yield a radioactivity dose of approximately 37 kBq (1000 nCi). Plasma, urine, and feces samples were collected over 56 days to permit sample collection for up to 5 elimination half-lives. Nonradioactive vismodegib was measured in plasma using liquid chromatographic-tandem mass spectrometry, and total radioactivity in plasma, urine, and feces was measured using accelerator mass spectrometry. Vismodegib was slowly eliminated by a combination of metabolism and excretion of parent drug, most of which was recovered in feces. The estimated excretion of the administered dose was 86.6% on average, with 82.2 and 4.43% recovered in feces and urine, respectively. Vismodegib was predominant in plasma, with concentrations representing >98% of the total circulating drug-related components. Metabolic pathways of vismodegib in humans included oxidation, glucuronidation, and uncommon pyridine ring cleavage. We conclude that vismodegib and any associated metabolic products are mainly eliminated through feces after oral administration in healthy volunteers.

  7. Mass spectrometry for biomarker development

    SciTech Connect

    Wu, Chaochao; Liu, Tao; Baker, Erin Shammel; Rodland, Karin D.; Smith, Richard D.

    2015-06-19

    Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

  8. Accelerator mass spectrometry in the study of vitamin and mineral metabolism in humans

    USDA-ARS?s Scientific Manuscript database

    Accelerator mass spectrometry is an isotopic ratio method that can estimate the concentrations of long-lived radioisotopes such as carbon-14 and calcium-41, making it useful in biochemical and physiological research. It is capable of measuring radio-labeled nutrients and their metabolites in attomol...

  9. Interlaboratory comparison study of serum total testosterone [corrected] measurements performed by mass spectrometry methods.

    PubMed

    Vesper, Hubert W; Bhasin, Shalender; Wang, Christina; Tai, Susan S; Dodge, Larry A; Singh, Ravinder J; Nelson, Judie; Ohorodnik, Susan; Clarke, Nigel J; Salameh, Wael A; Parker, C Richard; Razdan, Raj; Monsell, Elizabeth A; Myers, Gary L

    2009-06-01

    Though mass spectrometry (MS) assays are increasingly used for routine clinical measurements of serum total testosterone (TT), information about the variability of results is limited. This study assessed the variability of TT measurement results from routine MS assays. Twenty serum samples (12 females, 8 males) were analyzed on 2 days by seven high performance liquid chromatography (HPLC), and one gas chromatography (GC)-tandem mass spectrometry (HPLC-MS/MS, GC-MS/MS) assays. Two samples (male and female) were provided in five replicates to assess the within-run variability. Results were compared against those obtained at National Institute of Standards and Technology (NIST). The within- and between-laboratory variability was assessed for each sample. Comparisons to the NIST results were performed using bias plot and Deming regression analysis. The overall coefficient of variation of the results obtained with MS assays was <15%CV at >1.53 nmol/L and <34%CV at 0.3 nmol/L. The between-assay variability was the major contributor to the overall variability. The assay precision was the highest (<3%CV) with assays using liquid-liquid extraction for sample preparation or GC-MS/MS. The mean percent difference to the reference assay was 11%. The slopes of Deming regression analysis of the MS assays were between 0.903 and 1.138 (correlation coefficient: >0.996). TT concentrations for one assay were above the measurement range. The variability of TT measurement results among MS assays is substantially smaller than that reported for immunoassays. The type of sample preparation may affect assay precision. Standardizing assays can further reduce the variability of measurement results.

  10. Multistage fragmentation of ion trap mass spectrometry system and pseudo-MS3 of triple quadrupole mass spectrometry characterize certain (E)-3-(dimethylamino)-1-arylprop-2-en-1-ones: a comparative study.

    PubMed

    Abdelhameed, Ali S; Kadi, Adnan A; Abdel-Aziz, Hatem A; Angawi, Rihab F; Attwa, Mohamed W; Al-Rashood, Khalid A

    2014-01-01

    A new approach was recently introduced to improve the structure elucidation power of tandem mass spectrometry simulating the MS(3) of ion trap mass spectrometry system overcoming the different drawbacks of the latter. The fact that collision induced dissociation in the triple quadrupole mass spectrometer system provides richer fragment ions compared to those achieved in the ion trap mass spectrometer system utilizing resonance excitation. Moreover, extracting comprehensive spectra in the ion trap needs multistage fragmentation, whereas similar fragment ions may be acquired from one stage product ion scan using the triple quadrupole mass spectrometer. The new strategy was proven to enhance the qualitative performance of tandem mass spectrometry for structural elucidation of different chemical entities. In the current study we are endeavoring to prove our hypothesis of the efficiency of the new pseudo-MS(3) technique via its comparison with the MS(3) mode of ion trap mass spectrometry system. Ten pharmacologically and synthetically important (E)-3-(dimethylamino)-1-arylprop-2-en-1-ones (enaminones 4a-j) were chosen as model compounds for this study. This strategy permitted rigorous identification of all fragment ions using triple quadrupole mass spectrometer with sufficient specificity. It can be used to elucidate structures of different unknown components. The data presented in this paper provide clear evidence that our new pseudo-MS(3) may simulate the MS(3) of ion trap spectrometry system.

  11. Studies of selenium and xenon in inductively coupled plasma mass spectrometry

    SciTech Connect

    Bricker, Tonya

    1994-07-27

    Since its development, inductively coupled plasma mass spectrometry (ICP-MS) has been a widely used analytical technique. ICP-MS offers low detection limits, easy determination of isotope ratios, and simple mass spectra from analyte elements. ICP-MS has been successfully employed for many applications including geological, environmental, biological, metallurgical, food, medical, and industrial. One specific application important to many areas of study involves elemental speciation by using ICP-MS as an element specific detector interfaced to liquid chromatography. Elemental speciation information is important and cannot be obtained by atomic spectrometric methods alone which measure only the total concentration of the element present. Part 1 of this study describes the speciation of selenium in human serum by size exclusion chromatography (SEC) and detection by ICP-MS. Although ICP-MS has been widely sued, room for improvement still exists. Difficulties in ICP-MS include noise in the background, matrix effects, clogging of the sampling orifice with deposited solids, and spectral interference caused by polyatomic ions. Previous work has shown that the addition of xenon into the central channel of the ICP decreases polyatomic ion levels. In Part 2 of this work, a fundamental study involving the measurement of the excitation temperature is carried out to further understand xenon`s role in the reduction of polyatomic ions. 155 refs.

  12. Mass Spectrometry of Intact Membrane Protein Complexes

    PubMed Central

    Laganowsky, Arthur; Reading, Eamonn; Hopper, Jonathan T.S.; Robinson, Carol V.

    2014-01-01

    Mass spectrometry of intact soluble protein complexes has emerged as a powerful technique to study the stoichiometry, structure-function and dynamics of protein assemblies. Recent developments have extended this technique to the study of membrane protein complexes where it has already revealed subunit stoichiometries and specific phospholipid interactions. Here, we describe a protocol for mass spectrometry of membrane protein complexes. The protocol begins with preparation of the membrane protein complex enabling not only the direct assessment of stoichiometry, delipidation, and quality of the target complex, but also evaluation of the purification strategy. A detailed list of compatible non-ionic detergents is included, along with a protocol for screening detergents to find an optimal one for mass spectrometry, biochemical and structural studies. This protocol also covers the preparation of lipids for protein-lipid binding studies and includes detailed settings for a Q-ToF mass spectrometer after introduction of complexes from gold-coated nanoflow capillaries. PMID:23471109

  13. Ion Mobility Spectrometry (IMS) and Mass Spectrometry

    SciTech Connect

    Shvartsburg, Alexandre A.

    2010-04-20

    In a media of finite viscosity, the Coulomb force of external electric field moves ions with some terminal speed. This dynamics is controlled by “mobility” - a property of the interaction potential between ions and media molecules. This fact has been used to separate and characterize gas-phase ions in various modes of ion mobility spectrometry (IMS) developed since 1970. Commercial IMS devices were introduced in 1980-s for field detection of volatile traces such as explosives and chemical warfare agents. Coupling to soft-ionization sources, mass spectrometry (MS), and chromatographic methods in 1990-s had allowed IMS to handle complex samples, enabling new applications in biological and environmental analyses, nanoscience, and other areas. Since 2003, the introduction of commercial systems by major instrument vendors started bringing the IMS/MS capability to broad user community. The other major development of last decade has been the differential IMS or “field asymmetric waveform IMS” (FAIMS) that employs asymmetric time-dependent electric field to sort ions not by mobility itself, but by the difference between its values in strong and weak electric fields. Coupling of FAIMS to conventional IMS and stacking of conventional IMS stages have enabled two-dimensional separations that dramatically expand the power of ion mobility methods.

  14. Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Kelly, Ryan T.; Marginean, Ioan; Tang, Keqi

    2014-06-13

    Electrospray Ionization (ESI) is a process whereby gas phase ions are created from molecules in solution. As a solution exits a narrow tube in the presence of a strong electric field, an aerosol of charged droplets are is formed that produces gas phase ions as they it desolvates. ESI-MS comprises the creation of ions by ESI and the determination of their mass to charge ratio (m/z) by MS.

  15. Molecular interaction study of flavonoids with human serum albumin using native mass spectrometry and molecular modeling.

    PubMed

    Wang, Bohong; Qin, Qian; Chang, Mengmeng; Li, Shuyan; Shi, Xianzhe; Xu, Guowang

    2017-08-24

    Noncovalent interactions between proteins and small-molecule ligands widely exist in biological bodies and play significant roles in many physiological and pathological processes. Native mass spectrometry (MS) has emerged as a new powerful tool to study noncovalent interactions by directly analyzing the ligand-protein complexes. In this work, an ultrahigh-resolution native MS method based on a 15-T SolariX XR Fourier transform ion cyclotron resonance mass spectrometer was firstly used to investigate the interaction between human serum albumin (HSA) and flavonoids. Various flavonoids with similar structure were selected to unravel the relationship between the structure of flavonoids and their binding affinity for HSA. It was found that the position of the hydroxyl groups and double bond of flavonoids could influence the noncovalent interaction. Through a competitive experiment between HSA binding site markers and apigenin, the subdomain IIA (site 1) of HSA was determined as the binding site for flavonoids. Moreover, a cooperative allosteric interaction between apigenin and ibuprofen was found from their different HSA binding sites, which was further verified by circular dichroism spectroscopy and molecular docking studies. These results show that native MS is a useful tool to investigate the molecular interaction between a protein and its ligands. Graphical abstract Unravel the relationship between the structure of flavonoids and their binding affinity to HSA by native MS.

  16. A HUPO test sample study reveals common problems in mass spectrometry-based proteomics

    PubMed Central

    Bell, Alexander W.; Deutsch, Eric W.; Au, Catherine E.; Kearney, Robert E.; Beavis, Ron; Sechi, Salvatore; Nilsson, Tommy; Bergeron, John J.M.

    2009-01-01

    We carried out a test sample study to try to identify errors leading to irreproducibility, including incompleteness of peptide sampling, in LC-MS-based proteomics. We distributed a test sample consisting of an equimolar mix of 20 highly purified recombinant human proteins, to 27 laboratories for identification. Each protein contained one or more unique tryptic peptides of 1250 Da to also test for ion selection and sampling in the mass spectrometer. Of the 27 labs, initially only 7 labs reported all 20 proteins correctly, and only 1 lab reported all the tryptic peptides of 1250 Da. Nevertheless, a subsequent centralized analysis of the raw data revealed that all 20 proteins and most of the 1250 Da peptides had in fact been detected by all 27 labs. The centralized analysis allowed us to determine sources of problems encountered in the study, which include missed identifications (false negatives), environmental contamination, database matching, and curation of protein identifications. Improved search engines and databases are likely to increase the fidelity of mass spectrometry-based proteomics. PMID:19448641

  17. "EMERGING" POLLUTANTS, MASS SPECTROMETRY, AND ...

    EPA Pesticide Factsheets

    A foundation for Environmental Science - Mass Spectrometry: Historically fundamental to amassing our understanding of environmental processes and chemical pollution is the realm of mass spectrometry - the mainstay of analytical chemistry - the workhorse that supplies much of the definitive data that environmental scientists rely upon for identifying the molecular compositions (and ultimately the structures) of chemicals. This is not to ignore the complementary, critical roles played by the adjunct practices of sample enrichment (via any of various means of selective extraction) and analyte separation (via the myriad forms of chromatography and electrophoresis).While the power of mass spectrometry has long been highly visible to the practicing environmental chemist, it borders on continued obscurity to the lay public and most non-chemists. Even though mass spectrometry has played a long, historic (and largely invisible) role in establishing or undergirdidng our existing knowledge about environmental processes and pollution, what recognition it does enjoy is usually relegated to that of a tool. It is ususally the relevance of ssignificance of the knowledge acquired from the application of the tool that has ultimate meaning to the public and science at large - not how the knowledge was acquired. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in

  18. Does deamidation cause protein unfolding? A top-down tandem mass spectrometry study

    PubMed Central

    Soulby, Andrew J; Heal, Jack W; Barrow, Mark P; Roemer, Rudolf A; O'Connor, Peter B

    2015-01-01

    Deamidation is a nonenzymatic post-translational modification of asparagine to aspartic acid or glutamine to glutamic acid, converting an uncharged amino acid to a negatively charged residue. It is plausible that deamidation of asparagine and glutamine residues would result in disruption of a proteins' hydrogen bonding network and thus lead to protein unfolding. To test this hypothesis Calmodulin and B2M were deamidated and analyzed using tandem mass spectrometry on a Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS). The gas phase hydrogen bonding networks of deamidated and nondeamidated protein isoforms were probed by varying the infra-red multi-photon dissociation laser power in a linear fashion and plotting the resulting electron capture dissociation fragment intensities as a melting curve at each amino acid residue. Analysis of the unfolding maps highlighted increased fragmentation at lower laser powers localized around heavily deamidated regions of the proteins. In addition fragment intensities were decreased across the rest of the proteins which we propose is because of the formation of salt-bridges strengthening the intramolecular interactions of the central regions. These results were supported by a computational flexibility analysis of the mutant and unmodified proteins, which would suggest that deamidation can affect the global structure of a protein via modification of the hydrogen bonding network near the deamidation site and that top down FTICR-MS is an appropriate technique for studying protein folding. PMID:25653127

  19. Determination and pharmacokinetic studies of arecoline in dog plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Li, Bing; Zhou, Xu-Zheng; Li, Jian-Yong; Yang, Ya-Jun; Niu, Jian-Rong; Wei, Xiao-Juan; Liu, Xi-Wang; Li, Jin-Shan; Zhang, Ji-Yu

    2014-10-15

    A rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of arecoline concentration in dog plasma. Plasma sample was prepared by protein precipitation using n-hexane (containing 1% isoamyl alcohol) with β-pinene as an internal standard. Chromatographic separation was achieved on an Agilent C18 column (4.6×75mm, 3.5μm) using methanol: 5mM ammonium acetate as the mobile phase with isocratic elution. Mass detection was carried out using positive electrospray ionization in multiple reaction monitoring mode. The calibration curve for arecoline was linear over a concentration range of 2-500ng/mL. The intra-day and inter-day accuracy and precision were within the acceptable limits of ±10% at all concentrations. In summary, the LC-MS/MS method described herein was fully validated and successfully applied to the pharmacokinetic study of arecoline hydrobromide tablets in dogs after oral administration. Copyright © 2014. Published by Elsevier B.V.

  20. The mzQuantML data standard for mass spectrometry-based quantitative studies in proteomics.

    PubMed

    Walzer, Mathias; Qi, Da; Mayer, Gerhard; Uszkoreit, Julian; Eisenacher, Martin; Sachsenberg, Timo; Gonzalez-Galarza, Faviel F; Fan, Jun; Bessant, Conrad; Deutsch, Eric W; Reisinger, Florian; Vizcaíno, Juan Antonio; Medina-Aunon, J Alberto; Albar, Juan Pablo; Kohlbacher, Oliver; Jones, Andrew R

    2013-08-01

    The range of heterogeneous approaches available for quantifying protein abundance via mass spectrometry (MS)(1) leads to considerable challenges in modeling, archiving, exchanging, or submitting experimental data sets as supplemental material to journals. To date, there has been no widely accepted format for capturing the evidence trail of how quantitative analysis has been performed by software, for transferring data between software packages, or for submitting to public databases. In the context of the Proteomics Standards Initiative, we have developed the mzQuantML data standard. The standard can represent quantitative data about regions in two-dimensional retention time versus mass/charge space (called features), peptides, and proteins and protein groups (where there is ambiguity regarding peptide-to-protein inference), and it offers limited support for small molecule (metabolomic) data. The format has structures for representing replicate MS runs, grouping of replicates (for example, as study variables), and capturing the parameters used by software packages to arrive at these values. The format has the capability to reference other standards such as mzML and mzIdentML, and thus the evidence trail for the MS workflow as a whole can now be described. Several software implementations are available, and we encourage other bioinformatics groups to use mzQuantML as an input, internal, or output format for quantitative software and for structuring local repositories. All project resources are available in the public domain from the HUPO Proteomics Standards Initiative http://www.psidev.info/mzquantml.

  1. Isomerization of 4-vinylcyclohexene radical cation. A tandem mass spectrometry study

    SciTech Connect

    Vollmer, D.; Rempel, D.L.; Gross, M. L. ); Williams, F. )

    1995-02-08

    Investigation by matrix-isolation ESR has shown that 4-vinylcyclohexene, 1, surprisingly undergoes isomerization to the bicyclo[3.2.1]oct-2-ene ion, 3. Here we demonstrate the occurrence of this isomerization in the gas phase by use of tandem (MS/MS) sector and Fourier transform (FT) mass spectrometries. The radical cations of 4-vinylcyclohexene (IE = 8.93 eV) or bicyclo[3.2.1]oct-2-ene (approximately 14 kcal/mol more stable than that of 4-vinylcyclohexene) were formed, in separate trials, in a chemical ionization (CI) source by electron ionization (EI). The radical cations were then studied by obtaining their collisionally activated decomposition (CAD) spectra. The CAD spectra are similar, indicating that the isomerization has occurred. Both the sector and the FT mass spectrometer results reflect those obtained in the matrix-isolation ESR investigation. That is isomerizes to 3 at high internal energy, but is stable at low internal energy. Two mechanisms explain this rearrangement. The second mechanism is questionable because the most stable olefin radical cation formed from 5 is that of bicyclo[2.2.2]-2-octene, which gives different ESR and CAD spectra than those of 1 or 3. The CAD spectrum of bicyclo[2.2.2]-2-octene radical cation indicates that the retro-Diels-Alder loss of ethylene is more facile than that from 1 or 3. 18 refs., 3 figs.

  2. Adding value through accelerator mass spectrometry-enabled first in human studies.

    PubMed

    Seymour, Mark A

    2016-12-01

    Accelerator mass spectrometry (AMS) is an ultra-sensitive technique for the analysis of radiocarbon. It is applicable to bioanalysis of any (14) C-labelled analyte and any sample type. The increasing body of data generated using LC+AMS indicates that the methodology is robust and reliable, and capable of meeting the same validation criteria as conventional bioanalytical techniques. Because it is a tracer technique, AMS is capable of discriminating between an administered radiolabelled dose and endogenous compound or non-radiolabelled compound administered separately. This paper discusses how it can be used to enhance the design of first in human (FIH) clinical studies and generate significant additional data, including: fundamental pharmacokinetics (CL and V), absolute bioavailability, mass balance, routes and rates of excretion, metabolic fate (including first-pass metabolism, identification of biliary metabolites and quantitative data to address metabolite safety testing issues), and tissue disposition of parent compound and metabolites. Because the (14) C-labelled microtracer dose is administered at the same time as a pharmacologically relevant non-radiolabelled dose, there is no concern about dose-linearity. However the mass of the microtracer dose itself is negligible and therefore does not affect the outcome of the FIH study. The addition of microtracer doses to a FIH study typically requires little additional expense, apart from the AMS analytics, making the approach cost-effective. It can also save significant time, compared to conventional approaches, and, by providing reliable human in vivo data as early as possible, prevent unnecessary expenditure later in drug development.

  3. Characteristics of tyre dust in polluted air: Studies by single particle mass spectrometry (ATOFMS)

    NASA Astrophysics Data System (ADS)

    Dall'Osto, Manuel; Beddows, David C. S.; Gietl, Johanna K.; Olatunbosun, Oluremi A.; Yang, Xiaoguang; Harrison, Roy M.

    2014-09-01

    There is a paucity of quantitative knowledge on the contributions of non-exhaust (abrasion and re-suspension) sources to traffic emissions. Abrasive emissions can be broadly categorised as tyre wear, brake wear and road dust/road surface wear. Current research often considers road dust and tyre dust as externally mixed particles, the former mainly composed of mineral matter and the latter solely composed of mainly organic matter and some trace elements. The aim of this work was to characterise tyre wear from both laboratory and field studies by using Aerosol Time-Of-Flight Mass Spectrometry (ATOFMS). Real-time single particle chemical composition was obtained from a set of rubber tyres rotating on a metal surface. Bimodal particle number size distributions peaking at 35 nm and 85 nm were obtained from SMPS/APS measurements over the range 6-20,000 nm. ATOFMS mass spectra of tyre wear in the particle size range 200-3000 nm diameter show peaks due to exo-sulphur compounds, nitrate, Zn and ions of high molecular weight (m/z > 100) attributed to organic polymers. Two large ATOFMS datasets collected from a number of outdoor studies were examined. The former was constituted of 48 road dust samples collected on the roads of London. The latter consisted of ATOFMS ambient air field studies from Europe, overall composed of more than 2,000,000 single particle mass spectra. The majority (95%) of tyre wear particles present in the road dust samples and atmospheric samples are internally mixed with metals (Li, Na, Ca, Fe, Ti), as well as phosphate. It is concluded that the interaction of tyres with the road surface creates particles internally mixed from two sources: tyre rubber and road surface materials. Measurements of the tyre rubber component alone may underestimate the contribution of tyre wear to concentrations of airborne particulate matter. The results presented are especially relevant for urban aerosol source apportionment and PM2.5 exposure assessment.

  4. Accelerator mass spectrometry

    SciTech Connect

    Vogel, J.S.; Turteltaub, K.W.; Finkel, R.; Nelson, D.E.

    1995-06-01

    Accelerator mass spectroscopy (AMS) can be used for efficient detection of long-lived isotopes at part-per-quadrillion sensitivities with good precision. In this article we present an overview of AMS and its recent use in archaeology, geochemistry and biomolecular tracing. All AMS systems use cesium sputter ion sources to produce negative ions from a small button of a solid sample containing the element of interest, such as graphite, metal halide, or metal oxide, often mixed with a metal powder as binder and thermal conductor. Experience shows that both natural and biomedical samples are compatible in a single AMS system, but few other AMS sites make routine {sup 14}C measurements for both dating and tracing. AMS is, in one sense, just `a very sensitive decay counter`, but if AMS sensitivity is creatively coupled to analytical chemistry of certain isotopes, whole new areas of geosciences, archaeology, and life sciences can be explored. 29 refs., 2 figs., 1 tab.

  5. MASS SPECTROMETRY-BASED METABOLOMICS

    PubMed Central

    Dettmer, Katja; Aronov, Pavel A.; Hammock, Bruce D.

    2007-01-01

    This review presents an overview of the dynamically developing field of mass spectrometry-based metabolomics. Metabolomics aims at the comprehensive and quantitative analysis of wide arrays of metabolites in biological samples. These numerous analytes have very diverse physico-chemical properties and occur at different abundance levels. Consequently, comprehensive metabolomics investigations are primarily a challenge for analytical chemistry and specifically mass spectrometry has vast potential as a tool for this type of investigation. Metabolomics require special approaches for sample preparation, separation, and mass spectrometric analysis. Current examples of those approaches are described in this review. It primarily focuses on metabolic fingerprinting, a technique that analyzes all detectable analytes in a given sample with subsequent classification of samples and identification of differentially expressed metabolites, which define the sample classes. To perform this complex task, data analysis tools, metabolite libraries, and databases are required. Therefore, recent advances in metabolomics bioinformatics are also discussed. PMID:16921475

  6. Mass spectrometry of aerospace materials

    NASA Technical Reports Server (NTRS)

    Colony, J. A.

    1976-01-01

    Mass spectrometry is used for chemical analysis of aerospace materials and contaminants. Years of analytical aerospace experience have resulted in the development of specialized techniques of sampling and analysis which are required in order to optimize results. This work has resulted in the evolution of a hybrid method of indexing mass spectra which include both the largest peaks and the structurally significant peaks in a concise format. With this system, a library of mass spectra of aerospace materials was assembled, including the materials responsible for 80 to 90 percent of the contamination problems at Goddard Space Flight Center during the past several years.

  7. A study of the spiropyran-merocyanine system using ion mobility-mass spectrometry: experimental support for the cisoid conformation.

    PubMed

    Rogers, Robert A; Rodier, Allison R; Stanley, Jake A; Douglas, Nick A; Li, Xiaopeng; Brittain, William J

    2014-04-04

    The spiropyran-merocyanine system was studied using ion mobility-mass spectrometry (IM-MS) and three major conformers were identified. Assignment of conformers is based on DFT-B3LYP energy minimized structures and collision cross-sections as light-induced changes in IM-MS. The three conformers were assigned to the spiropyran, cisoid and transoid structures.

  8. Mass spectrometry and tandem mass spectrometry of citrus limonoids.

    PubMed

    Tian, Qingguo; Schwartz, Steven J

    2003-10-15

    Methods for atmospheric pressure chemical ionization tandem mass spectrometry (APCI-MS/MS) of citrus limonoid aglycones and electrospray ionization tandem mass spectrometry (ESI-MS/MS) of limonoid glucosides are reported. The fragmentation patterns of four citrus limonoid aglycones (limonin, nomilin, obacunone, and deacetylnomilin) and six limonoid glucosides, that is, limonin 17-beta-D-glucopyranoside (LG), nomilin 17-beta-D-glucopyranoside (NG), nomilinic acid 17-beta-D-glucopyranoside (NAG), deacetyl nomilinic acid 17-beta-D-glucopyranoside (DNAG), obacunone 17-beta-D-glucopyranoside (OG), and obacunoic acid 17-beta-D-glucopyranoside (OAG) were investigated using a quadruple mass spectrometer in low-energy collisionally activated dissociation (CAD). The four limonoid aglycones and four limonoid glucosides (LG, OG, NAG, and DNAG) were purified from citrus seeds; the other two limonoid glucosides (NG and OAG) were tentatively identified in the crude extract of grapefruit seeds by ESI mass spectrometry in both positive and negative ion analysis. Ammonium hydroxide or acetic acid was added to the mobile phase to facilitate ionization. During positive ion APCI analysis of limonoid aglycones, protonated molecular ion, [M + H]+, or adduct ion, [M + NH3 + H]-, was formed as base peaks when ammonium hydroxide was added to the mobile phase. Molecular anions or adduct ions with acetic acid ([M + HOAc - H] and [M + HOAc]-) or a deprotonated molecular ion were produced during negative ion APCI analysis of limonoid aglycones, depending on the mobile-phase modifier used. Positive ion ESI-MS of limonoid glucosides produced adduct ions of [M + H + NH3]+, [M + Na]+, and [M + K]+ when ammonium hydroxide was added to the mobile phase. After collisionally activated dissociation (CAD) of the limonoid aglycone molecular ions in negative ion APCI analysis, fragment ions indicated structural information of the precursor ions, showing the presence of methyl, carboxyl, and oxygenated ring

  9. Interlaboratory Study on Differential Analysis of Protein Glycosylation by Mass Spectrometry: The ABRF Glycoprotein Research Multi-Institutional Study 2012*

    PubMed Central

    Leymarie, Nancy; Griffin, Paula J.; Jonscher, Karen; Kolarich, Daniel; Orlando, Ron; McComb, Mark; Zaia, Joseph; Aguilan, Jennifer; Alley, William R.; Altmann, Friederich; Ball, Lauren E.; Basumallick, Lipika; Bazemore-Walker, Carthene R.; Behnken, Henning; Blank, Michael A.; Brown, Kristy J.; Bunz, Svenja-Catharina; Cairo, Christopher W.; Cipollo, John F.; Daneshfar, Rambod; Desaire, Heather; Drake, Richard R.; Go, Eden P.; Goldman, Radoslav; Gruber, Clemens; Halim, Adnan; Hathout, Yetrib; Hensbergen, Paul J.; Horn, David M.; Hurum, Deanna; Jabs, Wolfgang; Larson, Göran; Ly, Mellisa; Mann, Benjamin F.; Marx, Kristina; Mechref, Yehia; Meyer, Bernd; Möginger, Uwe; Neusüβ, Christian; Nilsson, Jonas; Novotny, Milos V.; Nyalwidhe, Julius O.; Packer, Nicolle H.; Pompach, Petr; Reiz, Bela; Resemann, Anja; Rohrer, Jeffrey S.; Ruthenbeck, Alexandra; Sanda, Miloslav; Schulz, Jan Mirco; Schweiger-Hufnagel, Ulrike; Sihlbom, Carina; Song, Ehwang; Staples, Gregory O.; Suckau, Detlev; Tang, Haixu; Thaysen-Andersen, Morten; Viner, Rosa I.; An, Yanming; Valmu, Leena; Wada, Yoshinao; Watson, Megan; Windwarder, Markus; Whittal, Randy; Wuhrer, Manfred; Zhu, Yiying; Zou, Chunxia

    2013-01-01

    One of the principal goals of glycoprotein research is to correlate glycan structure and function. Such correlation is necessary in order for one to understand the mechanisms whereby glycoprotein structure elaborates the functions of myriad proteins. The accurate comparison of glycoforms and quantification of glycosites are essential steps in this direction. Mass spectrometry has emerged as a powerful analytical technique in the field of glycoprotein characterization. Its sensitivity, high dynamic range, and mass accuracy provide both quantitative and sequence/structural information. As part of the 2012 ABRF Glycoprotein Research Group study, we explored the use of mass spectrometry and ancillary methodologies to characterize the glycoforms of two sources of human prostate specific antigen (PSA). PSA is used as a tumor marker for prostate cancer, with increasing blood levels used to distinguish between normal and cancer states. The glycans on PSA are believed to be biantennary N-linked, and it has been observed that prostate cancer tissues and cell lines contain more antennae than their benign counterparts. Thus, the ability to quantify differences in glycosylation associated with cancer has the potential to positively impact the use of PSA as a biomarker. We studied standard peptide-based proteomics/glycomics methodologies, including LC-MS/MS for peptide/glycopeptide sequencing and label-free approaches for differential quantification. We performed an interlaboratory study to determine the ability of different laboratories to correctly characterize the differences between glycoforms from two different sources using mass spectrometry methods. We used clustering analysis and ancillary statistical data treatment on the data sets submitted by participating laboratories to obtain a consensus of the glycoforms and abundances. The results demonstrate the relative strengths and weaknesses of top-down glycoproteomics, bottom-up glycoproteomics, and glycomics methods. PMID

  10. Interlaboratory study on differential analysis of protein glycosylation by mass spectrometry: the ABRF glycoprotein research multi-institutional study 2012.

    PubMed

    Leymarie, Nancy; Griffin, Paula J; Jonscher, Karen; Kolarich, Daniel; Orlando, Ron; McComb, Mark; Zaia, Joseph; Aguilan, Jennifer; Alley, William R; Altmann, Friederich; Ball, Lauren E; Basumallick, Lipika; Bazemore-Walker, Carthene R; Behnken, Henning; Blank, Michael A; Brown, Kristy J; Bunz, Svenja-Catharina; Cairo, Christopher W; Cipollo, John F; Daneshfar, Rambod; Desaire, Heather; Drake, Richard R; Go, Eden P; Goldman, Radoslav; Gruber, Clemens; Halim, Adnan; Hathout, Yetrib; Hensbergen, Paul J; Horn, David M; Hurum, Deanna; Jabs, Wolfgang; Larson, Göran; Ly, Mellisa; Mann, Benjamin F; Marx, Kristina; Mechref, Yehia; Meyer, Bernd; Möginger, Uwe; Neusüβ, Christian; Nilsson, Jonas; Novotny, Milos V; Nyalwidhe, Julius O; Packer, Nicolle H; Pompach, Petr; Reiz, Bela; Resemann, Anja; Rohrer, Jeffrey S; Ruthenbeck, Alexandra; Sanda, Miloslav; Schulz, Jan Mirco; Schweiger-Hufnagel, Ulrike; Sihlbom, Carina; Song, Ehwang; Staples, Gregory O; Suckau, Detlev; Tang, Haixu; Thaysen-Andersen, Morten; Viner, Rosa I; An, Yanming; Valmu, Leena; Wada, Yoshinao; Watson, Megan; Windwarder, Markus; Whittal, Randy; Wuhrer, Manfred; Zhu, Yiying; Zou, Chunxia

    2013-10-01

    One of the principal goals of glycoprotein research is to correlate glycan structure and function. Such correlation is necessary in order for one to understand the mechanisms whereby glycoprotein structure elaborates the functions of myriad proteins. The accurate comparison of glycoforms and quantification of glycosites are essential steps in this direction. Mass spectrometry has emerged as a powerful analytical technique in the field of glycoprotein characterization. Its sensitivity, high dynamic range, and mass accuracy provide both quantitative and sequence/structural information. As part of the 2012 ABRF Glycoprotein Research Group study, we explored the use of mass spectrometry and ancillary methodologies to characterize the glycoforms of two sources of human prostate specific antigen (PSA). PSA is used as a tumor marker for prostate cancer, with increasing blood levels used to distinguish between normal and cancer states. The glycans on PSA are believed to be biantennary N-linked, and it has been observed that prostate cancer tissues and cell lines contain more antennae than their benign counterparts. Thus, the ability to quantify differences in glycosylation associated with cancer has the potential to positively impact the use of PSA as a biomarker. We studied standard peptide-based proteomics/glycomics methodologies, including LC-MS/MS for peptide/glycopeptide sequencing and label-free approaches for differential quantification. We performed an interlaboratory study to determine the ability of different laboratories to correctly characterize the differences between glycoforms from two different sources using mass spectrometry methods. We used clustering analysis and ancillary statistical data treatment on the data sets submitted by participating laboratories to obtain a consensus of the glycoforms and abundances. The results demonstrate the relative strengths and weaknesses of top-down glycoproteomics, bottom-up glycoproteomics, and glycomics methods.

  11. Application of isotope dilution mass spectrometry: determination of ochratoxin A in the Canadian Total Diet Study

    PubMed Central

    Tam, J.; Pantazopoulos, P.; Scott, P.M.; Moisey, J.; Dabeka, R.W.; Richard, I.D.K.

    2011-01-01

    Analytical methods are generally developed and optimized for specific commodities. Total Diet Studies, representing typical food products ‘as consumed’, pose an analytical challenge since every food product is different. In order to address this technical challenge, a selective and sensitive analytical method was developed suitable for the quantitation of ochratoxin A (OTA) in Canadian Total Diet Study composites. The method uses an acidified solvent extraction, an immunoaffinity column (IAC) for clean-up, liquid chromatography-tandem mass spectrometry (LC-MS/MS) for identification and quantification, and a uniformly stable isotope-labelled OTA (U-[13C20]-OTA) as an internal recovery standard. Results are corrected for this standard. The method is accurate (101% average recovery) and precise (5.5% relative standard deviation (RSD)) based on 17 duplicate analysis of various food products over 2 years. A total of 140 diet composites were analysed for OTA as part of the Canadian Total Diet Study. Samples were collected at retail level from two Canadian cities, Quebec City and Calgary, in 2008 and 2009, respectively. The results indicate that 73% (102/140) of the samples had detectable levels of OTA, with some of the highest levels of OTA contamination found in the Canadian bread supply. PMID:21623499

  12. Vinegar Metabolomics: An Explorative Study of Commercial Balsamic Vinegars Using Gas Chromatography-Mass Spectrometry

    PubMed Central

    Pinu, Farhana R.; de Carvalho-Silva, Samuel; Trovatti Uetanabaro, Ana Paula; Villas-Boas, Silas G.

    2016-01-01

    Balsamic vinegar is a popular food condiment produced from cooked grape must by two successive fermentation (anaerobic and aerobic) processes. Although many studies have been performed to determine the composition of major metabolites, including sugars and aroma compounds, no study has been undertaken yet to characterize the comprehensive metabolite composition of balsamic vinegars. Here, we present the first metabolomics study of commercial balsamic vinegars by gas chromatography coupled to mass spectrometry (GC-MS). The combination of three GC-MS methods allowed us to detect >1500 features in vinegar samples, of which 123 metabolites were accurately identified, including 25 amino acids, 26 carboxylic acids, 13 sugars and sugar alcohols, four fatty acids, one vitamin, one tripeptide and over 47 aroma compounds. Moreover, we identified for the first time in vinegar five volatile metabolites: acetin, 2-methylpyrazine, 2-acetyl-1-pyroline, 4-anisidine and 1,3-diacetoxypropane. Therefore, we demonstrated the capability of metabolomics for detecting and identifying large number of metabolites and some of them could be used to distinguish vinegar samples based on their origin and potentially quality. PMID:27455339

  13. Electrochemistry-mass spectrometry for mechanistic studies and simulation of oxidation processes in the environment.

    PubMed

    Hoffmann, Th; Hofmann, D; Klumpp, E; Küppers, S

    2011-02-01

    Electrochemistry (EC) coupled to mass spectrometry (MS) has already been successfully applied to metabolism research for pharmaceutical applications, especially for the oxidation behaviour of drug substances. Xenobiotics (chemicals in the environment) also undergo various conversions; some of which are oxidative reactions. Therefore, EC-MS might be a suitable tool for the investigation of oxidative behaviour of xenobiotics. A further evaluation of this approach to environmental research is presented in the present paper using sulfonamide antibiotics. The results with sulfadiazine showed that EC-MS is a powerful tool for the elucidation of the oxidative degradation mechanism within a short time period. In addition, it was demonstrated that EC-MS can be used as a fast and easy method to model the chemical binding of xenobiotics to soil. The reaction of sulfadiazine with catechol, as a model substance for organic matter in soil, led to the expected chemical structure. Finally, by using EC-MS a first indication was obtained of the persistence of a component under chemical oxidation conditions for the comparison of the oxidative stability of different classes of xenobiotics. Overall, using just a few examples, the study demonstrates that EC-MS can be applied as a versatile tool for mechanistic studies of oxidative degradation pathways of xenobiotics and their possible interaction with soil organic matter as well as their oxidative stability in the environment. Further studies are needed to evaluate the full range of possibilities of the application of EC-MS in environmental research.

  14. High performance electrospray ionization mass spectrometry in the study of the noncovalent associations of proteins and DNA

    SciTech Connect

    Smith, R.D.; Hofstadler, S.A.; Bruce, J.A.

    1995-12-01

    The ability to study the non-covalent associations of biopolymers under near physiological conditions using electrospray ionization-mass spectrometry has opened new opportunities for the study of a range of crucial biological processes. The use of new instrumentation based upon Fourier transform ion cyclotron resonance mass spectrometry will also be presented, and shown to open new opportunities and applications based upon improved resolution, sensitivity, and extended multi-dimensional mass spectrometric capabilities. In this presentation, studies showing the broad utility of ESI-MS for studies of binding and stoichiometry of biomolecular structure and interactions will be presented. The conditions under which quantitative data can be obtained in such studies will be discussed. Systems described will include protein quaternary structure, protein-protein complexes of relevance to DNA repair, oligonucleotide duplexes and quadruplexes, and the interaction of smaller molecules with these biopolymers (e.g., protein inhibitors).

  15. Nontargeted modification-specific metabolomics study based on liquid chromatography-high-resolution mass spectrometry.

    PubMed

    Dai, Weidong; Yin, Peiyuan; Zeng, Zhongda; Kong, Hongwei; Tong, Hongwei; Xu, Zhiliang; Lu, Xin; Lehmann, Rainer; Xu, Guowang

    2014-09-16

    Modifications of genes and proteins have been extensively studied in systems biology using comprehensive analytical strategies. Although metabolites are frequently modified, these modifications have not been studied using -omics approaches. Here a general strategy for the nontargeted profiling of modified metabolites, which we call "nontargeted modification-specific metabolomics", is reported. A key aspect of this strategy was the combination of in-source collision-induced dissociation liquid chromatography-mass spectrometry (LC-MS) and global nontargeted LC-MS-based metabolomics. Characteristic neutral loss fragments that are specific for acetylation, sulfation, glucuronidation, glucosidation, or ribose conjugation were reproducibly detected using human urine as a model specimen for method development. The practical application of this method was demonstrated by profiling urine samples from liver cirrhosis patients. Approximately 900 features were identified as modified endogenous metabolites and xenobiotics. Moreover, this strategy supports the identification of compounds not included in traditional metabolomics databases (HMDB, Metlin, and KEGG), which are currently referred to as "unknowns" in metabolomics projects. Nontargeted modification-specific metabolomics opens a new perspective in systems biology.

  16. A Nanostructured Matrices Assessment to Study Drug Distribution in Solid Tumor Tissues by Mass Spectrometry Imaging

    PubMed Central

    Giordano, Silvia; Pifferi, Valentina; Morosi, Lavinia; Morelli, Melinda; Falciola, Luigi; Cappelletti, Giuseppe; Visentin, Sonja; Licandro, Simonetta A.; Frapolli, Roberta; Zucchetti, Massimo; Pastorelli, Roberta; Brunelli, Laura; D’Incalci, Maurizio; Davoli, Enrico

    2017-01-01

    The imaging of drugs inside tissues is pivotal in oncology to assess whether a drug reaches all cells in an adequate enough concentration to eradicate the tumor. Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) is one of the most promising imaging techniques that enables the simultaneous visualization of multiple compounds inside tissues. The choice of a suitable matrix constitutes a critical aspect during the development of a MALDI-MSI protocol since the matrix ionization efficiency changes depending on the analyte structure and its physico-chemical properties. The objective of this study is the improvement of the MALDI-MSI technique in the field of pharmacology; developing specifically designed nanostructured surfaces that allow the imaging of different drugs with high sensitivity and reproducibility. Among several nanomaterials, we tested the behavior of gold and titanium nanoparticles, and halloysites and carbon nanotubes as possible matrices. All nanomaterials were firstly screened by co-spotting them with drugs on a MALDI plate, evaluating the drug signal intensity and the signal-to-noise ratio. The best performing matrices were tested on control tumor slices, and were spotted with drugs to check the ion suppression effect of the biological matrix. Finally; the best nanomaterials were employed in a preliminary drug distribution study inside tumors from treated mice. PMID:28336905

  17. Mass spectrometry study of increased breakdown of an anticonvulsivant drug substance

    NASA Astrophysics Data System (ADS)

    Buret, D.; Breton, D.; Clair, P.; Lafosse, M.

    2006-06-01

    The French Military Health Service (SSA) developed a new pharmaceutic speciality as a treatment against neurotoxic organophosphate poisoning (NSP), as a substitute for existing therapeutics. The Armed Forces Central Pharmacy (PCA) is in charge of the development of therapeutic formulation and stability studies. This product includes three drug substances: atropine, pralidoxime and avizafone, an amine prodrug of diazepam, soluble in water. The PCA performed a stability study of this formulation according to the International Conference on Harmonization (ICH) recommendations: it was used to display interaction between the molecules and the plastic of the cartridge (the container turned yellow). Since no degradation product of atropine and pralidoxime was observed, a complementary evaluation of avizafone and its main known degradation products (diazepam, carbostyril and methylaminobenzochlorophenone [MACB]) was initiated. The results were used to determine the degradation products obtained under different conditions and the kind of mechanisms, which may occur as the formulation ages: adsorption or absorption by the bulk and/or increasing degradation products. The analytical methods developed here are a direct sample analysis by mass spectrometry (MS) using different ionization modes and liquid chromatography (LC) with UV detection to confirm the results obtain with MS.

  18. Study of RF-excited Diethylene Glycol Dimethyl Ether Plasmas by Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Algatti, M. A.; Mota, R. P.; Moreira Júnior, P. W. P.; Honda, R. Y.; Kayama, M. E.; Kostov, K. G.

    2012-12-01

    This paper deals with the study of the fragmentation process of diethylene glycol dimethyl ether (CH3O(CH2CH2O)2CH3) (diglyme here in) molecule in low pressure RF excited plasma discharges. The study was carried out using mass spectrometry. The results showed that for a fixed pressure, the increase of the RF power coupled to the plasma chamber from 1 to 35 W produced a plasma environment much more reactive which increases the population of the ionized species like CH2+ (15 amu), C2H4+ (28 amu), CH3O+ (31 amu), C2H4O+ (44 amu), CH3OCH2CH2+ (59 amu) and CH3OCH2CH2O+ (75 amu). This fact may be attributed to the increase of the electronic temperature that makes predominant the occurrence of inelastic processes that promotes molecular fragmentation. For a fixed value of RF power the increase of pressure from 50 mTorr to 100 mTorr produces the decreasing of the above mentioned chemical species due the lower electronic mean free path. These results suggest that if one wants to keep the monomer's functionality within the plasma deposited films resulting from such kind of discharges one must operate in low power conditions.

  19. A quantitative multiplexed mass spectrometry assay for studying the kinetic of residue-specific histone acetylation.

    PubMed

    Kuo, Yin-Ming; Henry, Ryan A; Andrews, Andrew J

    2014-12-01

    Histone acetylation is involved in gene regulation and, most importantly, aberrant regulation of histone acetylation is correlated with major human diseases. Although many lysine acetyltransferases (KATs) have been characterized as being capable of acetylating multiple lysine residues on histones, how different factors such as enzyme complexes or external stimuli (e.g. KAT activators or inhibitors) alter KAT specificity remains elusive. In order to comprehensively understand how the homeostasis of histone acetylation is maintained, a method that can quantitate acetylation levels of individual lysines on histones is needed. Here we demonstrate that our mass spectrometry (MS)-based method accomplishes this goal. In addition, the high throughput, high sensitivity, and high dynamic range of this method allows for effectively and accurately studying steady-state kinetics. Based on the kinetic parameters from in vitro enzymatic assays, we can determine the specificity and selectivity of a KAT and use this information to understand what factors influence histone acetylation. These approaches can be used to study the enzymatic mechanisms of histone acetylation as well as be adapted to other histone modifications. Understanding the post-translational modification of individual residues within the histones will provide a better picture of chromatin regulation in the cell.

  20. Measuring technique for thermal ionisation mass spectrometry of human tracer kinetic study with stable cerium isotopes.

    PubMed

    Keiser, Teresa; Höllriegl, Vera; Giussani, Augusto; Oeh, Uwe

    2011-06-01

    Thermal ionisation mass spectrometry (TIMS) method has been developed for the simultaneous detection of different cerium isotopes in biological samples (i.e., blood and urine) at very low concentrations. The work has been done in the frame of a biokinetic study, where different stable cerium isotopes have been administered orally and intravenously as tracers to the human body. In order to develop an appropriate detection method for the tracers in the biological samples, an optimum sample preparation technique has been set and adapted to the specific requirements of the analysis technique used, i.e., TIMS. For sample evaporation and ionisation, the double tantalum filament technique showed the best results. The ions produced were simultaneously collected on a secondary electron multiplier so that the isotopic ratios of the cerium isotopes in the biological samples could be measured. The technique has been optimised for the determination of cerium down to 1 ng loaded on the evaporation filament corresponding to cerium concentrations of down to 1 ng ml(-1) in the blood or urine samples. It has been shown that the technique is reliable in application and enables studies on cerium metabolism and biokinetics in humans without employing radioactive tracers.

  1. The role of mass spectrometry to study the Oklo-Bangombé natural reactors.

    PubMed

    De Laeter, J R; Hidaka, H

    2007-01-01

    The discovery of the existence of chain reactions at the Oklo natural reactors in Gabon, Central Africa in 1972 was a triumph for the accuracy of mass spectrometric measurements, in that a 0.5% anomaly in the (235)U/(238)U ratio of certain U ore samples indicated a depletion in (235)U. Mass spectrometric techniques thereafter played a dominant role in determining the nuclear parameters of the reactor zones themselves, and in deciphering the geochemical characteristics of various elements in the U-rich ore and in the surrounding rock strata. The variations in the isotopic composition of a large number of elements, caused by a combination of nuclear fission, neutron capture and radioactive decay, provide a powerful tool for investigating this unique geological environment. Mass spectrometry can be used to measure the present-day elemental and isotopic abundances of numerous elements, so as to decipher the past history of the reactors and examine the retentivity/mobility of these elements. Many of the fission products have a radioactive decay history that have been used to date the age and duration of the reactor zones, and to provide insight into their nuclear and geochemical behavior as a function of time. The Oklo fission reactors and their near neighbor at Bangombé, some 30 km to the south-east of Oklo, are unique in that not only did they become critical some 2 x 10(9) years ago, but also the deposits have been preserved over this period of geological time. The long-term geochemical behavior of actinides and fission products have been extensively studied by a variety of mass spectrometric techniques over the past 30 years to provide us with significant information on the mobility/retentivity of this material in a natural geological repository. The Oklo-Bangombé natural reactors are therefore geological analogs that can be evaluated in terms of possible radioactive waste containment sites. As more reactor zones were discovered, it was realized that they could be

  2. A fragmentation study of kaempferol using electrospray quadrupole time-of-flight mass spectrometry at high mass resolution

    NASA Astrophysics Data System (ADS)

    March, Raymond E.; Miao, Xiu-Sheng

    2004-02-01

    A mass spectrometric method based on the combined use of electrospray ionization, collision-induced dissociation and tandem mass spectrometry at high mass resolution has been applied to an investigation of the structural characterization of protonated and deprotonated kaempferol (3,5,7,4'-tetrahydroxyflavone). Low-energy product ion mass spectra of [M+H]+ ions showed simple fragmentations of the C ring that permitted characterization of the substituents in the A and B rings. In addition, four rearrangement reactions accompanied by losses of C2H2O, CHO[radical sign], CO, and H2O were observed. Low-energy product ion mass spectra of [M-H]- ions showed only four rearrangement reactions accompanied by losses of OH[radical sign], CO, CH2O, and C2H2O. The use of elevated cone voltages permitted observation of product ion mass spectra of selected primary and secondary fragment ions so that each fragment ion reported was observed as a direct product of its immediate precursor ion. Product ion mass spectra examined at high mass resolution allowed unambiguous determination of the elemental composition of fragment ions and resolution of two pairs of isobars. Fragmentation mechanisms and ion structures have been proposed.

  3. EMERGING POLLUTANTS, MASS SPECTROMETRY, AND ...

    EPA Pesticide Factsheets

    Historically fundamental to amassing our understanding of environmental processes and chemical pollution is the realm of mass spectrometry (MS) - the mainstay of analytical chemistry - the workhorse that supplies definitive data that environmental scientists and engineers reply upon for identifying molecular compositions (and ultimately structures) of chemicals. While the power of MS has long been visible to the practicing environmental chemist, it borders on obscurity to the lay public and many scientists. While MS has played a long, historic (and largely invisible) role in establishing our knowledge of environmental processes and pollution, what recognition it does enjoy is usually relegated to that of a tool. It is usually the relevance or significance of the knowledge acquired from the application of the tool that has ultimate meaning to the public and science at large - not how the data were acquired. Methods (736/800): Mass Spectrometry and the

  4. The vapour of imidazolium-based ionic liquids: a mass spectrometry study.

    PubMed

    Deyko, A; Lovelock, K R J; Licence, P; Jones, R G

    2011-10-06

    Eight common dialkylimidazolium-based ionic liquids have been successfully evaporated in ultra-high vacuum and their vapours analysed by line of sight mass spectrometry using electron ionisation. The ionic liquids investigated were 1-alkyl-3-methylimidazolium bis[(trifluoromethane)sulfonyl]imide, [C(n)C(1)Im][Tf(2)N] (where n = 2, 4, 6, 8), 1-alkyl-3-methylimidazolium tetrafluoroborate, [C(n)C(1)Im][BF(4)] (where n = 4, 8), 1-butyl-3-methylimidazolium octylsulfate, [C(4)C(1)Im][C(8)OSO(3)] and 1-butyl-3-methylimidazolium tetrachloroferrate, [C(4)C(1)Im][FeCl(4)]. All ionic liquids studied here evaporated as neutral ion pairs; no evidence of decomposition products in the vapour phase were observed. Key fragment cations of the ionised vapour of the ionic liquids are identified. The appearance energies, E(app), of the parent cation were measured and used to estimate the ionisation energies, E(i), for the vapour phase neutral ion pairs. Measured ionisation energies ranged from 10.5 eV to 13.0 eV. Using both the identity and E(app) values, the fragmentation pathways for a number of fragment cations are postulated. It will be shown that the enthalpy of vaporisation, Δ(vap)H, can successfully be measured using more than one fragment cation, although caution is required as many fragment cations can also be formed by ionisation of decomposition products.

  5. Study on volatile components in salami by reverse carrier gas headspace gas chromatography-mass spectrometry.

    PubMed

    Procida, G; Conte, L S; Fiorasi, S; Comi, G; Favretto, L G

    1999-01-08

    Salami are a typical seasoned sausage of Italy; a number of types are produced, according to local traditional recipes. As industrial production has taken place, a number of problems rise in obtaining products similar to the traditional ones. The use of selected microbial starters is permitted by Italian law for some years and at present, microbiological research is engaged in selecting starters similar to the ones isolated from traditional products, with the aim of obtaining organoleptic characteristics close to the ones of traditional recipes. A study was carried out concerning the characterisation of volatile components of salami by headspace capillary gas chromatography-mass spectrometry. As during the sampling step, analytes could reach the analytical column, the carrier gas rate was back flushed in the latter, while a pre column was used as cold trap. Then GC-MS analysis follows. By these techniques, we were able to highlight typical profiles of different salami, as well as monitoring the ripening of a traditional and a starter added salami. Main peaks are of fermentative origin, while also peaks from spices were detected. Ethyl propionate was used as internal standard to be able to normalise the peaks amounts.

  6. Study on essential oils from four species of Zhishi with gas chromatography–mass spectrometry

    PubMed Central

    2014-01-01

    Background Citrus fruits are widely used as food and or for medicinal purposes, and they contain a host of active substances that contribute to health. The immature fruits of Citrus sinensis Osbeck and its cultivars (CS), C. junos Sieb. ex Tanaka (CJ), C. aurantium L. and its cultivars (CA) and Poncirus trifoliate Raf. (PT) are the most commonly used medicinal herbs in Traditional Chinese Medicine, called Zhishi. And their mature fruits can be used as food. Results In this study, the essential oils of four different Zhishi species were extracted by steam distillation and detected using gas chromatography- mass spectrometry (GC-MS). A total of 39 volatiles from the four species were tentatively identified. The limonene was the most abundant amongst the four species. Principal component analysis (PCA) of essential oils showed a clear separation of volatiles among CS, CJ and PT. However, CA could not be separated from these three species. Additionally, the volatiles accounting for the variations among the widely separated species were characterized through their corresponding loading weight. Conclusion Sesquiterpenes were identified as characteristic markers for PT. The content of some monoterpenes could be as taxonomic markers between CS and CJ. This work is of great importance for the evaluation and authentication of Zhishi samples through essential oils. PMID:24708882

  7. A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

    PubMed Central

    Willms, J Alexander; Beel, Rita; Schmidt, Martin L; Mundt, Christian

    2014-01-01

    Summary A new 4-hydroxy-L-proline derivative with a charged 1-ethylpyridinium-4-phenoxy substituent has been synthesized with the aim of facilitating mechanistic studies of proline-catalyzed reactions by ESI mass spectrometry. The charged residue ensures a strongly enhanced ESI response compared to neutral unmodified proline. The connection by a rigid linker fixes the position of the charge tag far away from the catalytic center in order to avoid unwanted interactions. The use of a charged catalyst leads to significantly enhanced ESI signal abundances for every catalyst-derived species which are the ones of highest interest present in a reacting solution. The new charged proline catalyst has been tested in the direct asymmetric inverse aldol reaction between aldehydes and diethyl ketomalonate. Two intermediates in accordance with the List–Houk mechanism for enamine catalysis have been detected and characterized by gas-phase fragmentation. In addition, their temporal evolution has been followed using a microreactor continuous-flow technique. PMID:25246962

  8. Studies of phospholipid oxidation by electrospray mass spectrometry: from analysis in cells to biological effects.

    PubMed

    Spickett, Corinne M; Dever, Gary

    2005-01-01

    The oxidation of lipids is important in many pathological conditions and lipid peroxidation products such as 4-hydroxynonenal (HNE) and other aldehydes are commonly measured as biomarkers of oxidative stress. However, it is often useful to complement this with analysis of the original oxidized phospholipid. Electrospray mass spectrometry (ESMS) provides an informative method for detecting oxidative alterations to phospholipids, and has been used to investigate oxidative damage to cells, and low-density lipoprotein, as well as for the analysis of oxidized phosphatidylcholines present in atherosclerotic plaque material. There is increasing evidence that intact oxidized phospholipids have biological effects; in particular, oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycerophosphocholine (PAPC) have been found to cause inflammatory responses, which could be potentially important in the progression of atherosclerosis. The effects of chlorohydrin derivatives of lipids have been much less studied, but it is clear that free fatty acid chlorohydrins and phosphatidylcholine chlorohydrins are toxic to cells at concentrations above 10 micromolar, a range comparable to that of HNE and oxidized PAPC. There is some evidence that chlorohydrins have biological effects that may be relevant to atherosclerosis, but further work is needed to elucidate their pro-inflammatory properties, and to understand the mechanisms and balance of biological effects that could result from oxidation of complex mixtures of lipids in a pathophysiological situation.

  9. Using mass spectrometry to study the photo-affinity labeling of protein tyrosine phosphatase 1B

    NASA Astrophysics Data System (ADS)

    Leriche, Tammy; Skorey, Kathryn; Roy, Patrick; McKay, Dan; Bateman, Kevin P.

    2004-11-01

    Protein tyrosine phosphatase 1B (PTP1B) is a potential target for the treatment of Type II diabetes and several companies are developing small molecule inhibitors of this enzyme. Part of the characterization of these compounds as PTP1B inhibitors is the understanding of how they bind in the enzyme active site. The use of photo-activated inhibitors that target the active site can provide such insight. This paper describes the characterization of a photoprobe directed at the active site of PTP1B. Mass spectrometry revealed the specific binding of the probe to the intact protein. Digestion of the labeled protein followed by LC-MS and LC-MS/MS was used to show that the photoprobe binds to a specific active site amino acid. This was confirmed by comparison with the X-ray structure of PTP1B with a PTP1B inhibitor. The probe labels a conserved acidic residue (Asp) that is required for catalytic activity. This photoprobe may prove to be a useful tool for the development of a PTP1B inhibitor or for the study of PTPs in general.

  10. Studying Arsenite-Humic Acid Complexation Using Size Exclusion Chromatography-Inductively Coupled Plasma Mass Spectrometry

    PubMed Central

    Liu, Guangliang; Cai, Yong

    2012-01-01

    Arsenic (As) can form complexes with dissolved organic matter (DOM), which affects the fate of arsenic in waste sites and natural environments. It remains a challenge to analyze DOM-bound As, in particular by using a direct chromatographic separation method. Size exclusion chromatography (SEC) hyphenated with UV spectrophotometer and inductively coupled plasma mass spectrometry (ICP-MS) was developed to characterize the complexation of arsenite (AsIII) with DOM. This SEC-UV-ICP-MS method is able to differentiate AsIII-DOM complexes from free As species and has the advantage of direct determination of both free and DOM-bound AsIII through mild separation. The suitability of this method for studying AsIII-DOM complexation was demonstrated by its application, in combination with the Scatchard plot and nonlinear regression of ligand binding model, for characterizing AsIII complexation with humic acid (HA) in the absence or presence of natural sand. The results suggest that, consistent with polyelectrolytic nature of HA, the AsIII-HA complexation should be accounted for by multiple classes of binding sites. By loosely classifying the binding sites into strong (S1) and weak (S2) sites, the apparent stability constants (Ks) of the resulting As-DOM complexes were calculated as log Ks1 = 6.5–7.1 while log Ks2 = 4.7–5.0. PMID:22664255

  11. Accounting for Undetected Compounds in Statistical Analyses of Mass Spectrometry ‘Omic Studies

    PubMed Central

    Taylor, Sandra L.; Leiserowitz, Gary S.; Kim, Kyoungmi

    2014-01-01

    Mass spectrometry is an important high-throughput technique for profiling small molecular compounds in biological samples and is widely used to identify potential diagnostic and prognostic compounds associated with disease. Commonly, this data generated by mass spectrometry has many missing values resulting when a compound is absent from a sample or is present but at a concentration below the detection limit. Several strategies are available for statistically analyzing data with missing values. The accelerated failure time (AFT) model assumes all missing values result from censoring below a detection limit. Under a mixture model, missing values can result from a combination of censoring and the absence of a compound. We compare power and estimation of a mixture model to an AFT model. Based on simulated data, we found the AFT model to have greater power to detect differences in means and point mass proportions between groups. However, the AFT model yielded biased estimates with the bias increasing as the proportion of observations in the point mass increased while estimates were unbiased with the mixture model except if all missing observations came from censoring. These findings suggest using the AFT model for hypothesis testing and mixture model for estimation. We demonstrated this approach through application to glycomics data of serum samples from women with ovarian cancer and matched controls. PMID:24246290

  12. Glycosaminoglycan Glycomics Using Mass Spectrometry*

    PubMed Central

    Zaia, Joseph

    2013-01-01

    The fact that sulfated glycosaminoglycans (GAGs) are necessary for the functioning of all animal physiological systems drives the need to understand their biology. This understanding is limited, however, by the heterogeneous nature of GAG chains and their dynamic spatial and temporal expression patterns. GAGs have a regulated structure overlaid by heterogeneity but lack the detail necessary to build structure/function relationships. In order to provide this information, we need glycomics platforms that are sensitive, robust, high throughput, and information rich. This review summarizes progress on mass-spectrometry-based GAG glycomics methods. The areas covered include disaccharide analysis, oligosaccharide profiling, and tandem mass spectrometric sequencing. PMID:23325770

  13. Isotope ratio measurements by secondary ion mass spectrometry (SIMS) and glow discharge mass spectrometry (GDMS)

    NASA Astrophysics Data System (ADS)

    Betti, Maria

    2005-04-01

    The basic principles of secondary ion mass spectrometry and glow discharge mass spectrometry have been shortly revisited. The applications of both techniques as exploited for the isotope ratio measurements in several matrices have been reviewed. Emphasis has been given to research fields in expansions such as solar system studies, medicine, biology, environment and nuclear forensic. The characteristics of the two techniques are discussed in terms of sensitivity and methodology of quantification. Considerations on the different detection possibilities in SIMS are also presented.

  14. A mass spectrometry primer for mass spectrometry imaging

    PubMed Central

    Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2011-01-01

    Mass spectrometry imaging (MSI), a rapidly growing subfield of chemical imaging, employs mass spectrometry (MS) technologies to create single- and multi-dimensional localization maps for a variety of atoms and molecules. Complimentary to other imaging approaches, MSI provides high chemical specificity and broad analyte coverage. This powerful analytical toolset is capable of measuring the distribution of many classes of inorganics, metabolites, proteins and pharmaceuticals in chemically and structurally complex biological specimens in vivo, in vitro, and in situ. The MSI approaches highlighted in this Methods in Molecular Biology volume provide flexibility of detection, characterization, and identification of multiple known and unknown analytes. The goal of this chapter is to introduce investigators who may be unfamiliar with MS to the basic principles of the mass spectrometric approaches as used in MSI. In addition to guidelines for choosing the most suitable MSI method for specific investigations, cross-references are provided to the chapters in this volume that describe the appropriate experimental protocols. PMID:20680583

  15. Gas-phase dissociation study of erythrinian alkaloids by electrospray ionization mass spectrometry and computational methods.

    PubMed

    Guaratini, T; Feitosa, L G P; Silva, D B; Lopes, N P; Lopes, J L C; Vessecchi, R

    2017-09-01

    Alkaloids from plants of the genus Erythrina display important biological activities, including anxiolytic action. Characterization of these alkaloids by mass spectrometry (MS) has contributed to the construction of a spectral library, has improved understanding of their structures and has supported the proposal of fragmentation mechanisms in light of density functional calculations. In this study, we have used low-resolution and high-resolution MS(n) analyses to investigate the fragmentation patterns of erythrinian alkaloids; we have employed the B3LYP/6-31+G(d,p) model to obtain their reactive sites. To suggest the fragmentation mechanism of these alkaloids, we have studied their protonation sites by density functional calculation, and we have obtained their molecular electrostatic potential map and their gas-phase basicity values. These analyses have indicated the most basic sites on the basis of the proton affinities of the nitrogen and oxygen atoms. The protonated molecules were generated by two major fragmentations, namely, neutral loss of CH3 OH followed by elimination of H2 O. High-resolution analysis confirmed elimination of NH3 by comparison with the losses of H2 and •CH3 . NH3 was eliminated from compounds that did not bear a substituent on ring C. The benzylic carbocation initiated the dissociation mechanism, and the first reaction involved charge transfer from a lone pair of electrons in the oxygen atoms. The second reaction consisted of ring contraction with loss of a CO molecule. The presence of hydroxy and epoxy groups could change the intensity or the occurrence of the fragmentation pathways. Given that erythrinian alkaloids are applied in therapeutics and are promising leads for the development of new drugs, the present results could aid identification of several analogues of these alkaloids in biological samples and advance pharmacokinetic studies of new plant derivatives based on MS(n) and MS/MS analyses. Copyright © 2017 John Wiley & Sons

  16. Quantitative mass spectrometry: an overview

    NASA Astrophysics Data System (ADS)

    Urban, Pawel L.

    2016-10-01

    Mass spectrometry (MS) is a mainstream chemical analysis technique in the twenty-first century. It has contributed to numerous discoveries in chemistry, physics and biochemistry. Hundreds of research laboratories scattered all over the world use MS every day to investigate fundamental phenomena on the molecular level. MS is also widely used by industry-especially in drug discovery, quality control and food safety protocols. In some cases, mass spectrometers are indispensable and irreplaceable by any other metrological tools. The uniqueness of MS is due to the fact that it enables direct identification of molecules based on the mass-to-charge ratios as well as fragmentation patterns. Thus, for several decades now, MS has been used in qualitative chemical analysis. To address the pressing need for quantitative molecular measurements, a number of laboratories focused on technological and methodological improvements that could render MS a fully quantitative metrological platform. In this theme issue, the experts working for some of those laboratories share their knowledge and enthusiasm about quantitative MS. I hope this theme issue will benefit readers, and foster fundamental and applied research based on quantitative MS measurements. This article is part of the themed issue 'Quantitative mass spectrometry'.

  17. Vaporization study of sodium sulphate — potassium sulphate binary system by Knudsen effusion mass spectrometry

    NASA Astrophysics Data System (ADS)

    Armatys, K.; Miller, M.; Matraszek, A.; Wolter, A.

    2011-06-01

    The vaporization of samples of different chemical and phase compositions in the Na2SO4-K2SO4 system was investigated over the temperature range 1100 K-1400 K by the use of Knudsen effusion mass spectrometry. The gaseous species Na(g), Na2SO4(g), K(g), K2SO4(g), SO2(g), O2(g) and NaKSO4(g) were identified in the vapour over the samples investigated. The thermodynamic activities of sulphates in the examined system at 1350 K were obtained, which allowed calculating the chemical composition of the vapours present in the high temperature zone of cement kilns.

  18. Inosine octamer stabilized by alkali earth metal cations - as studied by electrospray ionization mass spectrometry.

    PubMed

    Frańska, Magdalena

    2014-01-01

    By using electrospray ionization mass spectrometry, inosine was found to be able to form an octamer stabilized by alkali earth metal cation, namely Ca(2+), Sr(2+) and Ba(2+), of which the most stable is that stabilized by Ca(2+) (ion [I8+Ca](2+)). It was established that 9-methylhypoxanthine (M) did not form an analogical octamer, since ion [M8+Ca](2+) was not detected. On the other hand, 9-methylhypoxanthine can form "mixed" octamers together with inosine (ions [InMm+Ca](2+), n + m = 8, were detected).

  19. Applications of liquid chromatography-mass spectrometry in metabolic studies of explosives.

    PubMed

    Yinon, J; Hwang, D G

    1987-05-08

    Liquid chromatography-mass spectrometry was used for the detection and identification of metabolites of 2,4,6-trinitrotoluene (TNT) in urine and blood. The metabolites were found in the urine of rats and in the blood of rabbits fed with TNT, in the urine of rats exposed to TNT by skin absorption and in the urine of TNT munition workers. The detected metabolites, formed by reduction processes, included 2-amino-4,6-dinitrotoluene, 4-amino-2,6-dinitrotoluene, 2,4-diamino-6-nitrotoluene and 2,6-diamino-4-nitrotoluene, in addition to untransformed TNT.

  20. pcPIR, a photocleavable and mass spectrometry identifiable cross-linker for protein interaction studies

    PubMed Central

    Yang, Li; Tang, Xiaoting; Weisbrod, Chad; Munske, Gerhard; Eng, Jimmy; von Haller, Priska; Kaiser, Nathan; Bruce, James E.

    2010-01-01

    In this paper, we present the results of proof-of-concept experiments using a novel photocleavable and mass spectrometry identifiable cross-linker pcPIR (photocleavable Protein Interaction Reporter). pcPIR can be dissociated under UV irradiation either off- or on-line before the introduction to the mass spectrometers. Photo dissociation of cross-linkers is different from either the gas phase or the chemical cleavage of cross-linkers. Different types of cross-links can be identified using the pcPIR mass relationships, where the mass of cross-linked precursor equals the sum of the masses of the released products and reporter. Since pcPIR is cleaved prior to the entrance to the mass spectrometer, the released peptides are available to be sequenced with routine CID MS/MS experiments and database search algorithms. In this report, the pcPIR strategy of identifying the cross-linked peptides with on- and off-line photocleavage coupled with novel targeted data dependent LC-MS/MS is demonstrated with the use of standard peptides, BSA and human hemoglobin tetramer protein complex. PMID:20373789

  1. [Use of time-of-flight mass spectrometry with ionization division fragments of californium-252 for studying the mechanisms of action of drugs on DNA and its components].

    PubMed

    Sukhodub, L F; Grebenik, L I; Chivanov, V D

    1994-01-01

    Using soft-ionization mass spectrometry (252-Cf particle desorption mass spectrometry, PDMS) a minor adduct of anticancer drug prospidine and deoxyguanosine-5-phosphate (pdG) has been found. It has been shown experimentally that PDMS is very useful for study of biological mixtures as well as mechanisms of interactions between drugs and biomolecules.

  2. Mass spectrometry assay for studying kinetic properties of dipeptidases: characterization of human and yeast dipeptidases.

    PubMed

    Pandya, Vaibhav; Ekka, Mary Krishna; Dutta, Rajesh Kumar; Kumaran, S

    2011-11-01

    Chemical modifications of substrate peptides are often necessary to monitor the hydrolysis of small bioactive peptides. We developed an electrospray ionization mass spectrometry (ESI-MS) assay for studying substrate distributions in reaction mixtures and determined steady-state kinetic parameters, the Michaelis-Menten constant (K(m)), and catalytic turnover rate (V(max)/[E](t)) for three metallodipeptidases: two carnosinases (CN1 and CN2) from human and Dug1p from yeast. The turnover rate (V(max)/[E](t)) of CN1 and CN2 determined at pH 8.0 (112.3 and 19.5s(-1), respectively) suggested that CN1 is approximately 6-fold more efficient. The turnover rate of Dug1p for Cys-Gly dipeptide at pH 8.0 was found to be slightly lower (73.8s(-1)). In addition, we determined kinetic parameters of CN2 at pH 9.2 and found that the turnover rate was increased by 4-fold with no significant change in the K(m). Kinetic parameters obtained by the ESI-MS method are consistent with results of a reverse-phase high-performance liquid chromatography (RP-HPLC)-based assay. Furthermore, we used tandem MS (MS/MS) analyses to characterize carnosine and measured its levels in CHO cell lines in a time-dependent manner. The ESI-MS method developed here obviates the need for substrate modification and provides a less laborious, accurate, and rapid assay for studying kinetic properties of dipeptidases in vitro as well as in vivo. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Spontaneous Mass and Charge Losses from Single Multi-Megadalton Ions Studied by Charge Detection Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Keifer, David Z.; Alexander, Andrew W.; Jarrold, Martin F.

    2017-01-01

    Spontaneous mass and charge losses from individual multi-megadalton ions have been observed with charge detection mass spectrometry (CDMS) by trapping single hepatitis B virus (HBV) capsids for 3 s. Gradual increases in the oscillation frequency of single ions in the ion trap are attributed mainly to mass loss (probably solvent, water, and/or salt). The total mass lost during the 3 s trapping period peaks at around 20 kDa for 4 MDa HBV T = 4 capsids. Discrete frequency drops punctuate the gradual increases in the oscillation frequencies. The drops are attributed to a sudden loss of charge. In most cases a single positive charge is lost along with some mass (on average around 1000 Da). Charge loss occurs for over 40% of the trapped ions. It usually occurs near the beginning of the trapping event, and it occurs preferentially in regions of the trap with strong electric fields, indicating that external electric fields promote charge loss. This process may contribute to the decrease in m/z resolution that often occurs with megadalton ions.

  4. Spontaneous Mass and Charge Losses from Single Multi-Megadalton Ions Studied by Charge Detection Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Keifer, David Z.; Alexander, Andrew W.; Jarrold, Martin F.

    2017-03-01

    Spontaneous mass and charge losses from individual multi-megadalton ions have been observed with charge detection mass spectrometry (CDMS) by trapping single hepatitis B virus (HBV) capsids for 3 s. Gradual increases in the oscillation frequency of single ions in the ion trap are attributed mainly to mass loss (probably solvent, water, and/or salt). The total mass lost during the 3 s trapping period peaks at around 20 kDa for 4 MDa HBV T = 4 capsids. Discrete frequency drops punctuate the gradual increases in the oscillation frequencies. The drops are attributed to a sudden loss of charge. In most cases a single positive charge is lost along with some mass (on average around 1000 Da). Charge loss occurs for over 40% of the trapped ions. It usually occurs near the beginning of the trapping event, and it occurs preferentially in regions of the trap with strong electric fields, indicating that external electric fields promote charge loss. This process may contribute to the decrease in m/ z resolution that often occurs with megadalton ions.

  5. Coded Apertures in Mass Spectrometry.

    PubMed

    Amsden, Jason J; Gehm, Michael E; Russell, Zachary E; Chen, Evan X; Di Dona, Shane T; Wolter, Scott D; Danell, Ryan M; Kibelka, Gottfried; Parker, Charles B; Stoner, Brian R; Brady, David J; Glass, Jeffrey T

    2017-06-12

    The use of coded apertures in mass spectrometry can break the trade-off between throughput and resolution that has historically plagued conventional instruments. Despite their very early stage of development, coded apertures have been shown to increase throughput by more than one order of magnitude, with no loss in resolution in a simple 90-degree magnetic sector. This enhanced throughput can increase the signal level with respect to the underlying noise, thereby significantly improving sensitivity to low concentrations of analyte. Simultaneous resolution can be maintained, preventing any decrease in selectivity. Both one- and two-dimensional (2D) codes have been demonstrated. A 2D code can provide increased measurement diversity and therefore improved numerical conditioning of the mass spectrum that is reconstructed from the coded signal. This review discusses the state of development, the applications where coding is expected to provide added value, and the various instrument modifications necessary to implement coded apertures in mass spectrometers.

  6. Electrophoresis-mass spectrometry probe

    DOEpatents

    Andresen, Brian D.; Fought, Eric R.

    1987-01-01

    The invention involves a new technique for the separation of complex mixtures of chemicals, which utilizes a unique interface probe for conventional mass spectrometers which allows the electrophoretically separated compounds to be analyzed in real-time by a mass spectrometer. This new chemical analysis interface, which couples electrophoresis with mass spectrometry, allows complex mixtures to be analyzed very rapidly, with much greater specificity, and with greater sensitivity. The interface or probe provides a means whereby large and/or polar molecules in complex mixtures to be completely characterized. The preferred embodiment of the probe utilizes a double capillary tip which allows the probe tip to be continually wetted by the buffer, which provides for increased heat dissipation, and results in a continually operating interface which is more durable and electronically stable than the illustrated single capillary tip probe interface.

  7. Electrophoresis-mass spectrometry probe

    DOEpatents

    Andresen, B.D.; Fought, E.R.

    1987-11-10

    The invention involves a new technique for the separation of complex mixtures of chemicals, which utilizes a unique interface probe for conventional mass spectrometers which allows the electrophoretically separated compounds to be analyzed in real-time by a mass spectrometer. This new chemical analysis interface, which couples electrophoresis with mass spectrometry, allows complex mixtures to be analyzed very rapidly, with much greater specificity, and with greater sensitivity. The interface or probe provides a means whereby large and/or polar molecules in complex mixtures to be completely characterized. The preferred embodiment of the probe utilizes a double capillary tip which allows the probe tip to be continually wetted by the buffer, which provides for increased heat dissipation, and results in a continually operating interface which is more durable and electronically stable than the illustrated single capillary tip probe interface. 8 figs.

  8. Affinity membrane introduction mass spectrometry

    SciTech Connect

    Xu, C.; Patrick, J.S.; Cooks, R.G. )

    1995-02-15

    A new technique, affinity membrane introduction mass spectrometry, is described. In this method, a chemically modified membrane is used to selectively adsorb analytes bearing a particular functional group and concentrate them from solution. Release of the bound analyte results in its transfer across the membrane and allows it to be monitored mass spectrometrically, using, in the present case, a benchtop ion trap instrument. Alkylamine-modified cellulose membranes are used to bind substituted benzaldehydes through imine formation at high pH. Release of the bound aldehyde is achieved by acid hydrolysis of the surface-bound imine. Benzaldehyde is detected with excellent specificity at 10 ppm in a complex mixture using this method. Using the enrichment capability of the membrane, a full mass spectrum of benzaldehyde can be measured at a concentration of 10 ppb. The behavior of a variety of other aldehydes is also discussed to illustrate the capabilities of the method. 21 refs., 5 figs., 2 tabs.

  9. Studies of polyisobutylene using time-of-flight secondary ion mass spectrometry (TOF-SIMS)

    NASA Astrophysics Data System (ADS)

    Xu, Keyang; Proctor, Andrew; Hercules, David M.

    1995-05-01

    A series of polyisobutylenes (PIBs) with average molecular weights from 800 to 4 × 105 were analyzed using time-of-flight secondary ion mass spectrometry (TOF-SIMS). The PIB spectra consist of a sequence of repeating patterns. Four clusters are observed within each pattern. Each cluster corresponds to several species, which are neutral fragments generated from polymer chain scission, cationized by a silver ion. The species formed have various numbers of double bonds and/or rings, and are separated by two mass units. The data indicate that the average molecular weight of PIB affects the ion formation. It changes the relative cluster intensities in a pattern, and also varies the cluster structures. More fragment-ion species can be detected from a high molecular weight polymer, and the unsaturated fragments are predominant. In addition to the large fragments, small fragment ions also provide information about some structurally important features.

  10. Measurement of Beryllium in Biological Samples by Accelerator Mass Spectrometry: Applications for Studying Chronic Beryllium Disease

    SciTech Connect

    Chiarappa-Zucca, M L; Finkel, R C; Martinelli, R E; McAninch, J E; Nelson, D O; Turtletaub, K W

    2004-04-15

    A method using accelerator mass spectrometry (AMS) has been developed for quantifying attomoles of beryllium (Be) in biological samples. This method provides the sensitivity to trace Be in biological samples at very low doses with the purpose of identifying the molecular targets involved in chronic beryllium disease. Proof of the method was tested by administering 0.001, 0.05, 0.5 and 5.0 {micro}g {sup 9}Be and {sup 10}Be by intraperitoneal injection to male mice and removing spleen, liver, femurs, blood, lung, and kidneys after 24 h exposure. These samples were prepared for AMS analysis by tissue digestion in nitric acid, followed by further organic oxidation with hydrogen peroxide and ammonium persulfate and lastly, precipitation of Be with ammonium hydroxide, and conversion to beryllium oxide at 800 C. The {sup 10}Be/{sup 9}Be ratio of the extracted beryllium oxide was measured by AMS and Be in the original sample was calculated. Results indicate that Be levels were dose-dependent in all tissues and the highest levels were measured in the spleen and liver. The measured {sup 10}Be/{sup 9}Be ratios spanned 4 orders of magnitude, from 10{sup -10} to 10{sup -14}, with a detection limit of 3.0 x 10{sup -14}, which is equivalent to 0.8 attomoles of {sup 10}Be. These results show that routine quantification of nanogram levels of Be in tissues is possible and that AMS is a sensitive method that can be used in biological studies to understand the molecular dosimetry of Be and mechanisms of toxicity.

  11. Application of mass spectrometry to study proteomics and interactomics in cystic fibrosis.

    PubMed

    Balch, William E; Yates, John R

    2011-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) does not function in isolation, but rather in a complex network of protein-protein interactions that dictate the physiology of a healthy cell and tissue and, when defective, the pathophysiology characteristic of cystic fibrosis (CF) disease. To begin to address the organization and operation of the extensive cystic fibrosis protein network dictated by simultaneous and sequential interactions, it will be necessary to understand the global protein environment (the proteome) in which CFTR functions in the cell and the local network that dictates CFTR folding, trafficking, and function at the cell surface. Emerging mass spectrometry (MS) technologies and methodologies offer an unprecedented opportunity to fully characterize both the proteome and the protein interactions directing normal CFTR function and to define what goes wrong in disease. Below we provide the CF investigator with a general introduction to the capabilities of modern mass spectrometry technologies and methodologies with the goal of inspiring further application of these technologies for development of a basic understanding of the disease and for the identification of novel pathways that may be amenable to therapeutic intervention in the clinic.

  12. Uranium passivation by C + implantation: A photoemission and secondary ion mass spectrometry study

    NASA Astrophysics Data System (ADS)

    Nelson, A. J.; Felter, T. E.; Wu, K. J.; Evans, C.; Ferreira, J. L.; Siekhaus, W. J.; McLean, W.

    2006-03-01

    Implantation of 33 keV C + ions into polycrystalline U 238 with a dose of 4.3 × 10 17 cm -2 produces a physically and chemically modified surface layer that prevents further air oxidation and corrosion. X-ray photoelectron spectroscopy and secondary ion mass spectrometry were used to investigate the surface chemistry and electronic structure of this C + ion implanted polycrystalline uranium and a non-implanted region of the sample, both regions exposed to air for more than a year. In addition, scanning electron microscopy was used to examine and compare the surface morphology of the two regions. The U 4f, O 1s and C 1s core-level and valence band spectra clearly indicate carbide formation in the modified surface layer. The time-of-flight secondary ion mass spectrometry depth profiling results reveal an oxy-carbide surface layer over an approximately 200 nm thick UC layer with little or no residual oxidation at the carbide layer/U metal transitional interface.

  13. Uranium passivation by C+ implantation: a photoemission and secondary ion mass spectrometry study

    SciTech Connect

    Nelson, A J; Felter, T E; Wu, K J; Evans, C; Ferreira, J; Siekhaus, W; McLean, W

    2005-01-20

    Implantation of 33 keV C{sup +} ions into polycrystalline U{sup 238} with a dose of 4.3 x 10{sup 17} cm{sup -2} produces a physically and chemically modified surface layer that prevents further air oxidation and corrosion. X-ray photoelectron spectroscopy and secondary ion mass spectrometry were used to investigate the surface chemistry and electronic structure of this C{sup +} ion implanted polycrystalline uranium and a non-implanted region of the sample, both regions exposed to air for more than a year. In addition, scanning electron microscopy was used to examine and compare the surface morphology of the two regions. The U 4f, O 1s and C 1s core-level and valence band spectra clearly indicate carbide formation in the modified surface layer. The time-of-flight secondary ion mass spectrometry depth profiling results reveal an oxy-carbide surface layer over an approximately 200 nm thick UC layer with little or no residual oxidation at the carbide layer/U metal transitional interface.

  14. Atmospheric Oxidation of Squalene: Molecular Study Using COBRA Modeling and High-Resolution Mass Spectrometry

    SciTech Connect

    Fooshee, David R.; Aiona, Paige K.; Laskin, Alexander; Laskin, Julia; Nizkorodov, Sergey; Baldi, Pierre

    2015-10-22

    Squalene is a major component of skin and plant surface lipids, and is known to be present at high concentrations in indoor dust. Its high reactivity toward ozone makes it an important ozone sink and a natural protectant against atmospheric oxidizing agents. While the volatile products of squalene ozonolysis are known, the condensed-phase products have not been characterized. We present an analysis of condensed-phase products resulting from an extensive oxidation of squalene by ozone probed by electrospray ionization (ESI) high-resolution mass spectrometry (HR-MS). A complex distribution of nearly 1,300 peaks assignable to molecular formulas is observed in direct infusion positive ion mode ESI mass spectra. The distribution of peaks in the mass spectra suggests that there are extensive cross-coupling reactions between hydroxy-carbonyl products of squalene ozonolysis. To get additional insights into the mechanism, we apply a Computational Brewing Application (COBRA) to simulate the oxidation of squalene in the presence of ozone, and compare predicted results with those observed by the HR-MS experiments. The system predicts over one billion molecular structures between 0-1450 Da, which correspond to about 27,000 distinct elemental formulas. Over 83% of the squalene oxidation products inferred from the mass spectrometry data are matched by the simulation. Simulation indicates a prevalence of peroxy groups, with hydroxyl and ether groups being the second-most important O-containing functional groups formed during squalene oxidation. These highly oxidized products of squalene ozonolysis may accumulate on indoor dust and surfaces, and contribute to their redox capacity.

  15. Atmospheric Oxidation of Squalene: Molecular Study Using COBRA Modeling and High-Resolution Mass Spectrometry.

    PubMed

    Fooshee, David R; Aiona, Paige K; Laskin, Alexander; Laskin, Julia; Nizkorodov, Sergey A; Baldi, Pierre F

    2015-11-17

    Squalene is a major component of skin and plant surface lipids and is known to be present at high concentrations in indoor dust. Its high reactivity toward ozone makes it an important ozone sink and a natural protectant against atmospheric oxidizing agents. While the volatile products of squalene ozonolysis are known, the condensed-phase products have not been characterized. We present an analysis of condensed-phase products resulting from an extensive oxidation of squalene by ozone probed by electrospray ionization (ESI) high-resolution mass spectrometry (HR-MS). A complex distribution of nearly 1300 peaks assignable to molecular formulas is observed in direct infusion positive ion mode ESI mass spectra. The distribution of peaks in the mass spectra suggests that there are extensive cross-coupling reactions between hydroxy-carbonyl products of squalene ozonolysis. To get additional insights into the mechanism, we apply a Computational Brewing Application (COBRA) to simulate the oxidation of squalene in the presence of ozone, and compare predicted results with those observed by the HR-MS experiments. The system predicts over one billion molecular structures between 0 and 1450 Da, which correspond to about 27 000 distinct elemental formulas. Over 83% of the squalene oxidation products inferred from the mass spectrometry data are matched by the simulation. The simulation indicates a prevalence of peroxy groups, with hydroxyl and ether groups being the second-most important O-containing functional groups formed during squalene oxidation. These highly oxidized products of squalene ozonolysis may accumulate on indoor dust and surfaces and contribute to their redox capacity.

  16. Faradaurate-940: Synthesis, Mass Spectrometry, STEM, PDF, and SAXS Study of Au~940(SR)~160 Nanocrystals

    SciTech Connect

    Kumara, Chanaka; Zuo, Xiaobing; Cullen, David A; Dass, Amala

    2014-01-01

    Obtaining monodisperse nanocrystals, and determining its composition to the atomic level and its atomic structure is highly desirable, but is generally lacking. Here, we report the discovery and comprehensive characterization of a 3-nm plasmonic nanocrystal with a composition of Au940 20(SCH2CH2Ph)160 4, which is, the largest mass spectrometrically characterized gold thiolate nanoparticle produced to date. The compositional assignment has been made using electrospray ionization (ESI) and matrix assisted laser desorption ionization (MALDI) mass spectrometry (MS). The MS results show an unprecedented size monodispersity, where the number of Au atoms vary by only 40 atoms (940 20). The mass spectrometrically-determined size and composition are supported by aberration-corrected scanning transmission electron microscopy (STEM) and synchrotron-based methods such as atomic pair distribution function (PDF) and small angle X-ray scattering (SAXS). Lower resolution STEM images show an ensemble of particles 1000 s per frame visually demonstrating monodispersity. Modelling of SAXS on statistically significant nanoparticle population approximately 1012 individual nanoparticles - shows that the diameter is 3.0 0.2nm, supporting mass spectrometry and electron microscopy results on monodispersity. Atomic PDF based on high energy X-ray diffraction experiments show decent match with either a Marks decahedral or truncated octrahedral structure. Atomic resolution STEM images of single particles and its FFT suggest face-centered cubic (fcc) arrangement. UV-visible spectroscopy data shows that the 940-atom size supports a surface plasmon resonance peak at 505 nm. These monodisperse plasmonic nanoparticles minimize averaging effects and has potential application in solar cells, nano-optical devices, catalysis and drug delivery.

  17. Study on the inclusion complexes of cyclodextrin and sulphonated azo dyes by electrospray ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Zhang, Huarong; Chen, Gang; Wang, Ling; Ding, Lan; Tian, Yuan; Jin, Weiqun; Zhang, Hanqi

    2006-05-01

    The inclusion complexes of [alpha]-, [beta]-cyclodextrin ([alpha]-, [beta]-CD) and sulphonated azo dyes ligands (Orange II, Ponceau SX, Allura red AC and Tartrazine) were studied by electrospray ionization mass spectrometry (ESI-MS) and the dissociation constants (KD) of the inclusion complexes were determined. A new method to obtain the dissociation constants of CD-ligand inclusion complexes without curve fitting was developed. Once the total concentrations of CD and ligand have been known, KD can be calculated from the sum peak intensities of free CD and inclusion complex and the number of binding site can be obtained from the mass spectrum. Ponceau SX, Allura red AC and Tartrazine binding to [alpha]-CD form 1:1 inclusion complexes with KD values of 1.33 × 10-5 mol L-1, 4.85 × 10-6 mol L-1 and 7.47 × 10-5 mol L-1, respectively. The obtained KD values of the inclusion complexes of above-mentioned three sulphonated azo dyes ligands binding to [beta]-CD in turn are 3.93 × 10-6 mol L-1, 6.50 × 10-6 mol L-1 and 1.12 × 10-4 mol L-1, respectively. The 1:1 and 1:2 inclusion complexes are found in the systems of CD and Orange II. KD,1 and KD,2 of [alpha]-CD and Orange II inclusion complexes are 4.05 × 10-4 mol L-1 and 4.60 × 10-7 (mol L-1)2, respectively. 3.94 × 10-5 mol L-1 and 1.72 × 10-7 (mol L-1)2 are the KD,1 and KD,2 of [beta]-CD and Orange II inclusion complexes, respectively. The competition experiments were performed to validate the results obtained by one ligand. According to the proposed method, the KD values of inclusion complexes regardless of any stoichiometric relation of host and guest can be obtained.

  18. A history of mass spectrometry in Australia.

    PubMed

    Downard, Kevin M; de Laeter, John R

    2005-09-01

    An interest in mass spectrometry in Australia can be traced back to the 1920s with an early correspondence with Francis Aston who first visited these shores a decade earlier. The region has a rich tradition in both the development of the field and its application, from early measurements of ionization and appearance potentials by Jim Morrison at the Council for Scientific and Industrial Research (CSIR) around 1950 to the design and construction of instrumentation including the first use of a triple quadrupole mass spectrometer for tandem mass spectrometry, the first suite of programs to simulate ion optics (SIMION), the development of early TOF/TOF instruments and orthogonal acceleration and the local design and construction of several generations of a sensitive high-resolution ion microprobe (SHRIMP) instrument. Mass spectrometry has been exploited in the study and characterization of the constituents of this nation's unique flora and fauna from Australian apples, honey, tea plant and eucalyptus oil, snake, spider, fish and frog venoms, coal, oil, sediments and shale, environmental studies of groundwater to geochronological dating of limestone and granite, other terrestrial and meteoritic rocks and coral from the Great Barrier Reef. Peter Jeffery's establishment of geochronological dating techniques in Western Australia in the early 1950s led to the establishment of geochronology research both at the Australian National University and at what is now the Curtin Institute of Technology in the 1960s. This article traces the history of mass spectrometry in its many guises and applications in the island continent of Australia. An article such as this can never be complete. It instead focuses on contributions of scientists who played a major role in the early establishment of mass spectrometry in Australia. In general, those who are presently active in the field, and whose histories are incomplete, have been mentioned at best only briefly despite their important

  19. Gas-phase intramolecular elimination reaction studies of steviol glycosides in positive electrospray and tandem mass spectrometry.

    PubMed

    Upreti, Mani; Clos, John F; Somayajula, Kasi V; Milanowski, Dennis J; Mocek, Ulla; Dubois, Grant E; Prakash, Indra

    2009-01-01

    This paper reports the first study of the gas-phase intramolecular elimination reaction of steviol glycosides in positive electrospray mass spectrometry. The observed glycosylated product ions are proposed to be formed via an intramolecular elimination of sugar units from the parent molecule ion. It was further proven by MS/MS studies and deuterium labeling experiments with one of the steviol glycosides, rebaudioside A. These mass spectrometric results confirmed that the new glycosylated product ions observed are most likely formed by the combination of glucose moieties (Glu) II-IV and Glu I via a gas-phase intramolecular elimination reaction.

  20. Liquid chromatography/tandem mass spectrometry study of forced degradation of azilsartan medoxomil potassium.

    PubMed

    Swain, Debasish; Patel, Prinesh N; Palaniappan, Ilayaraja; Sahu, Gayatri; Samanthula, Gananadhamu

    2015-08-15

    Azilsartan medoxomil potassium (AZM) is a new antihypertensive drug introduced in the year 2011. The presence of degradation products not only affects the quality, but also the safety aspects of the drug. Thus, it is essential to develop an efficient analytical method which could be useful to selectively separate and identify the degradation products of azilsartan medoxomil potassium. AZM was subjected to forced degradation under hydrolytic (acid, base and neutral), oxidative, photolytic and thermal stress conditions. Separation of the drug and degradation products was achieved by a liquid chromatography (LC) method using an Acquity UPLC(®) C18 CSH column with mobile phase consisting of 0.02% trifluoroacetic acid and acetonitrile using a gradient method. Identification and characterization of the degradation products was carried out using LC/electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOFMS). A total of five degradation products (DP 1 to DP 5) were formed under various stress conditions and their structures were proposed with the help of tandem mass spectrometry (MS/MS) experiments and accurate mass data. A common degradation product (DP 4) was observed under all the degradation conditions. DP 1, DP 2 and DP 5 were observed under acid hydrolytic conditions whereas DP 3 was observed under alkaline conditions. AZM was found to degrade under hydrolytic, oxidative and photolytic stress conditions. The structures of all the degradation products were proposed. The degradation pathway for the formation of degradation products was also hypothesized. A selective method was developed to quantify the drug in the presence of degradation products which is useful to monitor the quality of AZM. Copyright © 2015 John Wiley & Sons, Ltd.

  1. A safer method for studying hormone metabolism in an Asian elephant (Elephas maximus): accelerator mass spectrometry.

    PubMed

    Yon, Lisa; Faulkner, Brian; Kanchanapangka, Sumolya; Chaiyabutr, Narongsak; Meepan, Sompast; Lasley, Bill

    2010-01-01

    Noninvasive hormone assays provide a way to determine an animal's health or reproductive status without the need for physical or chemical restraint, both of which create unnecessary stress for the animal, and can potentially alter the hormones being measured. Because hormone metabolism is highly species-specific, each assay must be validated for use in the species of interest. Validation of noninvasive steroid hormone assays has traditionally required the administration of relatively high doses of radiolabelled compounds (100 µCi or more of (14)C labeled hormone) to permit subsequent detection of the excreted metabolites in the urine and feces. Accelerator mass spectrometry (AMS) is sensitive to extremely low levels of rare isotopes such as (14)C, and provides a way to validate hormone assays using much lower levels of radioactivity than those traditionally employed. A captive Asian bull elephant was given 1 µCi of (14)C-testosterone intravenously, and an opportunistic urine sample was collected 2 hr after the injection. The sample was separated by HPLC and the (14)C in the fractions was detected by AMS to characterize the metabolites present in the urine. A previously established HPLC protocol was used, which permitted the identification of fractions into which testosterone sulfate, testosterone glucuronide, and the parent compound testosterone elute. Results from this study indicate that the majority of testosterone excreted in the urine of the Asian bull elephant is in the form of testosterone sulfate. A small amount of testosterone glucuronide is also excreted, but there is no parent compound present in the urine at all. These results underscore the need for enzymatic hydrolysis to prepare urine samples for hormone assay measurement. Furthermore, they highlight the importance of proper hormone assay validation in order to ensure accurate measurement of the desired hormone. Although this study demonstrated the utility of AMS for safer validation of

  2. Application of accelerator mass spectrometry to macromolecules: preclinical pharmacokinetic studies on a polybisphosphonate.

    PubMed

    Salehpour, Mehran; Håkansson, Karl; Höglund, Urban; Grahn-Westin, Annika; Nilsson, Sten; Márquez, Marcela; Possnert, Göran; Holmberg, Anders R

    2011-09-15

    Data on the use of accelerator mass spectrometry (AMS) in conjunction with in vivo studies of macromolecular drugs are scarce. The present study shows the versatility of this technique when investigating the pharmacokinetics (PK) of a macromolecular drug candidate, a polybisphosphonate conjugate (ODX). The aforementioned is a polymer (molecular weight ~30 kDa) constituting a carbohydrate backbone with covalently linked ligands (aldendronate and aminoguanidine) and is intended for treatment of osteoporosis and the therapy of bone metastasis from prostate cancer. The conjugate is prepared through partial oxidation of the carbohydrate and sequential coupling of the ligands by reductive amination. (14)C was incorporated in the conjugate by means of coupling a commercially available (14)C-lysine in the conjugation sequence. Fifteen rats were injected intravenously with (14)C-labelled ODX (150 µg, 14 Bq/rat) and blood samples were collected at 1, 2, 4, 6, and 24 h post-injection (3 rats/time point). Liver, spleen and kidney samples were collected at 4 and 24 h post-injection. Blood from each time point (triplicate) were collected for AMS measurement determining the isotopic ratio ((14)C/(12)C) and consequently the drug concentration in blood. ODX showed a transient presence in blood circulation; 93% of the total dose was cleared from the circulation within 1 h. The half-life after 1 h was estimated to be about 3 h; 0.7% of the administered (14)C dose of ODX remained in circulation after 24 h. The major (14)C accumulation was in the liver, the spleen and the kidneys indicating the probable route of metabolism and excretion. This study demonstrates the versatility of AMS for pharmacological in vivo studies of macromolecules. Labelling with (14)C is relatively simple, inexpensive and the method requires minimal radioactivity, eliminating the need for radioprotection precautions in contrast to methods using scintillation counting. Copyright © 2011 John

  3. Isolation and Preparation of Extracellular Proteins from Lignocellulose Degrading Fungi for Comparative Proteomic Studies Using Mass Spectrometry.

    PubMed

    Gruninger, Robert J; Tsang, Adrian; McAllister, Tim A

    2017-01-01

    Fungi utilize a unique mechanism of nutrient acquisition involving extracellular digestion. To understand the biology of these microbes, it is important to identify and characterize the function of proteins that are secreted and involved in this process. Mass spectrometry-based proteomics is a powerful tool to study complex mixtures of proteins and understand how the proteins produced by an organism change in response to different conditions. Many fungi are efficient decomposers of plant cell wall, and anaerobic fungi are well recognized for their ability to digest lignocellulose. Here, we outline a protocol for the enrichment and isolation of proteins secreted by anaerobic fungi after growth on simple (glucose) and complex (straw and alfalfa hay) carbon sources. We provide detailed instruction on generating protein fragments and preparing these for proteomic analysis using reversed phase chromatography and mass spectrometry.

  4. Mass spectrometry in combinatorial chemistry.

    PubMed

    Enjalbal, C; Martinez, J; Aubagnac, J L

    2000-01-01

    In the fast expanding field of combinatorial chemistry, profiling libraries has always been a matter of concern--as illustrated by the buoyant literature over the past seven years. Spectroscopic methods, including especially mass spectrometry and to a lesser extent IR and NMR, have been applied at different levels of combinatorial library synthesis: in the rehearsal phase to optimize the chemistry prior to library generation, to confirm library composition, and to characterize after screening each structure that exhibits positive response. Most of the efforts have been concentrated on library composition assessment. The difficulties of such analyses have evolved from the infancy of the combinatorial concept, where large mixtures were prepared, to the recent parallel syntheses of collections of discrete compounds. Whereas the complexity of the analyses has diminished, an increased degree of automation was simultaneously required to achieve efficient library component identification and quantification. In this respect, mass spectrometry has been found to be the method of choice, providing rapid, sensitive, and informative analyses, especially when coupled to chromatographic separation. Fully automated workstations able to cope with several hundreds of compounds per day have been designed. After a brief introduction to describe the combinatorial approach, library characterization will be discussed in detail, considering first the solution-based methodologies and secondly the support-bound material analyses.

  5. Ultracentrifugation and inductively coupled plasma mass spectrometry for metal-protein equilibrium studies

    NASA Astrophysics Data System (ADS)

    Arnquist, Isaac J.; Holcombe, James A.

    2012-10-01

    The coupling of separation by preparative ultracentrifugation and metal detection by inductively coupled plasma mass spectrometry (ICP-MS) has been explored for metal-protein equilibrium determinations. This study characterizes the stoichiometry as well as apparent (Kapp) and intrinsic (Kint) binding affinities of the metal-protein association for a model protein. In particular, the affinity of Cu2 + for the high affinity binding site in bovine serum albumin (BSA) is determined. Once equilibrium is established between Cu2 + and BSA, preparative ultracentrifugation moves the metalloprotein away from the meniscus, leaving unbound equilibrium copper in the protein free solution. Since the initial (total) concentrations of purified BSA and Cu2 + can be determined, the free copper concentration at equilibrium can also be determined by taking a small aliquot above the sedimenting boundary for analysis using ICP-MS. This analysis allows for the determination of free Cu2 + ion, which is identical to the equilibrium concentration prior to ultracentrifugation. From these data Kapp and Kint were determined at two different conditions, 100 mM Tris(hydroxymethyl)aminomethane (Tris) at pH 9.53 and pH 7.93. log Kapp values of 17.6 and 14.6 were determined at pH 9.53 and pH 7.93, respectively. Furthermore, pH-independent log Kint values of - 1.43 and - 1.04 were determined at pH 9.53 and 7.93, respectively. While the log Kint at pH 9.53 was in good agreement with literature values obtained from alternative methods, Kint at pH 7.93 was about 2.5 × larger than previously reported. BSA undergoes a structural rearrangement between pH 7-9, and the generally accepted pH-dependency of protein tertiary structure may be responsible for the variations in the "intrinsic" binding constant. The Cu-BSA binding affinity was also monitored in 100 mM Tris 0.1% sodium dodecyl sulfate (SDS) solution at pH 7.93 in order to determine the effect of a denaturant on metal binding. Results for both log

  6. Study of the conversion products of dipin in hydrochloric acid and alkaline media by TLC and mass spectrometry

    SciTech Connect

    Chistyakov, V.V.; Anisimova, O.S.; Sheinker, Yu.N.; Safonova, T.S.

    1986-03-01

    In an investigation of the metabolism of the antitumor preparation dipin(tetraethylenimide of 1,4-diperazinediphosphoric acid) the authors studied its conversion in hydrochloric acid and in alkaline media. The mass spectra of the isolated compounds are given. The chromatographic separation of dipin conversion products is presented. A check on the composition of the solutions was done by mass spectrometry and TLC. Dipin in hydrochloric acid medium is subject to conversion with the formation of products of addition of HCl at the ethylenimine groups with formation of a beta-chloroethylamine group and also of products of hydrolysis at P-N bonds.

  7. [Study on the determination of 14 inorganic elements in coffee by inductively coupled plasma mass spectrometry].

    PubMed

    Nie, Xi-Du; Fu, Liang

    2013-07-01

    Samples of coffee were digested by microwave digestion, and inorganic elements amounts of Na, Mg, P, Ca, Cr, Mn, Fe, Co, Cu, Zn, As, Se, Mo and Pb in sample solutions were determined by inductively coupled plasma mass spectrometry (ICP-MS). HNO3 + H2O2 was used to achieve the complete decomposition of the organic matrix in a closed-vessel microwave oven. The working parameters of the instrument were optimized. The results showed that the relative standard deviation (RSD) was less than 3.84% for all the elements, and the recovery was found to be 92.00% -106.52% by adding standard recovery experiment. This method was simple, sensitive and precise and can perform simultaneous multi-elements determination of coffee, which could satisfy the sample examination request and provide scientific rationale for determining inorganic elements of coffee.

  8. Molecular beam mass spectrometry studies of the thermal decomposition of tetraethoxysilane (TEOS)

    SciTech Connect

    Wierda, C.A.; Zachariah, M.R.; Burgess, D.R.F. Jr.

    1995-03-01

    Molecular beam mass spectrometry and time-of-flight techniques have been used to reveal the gas phase chemistry that occurs during the thermal decomposition of TEOS. Evidence in the authors` laboratory was consistent with the presence of the following species during decomposition at 600{degrees}C: ethylene, ethanol, acetaldehyde, possibly diethoxysilanone, triethoxysilanol, hexaethoxysiloxane. A grayish white powder, which presumably consists of silicon oxides containing residual carbon and hydrogen, was also produced. Under the following reaction conditions: reactor pressure=266 Pa (2 torr), residence time=6 ms, and TEOS partial pressure=26 Pa (0.2 torr), the onset of decomposition occurs at 400{degrees}C. The amount of TEOS decreases at residence times greater than 6 ms with concurrent increase in ethanol and ethylene. Hexaethoxysiloxane also increases at residence times between 6 and 20 ms, but then decreases at longer times probably because it reacts to form larger siloxanes and silicon oxides.

  9. Ultra-trace analysis of 36Cl by accelerator mass spectrometry: an interlaboratory study.

    PubMed

    Merchel, S; Bremser, W; Alfimov, V; Arnold, M; Aumaître, G; Benedetti, L; Bourlès, D L; Caffee, M; Fifield, L K; Finkel, R C; Freeman, S P H T; Martschini, M; Matsushi, Y; Rood, D H; Sasa, K; Steier, P; Takahashi, T; Tamari, M; Tims, S G; Tosaki, Y; Wilcken, K M; Xu, S

    2011-07-01

    A first international (36)Cl interlaboratory comparison has been initiated. Evaluation of the final results of the eight participating accelerator mass spectrometry (AMS) laboratories on three synthetic AgCl samples with (36)Cl/Cl ratios at the 10(-11), 10(-12), and 10(-13) level shows no difference in the sense of simple statistical significance. However, more detailed statistical analyses demonstrate certain interlaboratory bias and underestimation of uncertainties by some laboratories. Following subsequent remeasurement and reanalysis of the data from some AMS facilities, the round-robin data indicate that (36)Cl/Cl data from two individual AMS laboratories can differ by up to 17%. Thus, the demand for further work on harmonising the (36)Cl-system on a worldwide scale and enlarging the improvement of measurements is obvious.

  10. [Study on the determination of trace elements in bitter almond by inductively coupled plasma mass spectrometry].

    PubMed

    Liu, Hong-Wei; Xie, Hua-Lin; Nie, Xi-Du

    2013-05-01

    Samples of bitter almond were digested by microwave digestion, and trace elements amounts of B, Na, Mg, Al, P, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Mo, Cd, Ba and Pb in sample solutions were determined by inductively coupled plasma mass spectrometry (ICP-MS). HNO3 + H2O2 was used to achieve the complete decomposition of the organic matrix in a closed-vessel microwave oven. The working parameters of the instrument were optimized. The result showed that the relative standard deviation (RSD) was less than 4.79% for all the elements, and the recovery was 90.00%-109.30% by adding standard recovery experiment. This method was simple, sensitive and precise and can perform simultaneo multi-elements determination for bitter almond, which could satisfy the sample examination request and provide scientific rationale for determining inorganic elements in bitter almond.

  11. A chemical precursor to optical damage. Studies by laser ionization mass spectrometry

    SciTech Connect

    Nogar, N.S.; Estler, R.C.

    1987-01-01

    Mass spectrometry has been used in conjunction with Nomarski microscopy to characterize the initiation of optical damage in selected commercial optics. For a sample with an Al/sub 2/O/sub 3//SiO/sub 2/ multilayer coating (351 nm) on a Si substrate, our results suggest layer by layer removal of the coating material with low-fluence irradiation at 1.06 mu. In addition, carbon impurities were observed in the low-damage threshold sample. For the Sc/sub 2/O/sub 3//SiO/sub 2/ multilayer coated (351 nm) 7940 substrates, transient iron signals were observed at each increasing fluence level, with concomitant appearance of small circular (10 mu) pits in the surface. These pits were also associated with macroscopic damage features due to threshold testing.

  12. Advances in high-resolution mass spectrometry based on metabolomics studies for food--a review.

    PubMed

    Rubert, Josep; Zachariasova, Milena; Hajslova, Jana

    2015-01-01

    Food authenticity becomes a necessity for global food policies, since food placed in the market without fail has to be authentic. It has always been a challenge, since in the past minor components, called also markers, have been mainly monitored by chromatographic methods in order to authenticate the food. Nevertheless, nowadays, advanced analytical methods have allowed food fingerprints to be achieved. At the same time they have been also combined with chemometrics, which uses statistical methods in order to verify food and to provide maximum information by analysing chemical data. These sophisticated methods based on different separation techniques or stand alone have been recently coupled to high-resolution mass spectrometry (HRMS) in order to verify the authenticity of food. The new generation of HRMS detectors have experienced significant advances in resolving power, sensitivity, robustness, extended dynamic range, easier mass calibration and tandem mass capabilities, making HRMS more attractive and useful to the food metabolomics community, therefore becoming a reliable tool for food authenticity. The purpose of this review is to summarise and describe the most recent metabolomics approaches in the area of food metabolomics, and to discuss the strengths and drawbacks of the HRMS analytical platforms combined with chemometrics.

  13. Study of fluorocarbon plasma in 60 and 100 MHz capacitively coupled discharges using mass spectrometry

    SciTech Connect

    Ushakov, Andrey; Volynets, Vladimir; Jeong, Sangmin; Sung, Dougyong; Ihm, Yongho; Woo, Jehun; Han, Moonhyeong

    2008-09-15

    The signals of positive ions and radicals formed in the fluorocarbon plasma of the capacitively coupled plasma reactor were measured using a quadrupole mass spectrometry and optical emission actinometry. The plasma was produced at 60 and 100 MHz frequencies for the same reactor configuration and gas mixtures. Experiments were performed at 25 mTorr with a SiO{sub 2} wafer on the grounded electrode. Mass spectra of ions were measured in C{sub 4}F{sub 8}/O{sub 2}/Ar and C{sub 4}F{sub 6}/O{sub 2}/Ar gas mixtures at 500-1500 W generator powers. For 60 and 100 MHz discharges production of fluorocarbon ions and radicals is discussed. It was found that the production of heavy species increases with frequency. The high mass signals such as C{sub 3}F{sub 3}{sup +}, C{sub 2}F{sub 4}{sup +}, C{sub 2}F{sub 5}{sup +}, C{sub 3}F{sub 5}{sup +}, C{sub 4}F{sub 7}{sup +} decrease when CHF{sub 3} is added to the gas mixture. However, the signals of CF{sub x}{sup +} (x=1,2,3) do not change significantly. These results are compared to the results of polymer film deposition on the wafer. It was suggested to control the polymerization film formation by adding small amount of CHF{sub 3} to the process mixture.

  14. Interlaboratory study of the ion source memory effect in 36Cl accelerator mass spectrometry

    NASA Astrophysics Data System (ADS)

    Pavetich, Stefan; Akhmadaliev, Shavkat; Arnold, Maurice; Aumaître, Georges; Bourlès, Didier; Buchriegler, Josef; Golser, Robin; Keddadouche, Karim; Martschini, Martin; Merchel, Silke; Rugel, Georg; Steier, Peter

    2014-06-01

    Understanding and minimization of contaminations in the ion source due to cross-contamination and long-term memory effect is one of the key issues for accurate accelerator mass spectrometry (AMS) measurements of volatile elements. The focus of this work is on the investigation of the long-term memory effect for the volatile element chlorine, and the minimization of this effect in the ion source of the Dresden accelerator mass spectrometry facility (DREAMS). For this purpose, one of the two original HVE ion sources at the DREAMS facility was modified, allowing the use of larger sample holders having individual target apertures. Additionally, a more open geometry was used to improve the vacuum level. To evaluate this improvement in comparison to other up-to-date ion sources, an interlaboratory comparison had been initiated. The long-term memory effect of the four Cs sputter ion sources at DREAMS (two sources: original and modified), ASTER (Accélérateur pour les Sciences de la Terre, Environnement, Risques) and VERA (Vienna Environmental Research Accelerator) had been investigated by measuring samples of natural 35Cl/37Cl-ratio and samples highly-enriched in 35Cl (35Cl/37Cl ∼ 999). Besides investigating and comparing the individual levels of long-term memory, recovery time constants could be calculated. The tests show that all four sources suffer from long-term memory, but the modified DREAMS ion source showed the lowest level of contamination. The recovery times of the four ion sources were widely spread between 61 and 1390 s, where the modified DREAMS ion source with values between 156 and 262 s showed the fastest recovery in 80% of the measurements.

  15. Quantitative mass spectrometry: an overview

    PubMed Central

    2016-01-01

    Mass spectrometry (MS) is a mainstream chemical analysis technique in the twenty-first century. It has contributed to numerous discoveries in chemistry, physics and biochemistry. Hundreds of research laboratories scattered all over the world use MS every day to investigate fundamental phenomena on the molecular level. MS is also widely used by industry—especially in drug discovery, quality control and food safety protocols. In some cases, mass spectrometers are indispensable and irreplaceable by any other metrological tools. The uniqueness of MS is due to the fact that it enables direct identification of molecules based on the mass-to-charge ratios as well as fragmentation patterns. Thus, for several decades now, MS has been used in qualitative chemical analysis. To address the pressing need for quantitative molecular measurements, a number of laboratories focused on technological and methodological improvements that could render MS a fully quantitative metrological platform. In this theme issue, the experts working for some of those laboratories share their knowledge and enthusiasm about quantitative MS. I hope this theme issue will benefit readers, and foster fundamental and applied research based on quantitative MS measurements. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644965

  16. Evolution of Instrumentation for the Study of Gas-Phase Ion/Ion Chemistry via Mass Spectrometry

    PubMed Central

    Xia, Yu; McLuckey, Scott A.

    2008-01-01

    The scope of gas phase ion/ion chemistry accessible to mass spectrometry is largely defined by the available tools. Due to the development of novel instrumentation, a wide range of reaction phenomenologies have been noted, many of which have been studied extensively and exploited for analytical applications. This perspective presents the development of mass spectrometry-based instrumentation for the study of the gas phase ion/ion chemistry in which at least one of the reactants is multiply-charged. The instrument evolution is presented within the context of three essential elements required for any ion/ion reaction study: the ionization source(s), the reaction vessel or environment, and the mass analyzer. Ionization source arrangements have included source combinations that allow for reactions between multiply charged ions of one polarity and singly charged ions of opposite polarity, arrangements that enable the study of reactions of multiply charged ions of opposite polarity, and most recently, arrangements that allow for ion formation from more than two ion sources. Gas phase ion/ion reaction studies have been performed at near atmospheric pressure in flow reactor designs and within electrodynamic ion traps operated in the mTorr range. With ion trap as a reaction vessel, ionization and reaction processes can be independently optimized and ion/ion reactions can be implemented within the context of MSn experiments. Spatial separation of the reaction vessel from the mass analyzer allows for the use of any form of mass analysis in conjunction with ion/ion reactions. Time-of-flight mass analysis, for example, has provided significant improvements in mass analysis figures of merit relative to mass filters and ion traps. PMID:18083527

  17. Metabolomic study in plasma, liver and kidney of mice exposed to inorganic arsenic based on mass spectrometry.

    PubMed

    García-Sevillano, M A; Contreras-Acuña, M; García-Barrera, T; Navarro, F; Gómez-Ariza, J L

    2014-02-01

    The mechanism of arsenic toxicity still remains unclear, although enzymatic inhibition, impaired antioxidants metabolism and oxidative stress may play a role. The toxicological effects of trivalent inorganic arsenic on laboratory mouse Mus musculus after oral administration (3 mg/kg body weight/day) were investigated along 12 days, using a metabolomic approach based on direct infusion mass spectrometry to polar and lipophilic extracts from different organs and fluids (liver, kidney, and plasma). Positive and negative acquisition modes (ESI(+)/ESI(-)) were used throughout the experiments. The most significant endogenous metabolites affected by exposure were traced by partial least square-discriminant analysis and confirmed by tandem mass spectrometry (MS/MS) and gas chromatography coupled to MS. In this work, the toxic effect of arsenic has been related with important metabolic pathways, such as energy metabolism (e.g., glycolysis, Krebs cycle), amino acids metabolism, choline metabolism, methionine cycle, and degradation of membrane phospholipids (cell apoptosis). In addition, this work illustrates the high reliability of mass spectrometry based on a metabolomic approach to study the biochemical effects induced by metal exposure.

  18. A competitive binding study of chemokine, sulfated receptor, and glycosaminoglycan interactions by nano-electrospray ionization mass spectrometry

    PubMed Central

    Jen, Connie H.; Leary, Julie A.

    2010-01-01

    Chemokines are secreted proteins that play roles in inducing chemotaxis, extravasation, and activation of leukocytes associated with inflammatory or homeostatic processes. Tyrosine sulfation of the chemokine receptor has been shown to be important for binding and signaling. We have applied a mass spectrometry method to measure the contribution of this posttranslational modification to binding of its ligand chemokine. Using Nano-electrospray time-of-flight mass spectrometry, we determined the association constant of chemokine, CCL7 with CCR2, monosulfated CCR2, and disulfated CCR2 peptides to be 1.1 × 104 M−1, 3.9 × 104 M−1, and 4.0 × 105 M−1, respectively. To our knowledge, this is the first reported association constant measurement between a protein and sulfated peptide using mass spectrometry. Furthermore, nano-ESI MS was used to characterize noncovalent binding interactions between CCL7, Arixtra (a pentasaccharide GAG analog) and disulfated CCR2 peptide. A lack of observable ternary complex formation prompted investigation of competitive binding. Results in this study suggest that CCR2 competes partially with GAG for CCL7 binding and that disulfated CCR2 peptide has a higher binding affinity than Arixtra, which correlates with data from association constant measurements for CCL7-disulfated CCR2 and CCL7-Arixtra. PMID:20696123

  19. Initial results of positron ionization mass spectrometry

    NASA Technical Reports Server (NTRS)

    Donohue, D. L.; Hulett, L. D., Jr.; Mcluckey, S. A.; Glish, G. L.; Eckenrode, B. A.

    1990-01-01

    The use of monoenergetic positrons for the ionization of organic molecules in the gas phase is described. The ionic products are analyzed with a time-of-flight mass spectrometer and detected to produce a mass spectrum. The ionization mechanisms which can be studied in this way include positron impact at energies above the ionization limit of the target molecules, positronium formation in the Ore gap energy range, and positron attachment at energies less than 1eV. The technique of positron ionization mass spectrometry (PIMS) may have analytical utility in that chemical selectivity is observed for one or more of these processes.

  20. Application of mass spectrometry for metabolite identification.

    PubMed

    Ma, Shuguang; Chowdhury, Swapan K; Alton, Kevin B

    2006-06-01

    Metabolism studies play a pivotal role in drug discovery and development. Characterization of metabolic "hot-spots" as well as reactive and pharmacologically active metabolites is critical to designing new drug candidates with improved metabolic stability, toxicological profile and efficacy. Metabolite identification in the preclinical species used for safety evaluation is required in order to determine whether human metabolites have been adequately tested during non-clinical safety assessment. From an instrumental standpoint, high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) dominates all analytical tools used for metabolite identification. The general strategies employed for metabolite identification in both drug discovery and drug development settings together with sample preparation techniques are reviewed herein. These include a discussion of the various ionization methods, mass analyzers, and tandem mass spectrometry (MS/MS) techniques that are used for structural characterization in a modern drug metabolism laboratory. Mass spectrometry-based techniques, such as stable isotope labeling, on-line H/D exchange, accurate mass measurement to enhance metabolite identification and recent improvements in data acquisition and processing for accelerating metabolite identification are also described. Rounding out this review, we offer additional thoughts about the potential of alternative and less frequently used techniques such as LC-NMR/MS, CRIMS and ICPMS.

  1. Dissecting the ubiquitin pathway by mass spectrometry

    PubMed Central

    Xu, Ping; Peng, Junmin

    2007-01-01

    Summary Protein modification by ubiquitin is a central regulatory mechanism in eukaryotic cells. Recent proteomics developments in mass spectrometry enable systematic analysis of cellular components in the ubiquitin pathway. Here, we review the advances in analyzing ubiquitinated substrates, determining modified lysine residues, quantifying polyubiquitin chain topologies, as well as profiling deubiquitinating enzymes based on the activity. Moreover, proteomic approaches have been developed for probing the interactome of proteasome and for identifying proteins with ubiquitin-binding domains. Similar strategies have been applied on the studies of the modification by ubiquitin-like proteins as well. These strategies are discussed with respect to their advantages, limitations and potential improvements. While the utilization of current methodologies has rapidly expanded the scope of protein modification by the ubiquitin family, a more active role is anticipated in the functional studies with the emerging of quantitative mass spectrometry. PMID:17055348

  2. Counting Molecules by Desorption Ionization and Mass Spectrometry/Mass Spectrometry.

    ERIC Educational Resources Information Center

    Cooks, R. G.; Busch, K. L.

    1982-01-01

    Discusses two newer methods in mass spectrometry and shows how they can increase signal and signal-to-noise ratios, respectively. The first method, desorption ionization (DI), increases sensitivity while the second method, mass spectrometry/mass spectrometry (MS/MS), increases specificity. Together, the two methods offer improved analytical…

  3. Nuclear applications of inorganic mass spectrometry.

    PubMed

    De Laeter, John

    2010-01-01

    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

  4. Study of the release of gallic acid from (-)-epigallocatechin gallate in old oolong tea by mass spectrometry.

    PubMed

    Lee, Ren-Jye; Lee, Viola S Y; Tzen, Jason T C; Lee, Maw-Rong

    2010-04-15

    Liquid chromatography combined with multiple-stage mass spectrometry (LC/MS(n)) was used to study the pathway of the release of gallic acid (GA) from epigallocatechin gallate (EGCG) in infusion of old oolong tea. The possibility of releasing GA from EGCG in old tea preparations was supported by an in vitro observation of GA degraded from EGCG under heating conditions mimicking the drying process. Negative electrospray ionization with the data-dependent mode of MS(n) was used to study the formation pathway of GA in old oolong tea. The MS(n) data show that GA was released from the dimer of EGCG, not directly degraded from EGCG.

  5. Selective detection of isomers with photoionization mass spectrometry for studies of hydrocarbon flame chemistry

    NASA Astrophysics Data System (ADS)

    Cool, Terrill A.; Nakajima, Koichi; Mostefaoui, Toufik A.; Qi, Fei; McIlroy, Andrew; Westmoreland, Phillip R.; Law, Matthew E.; Poisson, Lionel; Peterka, Darcy S.; Ahmed, Musahid

    2003-10-01

    We report the first use of synchrotron radiation, continuously tunable from 8 to 15 eV, for flame-sampling photoionization mass spectrometry (PIMS). Synchrotron radiation offers important advantages over the use of pulsed vacuum ultraviolet lasers for PIMS; these include superior signal-to-noise, soft ionization, and access to photon energies outside the limited tuning ranges of current VUV laser sources. Near-threshold photoionization efficiency measurements were used to determine the absolute concentrations of the allene and propyne isomers of C3H4 in low-pressure laminar ethylene-oxygen and benzene-oxygen flames. Similar measurements of the isomeric composition of C2H4O species in a fuel-rich ethylene-oxygen flame revealed the presence of substantial concentrations of ethenol (vinyl alcohol) and acetaldehyde. Ethenol has not been previously detected in hydrocarbon flames. Absolute photoionization cross sections were measured for ethylene, allene, propyne, and acetaldehyde, using propene as a calibration standard. PIE curves are presented for several additional reaction intermediates prominent in hydrocarbon flames.

  6. Advances in mass spectrometry based strategies to study receptor tyrosine kinases.

    PubMed

    Vyse, Simon; Desmond, Howard; Huang, Paul H

    2017-03-01

    Receptor tyrosine kinases (RTKs) are key transmembrane environmental sensors that are capable of transmitting extracellular information into phenotypic responses, including cell proliferation, survival and metabolism. Advances in mass spectrometry (MS)-based phosphoproteomics have been instrumental in providing the foundations of much of our current understanding of RTK signalling networks and activation dynamics. Furthermore, new insights relating to the deregulation of RTKs in disease, for instance receptor co-activation and kinome reprogramming, have largely been identified using phosphoproteomic-based strategies. This review outlines the current approaches employed in phosphoproteomic workflows, including phosphopeptide enrichment and MS data-acquisition methods. Here, recent advances in the application of MS-based phosphoproteomics to bridge critical gaps in our knowledge of RTK signalling are focused on. The current limitations of the technology are discussed and emerging areas such as computational modelling, high-throughput phospho-proteomic workflows and next-generation single-cell approaches to further our understanding in new areas of RTK biology are highlighted.

  7. Advances in mass spectrometry based strategies to study receptor tyrosine kinases

    PubMed Central

    Vyse, Simon; Desmond, Howard; Huang, Paul H.

    2017-01-01

    Receptor tyrosine kinases (RTKs) are key transmembrane environmental sensors that are capable of transmitting extracellular information into phenotypic responses, including cell proliferation, survival and metabolism. Advances in mass spectrometry (MS)-based phosphoproteomics have been instrumental in providing the foundations of much of our current understanding of RTK signalling networks and activation dynamics. Furthermore, new insights relating to the deregulation of RTKs in disease, for instance receptor co-activation and kinome reprogramming, have largely been identified using phosphoproteomic-based strategies. This review outlines the current approaches employed in phosphoproteomic workflows, including phosphopeptide enrichment and MS data-acquisition methods. Here, recent advances in the application of MS-based phosphoproteomics to bridge critical gaps in our knowledge of RTK signalling are focused on. The current limitations of the technology are discussed and emerging areas such as computational modelling, high-throughput phospho­proteomic workflows and next-generation single-cell approaches to further our understanding in new areas of RTK biology are highlighted. PMID:28250950

  8. Mechanistic study of maleic anhydride grafting onto fatty double bonds using mass spectrometry.

    PubMed

    Loutelier-Bourhis, Corinne; Zovi, Ornella; Lecamp, Laurence; Bunel, Claude; Hubert-Roux, Marie; Lange, Catherine M

    2012-06-15

    The grafting of maleic anhydride onto fatty C=C double bonds is a well-known and used method to functionalize triglyceride molecules. Nevertheless, grafted products are not actually structurally well defined. In this work, the thermal grafting of maleic anhydride onto (un)saturated fatty acid esters without the use of an initiator was characterized in order to determine the nature of the products formed during this reaction. Complementary spectrometric techniques, ESI-MS(n) (ion-trap mass spectrometer), IMS-MS(n) (Q-IMS-TOFMS) and GC/MS, were used to identify the grafted products which were prepared using either ethyl oleate (EtO) or methyl linoleate (MeL) as model molecules and maleic anhydride (MA). Lithiated adducts were investigated since they yield useful structural information when subjected to collision-induced dissociation (CID) in tandem mass spectrometry. A high number of products are formed during MA grafting and various reaction types could occur. Radical addition of maleic anhydride followed by combination or elimination reactions led to succinic and maleic anhydride grafting, respectively. The addition occurred with or without double-bond shift; the resulting derivatives showed succinic and maleic anhydride branching in the α-position relative to the double bond or onto the carbon atom of the initial double bond. Some structures obtained by radical addition and combination were also consistent with the Alder ene functionalization reaction. The Diels-Alder addition between di-unsaturated fatty acid chains and maleic anhydride could yield cyclic forms of MA-grafted derivatives. We have shown that ESI-MS(n) and IMS-MS(n) allow the identification of grafted products providing relevant structural information concerning isomers. These methods permit the rapid and direct analyses of 'crude reaction mixtures'. Copyright © 2012 John Wiley & Sons, Ltd.

  9. Photoionization and Dissociative Photoionization Study of Cholesterol by IR Laser Desorption/Tunable Synchrotron VUV Photoionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Pan, Yang; Zhang, Li-dong; Guo, Hui-jun; Yin, Hao; Qi, Fei

    2009-04-01

    Elementary cholesterol was analyzed with IR laser desorption/tunable synchrotron vacuum ultraviolet photoionization mass spectrometry. An exclusive molecular ion of cholesterol is observed by near threshold single-photon ionization with high efficiency. Fragments are yielded with the increase of photon energy. The structures of various fragments are determined with commercial electron ionization time-of-flight mass spectrometry. Dominant fragmentation pathways are discussed in detail with the aid of ab initio calculations.

  10. Advances in imaging secondary ion mass spectrometry for biological samples

    SciTech Connect

    Boxer, Steven G.; Kraft, Mary L.; Weber, Peter K.

    2008-12-16

    Imaging mass spectrometry combines the power of mass spectrometry to identify complex molecules based on mass with sample imaging. Recent advances in secondary ion mass spectrometry have improved sensitivity and spatial resolution, so that these methods have the potential to bridge between high-resolution structures obtained by X-ray crystallography and cyro-electron microscopy and ultrastructure visualized by conventional light microscopy. Following background information on the method and instrumentation, we address the key issue of sample preparation. Because mass spectrometry is performed in high vacuum, it is essential to preserve the lateral organization of the sample while removing bulk water, and this has been a major barrier for applications to biological systems. Furthermore, recent applications of imaging mass spectrometry to cell biology, microbial communities, and biosynthetic pathways are summarized briefly, and studies of biological membrane organization are described in greater depth.

  11. Advances in imaging secondary ion mass spectrometry for biological samples

    DOE PAGES

    Boxer, Steven G.; Kraft, Mary L.; Weber, Peter K.

    2008-12-16

    Imaging mass spectrometry combines the power of mass spectrometry to identify complex molecules based on mass with sample imaging. Recent advances in secondary ion mass spectrometry have improved sensitivity and spatial resolution, so that these methods have the potential to bridge between high-resolution structures obtained by X-ray crystallography and cyro-electron microscopy and ultrastructure visualized by conventional light microscopy. Following background information on the method and instrumentation, we address the key issue of sample preparation. Because mass spectrometry is performed in high vacuum, it is essential to preserve the lateral organization of the sample while removing bulk water, and this hasmore » been a major barrier for applications to biological systems. Furthermore, recent applications of imaging mass spectrometry to cell biology, microbial communities, and biosynthetic pathways are summarized briefly, and studies of biological membrane organization are described in greater depth.« less

  12. Inorganic trace analysis by mass spectrometry

    NASA Astrophysics Data System (ADS)

    Becker, Johanna Sabine; Dietze, Hans-Joachim

    1998-10-01

    Mass spectrometric methods for the trace analysis of inorganic materials with their ability to provide a very sensitive multielemental analysis have been established for the determination of trace and ultratrace elements in high-purity materials (metals, semiconductors and insulators), in different technical samples (e.g. alloys, pure chemicals, ceramics, thin films, ion-implanted semiconductors), in environmental samples (waters, soils, biological and medical materials) and geological samples. Whereas such techniques as spark source mass spectrometry (SSMS), laser ionization mass spectrometry (LIMS), laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), glow discharge mass spectrometry (GDMS), secondary ion mass spectrometry (SIMS) and inductively coupled plasma mass spectrometry (ICP-MS) have multielemental capability, other methods such as thermal ionization mass spectrometry (TIMS), accelerator mass spectrometry (AMS) and resonance ionization mass spectrometry (RIMS) have been used for sensitive mono- or oligoelemental ultratrace analysis (and precise determination of isotopic ratios) in solid samples. The limits of detection for chemical elements using these mass spectrometric techniques are in the low ng g -1 concentration range. The quantification of the analytical results of mass spectrometric methods is sometimes difficult due to a lack of matrix-fitted multielement standard reference materials (SRMs) for many solid samples. Therefore, owing to the simple quantification procedure of the aqueous solution, inductively coupled plasma mass spectrometry (ICP-MS) is being increasingly used for the characterization of solid samples after sample dissolution. ICP-MS is often combined with special sample introduction equipment (e.g. flow injection, hydride generation, high performance liquid chromatography (HPLC) or electrothermal vaporization) or an off-line matrix separation and enrichment of trace impurities (especially for characterization of

  13. Kinetics and product studies of the reaction ClO + BrO using discharge-flow mass spectrometry

    NASA Technical Reports Server (NTRS)

    Friedl, Randall R.; Sander, Stanley P.

    1989-01-01

    The kinetics and product branching ratios of the reaction between ClO and BrO were studied at 1 torr pressure over the temperature range 220-400 K, using the method of discharge-flow mass spectrometry. Three product channels were identified and quantified: Br + ClOO, Br + OClO, and BrCl + O2, indicating that the reaction mechanism of ClO + BrO involves metastable intermediates. The overall reaction rate coefficient and the rate coefficients for the three channel reactions are given.

  14. Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry.

    PubMed

    Ueland, Per Magne; Midttun, Oivind; Windelberg, Amrei; Svardal, Asbjørn; Skålevik, Rita; Hustad, Steinar

    2007-01-01

    Derangements of one-carbon metabolism have been related to the development of chronic diseases. Metabolic profiling as part of epidemiological studies in this area should include intermediates involved in the transfer of one-carbon units, cofactors for the relevant enzymes and markers of inflammation, kidney function and smoking. We established five platforms that measured 6-16 analytes each. Platforms A (gas chromatography-mass spectrometry; GC-MS) and B (gas chromatography-tandem mass spectrometry; GC-MS/MS) involved methylchloroformate derivatization of primary amines, thiols and carboxylic acids. Platform C determined basic compounds by liquid chromatography-tandem mass spectrometry (LC-MS/MS), using an ether-linked phenyl reversed-phase column. Platforms D and E (LC-MS/MS) exploited the efficient ionization and high sensitivity obtained for a wide range of analytes, using a mobile phase containing a high concentration of acetic acid. The chromatographic run times ranged from 3 to 8 min. The analyte concentrations ranged from 0.2 nmol/L to 400 micromol/L. Platforms A and B both measured methylmalonic acid, total homocysteine and related amino acids. Platform B also included sarcosine, cystathionine, tryptophan and kynurenine. Platform C was optimized for the measurement of choline and betaine, but also included arginine, asymmetric and symmetric dimethylarginine and creatinine. A diversity of low abundance compounds mainly occurring in the nanomolar range were measured on platform D. These were vitamin B(2) and B(6) species, neopterin, cotinine and tryptophan metabolites. Platform E measured folates and folate catabolites. Approximately 40 analytes related to one-carbon metabolism were determined in less than 1 mL of plasma/serum using five complementary analytical platforms. As a method control, several metabolites were measured on two or more platforms. Logistics and data handling were carried out by specially designed software. This strategy allows profiling

  15. Characterization of microbial siderophores by mass spectrometry.

    PubMed

    Pluháček, Tomáš; Lemr, Karel; Ghosh, Dipankar; Milde, David; Novák, Jiří; Havlíček, Vladimír

    2016-01-01

    Siderophores play important roles in microbial iron piracy, and are applied as infectious disease biomarkers and novel pharmaceutical drugs. Inductively coupled plasma and molecular mass spectrometry (ICP-MS) combined with high resolution separations allow characterization of siderophores in complex samples taking advantages of mass defect data filtering, tandem mass spectrometry, and iron-containing compound quantitation. The enrichment approaches used in siderophore analysis and current ICP-MS technologies are reviewed. The recent tools for fast dereplication of secondary metabolites and their databases are reported. This review on siderophores is concluded with their recent medical, biochemical, geochemical, and agricultural applications in mass spectrometry context.

  16. Surface ionization mass spectrometry of drugs in the thermal and hyperthermal energy range -- a comparative study

    NASA Astrophysics Data System (ADS)

    Dagan, Shai; Amirav, Aviv; Fujü, Toshihiro

    1995-12-01

    Thermal and hyperthermal surface ionization (SI) mass spectra of nicotine, caffeine and lidocaine were obtained using a rhenium oxide surface. Thermal surface ionization was studied on an oxidized surface positioned inside an electron impact ion source, while hyperthermal surface ionization (HSI) was obtained upon seeding the compounds into a hydrogen or helium supersonic molecular beam that scattered from the rhenium oxide surface. Both HSI and SI provide rich, informative and complementary mass spectral information. The results indicate that SI follows thermal dissociation processes on the surface prior to the desorption of the ion, while in HSI no thermal equilibrium is established and the ionization process is impulsive, followed by mostly unimolecular ion dissociation. HSI mass spectra are similar to electron impact mass spectra in the fragment ion masses, but the observed relative intensities are different. HSI is a softer ionization method compared to SI, and enables the degree of ion fragmentation to be tuned so that it can be minimized to a low level at low molecular kinetic energy. In SI, limited control over the degree of fragmentation is possible through the surface temperature. The analytical mass spectrometric applications of SI and HSI are briefly mentioned.

  17. Mass Spectrometry of Proteins in Liquids

    NASA Astrophysics Data System (ADS)

    Baltz-Knorr, Michelle; Papantonakis, Michael; Ermer Haglund, David, Jr.

    1999-11-01

    Infrared matrix assisted laser desorption/ionization mass spectrometry (IR-MALDI) is an effective technique for mass identification and structural analysis of biomolecules. We are using liquid glycerol/water matrices in a reflectron time-of-flight mass spectrometer equipped with a liquid nitrogen cooled sample stage to provide a more natural environment for biomolecules. An Er:YAG laser (2.94 μm) and also a tunable free electron laser (2-9 μm) are used to induce desorption and ionization by exciting the O-H and CH2 stretching vibrations in the glycerol. This vibrationally enhanced ionization makes IR-MALDI very efficient, as observed in the mass spectra of small peptides. This work is a first step toward using mass spectrometry to study noncovalently bound protein complexes in vitro and to study proteins in their cellular environment. Supported by the Medical Free Electron Laser Program of the Office of Naval Research and the Vanderbilt Molecular Biophysics Training Grant of the National Institutes of Health

  18. Mass Spectrometry Imaging Quick View

    SciTech Connect

    2013-01-24

    MSI QuickView is a software designed to provide a graphical user interface (GUI) for greatly speeding up experimental feedback (visualization and analysis) of mass spectrometry imaging (MSI or IMS) data during data acquisition. Often different software loads the entire data set, i.e., all lines of data into computer memory (RAM). This causes out of memory errors for larger datasets. We solved this in MSI QuickView by reading in the data one line at a time. Only the required information (e.g. the final pixel values for that line of heat map) is maintained in RAM. Interim analysis options include the mean intensity vs. m/z spectrum, intensity vs. time spectrums for up to 6 different m/z values or ranges chosen by the user and heat maps for each line. This assists in validating the usefulness of the particular experiment after scanning the first few lines. In addition, the tool facilitates further processing and analysis of the massive datasets. The user can manually pick different m/z values, time ranges, scroll through the spectra for any line in the data without having to load it in manually, save multiple images, change aspect ratios for the heat maps, and process the heat maps in multiple ways including overlaying images at different m/z values, displaying up to 9 different heat maps, alignment of scans along each line etc. There is no manipulation of the data required by the user to visualize the data.

  19. Mass spectrometry of extracellular vesicles.

    PubMed

    Pocsfalvi, Gabriella; Stanly, Christopher; Vilasi, Annalisa; Fiume, Immacolata; Capasso, Giovambattista; Turiák, Lilla; Buzas, Edit I; Vékey, Károly

    2016-01-01

    The review briefly summaries main features of extracellular vesicles, a joint terminology for exosomes, microvesicles, and apoptotic vesicles. These vesicles are in the center of interest in biology and medical sciences, and form a very active field of research. Mass spectrometry (MS), with its specificity and sensitivity, has the potential to identify and characterize molecular composition of these vesicles; but as yet there are only a limited, but fast-growing, number of publications that use MS workflows in this field. MS is the major tool to assess protein composition of extracellular vesicles: qualitative and quantitative proteomics approaches are both reviewed. Beside proteins, lipid and metabolite composition of vesicles might also be best assessed by MS techniques; however there are few applications as yet in this respect. The role of alternative analytical approaches, like gel-based proteomics and antibody-based immunoassays, are also mentioned. The objective of the review is to give an overview of this fast-growing field to help orient MS-based research on extracellular vesicles. © 2015 Wiley Periodicals, Inc.

  20. Alkali metal-cationized serine clusters studied by sonic spray ionization tandem mass spectrometry.

    PubMed

    Nanita, Sergio C; Sokol, Ewa; Cooks, R Graham

    2007-05-01

    Serine solutions containing salts of alkali metals yield magic number clusters of the type (Ser(4)+C)(+), (Ser(8)+C)(+), (Ser(12)+C)(+), and (Ser(17)+2C)(+2) (where C = Li(+), Na(+), K(+), Rb(+), or Cs(+)), in relative abundances which are strongly dependent on the cation size. Strong selectivity for homochirality is involved in the formation of serine tetramers cationized by K(+), Rb(+), and Cs(+). This is also the case for the octamers cationized by the smaller alkalis but there is a strong preference for heterochirality in the octamers cationized by the larger alkali cations. Tandem mass spectrometry shows that the octamers and dodecamers cationized by K(+), Rb(+), and Cs(+) dissociate mainly by the loss of Ser(4) units, suggesting that the neutral tetramers are the stable building blocks of the observed larger aggregates, (Ser(8)+C)(+) and (Ser(12)+C)(+). Remarkably, although the Ser(4) units are formed with a strong preference for homochirality, they aggregate further regardless of their handedness and, therefore, with a preference for the nominally racemic 4D:4L structure and an overall strong heterochiral preference. The octamers cationized by K(+), Rb(+), or Cs(+) therefore represent a new type of cluster ion that is homochiral in its internal subunits, which then assemble in a random fashion to form octamers. We tentatively interpret the homochirality of these tetramers as a consequence of assembly of the serine molecules around a central metal ion. The data provide additional evidence that the neutral serine octamer is homochiral and is readily cationized by smaller ions.

  1. Liquid chromatographic study of the enzymatic degradation of endomorphins, with identification by electrospray ionization mass spectrometry.

    PubMed

    Péter, A; Tóth, G; Tömböly, C; Laus, G; Tourwè, D

    1999-06-18

    The recently discovered native endomorphins play an important role in opioid analgesia, but their metabolic fate in the organism remains relatively little known. This paper describes the application of high-performance liquid chromatography combined with electrospray ionization mass spectrometry to identify the degradation products resulting from the incubation of endomorphins with proteolytic enzymes. The native endomorphin-1, H-Tyr-Pro-Trp-Phe-NH2 (1), and endomorphin-2, H-Tyr-Pro-Phe-Phe-NH2 (2), and an analog of endomorphin-2, H-Tyr-Pro-Phe-Phe-OH (3), were synthetized, and the levels of their resistance against carboxypeptidase A, carboxypeptidase Y, aminopeptidase M and proteinase A were determined. The patterns of peptide metabolites identified by this method indicated that carboxypeptidase Y first hydrolyzes the C-terminal amide group to a carboxy group, and then splits the peptides at the Trp3-Phe4 or Phe3-Phe4 bond. The remaining fragment peptides are stable against the enzymes investigated. Carboxypeptidase A degrades only analog 3 at the Phe3-Phe4 bond. Aminopeptidase M cleaves the peptides at the Pro2-Trp3 or Pro2-Phe3 bond. The C-terminal fragments hydrolyze further, giving amino acids and Phe-NH2-s while the N-terminal part displays a resistance to further aminopeptidase M digestion. Proteinase A exhibits a similar effect to carboxypeptidase Y: the C-terminal amide group is first converted to a carboxy group, and one amino acid is then split off from the C-terminal side.

  2. Study of Highly Selective and Efficient Thiol Derivatization using Selenium Reagents by Mass Spectrometry

    SciTech Connect

    Xu, Kehua; Zhang, Yun W.; Tang, Bo; Laskin, Julia; Roach, Patrick J.; Chen, Hao

    2010-08-15

    Biological thiols are critical physiological components and their detection often involves derivatization. This paper reports a systemic mass spectrometry (MS) investigation of the cleavage of Se-N bond by thiol to form a new Se-S bond, the new selenium chemistry for thiol labeling. Our data shows that the reaction is highly selective, rapid, reversible and efficient. For instance, among twenty amino acids, only cysteine was found to be reactive with Se-N containing reagents and the reaction takes place in seconds. By adding dithiothreitol (DTT), the newly formed Se-S bond of peptides/proteins can be reduced back to free thiol. The high selectivity and excellent reversibility of the reaction provide potential of using this chemistry for selective identification of thiol compounds or enriching and purifying thiol peptides/proteins. In addition, the derivatized thiol peptides have interesting dissociation behavior, which is tunable using different selenium reagents. For example, by introducing an adjacent nucleophilic group into the selenium reagent in the case of using ebselen, the reaction product of ebselen with glutathione (GSH) is easy to lose the selenium tag upon collision-induced dissociation (CID), which is useful to "fish out" those peptides containing free cysteine residues by precursor ion scan. By contrast, the selenium tag of N-(phenylseleno) phthalimide reagent can be stable and survive in CID process, which would be of value in pinpointing thiol location using a top-down proteomic approach. Also, the high conversion yield of the reaction allows the counting of total number of thiol in proteins. We believe that ebselen or N-(phenylseleno) phthalimide as tagging thiol-protein reagents will have important applications in both qualitative and quantitative analysis of different thiol-proteins derived from living cells by MS method.

  3. Whole Microorganisms Studied by Pyrolysis-Gas Chromatography-Mass Spectrometry: Significance for Extraterrestrial Life Detection Experiments 1

    PubMed Central

    Simmonds, Peter G.

    1970-01-01

    Pyrolysis-gas chromatography-mass spectrometric studies of two microorganisms, Micrococcus luteus and Bacillus subtilis var. niger, indicate that the majority of thermal fragments originate from the principal classes of bio-organic matter found in living systems such as protein and carbohydrate. Furthermore, there is a close qualitative similarity between the type of pyrolysis products found in microorganisms and the pyrolysates of other biological materials. Conversely, there is very little correlation between microbial pyrolysates and comparable pyrolysis studies of meteoritic and fossil organic matter. These observations will aid in the interpretation of a soil organic analysis experiment to be performed on the surface of Mars in 1975. The science payload of this landed mission will include a combined pyrolysis-gas chromatography-mass spectrometry instrument as well as several “direct biology experiments” which are designed to search for extraterrestrial life. PMID:16349890

  4. Newborn screening for sickling and other haemoglobin disorders using tandem mass spectrometry: A pilot study of methodology in laboratories in England.

    PubMed

    Daniel, Yvonne A; Henthorn, Joan

    2016-12-01

    To determine (i) if electrospray mass spectrometry-mass spectrometry with the SpOtOn Diagnostics Ltd reagent kit for sickle cell screening could be integrated into the English newborn screening programme, under routine screening conditions, and provide mass spectrometry-mass spectrometry results which match existing methods, and (ii) if common action values could be set for all manufacturers in the study, for all assessed haemoglobins, to indicate which samples require further investigation. Anonymised residual blood spots were analysed using the SpOtOn reagent kit as per manufacturer's instructions, in parallel with existing techniques at four laboratories. Mass spectrometry-mass spectrometry instrumentation at Laboratories A and B was AB Sciex (Warrington, UK) AP4000, and at Laboratories C and D, Waters Micromass (Manchester, UK), Xevo TQMS and Premier, respectively. There were 23,898 results accepted from the four laboratories. Excellent specificity at 100% sensitivity was observed for haemoglobin S, haemoglobin C, haemoglobin E and haemoglobin O(Arab). A common action value was not possible for Hb C, but action values were set by manufacturer. The two haemoglobin D(Punjab) cases at Laboratory D were not detected using the common action value. Conversely, false-positive results with haemoglobin D(Punjab) were a problem at the remaining three laboratories. This multicentre study demonstrates that it is possible to implement mass spectrometry-mass spectrometry into an established screening programme while maintaining consistency with existing methods for haemoglobinopathy screening. However, one of the instruments investigated cannot be recommended for use with this application. © The Author(s) 2016.

  5. Lead(II)-catalyzed oxidation of guanine in solution studied with electrospray ionization mass spectrometry.

    PubMed

    Banu, Laura; Blagojevic, Voislav; Bohme, Diethard K

    2012-10-04

    The oxidation of guanine was investigated in water/methanol solution both in the absence and in the presence of Pb(II) with a variable temperature reactor coupled to a tandem mass spectrometer that allowed signature ions of solution reagents and products to be monitored by electrospray ionization (ESI). Two different oxidizing agents were employed, one strong (peroxymonosulfuric acid) and one weaker (hydrogen peroxide). Peroxymonosulfuric acid was observed to oxidize guanine rapidly at room temperature, k(app) > 10(-2) s(-1), whether in the absence or in the presence of Pb(II), to produce spiroiminohydantoin. Guanine did not show measurable oxidation by hydrogen peroxide in the absence of Pb(II) at concentrations of H(2)O(2) up to 1 M at temperatures up to 333 K (k(app) < 3 × 10(-8) s(-1) at 298 K), but in the presence of Pb(II), it was observed to produce both 5-carboxamido-5-formamido-2-iminohydantoin (2-Ih) and imidazolone (Iz) in a ratio of 2.3 ± 0.1 with a total rate enhancement of more than 4 × 10(3). The activation energy was measured to be 82 ± 11 kJ mol(-1) and is more than 120 kJ mol(-1) lower than that for the uncatalyzed oxidation with hydrogen peroxide measured to be at least 208 ± 26 kJ mol(-1). An activation energy of 113 ± 9 kJ mol(-1) has been reported by Bruskov et al. (Nucleic Acids Res.2002, 30, 1354) for the heat-induced oxidation by hydrogen peroxide of guanine embedded as guanosine in DNA which leads to the production of 8-oxo-7,8-dihydro-guanine (8-oxo-Gua). The atomic lead dication lowers the activation energy by activating the hydrogen peroxide oxidant, possibly by O-O bond activation, and by directing the oxidation, possibly through coordination to the functional groups adjacent to the carbon C5: the C6 carbonyl group and the N7 nitrogen. The coupling of tandem mass spectrometry (MS(2)) with a simple variable temperature reactor by ESI proved to be very effective for measuring reaction kinetics and activation energies in solution

  6. Broadband Analysis of Bioagents by Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Fenselau, Catherine; Wynne, Colin; Edwards, Nathan

    Mass spectrometry was first reported to provide analysis of intact metabolite biomarkers from whole cells in 1975.1 Since then advances in ionization techniques have extended our capabilities to polar lipids and, eventually, to proteins.2, 3 Mass spectrometry provides a broadband detection system, which, however, has great specificity. Bioinformatics plays an important role in providing flexible and rapid characterization of species, based on protein and peptide mass spectra collected in the field.

  7. Study of an Unusual Advanced Glycation End-Product (AGE) Derived from Glyoxal Using Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Lopez-Clavijo, Andrea F.; Duque-Daza, Carlos A.; Romero Canelon, Isolda; Barrow, Mark P.; Kilgour, David; Rabbani, Naila; Thornalley, Paul J.; O'Connor, Peter B.

    2014-04-01

    Glycation is a post-translational modification (PTM) that affects the physiological properties of peptides and proteins. In particular, during hyperglycaemia, glycation by α-dicarbonyl compounds generate α-dicarbonyl-derived glycation products also called α-dicarbonyl-derived advanced glycation end products. Glycation by the α-dicarbonyl compound known as glyoxal was studied in model peptides by MS/MS using a Fourier transform ion cyclotron resonance mass spectrometer. An unusual type of glyoxal-derived AGE with a mass addition of 21.98436 Da is reported in peptides containing combinations of two arginine-two lysine, and one arginine-three lysine amino acid residues. Electron capture dissociation and collisionally activated dissociation results supported that the unusual glyoxal-derived AGE is formed at the guanidino group of arginine, and a possible structure is proposed to illustrate the 21.9843 Da mass addition.

  8. Application of mass spectrometry in proteomics.

    PubMed

    Guerrera, Ida Chiara; Kleiner, Oliver

    2005-01-01

    Mass spectrometry has arguably become the core technology in proteomics. The application of mass spectrometry based techniques for the qualitative and quantitative analysis of global proteome samples derived from complex mixtures has had a big impact in the understanding of cellular function. Here, we give a brief introduction to principles of mass spectrometry and instrumentation currently used in proteomics experiments. In addition, recent developments in the application of mass spectrometry in proteomics are summarised. Strategies allowing high-throughput identification of proteins from highly complex mixtures include accurate mass measurement of peptides derived from total proteome digests and multidimensional peptide separations coupled with mass spectrometry. Mass spectrometric analysis of intact proteins permits the characterisation of protein isoforms. Recent developments in stable isotope labelling techniques and chemical tagging allow the mass spectrometry based differential display and quantitation of proteins, and newly established affinity procedures enable the targeted characterisation of post-translationally modified proteins. Finally, advances in mass spectrometric imaging allow the gathering of specific information on the local molecular composition, relative abundance and spatial distribution of peptides and proteins in thin tissue sections.

  9. Time Resolved Studies of Interfacial Reactions of Ozone with Pulmonary Phospholipid Surfactants Using Field Induced Droplet Ionization Mass Spectrometry

    PubMed Central

    Kim, Hugh I.; Kim, Hyungjun; Shin, Young Shik; Beegle, Luther W.; Goddard, William A.; Heath, James R.; Kanik, Isik; Beauchamp, J. L.

    2013-01-01

    Field induced droplet ionization mass spectrometry (FIDI-MS) comprises a soft ionization method to sample ions from the surface of microliter droplets. A pulsed electric field stretches neutral droplets until they develop dual Taylor cones, emitting streams of positively and negatively charged submicrometer droplets in opposite directions, with the desired polarity being directed into a mass spectrometer for analysis. This methodology is employed to study the heterogeneous ozonolysis of 1-palmitoyl-2-oleoyl-sn-phosphatidylglycerol (POPG) at the air–liquid interface in negative ion mode using FIDI mass spectrometry. Our results demonstrate unique characteristics of the heterogeneous reactions at the air–liquid interface. We observe the hydroxyhydroperoxide and the secondary ozonide as major products of POPG ozonolysis in the FIDI-MS spectra. These products are metastable and difficult to observe in the bulk phase, using standard electrospray ionization (ESI) for mass spectrometric analysis. We also present studies of the heterogeneous ozonolysis of a mixture of saturated and unsaturated phospholipids at the air–liquid interface. A mixture of the saturated phospholipid 1,2-dipalmitoyl-sn-phosphatidylglycerol (DPPG) and unsaturated POPG is investigated in negative ion mode using FIDI-MS while a mixture of 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) and 1-stearoyl-2-oleoyl-sn-phosphatidylcholine (SOPC) surfactant is studied in positive ion mode. In both cases FIDI-MS shows the saturated and unsaturated pulmonary surfactants form a mixed interfacial layer. Only the unsaturated phospholipid reacts with ozone, forming products that are more hydrophilic than the saturated phospholipid. With extensive ozonolysis only the saturated phospholipid remains at the droplet surface. Combining these experimental observations with the results of computational analysis provides an improved understanding of the interfacial structure and chemistry of a surfactant layer system

  10. Time resolved studies of interfacial reactions of ozone with pulmonary phospholipid surfactants using field induced droplet ionization mass spectrometry.

    PubMed

    Kim, Hugh I; Kim, Hyungjun; Shin, Young Shik; Beegle, Luther W; Goddard, William A; Heath, James R; Kanik, Isik; Beauchamp, J L

    2010-07-29

    Field induced droplet ionization mass spectrometry (FIDI-MS) comprises a soft ionization method to sample ions from the surface of microliter droplets. A pulsed electric field stretches neutral droplets until they develop dual Taylor cones, emitting streams of positively and negatively charged submicrometer droplets in opposite directions, with the desired polarity being directed into a mass spectrometer for analysis. This methodology is employed to study the heterogeneous ozonolysis of 1-palmitoyl-2-oleoyl-sn-phosphatidylglycerol (POPG) at the air-liquid interface in negative ion mode using FIDI mass spectrometry. Our results demonstrate unique characteristics of the heterogeneous reactions at the air-liquid interface. We observe the hydroxyhydroperoxide and the secondary ozonide as major products of POPG ozonolysis in the FIDI-MS spectra. These products are metastable and difficult to observe in the bulk phase, using standard electrospray ionization (ESI) for mass spectrometric analysis. We also present studies of the heterogeneous ozonolysis of a mixture of saturated and unsaturated phospholipids at the air-liquid interface. A mixture of the saturated phospholipid 1,2-dipalmitoyl-sn-phosphatidylglycerol (DPPG) and unsaturated POPG is investigated in negative ion mode using FIDI-MS while a mixture of 1,2-dipalmitoyl-sn-phosphatidylcholine (DPPC) and 1-stearoyl-2-oleoyl-sn-phosphatidylcholine (SOPC) surfactant is studied in positive ion mode. In both cases FIDI-MS shows the saturated and unsaturated pulmonary surfactants form a mixed interfacial layer. Only the unsaturated phospholipid reacts with ozone, forming products that are more hydrophilic than the saturated phospholipid. With extensive ozonolysis only the saturated phospholipid remains at the droplet surface. Combining these experimental observations with the results of computational analysis provides an improved understanding of the interfacial structure and chemistry of a surfactant layer system when

  11. Structural studies of the allelic wheat glutenin subunits 1Bx7 and 1Bx20 by matrix-assisted laser desorption/ionization mass spectrometry and high-performance liquid chromatography/electrospray ionization mass spectrometry.

    PubMed

    Cunsolo, Vincenzo; Foti, Salvatore; Saletti, Rosaria; Gilbert, Simon; Tatham, Arthur S; Shewry, Peter R

    2004-01-01

    Structural studies of the high molecular mass (HMM) glutenin subunits 1Bx7 (from cvs Hereward and Galatea) and 1Bx20 (from cv. Bidi17) of bread wheat were conducted using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) and reversed-phase high-performance liquid chromatography/electrospray ionization mass spectrometry (RP-HPLC/ESI-MS). For all three proteins, MALDI-TOFMS analysis showed that the isolated fractions contained a second component with a mass about 650 Da lower than the major component. The testing and correction of the gene-derived amino acid sequences of the three proteins were performed by direct MALDI-TOFMS analysis of their tryptic peptide mixture. Analysis of the digest was performed by recording several MALDI mass spectra of the mixture at low, medium and high mass ranges, optimizing the matrix and the acquisition parameters for each mass range. Complementary data were obtained by RP-HPLC/ESI-MS analysis of the tryptic digest. This resulted in coverage of about 98% of the sequences. In contrast to the gene-derived data, the results obtained demonstrate the insertion of the sequence QPGQGQ between Trp716 and Gln717 of subunit 1Bx7 (cv. Galatea) and a possible single amino acid substitution within the T20 peptide of subunit 1Bx20. Moreover, the mass spectrometric data demonstrated that the lower mass components present in all the fractions correspond to the major components but lack about six amino acid residues, which are probably lost from the protein C-terminus. Finally, the results obtained provide evidence for the lack of glycosylation or other post-translational modifications of these subunits. Copyright 2004 John Wiley & Sons, Ltd.

  12. Ion mobility-mass spectrometry and orthogonal gas-phase techniques to study amyloid formation and inhibition.

    PubMed

    Hoffmann, Waldemar; von Helden, Gert; Pagel, Kevin

    2017-03-23

    Amyloidogenic peptide oligomers are responsible for a variety of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Due to their dynamic, polydisperse, and polymorphic nature, these oligomers are very challenging to characterize using traditional condensed-phase methods. In the last decade, ion mobility-mass spectrometry (IM-MS) and related gas-phase techniques have emerged as a powerful alternative to disentangle the structure and assembly characteristics of amyloid forming systems. This review highlights recent advances in which IM-MS was used to characterize amyloid oligomers and their underlying assembly pathway. In addition, we summarize recent studies in which IM-MS was used to size- and mass-select species for a further spectroscopic investigation and outline the potential of IM-MS as a tool for the screening of amyloid inhibitors.

  13. Mass spectrometry innovations in drug discovery and development.

    PubMed

    Papac, D I; Shahrokh, Z

    2001-02-01

    This review highlights the many roles mass spectrometry plays in the discovery and development of new therapeutics by both the pharmaceutical and the biotechnology industries. Innovations in mass spectrometer source design, improvements to mass accuracy, and implementation of computer-controlled automation have accelerated the purification and characterization of compounds derived from combinatorial libraries, as well as the throughput of pharmacokinetics studies. The use of accelerator mass spectrometry, chemical reaction interface-mass spectrometry and continuous flow-isotope ratio mass spectrometry are promising alternatives for conducting mass balance studies in man. To meet the technical challenges of proteomics, discovery groups in biotechnology companies have led the way to development of instruments with greater sensitivity and mass accuracy (e.g., MALDI-TOF, ESI-Q-TOF, Ion Trap), the miniaturization of separation techniques and ion sources (e.g., capillary HPLC and nanospray), and the utilization of bioinformatics. Affinity-based methods coupled to mass spectrometry are allowing rapid and selective identification of both synthetic and biological molecules. With decreasing instrument cost and size and increasing reliability, mass spectrometers are penetrating both the manufacturing and the quality control arenas. The next generation of technologies to simplify the investigation of the complex fate of novel pharmaceutical entities in vitro and in vivo will be chip-based approaches coupled with mass spectrometry.

  14. An introduction to artificial neural networks in bioinformatics--application to complex microarray and mass spectrometry datasets in cancer studies.

    PubMed

    Lancashire, Lee J; Lemetre, Christophe; Ball, Graham R

    2009-05-01

    Applications of genomic and proteomic technologies have seen a major increase, resulting in an explosion in the amount of highly dimensional and complex data being generated. Subsequently this has increased the effort by the bioinformatics community to develop novel computational approaches that allow for meaningful information to be extracted. This information must be of biological relevance and thus correlate to disease phenotypes of interest. Artificial neural networks are a form of machine learning from the field of artificial intelligence with proven pattern recognition capabilities and have been utilized in many areas of bioinformatics. This is due to their ability to cope with highly dimensional complex datasets such as those developed by protein mass spectrometry and DNA microarray experiments. As such, neural networks have been applied to problems such as disease classification and identification of biomarkers. This review introduces and describes the concepts related to neural networks, the advantages and caveats to their use, examples of their applications in mass spectrometry and microarray research (with a particular focus on cancer studies), and illustrations from recent literature showing where neural networks have performed well in comparison to other machine learning methods. This should form the necessary background knowledge and information enabling researchers with an interest in these methodologies, but not necessarily from a machine learning background, to apply the concepts to their own datasets, thus maximizing the information gain from these complex biological systems.

  15. Metabolomics of adherent mammalian cells by capillary electrophoresis-mass spectrometry: HT-29 cells as case study.

    PubMed

    Ibáñez, Clara; Simó, Carolina; Valdés, Alberto; Campone, Luca; Piccinelli, Anna Lisa; García-Cañas, Virginia; Cifuentes, Alejandro

    2015-06-10

    In this work, the optimization of an effective protocol for cell metabolomics is described with special emphasis in the sample preparation and subsequent analysis of intracellular metabolites from adherent mammalian cells by capillary electrophoresis-mass spectrometry. As case study, colon cancer HT-29 cells, a human cell model to investigate colon cancer, are employed. The feasibility of the whole method for cell metabolomics is demonstrated via a fast and sensitive profiling of the intracellular metabolites HT-29 cells by capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF MS). The suitability of this methodology is further corroborated through the examination of the metabolic changes in the polyamines pathway produced in colon cancer HT-29 cells by difluoromethylornithine (DFMO), a known potent ornithine decarboxylase inhibitor. The selection of the optimum extraction conditions allowed a higher sample volume injection that led to an increase in CE-TOF MS sensitivity. Following a non-targeted metabolomics approach, 10 metabolites (namely, putrescine, ornithine, gamma-aminobutyric acid (GABA), oxidized and reduced glutathione, 5'-deoxy-5'-(methylthio)adenosine, N-acetylputrescine, cysteinyl-glycine, spermidine and an unknown compound) were found to be significantly altered by DFMO (p<0.05) in HT-29 cells. In addition to the effect of DFMO on polyamine metabolism, minor modifications of other metabolic pathways (e.g., related to intracellular thiol redox state) were observed.

  16. Atmospheric pressure chemical ionization studies of non-polar isomeric hydrocarbons using ion mobility spectrometry and mass spectrometry with different ionization techniques

    NASA Technical Reports Server (NTRS)

    Borsdorf, H.; Nazarov, E. G.; Eiceman, G. A.

    2002-01-01

    The ionization pathways were determined for sets of isomeric non-polar hydrocarbons (structural isomers, cis/trans isomers) using ion mobility spectrometry and mass spectrometry with different techniques of atmospheric pressure chemical ionization to assess the influence of structural features on ion formation. Depending on the structural features, different ions were observed using mass spectrometry. Unsaturated hydrocarbons formed mostly [M - 1]+ and [(M - 1)2H]+ ions while mainly [M - 3]+ and [(M - 3)H2O]+ ions were found for saturated cis/trans isomers using photoionization and 63Ni ionization. These ionization methods and corona discharge ionization were used for ion mobility measurements of these compounds. Different ions were detected for compounds with different structural features. 63Ni ionization and photoionization provide comparable ions for every set of isomers. The product ions formed can be clearly attributed to the structures identified. However, differences in relative abundance of product ions were found. Although corona discharge ionization permits the most sensitive detection of non-polar hydrocarbons, the spectra detected are complex and differ from those obtained with 63Ni ionization and photoionization. c. 2002 American Society for Mass Spectrometry.

  17. Atmospheric pressure chemical ionization studies of non-polar isomeric hydrocarbons using ion mobility spectrometry and mass spectrometry with different ionization techniques

    NASA Technical Reports Server (NTRS)

    Borsdorf, H.; Nazarov, E. G.; Eiceman, G. A.

    2002-01-01

    The ionization pathways were determined for sets of isomeric non-polar hydrocarbons (structural isomers, cis/trans isomers) using ion mobility spectrometry and mass spectrometry with different techniques of atmospheric pressure chemical ionization to assess the influence of structural features on ion formation. Depending on the structural features, different ions were observed using mass spectrometry. Unsaturated hydrocarbons formed mostly [M - 1]+ and [(M - 1)2H]+ ions while mainly [M - 3]+ and [(M - 3)H2O]+ ions were found for saturated cis/trans isomers using photoionization and 63Ni ionization. These ionization methods and corona discharge ionization were used for ion mobility measurements of these compounds. Different ions were detected for compounds with different structural features. 63Ni ionization and photoionization provide comparable ions for every set of isomers. The product ions formed can be clearly attributed to the structures identified. However, differences in relative abundance of product ions were found. Although corona discharge ionization permits the most sensitive detection of non-polar hydrocarbons, the spectra detected are complex and differ from those obtained with 63Ni ionization and photoionization. c. 2002 American Society for Mass Spectrometry.

  18. Boundaries of Mass Resolution in Native Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Lössl, Philip; Snijder, Joost; Heck, Albert J. R.

    2014-06-01

    Over the last two decades, native mass spectrometry (MS) has emerged as a valuable tool to study intact proteins and noncovalent protein complexes. Studied experimental systems range from small-molecule (drug)-protein interactions, to nanomachineries such as the proteasome and ribosome, to even virus assembly. In native MS, ions attain high m/z values, requiring special mass analyzers for their detection. Depending on the particular mass analyzer used, instrumental mass resolution does often decrease at higher m/z but can still be above a couple of thousand at m/z 5000. However, the mass resolving power obtained on charge states of protein complexes in this m/z region is experimentally found to remain well below the inherent instrument resolution of the mass analyzers employed. Here, we inquire into reasons for this discrepancy and ask how native MS would benefit from higher instrumental mass resolution. To answer this question, we discuss advantages and shortcomings of mass analyzers used to study intact biomolecules and biomolecular complexes in their native state, and we review which other factors determine mass resolving power in native MS analyses. Recent examples from the literature are given to illustrate the current status and limitations.

  19. Methods for recalibration of mass spectrometry data

    DOEpatents

    Tolmachev, Aleksey V.; Smith, Richard D.

    2009-03-03

    Disclosed are methods for recalibrating mass spectrometry data that provide improvement in both mass accuracy and precision by adjusting for experimental variance in parameters that have a substantial impact on mass measurement accuracy. Optimal coefficients are determined using correlated pairs of mass values compiled by matching sets of measured and putative mass values that minimize overall effective mass error and mass error spread. Coefficients are subsequently used to correct mass values for peaks detected in the measured dataset, providing recalibration thereof. Sub-ppm mass measurement accuracy has been demonstrated on a complex fungal proteome after recalibration, providing improved confidence for peptide identifications.

  20. Studies on the microbial biotransformation of the novel psychoactive substance methylenedioxypyrovalerone (MDPV) in wastewater by means of liquid chromatography-high resolution mass spectrometry/mass spectrometry.

    PubMed

    Mardal, Marie; Meyer, Markus R

    2014-09-15

    Sewage profiling as a mean to estimate consumption of drugs of abuse is gaining increasing attention. However, only scarce data are available so far on the impact of microbial biotransformation on the presence and hence detectability of drugs of abuse and their metabolites in wastewater (WW) samples. The aim of this work was therefore to study the biotransformation pathways of the novel psychoactive substance 3,4-methylenedioxypyrovalerone (MPDV) in WW by incubating it, based on the OECD guideline 314 A. MDPV was incubated (100 μg/L) for 10d at 22 °C in WW from a local WW treatment plant. Furthermore, urine and feces collected from rats administered 20mg MDPV/kg BW were incubated correspondingly. Samples were worked-up either by centrifugation/filtration and solid-phase (HCX) extraction or QuEChERS. High resolution (HR) mass spectra (MS) were recorded using an Orbitrap mass spectrometer. All products were identified via their HR-MS(2) spectra and chromatographic properties. The observed biotransformations in WW were: demethylenation and subsequent O-methylation, hydroxylation at the phenyl part, hydroxylation at the pyrrolidine part with subsequent methylation or oxidation, N-demethylation, and hydroxylation at the alkyl part as well as combination of them. In total, 12 biotransformation products were identified after 10 days of incubation. Three of these biotransformation products were previously reported to be also rat and human metabolites. No additional MDPV biotransformation products could be found after incubating the rat urine and feces samples. Instead, the urinary phase II glucuronides were nearly completely cleaved after one day of WW incubation. The presented study indicates that demethylenyl-methyl MDPV, the most abundant metabolite in human urine, should be the best indicator in WW to estimate its use. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Universal Mass Spectrometry-Based Life Detection

    NASA Astrophysics Data System (ADS)

    Cleaves, H. J.; Giri, C.

    2017-02-01

    The search for ET life will be an important 21st century solar system exploration goal. Mass spectrometry offers a comprehensive, rapid way of "chemotyping" environmental samples. Preparation of a reference catalogue of abiotic and biological samples is described.

  2. Plasma Desorption Mass Spectrometry: Coming of Age.

    ERIC Educational Resources Information Center

    Cotter, Robert J.

    1988-01-01

    Discusses the history and development of Plasma Desorption Mass Spectrometry to determine molecular weights and structures of proteins and polymers. Outlines theory, instrumentation, and sample preparation commonly used. Gives several examples of resulting spectra. (ML)

  3. Plasma Desorption Mass Spectrometry: Coming of Age.

    ERIC Educational Resources Information Center

    Cotter, Robert J.

    1988-01-01

    Discusses the history and development of Plasma Desorption Mass Spectrometry to determine molecular weights and structures of proteins and polymers. Outlines theory, instrumentation, and sample preparation commonly used. Gives several examples of resulting spectra. (ML)

  4. Comparative study of laser induced breakdown spectroscopy and mass spectrometry for the analysis of cultural heritage materials

    NASA Astrophysics Data System (ADS)

    Kokkinaki, O.; Mihesan, C.; Velegrakis, M.; Anglos, D.

    2013-07-01

    Analysis by laser-induced breakdown spectroscopy (LIBS) is compared, on the basis of a hybrid experimental set-up, with laser ablation time-of-flight mass spectrometry (LA-TOF-MS) for the characterization of materials relevant to cultural heritage. The present study focuses on the analysis of selected paint materials such as lithopone, a white inorganic pigment, and two synthetic organic paint formulations, lemon yellow and phthalocyanine blue. Optical emission spectra, obtained by LIBS, lead to rapid, straightforward identification of the elemental content of the paint samples while mass spectra yield, additionally to elemental analysis, complementary isotopic analysis and, more importantly, enable detection of molecules and molecular fragments, permitting a more complete structural and compositional characterization of composite materials. Mass spectra were recorded either simultaneously with the optical emission ones, or sequentially. The latter was preferred for materials having significantly lower fluence threshold for desorption/ionization relative to plasma formation resulting to optimum mass resolution and minimal surface damage. In all, the results of this study demonstrate the advantages of instrumentally complementing LIBS with TOF-MS in relation to applications in cultural heritage materials analysis, with exciting prospects when laser ablation sampling can be carried out under ambient atmosphere.

  5. Cluster-based comparison of the peptide mass fingerprint obtained by MALDI-TOF mass spectrometry. A case study: long-term stability of rituximab.

    PubMed

    Villacorta, Pablo J; Salmerón-García, Antonio; Pelta, David A; Cabeza, José; Lario, Antonio; Navas, Natalia

    2015-03-07

    We evaluated the use of the peptide mass fingerprint (PMF) obtained by matrix assisted laser desorption and ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) to track changes in the structure of a protein. The first problem we had to overcome was the inherent complexity of the PMF, which makes it difficult to compare. We dealt with this problem by developing a cluster-based comparison algorithm which takes into account the proportional error made by the mass spectrometer. This procedure involves grouping together similar masses in an intelligent manner, so that we can determine which data correspond to the same peptide (any slight differences can be explained as experimental errors), and which of them are too different and thus more likely to represent different peptides. The proposed algorithm was applied to track changes in a commercially available monoclonal antibody (mAb), namely rituximab (RTX), prepared under the usual hospital conditions and stored refrigerated (4 °C) and frozen (-20 °C) for a long term study. PMFs were obtained periodically over three months. For each checked time, five replicates of the PMFs were obtained in order to evaluate the similarities between them by means of the occurrences of the particular peptides (m/z). After applying the algorithm to the PMF, different approaches were used to analyse the results. Surprisingly, all of them suggested that there were no differences between the two storage conditions tested, i.e. the RTX samples were almost equally well preserved when stored refrigerated at 4 °C or frozen at -20 °C. The cluster-based methodology is new in protein mass spectrometry and could be useful as an easy test for major changes in proteins and biopharmaceutics for diverse applications in industry and other fields, and could provide additional stability data in relation to the practical use of anticancer drugs.

  6. The future of liquid chromatography-mass spectrometry (LC-MS) in metabolic profiling and metabolomic studies for biomarker discovery

    PubMed Central

    Metz, Thomas O.; Zhang, Qibin; Page, Jason S.; Shen, Yufeng; Callister, Stephen J.; Jacobs, Jon M.; Smith, Richard D.

    2008-01-01

    SUMMARY The future utility of liquid chromatography-mass spectrometry (LC-MS) in metabolic profiling and metabolomic studies for biomarker discover will be discussed, beginning with a brief description of the evolution of metabolomics and the utilization of the three most popular analytical platforms in such studies: NMR, GC-MS, and LC-MS. Emphasis is placed on recent developments in high-efficiency LC separations, sensitive electrospray ionization approaches, and the benefits to incorporating both in LC-MS-based approaches. The advantages and disadvantages of various quantitative approaches are reviewed, followed by the current LC-MS-based tools available for candidate biomarker characterization and identification. Finally, a brief prediction on the future path of LC-MS-based methods in metabolic profiling and metabolomic studies is given. PMID:19177179

  7. Biological accelerator mass spectrometry at Uppsala University.

    PubMed

    Salehpour, Mehran; Possnert, Göran; Bryhni, Helge; Palminger-Hallén, Ira; Ståhle, Lars

    2009-03-01

    A new research programme for the biological applications of accelerator mass spectrometry has been initiated at Uppsala University and the first results are presented. A (14)C-labelled pharmaceutical substance has been dissolved in human blood, plasma and urine and diluted over 3 orders of magnitude. The measured drug concentrations were found to be in good agreement with the predicted values. Furthermore, the effect of the sample preparation background contribution has been studied as the sample amount was varied down to sub-microl sizes.

  8. Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry: Mechanistic Studies and Methods for Improving the Structural Identification of Carbohydrates

    PubMed Central

    Lai, Yin-Hung; Wang, Yi-Sheng

    2017-01-01

    Although matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is one of the most widely used soft ionization methods for biomolecules, the lack of detailed understanding of ionization mechanisms restricts its application in the analysis of carbohydrates. Structural identification of carbohydrates achieved by MALDI mass spectrometry helps us to gain insights into biological functions and pathogenesis of disease. In this review, we highlight mechanistic details of MALDI, including both ionization and desorption. Strategies to improve the ion yield of carbohydrates are also reviewed. Furthermore, commonly used fragmentation methods to identify the structure are discussed. PMID:28959517

  9. Mass spectrometry in the home and garden.

    PubMed

    Pulliam, Christopher J; Bain, Ryan M; Wiley, Joshua S; Ouyang, Zheng; Cooks, R Graham

    2015-02-01

    Identification of active components in a variety of chemical products used directly by consumers is described at both trace and bulk levels using mass spectrometry. The combination of external ambient ionization with a portable mass spectrometer capable of tandem mass spectrometry provides high chemical specificity and sensitivity as well as allowing on-site monitoring. These experiments were done using a custom-built portable ion trap mass spectrometer in combination with the ambient ionization methods of paper spray, leaf spray, and low temperature plasma ionization. Bactericides, garden chemicals, air fresheners, and other products were examined. Herbicide applied to suburban lawns was detected in situ on single leaves 5 d after application.

  10. Mass Spectrometry in the Home and Garden

    NASA Astrophysics Data System (ADS)

    Pulliam, Christopher J.; Bain, Ryan M.; Wiley, Joshua S.; Ouyang, Zheng; Cooks, R. Graham

    2015-02-01

    Identification of active components in a variety of chemical products used directly by consumers is described at both trace and bulk levels using mass spectrometry. The combination of external ambient ionization with a portable mass spectrometer capable of tandem mass spectrometry provides high chemical specificity and sensitivity as well as allowing on-site monitoring. These experiments were done using a custom-built portable ion trap mass spectrometer in combination with the ambient ionization methods of paper spray, leaf spray, and low temperature plasma ionization. Bactericides, garden chemicals, air fresheners, and other products were examined. Herbicide applied to suburban lawns was detected in situ on single leaves 5 d after application.

  11. Mechanistic and Kinetic Study of Singlet O2 Oxidation of Methionine by On-Line Electrospray Ionization Mass Spectrometry.

    PubMed

    Liu, Fangwei; Lu, Wenchao; Yin, Xunlong; Liu, Jianbo

    2016-01-01

    We report a reaction apparatus developed to monitor singlet oxygen ((1)O2) reactions in solution using on-line ESI mass spectrometry and spectroscopy measurements. (1)O2 was generated in the gas phase by the reaction of H2O2 with Cl2, detected by its emission at 1270 nm, and bubbled into aqueous solution continuously. (1)O2 concentrations in solution were linearly related to the emission intensities of airborne (1)O2, and their absolute scales were established based on a calibration using 9,10-anthracene dipropionate dianion as an (1)O2 trapping agent. Products from (1)O2 oxidation were monitored by UV-Vis absorption and positive/negative ESI mass spectra, and product structures were elucidated using collision-induced dissociation-tandem mass spectrometry. To suppress electrical discharge in negative ESI of aqueous solution, methanol was added to electrospray via in-spray solution mixing using theta-glass ESI emitters. Capitalizing on this apparatus, the reaction of (1)O2 with methionine was investigated. We have identified methionine oxidation intermediates and products at different pH, and measured reaction rate constants. (1)O2 oxidation of methionine is mediated by persulfoxide in both acidic and basic solutions. Persulfoxide continues to react with another methionine, yielding methionine sulfoxide as end-product albeit with a much lower reaction rate in basic solution. Density functional theory was used to explore reaction potential energy surfaces and establish kinetic models, with solvation effects simulated using the polarized continuum model. Combined with our previous study of gas-phase methionine ions with (1)O2, evolution of methionine oxidation pathways at different ionization states and in different media is described.

  12. Mechanistic and Kinetic Study of Singlet O2 Oxidation of Methionine by On-Line Electrospray Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Liu, Fangwei; Lu, Wenchao; Yin, Xunlong; Liu, Jianbo

    2016-01-01

    We report a reaction apparatus developed to monitor singlet oxygen (1O2) reactions in solution using on-line ESI mass spectrometry and spectroscopy measurements. 1O2 was generated in the gas phase by the reaction of H2O2 with Cl2, detected by its emission at 1270 nm, and bubbled into aqueous solution continuously. 1O2 concentrations in solution were linearly related to the emission intensities of airborne 1O2, and their absolute scales were established based on a calibration using 9,10-anthracene dipropionate dianion as an 1O2 trapping agent. Products from 1O2 oxidation were monitored by UV-Vis absorption and positive/negative ESI mass spectra, and product structures were elucidated using collision-induced dissociation-tandem mass spectrometry. To suppress electrical discharge in negative ESI of aqueous solution, methanol was added to electrospray via in-spray solution mixing using theta-glass ESI emitters. Capitalizing on this apparatus, the reaction of 1O2 with methionine was investigated. We have identified methionine oxidation intermediates and products at different pH, and measured reaction rate constants. 1O2 oxidation of methionine is mediated by persulfoxide in both acidic and basic solutions. Persulfoxide continues to react with another methionine, yielding methionine sulfoxide as end-product albeit with a much lower reaction rate in basic solution. Density functional theory was used to explore reaction potential energy surfaces and establish kinetic models, with solvation effects simulated using the polarized continuum model. Combined with our previous study of gas-phase methionine ions with 1O2, evolution of methionine oxidation pathways at different ionization states and in different media is described.

  13. Protein Sequencing with Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Ziady, Assem G.; Kinter, Michael

    The recent introduction of electrospray ionization techniques that are suitable for peptides and whole proteins has allowed for the design of mass spectrometric protocols that provide accurate sequence information for proteins. The advantages gained by these approaches over traditional Edman Degradation sequencing include faster analysis and femtomole, sometimes attomole, sensitivity. The ability to efficiently identify proteins has allowed investigators to conduct studies on their differential expression or modification in response to various treatments or disease states. In this chapter, we discuss the use of electrospray tandem mass spectrometry, a technique whereby protein-derived peptides are subjected to fragmentation in the gas phase, revealing sequence information for the protein. This powerful technique has been instrumental for the study of proteins and markers associated with various disorders, including heart disease, cancer, and cystic fibrosis. We use the study of protein expression in cystic fibrosis as an example.

  14. Metabolomic study of lipids in serum for biomarker discovery in Alzheimer's disease using direct infusion mass spectrometry.

    PubMed

    González-Domínguez, R; García-Barrera, T; Gómez-Ariza, J L

    2014-09-01

    In this study, we demonstrated the potential of direct infusion mass spectrometry for the lipidomic characterization of Alzheimer's disease. Serum samples were extracted for lipids recovery, and directly analyzed using an electrospray source. Metabolomic fingerprints were subjected to multivariate analysis in order to discriminate between groups of patients and healthy controls, and then some key-compounds were identified as possible markers of Alzheimer's disease. Major differences were found in lipids, although some low molecular weight metabolites also showed significant changes. Thus, important metabolic pathways involved in neurodegeneration could be studied on the basis of these perturbations, such as membrane breakdown (phospholipids and diacylglycerols), oxidative stress (prostaglandins, imidazole and histidine), alterations in neurotransmission systems (oleamide and putrescine) and hyperammonaemia (guanidine and arginine). Moreover, it is noteworthy that some of these potential biomarkers have not been previously described for Alzheimer's disease.

  15. Pharmacokinetic Studies of Chinese Medicinal Herbs Using an Automated Blood Sampling System and Liquid Chromatography-mass Spectrometry

    PubMed Central

    Wu, Yu-Tse; Wu, Ming-Tsang; Lin, Chia-Chun; Chien, Chao-Feng; Tsai, Tung-Hu

    2012-01-01

    The safety of herbal products is one of the major concerns for the modernization of traditional Chinese medicine, and pharmacokinetic data of medicinal herbs guide us to design the rational use of the herbal formula. This article reviews the advantages of the automated blood sampling (ABS) systems for pharmacokinetic studies. In addition, three commonly used sample preparative methods, protein precipitation, liquid-liquid extraction and solid-phase extraction, are introduced. Furthermore, the definition, causes and evaluation of matrix effects in liquid chromatography-mass spectrometry (LC/MS) analysis are demonstrated. Finally, we present our previous works as practical examples of the application of ABS systems and LC/MS for the pharmacokinetic studies of Chinese medicinal herbs. PMID:24716112

  16. Stable Isotope Labeling Strategy for Curcumin Metabolite Study in Human Liver Microsomes by Liquid Chromatography-Tandem Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Gao, Dan; Chen, Xiaowu; Yang, Xiaomei; Wu, Qin; Jin, Feng; Wen, Hongliang; Jiang, Yuyang; Liu, Hongxia

    2015-04-01

    The identification of drug metabolites is very important in drug development. Nowadays, the most widely used methods are isotopes and mass spectrometry. However, the commercial isotopic labeled reagents are usually very expensive, and the rapid and convenient identification of metabolites is still difficult. In this paper, an 18O isotope labeling strategy was developed and the isotopes were used as a tool to identify drug metabolites using mass spectrometry. Curcumin was selected as a model drug to evaluate the established method, and the 18O labeled curcumin was successfully synthesized. The non-labeled and 18O labeled curcumin were simultaneously metabolized in human liver microsomes (HLMs) and analyzed by liquid chromatography/mass spectrometry (LC-MS). The two groups of chromatograms obtained from metabolic reaction mixture with and without cofactors were compared and analyzed using Metabolynx software (Waters Corp., Milford, MA, USA). The mass spectra of the newly appearing chromatographic peaks in the experimental sample were further analyzed to find the metabolite candidates. Their chemical structures were confirmed by tandem mass spectrometry. Three metabolites, including two reduction products and a glucuronide conjugate, were successfully detected under their specific HLMs metabolic conditions, which were in accordance with the literature reported results. The results demonstrated that the developed isotope labeling method, together with post-acquisition data processing using Metabolynx software, could be used for fast identification of new drug metabolites.

  17. Stable isotope labeling strategy for curcumin metabolite study in human liver microsomes by liquid chromatography-tandem mass spectrometry.

    PubMed

    Gao, Dan; Chen, Xiaowu; Yang, Xiaomei; Wu, Qin; Jin, Feng; Wen, Hongliang; Jiang, Yuyang; Liu, Hongxia

    2015-04-01

    The identification of drug metabolites is very important in drug development. Nowadays, the most widely used methods are isotopes and mass spectrometry. However, the commercial isotopic labeled reagents are usually very expensive, and the rapid and convenient identification of metabolites is still difficult. In this paper, an (18)O isotope labeling strategy was developed and the isotopes were used as a tool to identify drug metabolites using mass spectrometry. Curcumin was selected as a model drug to evaluate the established method, and the (18)O labeled curcumin was successfully synthesized. The non-labeled and (18)O labeled curcumin were simultaneously metabolized in human liver microsomes (HLMs) and analyzed by liquid chromatography/mass spectrometry (LC-MS). The two groups of chromatograms obtained from metabolic reaction mixture with and without cofactors were compared and analyzed using Metabolynx software (Waters Corp., Milford, MA, USA). The mass spectra of the newly appearing chromatographic peaks in the experimental sample were further analyzed to find the metabolite candidates. Their chemical structures were confirmed by tandem mass spectrometry. Three metabolites, including two reduction products and a glucuronide conjugate, were successfully detected under their specific HLMs metabolic conditions, which were in accordance with the literature reported results. The results demonstrated that the developed isotope labeling method, together with post-acquisition data processing using Metabolynx software, could be used for fast identification of new drug metabolites.

  18. Liquid Chromatography Mass Spectrometry Profiling of Histones

    PubMed Central

    Su, Xiaodan; Jacob, Naduparambil K.; Amunugama, Ravindra; Lucas, David M.; Knapp, Amy R.; Ren, Chen; Davis, Melanie E.; Marcucci, Guido; Parthun, Mark R.; Byrd, John C.; Fishel, Richard A.; Freitas, Michael A.

    2007-01-01

    Here we describe the use of reverse-phase liquid chromatography mass spectrometry (RP-LC-MS) to simultaneously characterize variants and post-translationally modified isoforms for each histone. The analysis of intact proteins significantly reduces the time of sample preparation and simplifies data interpretation. LC-MS analysis and peptide mass mapping have previously been applied to identify histone proteins and to characterize their post-translational modifications. However, these studies provided limited characterization of both linker histones and core histones. The current LC-MS analysis allows for the simultaneous observation of all histone PTMs and variants (both replacement and bulk histones) without further enrichment, which will be valuable in comparative studies. Protein identities were verified by the analysis of histone H2A species using RPLC fractionation, AU-PAGE separation and nano-LC-MS/MS. PMID:17254850

  19. Mass spectrometry studies of fission product behavior: 2, Gas phase species

    SciTech Connect

    Blackburn, P.E.; Johnson, C.E.

    1987-01-01

    Revaporization of fission products from reactor system surfaces has become a complicating factor in source term definition. Critical to this phenomena is understanding the nature and behavior of the vapor phase species. This study characterizes the stability of the CsI . CsOH vapor phase complex. Vapor pressures were measured with a mass spectrometer. Thermodynamic data were obtained for CsOH(g), Cs/sub 2/(OH)/sub 2/(g), CsI(g), Cs/sub 2/I/sub 2/(g) and CsI . CsOH(g). Activity coefficients were derived for the CsI-CsOH system. The relative ionization cross section of CsOH is about ten times the cross section of CsI(g). CsI . CsOH fragments to Cs/sub 2/OH/sup +/ and an iodine atom. 17 refs., 4 figs., 6 tabs.

  20. The study of trace metal absoption using stable isotopes and mass spectrometry

    NASA Astrophysics Data System (ADS)

    Fennessey, P. V.; Lloyd-Kindstrand, L.; Hambidge, K. M.

    1991-12-01

    The absorption and excretion of zinc stable isotopes have been followed in more than 120 human subjects. The isotope enrichment determinations were made using a standard VG 7070E HF mass spectrometer. A fast atom gun (FAB) was used to form the ions from a dry residue on a pure silver probe tip. Isotope ratio measurements were found to have a precision of better than 2% (relative standard deviation) and required a sample size of 1-5 [mu]g. The average true absorption of zinc was found to be 73 ± 12% (2[sigma]) when the metal was taken in a fasting state. This absorption figure was corrected for tracer that had been absorbed and secreted into the gastrointestinal (GI) tract over the time course of the study. The average time for a majority of the stable isotope tracer to pass through the GI tract was 4.7 ± 1.9 (2[sigma]) days.

  1. Comparative study on pyrolysis of lignocellulosic and algal biomass using pyrolysis-gas chromatography/mass spectrometry.

    PubMed

    Li, Kai; Zhang, Liqiang; Zhu, Liang; Zhu, Xifeng

    2017-06-01

    The cornstalk and chlorella were selected as the representative of lignocelulosic and algal biomass, and the pyrolysis experiments of them were carried out using pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). The physicochemical properties of samples and the pyrolytic product distribution were presented. And then the compositional differences between the two kinds of pyrolytic products were studied, the relevant pyrolysis mechanisms were analyzed systematically. Pyrolytic vapor from lignocellulosic biomass contained more phenolic and carbonyl compounds while that from algal biomass contained more long-chain fatty acids, nitrogen-containing compounds and fewer carbonyl compounds. Maillard reaction is conducive to the conversion of carbonyl compounds to nitrogenous heterocyclic compounds with better thermal stability. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Laser desorption ionization mass spectrometry in the study of natural and synthetic melanins. II--Serotonin melanins.

    PubMed

    Bertazzo, A; Biasiolo, M; Costa, C; Allegri, G; Elli, G; Seraglia, R; Traldi, P

    1994-07-01

    Various biosynthetic melanins obtained by enzymic oxidation of serotonin with polyphenol oxidase from Psalliota campestris mushroom or potato, and with tyrosinase from Sepia officinalis or from Sigma were studied by means of laser desorption ionization mass spectrometry. Various oligomeric clusters were evidenced, proving that the examined melanins are composed of sets of different oligomers, the production of which strongly depends on the enzyme reaction. While serotonin melanins obtained with polyphenol oxidase from potato showed wide species distribution with molecular weights ranging from 2008 to 13,000 Da, the same melanins obtained from mushroom showed oligomer distributions from 1505 to 9000 Da. Serotonin melanins prepared with tyrosinase from Sepia showed oligomers from 1636 to 18,000 Da. A dopa-melanin obtained with mushroom polyphenol oxidase showed oligomer species from 1709 to 17,874 Da. Comparison of molecular weight distributions of the various oligomer sets in serotonin melanins with those in tyrosine melanins revealed clear differences, which are investigated and discussed.

  3. Complexation of diazaperylene and bisisoquinoline with transition metal ions in the gas phase studied by electrospray ionization mass spectrometry.

    PubMed

    Starke, Ines; Kammer, Stefan; Grunwald, Nicolas; Schilde, Uwe; Holdt, Hans-Jürgen; Kleinpeter, Erich

    2008-01-01

    The complex formation of the ligands 1,12-diazaperylene (dap), 1,1'-bisisoquinoline (bis), 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen) with transition metal ions (M = Fe, Co, Ni, Cu, Zn, Ru, Os, Re, Pd, Pt, Ag and Cd) in the gas phase has been studied by electrospray ionization mass spectrometry. With the exception of Ru, Os, Fe, Ni and Cu, singly charged complexes [MLn](+) (n = 1,2) were observed. The complexes of dap and bis with Ru, Os, Fe and Ni ions, and the mixed ligand complexes with bpy and phen, are preferably of the doubly charged type [ML3]2+. In addition, collision-induced dissociation (CID) measurements were employed to evaluate the relative stabilities of these complexes. The CID experiments of mixed-ligand complexes which contain both dap and phen or dap and bpy exhibit preferential elimination of bpy, indicating that bpy is a weaker ligand than phen and dap.

  4. Research Using Accelerator Mass Spectrometry at Arizona

    NASA Astrophysics Data System (ADS)

    Jull, A.; Donahue, D. J.; Burr, G. S.; Beck, W.; Hatheway, A. L.; Biddulph, D. L.; McHargue, L. R.

    2002-12-01

    An Accelerator Mass Spectrometry (AMS) facility has been operated at the University of Arizona since 1982. This is an excellent example of a facility which has benefitted from the NSF Earth Sciences Instrumentation and Facilities Program. AMS has many applications to the fields of geochronology, geoarchaeology, paleoclimatology. A wide range of climatic, geologic and archeological records can be characterized by measuring their 14C and 10Be concentrations, using accelerator mass spectrometry (AMS). These records are found not only in the traditional sampling sites such as lake sediments and ice cores, but also in diverse natural accumulates and biogeochemical products such as: loess/paleosol deposits, corals, speleothems, and forest-fire horizons. The in-situ production of cosmogenic radionuclides in terrestrial and extraterrestrial materials provides several possibilities of determining their chronology. Thes studies are important for understanding cosmic-ray production of radionuclides in rock surfaces, by which we can draw conclusions about exposure time and erosion. Studies on extraterrestrial materials such as lunar samples allow us to determine the solar and galactic cosmic-ray fluxes in the past, and the cosmogenic 14C and 10Be in meteorites can be used to determine terrestrial ages. In this paper, we will highlight some selected applications of AMS, including dating of some interesting art works and artifacts, to show some of the great range of studies which can be undertaken.

  5. Effects of anthropogenic emissions on the molecular composition of urban organic aerosols: An ultrahigh resolution mass spectrometry study

    NASA Astrophysics Data System (ADS)

    Kourtchev, I.; O'Connor, I. P.; Giorio, C.; Fuller, S. J.; Kristensen, K.; Maenhaut, W.; Wenger, J. C.; Sodeau, J. R.; Glasius, M.; Kalberer, M.

    2014-06-01

    Identification of the organic composition of atmospheric aerosols is necessary to develop effective air pollution mitigation strategies. However, the majority of the organic aerosol mass is poorly characterized and its detailed analysis is a major analytical challenge. In this study, we applied state-of-the-art direct infusion nano-electrospray (nanoESI) ultrahigh resolution mass spectrometry (UHRMS) and liquid chromatography ESI Quadrupole Time-of-Flight (Q-TOF) MS for the analysis of the organic fraction of fine particulate matter (PM2.5) collected at an urban location in Cork, Ireland. Comprehensive mass spectral data evaluation methods (e.g., Kendrick Mass Defect and Van Krevelen) were used to identify compound classes and mass distributions of the detected species. Up to 850 elemental formulae were identified in negative mode nanoESI-UHR-MS. Nitrogen and/or sulphur containing organic species contributed up to 40% of the total identified formulae and exhibited strong diurnal variations suggesting the importance of night-time NO3 chemistry at the site. The presence of a large number of oxidised aromatic and nitroaromatic compounds in the samples indicated a strong anthropogenic influence, i.e., from traffic emissions and domestic solid fuel (DSF) burning. Most of the identified biogenic secondary organic aerosol (SOA) compounds are later-generation nitrogen- and sulphur-containing products, indicating that SOA composition is strongly affected by anthropogenic species such as NOx and SO2. Unsaturated and saturated C12-C20 fatty acids were found to be the most abundant homologs with a composition reflecting a primary marine origin. The results of this work demonstrate that the studied site is a very complex environment affected by a variety of anthropogenic activities and natural sources.

  6. Clarification of pathway-specific inhibition by Fourier transform ion cyclotron resonance/mass spectrometry-based metabolic phenotyping studies.

    PubMed

    Oikawa, Akira; Nakamura, Yukiko; Ogura, Tomonori; Kimura, Atsuko; Suzuki, Hideyuki; Sakurai, Nozomu; Shinbo, Yoko; Shibata, Daisuke; Kanaya, Shigehiko; Ohta, Daisaku

    2006-10-01

    We have developed a metabolic profiling scheme based on direct-infusion Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR/MS). The scheme consists of: (1) reproducible data collection under optimized FT-ICR/MS analytical conditions; (2) automatic mass-error correction and multivariate analyses for metabolome characterization using a newly developed metabolomics tool (DMASS software); (3) identification of marker metabolite candidates by searching a species-metabolite relationship database, KNApSAcK; and (4) structural analyses by an MS/MS method. The scheme was applied to metabolic phenotyping of Arabidopsis (Arabidopsis thaliana) seedlings treated with different herbicidal chemical classes for pathway-specific inhibitions. Arabidopsis extracts were directly infused into an electrospray ionization source on an FT-ICR/MS system. Acquired metabolomics data were comprised of mass-to-charge ratio values with ion intensity information subjected to principal component analysis, and metabolic phenotypes from the herbicide treatments were clearly differentiated from those of the herbicide-free treatment. From each herbicide treatment, candidate metabolites representing such metabolic phenotypes were found through the KNApSAcK database search. The database search and MS/MS analyses suggested dose-dependent accumulation patterns of specific metabolites including several flavonoid glycosides. The metabolic phenotyping scheme on the basis of FT-ICR/MS coupled with the DMASS program is discussed as a general tool for high throughput metabolic phenotyping studies.

  7. Alkali-cation affinities of polyoxyethylene dodecylethers and helical conformations of their cationized molecules studied by electrospray mass spectrometry.

    PubMed

    Yokoyama, Yukio; Hirajima, Rui; Morigaki, Ken; Yamaguchi, Yoshitaka; Ueda, Kazuyoshi

    2007-11-01

    Relative alkali-cation affinity of polyoxyethylene (POE) dodecylethers in gas phase was studied by electrospray ionization (ESI) mass spectrometry using dodecylether-poly-ethoxylate (C(12)EO:n, "n" denotes ethyleneoxide unit number) nonionic surfactants, and possible helical conformations of the cationized molecules were demonstrated. The alkali-cation affinity highly depended on the cation diameters. The mass spectra of C(12)EO:8 cationized by alkali-metal ions were dominated by potassiated molecules. The results indicated that the POE moiety could have specific affinity to K(+) ions based on a host-guest interaction between POE helix and potassium ions. This is very similar to the relationships between 18-crown-6 and K(+). The ESI mass spectra exhibited the multiply cationized C(12)EO:n in addition to the singly cationized molecules. The critical EO unit numbers necessary for producing the multiply-charged cationized molecules also depended on the cation diameters. In addition, the POE surfactants highly preferred alkali cations to proton. The results were strongly supported by molecular mechanics/dynamics calculations. A helical conformation of the POE moiety of C(12)EO:15 including two K(+) ions gave a potential minimum, while a lowest energy structure of the protonated molecule took irregular conformations due to the formation of local hydrogen bonds.

  8. Challenges in mass spectrometry-based quantification of bioactive peptides: a case study exploring the neuropeptide Y family.

    PubMed

    Xi, Li; Jin, Yaping; Parker, Edward A; Josh, Peter; Jones, Alun; Wijffels, Gene; Colgrave, Michelle L

    2012-01-01

    The study of biologically active peptides is critical to the understanding of physiological pathways, especially those involved in the development of disease. Historically, the measurement of biologically active endogenous peptides has been undertaken by radioimmunoassay, a highly sensitive and robust technique that permits the detection of physiological concentrations in different biofluid and tissue extracts. Over recent years, a range of mass spectrometric approaches have been applied to peptide quantification with limited degrees of success. Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) belong to the NPY family exhibiting regulatory effects on appetite and feeding behavior. The physiological significance of these peptides depends on their molecular forms and in vivo concentrations systemically and at local sites within tissues. In this report, we describe an approach for quantification of individual peptides within mixtures using high-performance liquid chromatography electrospray ionization tandem mass spectrometry analysis of the NPY family peptides. Aspects of quantification including sample preparation, the use of matrix-matched calibration curves, and internal standards will be discussed. This method for the simultaneous determination of NPY, PYY, and PP was accurate and reproducible but lacks the sensitivity required for measurement of their endogenous concentration in plasma. The advantages of mass spectrometric quantification will be discussed alongside the current obstacles and challenges.

  9. Systematic study of high molecular weight compounds in Amazonian plants by high temperature gas chromatography-mass spectrometry.

    PubMed

    de Siqueira, D S; Pereira, A S; Cabral, J A; Cid Ferreira, C A; de Aquino Neto, F R

    2000-01-01

    The fractions of hexane and dichloromethane extraction from marupá (Simaruba amara) and (Bertholletia excelsa) leaves were analyzed by HT-HRGC (high temperature high resolution gas chromatography) and HT-HRGC coupled to mass spectrometry (HT-HRGC-MS). Several compounds can be characterized including unusual high molecular weight compounds.

  10. MALDI mass spectrometry imaging in rheumatic diseases.

    PubMed

    Rocha, Beatriz; Cillero-Pastor, Berta; Blanco, Francisco J; Ruiz-Romero, Cristina

    2017-07-01

    Mass spectrometry imaging (MSI) is a technique used to visualize the spatial distribution of biomolecules such as peptides, proteins, lipids or other organic compounds by their molecular masses. Among the different MSI strategies, MALDI-MSI provides a sensitive and label-free approach for imaging of a wide variety of protein or peptide biomarkers from the surface of tissue sections, being currently used in an increasing number of biomedical applications such as biomarker discovery and tissue classification. In the field of rheumatology, MALDI-MSI has been applied to date for the analysis of joint tissues such as synovial membrane or cartilage. This review summarizes the studies and key achievements obtained using MALDI-MSI to increase understanding on rheumatic pathologies and to describe potential diagnostic or prognostic biomarkers of these diseases. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Glossary of terms for separations coupled to mass spectrometry.

    PubMed

    Murray, Kermit K

    2010-06-18

    This document is a glossary of terms for separations coupled to mass spectrometry. It covers gas chromatography/mass spectrometry, liquid chromatography/mass spectrometry, and supercritical fluid chromatography/mass spectrometry and the sample introduction, ionization, and data analysis methods used with these combined techniques. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  12. Mass spectrometry: a revolution in clinical microbiology?

    PubMed

    Lavigne, Jean-Philippe; Espinal, Paula; Dunyach-Remy, Catherine; Messad, Nourredine; Pantel, Alix; Sotto, Albert

    2013-02-01

    Recently, different bacteriological laboratory interventions that decrease reporting time have been developed. These promising new broad-based techniques have merit, based on their ability to identify rapidly many bacteria, organisms difficult to grow or newly emerging strains, as well as their capacity to track disease transmission. The benefit of rapid reporting of identification and/or resistance of bacteria can greatly impact patient outcomes, with an improvement in the use of antibiotics, in the reduction of the emergence of multidrug resistant bacteria and in mortality rates. Different techniques revolve around mass spectrometry (MS) technology: matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), PCR combined with electrospray ionization-mass spectrometry (PCR/ESIMS), iPLEX MassArray system and other new evolutions combining different techniques. This report emphasizes the (r)evolution of these technologies in clinical microbiology.

  13. Analytical aspects of hydrogen exchange mass spectrometry

    PubMed Central

    Engen, John R.; Wales, Thomas E.

    2016-01-01

    The analytical aspects of measuring hydrogen exchange by mass spectrometry are reviewed. The nature of analytical selectivity in hydrogen exchange is described followed by review of the analytical tools required to accomplish fragmentation, separation, and the mass spectrometry measurements under restrictive exchange quench conditions. In contrast to analytical quantitation that relies on measurements of peak intensity or area, quantitation in hydrogen exchange mass spectrometry depends on measuring a mass change with respect to an undeuterated or deuterated control, resulting in a value between zero and the maximum amount of deuterium that could be incorporated. Reliable quantitation is a function of experimental fidelity and to achieve high measurement reproducibility, a large number of experimental variables must be controlled during sample preparation and analysis. The method also reports on important qualitative aspects of the sample, including conformational heterogeneity and population dynamics. PMID:26048552

  14. Mass Spectrometry: A Technique of Many Faces

    PubMed Central

    Olshina, Maya A.; Sharon, Michal

    2016-01-01

    Protein complexes form the critical foundation for a wide range of biological process, however understanding the intricate details of their activities is often challenging. In this review we describe how mass spectrometry plays a key role in the analysis of protein assemblies and the cellular pathways which they are involved in. Specifically, we discuss how the versatility of mass spectrometric approaches provides unprecedented information on multiple levels. We demonstrate this on the ubiquitin-proteasome proteolytic pathway, a process that is responsible for protein turnover. We follow the various steps of this degradation route and illustrate the different mass spectrometry workflows that were applied for elucidating molecular information. Overall, this review aims to stimulate the integrated use of multiple mass spectrometry approaches for analyzing complex biological systems. PMID:28100928

  15. Studying interfacial reactions of cholesterol sulfate in an unsaturated phosphatidylglycerol layer with ozone using field induced droplet ionization mass spectrometry.

    PubMed

    Ko, Jae Yoon; Choi, Sun Mi; Rhee, Young Min; Beauchamp, J L; Kim, Hugh I

    2012-01-01

    Field-induced droplet ionization (FIDI) is a recently developed ionization technique that can transfer ions from the surface of microliter droplets to the gas phase intact. The air-liquid interfacial reactions of cholesterol sulfate (CholSO(4)) in a 1-palmitoyl-2-oleoyl-sn-phosphatidylglycerol (POPG) surfactant layer with ozone (O(3)) are investigated using field-induced droplet ionization mass spectrometry (FIDI-MS). Time-resolved studies of interfacial ozonolysis of CholSO(4) reveal that water plays an important role in forming oxygenated products. An epoxide derivative is observed as a major product of CholSO(4) oxidation in the FIDI-MS spectrum after exposure of the droplet to O(3) for 5 s. The abundance of the epoxide product then decreases with continued O(3) exposure as the finite number of water molecules at the air-liquid interface becomes exhausted. Competitive oxidation of CholSO(4) and POPG is observed when they are present together in a lipid surfactant layer at the air-liquid interface. Competitive reactions of CholSO(4) and POPG with O(3) suggest that CholSO(4) is present with POPG as a well-mixed interfacial layer. Compared with CholSO(4) and POPG alone, the overall ozonolysis rates of both CholSO(4) and POPG are reduced in a mixed layer, suggesting the double bonds of both molecules are shielded by additional hydrocarbons from one another. Molecular dynamics simulations of a monolayer comprising POPG and CholSO(4) correlate well with experimental observations and provide a detailed picture of the interactions between CholSO(4), lipids, and water molecules in the interfacial region. © American Society for Mass Spectrometry, 2011

  16. Study of Adsorption and Desorption Performances of Zr-Based Metal-Organic Frameworks Using Paper Spray Mass Spectrometry.

    PubMed

    Wang, Xiaoting; Chen, Ying; Zheng, Yajun; Zhang, Zhiping

    2017-07-08

    The dynamic pore systems and high surface areas of flexible metal-organic framework materials make them excellent candidates to be used in different kinds of adsorption processes. However, the adsorption and desorption behaviors of therapeutic drugs on metal-organic frameworks in solution are not fully developed. Here, we systematically investigated the adsorption and desorption behaviors of a typical therapeutic drug, verapamil, over several Zr-based metal-organic frameworks [e.g., Zr-FUM, UiO-66(Zr), UiO-66(Zr)-NH₂ and UiO-66(Zr)-2COOH] as well as ZrO₂ in an acetonitrile solution by using paper spray mass spectrometry. In contrast to other materials, UiO-66(Zr)-2COOH demonstrated a superior adsorption performance to verapamil due to their strong acid-base and/or hydrogen-bond interactions, and the adsorption process fitted well with the pseudo-second-order kinetic model. As verapamil-adsorbed materials were used for desorption experiments, ZrO₂ demonstrated the most favorable desorption performance, whereas UiO-66(Zr)-2COOH yielded the poorest desorption capability. These Zr-based materials had also been coated at the surface with filter papers for the analysis of various drugs and proteins in the process of paper spray mass spectrometry. The results demonstrated that among the studied materials, ZrO₂-coated paper gave the most favorable desorption performance as a pure drug solution, whereas the paper from UiO-66(Zr) demonstrated the optimal capability in the analyses of therapeutic drugs in a complex matrix (e.g., blood) and a protein (e.g., myoglobin).

  17. When is Mass Spectrometry Combined with Affinity Approaches Essential? A Case Study of Tyrosine Nitration in Proteins

    NASA Astrophysics Data System (ADS)

    Petre, Brînduşa-Alina; Ulrich, Martina; Stumbaum, Mihaela; Bernevic, Bogdan; Moise, Adrian; Döring, Gerd; Przybylski, Michael

    2012-11-01

    Tyrosine nitration in proteins occurs under physiologic conditions and is increased at disease conditions associated with oxidative stress, such as inflammation and Alzheimer's disease. Identification and quantification of tyrosine-nitrations are crucial for understanding nitration mechanism(s) and their functional consequences. Mass spectrometry (MS) is best suited to identify nitration sites, but is hampered by low stabilities and modification levels and possible structural changes induced by nitration. In this insight, we discuss methods for identifying and quantifying nitration sites by proteolytic affinity extraction using nitrotyrosine (NT)-specific antibodies, in combination with electrospray-MS. The efficiency of this approach is illustrated by identification of specific nitration sites in two proteins in eosinophil granules from several biological samples, eosinophil-cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). Affinity extraction combined with Edman sequencing enabled the quantification of nitration levels, which were found to be 8 % and 15 % for ECP and EDN, respectively. Structure modeling utilizing available crystal structures and affinity studies using synthetic NT-peptides suggest a tyrosine nitration sequence motif comprising positively charged residues in the vicinity of the NT- residue, located at specific surface- accessible sites of the protein structure. Affinities of Tyr-nitrated peptides from ECP and EDN to NT-antibodies, determined by online bioaffinity- MS, provided nanomolar KD values. In contrast, false-positive identifications of nitrations were obtained in proteins from cystic fibrosis patients upon using NT-specific antibodies, and were shown to be hydroxy-tyrosine modifications. These results demonstrate affinity- mass spectrometry approaches to be essential for unequivocal identification of biological tyrosine nitrations.

  18. Study of Adsorption and Desorption Performances of Zr-Based Metal–Organic Frameworks Using Paper Spray Mass Spectrometry

    PubMed Central

    Wang, Xiaoting; Chen, Ying; Zheng, Yajun

    2017-01-01

    The dynamic pore systems and high surface areas of flexible metal–organic framework materials make them excellent candidates to be used in different kinds of adsorption processes. However, the adsorption and desorption behaviors of therapeutic drugs on metal–organic frameworks in solution are not fully developed. Here, we systematically investigated the adsorption and desorption behaviors of a typical therapeutic drug, verapamil, over several Zr-based metal–organic frameworks [e.g., Zr-FUM, UiO-66(Zr), UiO-66(Zr)-NH2 and UiO-66(Zr)-2COOH] as well as ZrO2 in an acetonitrile solution by using paper spray mass spectrometry. In contrast to other materials, UiO-66(Zr)-2COOH demonstrated a superior adsorption performance to verapamil due to their strong acid-base and/or hydrogen-bond interactions, and the adsorption process fitted well with the pseudo-second-order kinetic model. As verapamil-adsorbed materials were used for desorption experiments, ZrO2 demonstrated the most favorable desorption performance, whereas UiO-66(Zr)-2COOH yielded the poorest desorption capability. These Zr-based materials had also been coated at the surface with filter papers for the analysis of various drugs and proteins in the process of paper spray mass spectrometry. The results demonstrated that among the studied materials, ZrO2-coated paper gave the most favorable desorption performance as a pure drug solution, whereas the paper from UiO-66(Zr) demonstrated the optimal capability in the analyses of therapeutic drugs in a complex matrix (e.g., blood) and a protein (e.g., myoglobin). PMID:28773131

  19. The study of large biopolymer complexes in solution and the gas phase using electrospray ionization-FTICR mass spectrometry

    SciTech Connect

    Smith, R.D.; Lei, Q.P.; Wu, Qinyuan; Hofstadler, A.

    1997-12-31

    Electrospray ionization (ESI) can transfer large biopolymers and many noncovalently bound complexes into the gas phase and to preserve specific noncovalent biomolecular associations for subsequent mass spectrometric analysis. Although a number of details of the ESI process remain a subject of debate, it is now incontestable that many weak associations can survive transfer to the gas phase and are stable for periods of at least seconds. In this presentation, the application of ESI-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry methods for the study of large biopolymers and their noncovalent complexes will be described. It will also be shown that competitive binding studies can be used to quickly establish relative binding affinities in solution, allowing combinatorial libraries to be rapidly screened. After measurements of the intact complex, dissociation studies can be conducted to probe the structure of the individual constituents of complexes. Studies comparing the relative stabilities of protein-ligand complexes in solution and desolvated in the gas phase will also be presented, and discussed from both fundamental and analytical perspectives.

  20. Pharmacokinetic studies of novel berberine derivatives with ultra-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Wang, Wenchao; Shen, Qin; Liang, Hui; Hua, Changlong; Liu, Yuhui; Li, Fengzhi; Li, Qingyong

    2016-09-15

    An ultra-performance liquid chromatography with tandem mass spectrometric detection method was developed for the detection of berberine and its derivatives (A4, B4) in rat plasma and other organs. This validated method was successfully applied to our pharmacokinetic study of BBR derivatives in rats. At the same dose of administration, the Cmax of B4 was about eight times higher than BBR, and its half-life was approximately two times longer than BBR, according to the bigger areas under plasma concentration curves. Inversely, the pharmacokinetic parameter levels of A4 were all inferior to BBR, suggesting a tight structure-activity relationship of these compounds. Small dose of parenteral administration was used for the study of absolute oral bioavailability of A4, B4, and BBR, and the results calculated were 0.12%, 3.4% and 0.7%, respectively. The accumulations of B4 among all organs were intestine>liver>heart>kidney>lung>spleen>plasma, proving a deeply targeting property of B4, which met our experimental assumption. Together, the experimental results proved that compared with BBR and A4, the derivative B4 had higher absolute oral bioavailability and the ability of deeply targeting so that can be likely used in some organ-targeted diseases.

  1. Thermodynamic study of gaseous CsBO2 by Knudsen effusion mass spectrometry

    NASA Astrophysics Data System (ADS)

    Nakajima, K.; Takai, T.; Furukawa, T.; Osaka, M.

    2017-08-01

    One of the main chemical forms of cesium in the gas phase during severe light-water reactor accidents is expected to be cesium metaborate, CsBO2, according to thermodynamic equilibrium calculations considering its reaction with boron. However, the accuracy of the thermodynamic data of the gaseous metaborate, CsBO2(g), has been judged as poor. Thus, Knudsen effusion mass spectrometric measurements of CsBO2 were carried out to obtain reliable thermodynamic data. The evaluated values of the standard enthalpy of formation of CsBO2(g), obtained by the 2nd and 3rd-law treatments, are -700.7 ± 10.7 kJ/mol and -697.0 ± 10.6 kJ/mol, respectively, and agree with each other within the experimental errors, which indicates that our data are reliable. Furthermore, it was found that the existing data of the Gibbs energy function and the standard enthalpy of formation agreed well with the values evaluated in this study, which indicates that the existing thermodynamic data are also reliable.

  2. High Resolution Studies of the Origins of Polyatomic Ions in Inductively Coupled Plasma-Mass Spectrometry

    SciTech Connect

    Ferguson, Jill Wisnewski

    2006-01-01

    The inductively coupled plasma (ICP) is an atmospheric pressure ionization source. Traditionally, the plasma is sampled via a sampler cone. A supersonic jet develops behind the sampler, and this region is pumped down to a pressure of approximately one Torr. A skimmer cone is located inside this zone of silence to transmit ions into the mass spectrometer. The position of the sampler and skimmer cones relative to the initial radiation and normal analytical zones of the plasma is key to optimizing the useful analytical signal [1]. The ICP both atomizes and ionizes the sample. Polyatomic ions form through ion-molecule interactions either in the ICP or during ion extraction [l]. Common polyatomic ions that inhibit analysis include metal oxides (MO+), adducts with argon, the gas most commonly used to make up the plasma, and hydride species. While high resolution devices can separate many analytes from common interferences, this is done at great cost in ion transmission efficiency--a loss of 99% when using high versus low resolution on the same instrument [2]. Simple quadrupole devices, which make up the bulk of ICP-MS instruments in existence, do not present this option. Therefore, if the source of polyatomic interferences can be determined and then manipulated, this could potentially improve the figures of merit on all ICP-MS devices, not just the high resolution devices often utilized to study polyatomic interferences.

  3. Liquid chromatography-mass spectrometry analysis of diethylcarbamazine in human plasma for clinical pharmacokinetic studies.

    PubMed

    Schmidt, Mark S; King, Christopher L; Thomsen, Edward K; Siba, Peter M; Sanuku, Nelly; Fleckenstein, Lawrence

    2014-09-01

    A sensitive and selective liquid chromatographic method using mass spectrometric detection was developed for the determination of diethylcarbamazine (DEC) in human plasma. DEC and its stable isotope internal standard d3-DEC were extracted from 0.25mL of human plasma using solid phase extraction. Chromatography was performed using a Phenomenex Synergi 4μ Fusion-RP column (2mm×250mm) with gradient elution. The retention time was approximately 4.8min. The assay was linear from 4 to 2200ng/mL. Analysis of quality control samples at 12, 300, and 1700ng/mL (N=15) had interday coefficients of variation of 8.4%, 5.4%, and 6.2%, respectively (N=15). Interday bias results were -2.2%, 6.0%, and 0.8%, respectively. Recovery of DEC from plasma ranged from 84.2% to 90.1%. The method was successfully applied to clinical samples from patients with lymphatic filariasis from a drug-drug interaction study between DEC and albendazole and/or ivermectin.

  4. Aerosol Composition in the Los Angeles Basin Studied by High Resolution Aerosol Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Hayes, P. L.; Ortega, A. M.; Cubison, M.; Hu, W.; Toohey, D. W.; Flynn, J. H.; Grossberg, N.; Lefer, B. L.; Alvarez, S. L.; Rappenglueck, B.; Allan, J. D.; Taylor, J.; Holloway, J. S.; Gilman, J. B.; Kuster, W. C.; De Gouw, J. A.; Massoli, P.; Zhang, X.; Weber, R.; Zhao, Y.; Cliff, S. S.; Wexler, A. S.; Isaacman, G. A.; Worton, D. R.; Kreisberg, N. M.; Hering, S. V.; Goldstein, A. H.; Jimenez, J. L.

    2011-12-01

    Atmospheric aerosols impact climate and health, but their sources and composition are poorly understood. To address this knowledge gap, a high-resolution aerosol mass spectrometer (AMS) and complementary instrumentation were deployed during the 2010 CalNex campaign to characterize aerosol composition in the Los Angeles (LA) area. Total mass concentrations as well as the species concentrations measured by the AMS compare well with most other instruments. Nitrate dominates in the mornings, but its concentration is reduced in the afternoon when organic aerosols (OA) increase and dominate. The diurnal variations in concentrations are strongly influenced by emission transport from the source-rich western basin. The average OA to enhanced CO ratio increases with photochemical age from 25 to 80 μg m-3 ppm-1, which indicates significant secondary OA (SOA) production and that a large majority of OA is secondary in aged air. The ratio values are similar to those from Mexico City as well as New England and the Mid-Atlantic States. Positive matrix factorization (PMF) is used to assess the concentrations of different OA components. The major OA classes are oxygenated OA (OOA, a surrogate for total SOA), and hydrocarbon-like OA (HOA, a surrogate for primary combustion OA). Several subclasses of OA are identified as well including diesel-influenced HOA (DI-HOA) and non-diesel HOA. DI-HOA exhibits low concentrations on Sundays consistent with the well-known weekday/weekend effect in LA. PMF analysis finds that OOA is 67% of the total OA concentration. A strong correlation between OOA and Ox (O3 + NO2) concentrations is observed with a slope of 0.15 that suggests the production of fresh SOA in Pasadena. Plotting the OA elemental ratios in a Van Krevelen diagram (H:C vs. O:C) yields a slope of -0.6, which is less steep than that observed in Riverside during the SOAR-2005 campaign. The difference in slopes may be attributed to the highly oxidized HOA present in Pasadena that is

  5. Isotope ratio mass spectrometry in nutrition research

    SciTech Connect

    Luke, A.H.

    1994-12-31

    Many of the biochemical pathways and processes that form the foundation of modern nutrition research was elucidated using stable isotopes as physiological tracers. Since the discovery of stable isotopes, improvements and innovations in mass spectrometry and chromatography have led to greatly expanded applications. This research project was designed to evaluate gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) as a tool for isotopic tracer studies and to delineate the operational parameters for the analysis of {sup 13}C-labeled cholesterol, leucine and {alpha}-ketoisocaproate. The same isotope ratio mass spectrometer was then used as the base instrument for the ratio mass spectrometer was then used as the base instrument for the development of two additional inlet systems: a continuous-flow inlet for the analyses of {sup 13}C and {sup 18}O as CO{sub 2} and a filament inlet for on-line combustion and isotopic analysis of non-volatile organic compounds. Each of these three inlets was evaluated and their utility in nutrition research illustrated. GC/C/IRMS was used to analyze cholesterol, leucine and {alpha}-ketoisocaproate with good accuracy, precision and little isotopic memory. For all three compounds the detection limits achieved well surpassed currently used technologies. For compounds that can be well separated by GC, GC/C/IRMS is a valuable analytical tool. The continuous-flow inlet provided good accuracy and precision for measurements of {sup 13}CO{sub 2} from breath tests and {sup 18}O as CO{sub 2} from total energy expenditure tests. Most importantly, the continuous-flow inlet increased sample throughput by at least a factor of three over conventional analytical techniques. The filament inlet provided accurate and precise {sup 13}C ratio measurements of both natural abundance and enriched standards of non-volatile organic compounds of physiological interest.

  6. The allure of mass spectrometry: From an earlyday chemist's perspective.

    PubMed

    Tőkés, László

    2017-07-01

    This reminiscing review article is an account of the author's fascination and involvements with mass spectrometry from the perspective of an organic chemist with an interest in natural product chemistry. It covers a period from 1961 through the mid 1990s as mass spectrometry evolved form a novelty technique to become a most widely used analytical technique. Following a brief synopsis of my pathway to mass spectrometry, my research efforts in this field are presented with a focus mainly on evolving principles and technologies which I had personal involvements with. To provide historical perspectives, discussions of these developments are accompanied by brief outlines of the relevant state-of-the-art, shedding light on the technical and conceptual challenges encountered during those early days in mass spectrometry. Examples are presented of my involvements with basic and applied research in mass spectrometry during graduate studies at Stanford University and close to three decade tenure in pharmaceutical research at Syntex Research. My basic research interests focused mainly on principles of electron ionization induced fragmentation mechanisms, with an emphasis on steroids and other model compounds. Extensive deuterium labeling evidence was used to determine the fragmentation mechanisms of the diagnostically significant ions in the spectra of numerous model compounds, uncovering examples of wide-ranging hydrogen transfers, skeletal rearrangements, methyl and phenyl migrations, stereoselective fragmentations and low and high energy fragmentation processes. Depiction of the industrial research phase of my career includes comments on the pivotal role mass spectrometry played on advancing modern pharmaceutical research. Examples are presented of involvements with instrumental developments and a few select cases of applied research, including studies of bile mechanisms in vertebrates, identification of bisphenol-A leaching from sterilized polycarbonate containers, high

  7. Protein Quantitation of the Developing Cochlea Using Mass Spectrometry.

    PubMed

    Darville, Lancia N F; Sokolowski, Bernd H A

    2016-01-01

    Mass spectrometry-based proteomics allows for the measurement of hundreds to thousands of proteins in a biological system. Additionally, mass spectrometry can also be used to quantify proteins and peptides. However, observing quantitative differences between biological systems using mass spectrometry-based proteomics can be challenging because it is critical to have a method that is fast, reproducible, and accurate. Therefore, to study differential protein expression in biological samples labeling or label-free quantitative methods can be used. Labeling methods have been widely used in quantitative proteomics, however label-free methods have become equally as popular and more preferred because they produce faster, cleaner, and simpler results. Here, we describe the methods by which proteins are isolated and identified from cochlear sensory epithelia tissues at different ages and quantitatively differentiated using label-free mass spectrometry.

  8. Mass Spectrometry of Membrane Proteins: A Focus on Aquaporins

    PubMed Central

    Schey, Kevin L.; Grey, Angus C.; Nicklay, Joshua J.

    2015-01-01

    Membrane proteins are abundant, critically important biomolecules that conduct essential functions in all cells and are the targets of a significant number of therapeutic drugs. However, the analysis of their expression, modification, protein–protein interactions, and structure by mass spectrometry has lagged behind similar studies of soluble proteins. Here we review the limitations to analysis of integral membrane and membrane-associated proteins and highlight advances in sample preparation and mass spectrometry methods that have led to the successful analysis of this protein class. Advances in the analysis of membrane protein posttranslational modification, protein–protein interaction, protein structure, and tissue distributions by imaging mass spectrometry are discussed. Furthermore, we focus our discussion on the application of mass spectrometry for the analysis of aquaporins as a prototypical integral membrane protein and how advances in analytical methods have revealed new biological insights into the structure and function of this family of proteins. PMID:23394619

  9. Mass spectrometry of membrane proteins: a focus on aquaporins.

    PubMed

    Schey, Kevin L; Grey, Angus C; Nicklay, Joshua J

    2013-06-04

    Membrane proteins are abundant, critically important biomolecules that conduct essential functions in all cells and are the targets of a significant number of therapeutic drugs. However, the analysis of their expression, modification, protein-protein interactions, and structure by mass spectrometry has lagged behind similar studies of soluble proteins. Here we review the limitations to analysis of integral membrane and membrane-associated proteins and highlight advances in sample preparation and mass spectrometry methods that have led to the successful analysis of this protein class. Advances in the analysis of membrane protein posttranslational modification, protein-protein interaction, protein structure, and tissue distributions by imaging mass spectrometry are discussed. Furthermore, we focus our discussion on the application of mass spectrometry for the analysis of aquaporins as a prototypical integral membrane protein and how advances in analytical methods have revealed new biological insights into the structure and function of this family of proteins.

  10. Optimization study for metabolomics analysis of human sweat by liquid chromatography-tandem mass spectrometry in high resolution mode.

    PubMed

    Calderón-Santiago, M; Priego-Capote, F; Jurado-Gámez, B; Luque de Castro, M D

    2014-03-14

    Sweat has recently gained popularity as a potential tool for diagnostics and biomarker monitoring as it is a non-invasive biofluid the composition of which could be modified by certain pathologies, as is the case with cystic fibrosis, which increases chloride levels in sweat. The aim of the present study was to develop an analytical method for analysis of human sweat by liquid chromatography-mass spectrometry (LC-Q-TOF MS/MS) in high resolution mode. Thus, different sample preparation strategies and different chromatographic modes (HILIC and C18 reverse modes) were compared to check their effect on the profile of sweat metabolites. Forty-one compounds were identified by the MS/MS information obtained with a mass tolerance window below 4 ppm. Amino acids, dicarboxylic acids and other interesting metabolites such as inosine, choline, uric acid and tyramine were identified. Among the tested protocols, direct analysis after dilution was a suited option to obtain a representative snapshot of sweat metabolome. In addition, sample clean up by C18 SpinColumn SPE cartridges improved the sensitivity of most identified compounds and reduced the number of interferents. As most of the identified metabolites are involved in key biochemical pathways, this study opens new possibilities to the use of sweat as a source of metabolite biomarkers of specific disorders.

  11. Structural varieties of selectively mixed G- and C-rich short DNA sequences studied with electrospray ionization mass spectrometry.

    PubMed

    Cao, Yanwei; Gao, Shang; Li, Caijin; Yan, Yuting; Wang, Bing; Guo, Xinhua

    2016-10-01

    Short guanine(G)-repeat and cytosine(C)-repeat DNA strands can self-assemble to form four-stranded G-quadruplexes and i-motifs, respectively. Herein, G-rich and C-rich strands with non-G or non-C terminal bases and different lengths of G- or C-repeats are mixed selectively in pH 4.5 and 6.7 ammonium acetate buffer solutions and studied by electrospray ionization mass spectrometry (ESI-MS). Various strand associations corresponding to bi-, tri- and tetramolecular ions are observed in mass spectra, indicating that the formation of quadruplex structures is a random strand by strand association process. However, with increasing incubation time for the mixtures, initially associated hybrid tetramers will transform into self-assembled conformations, which is mainly driven by the structural stability. The melting temperature values of self-assembled quadruplexes suggest that the length of G-repeats or C-repeats shows more significant effect on the stability of quadruplex structures than that of terminal residues. Accordingly, we can obtain the self-associated tetrameric species generated from the mixtures of various homologous G- or C-strands efficiently by altering the length of G- or C-repeats. Our studies demonstrate that ESI-MS is a very direct, fast and sensitive tool to provide significant information on DNA strand associations and stoichiometric transitions, particularly for complex mixtures. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Cadmium binding studies to the earthworm Lumbricus rubellus metallothionein by electrospray mass spectrometry and circular dichroism spectroscopy

    SciTech Connect

    Ngu, Thanh T.; Sturzenbaum, Stephen R.; Stillman, Martin J. . E-mail: Martin.Stillman@uwo.ca

    2006-12-08

    The earthworm Lumbricus rubellus has been found to inhabit cadmium-rich soils and accumulate cadmium within its tissues. Two metallothionein (MT) isoforms (1 and 2) have been identified and cloned from L. rubellus. In this study, we address the metalation status, metal coordination, and structure of recombinant MT-2 from L. rubellus using electrospray ionization mass spectrometry (ESI-MS), UV absorption, and circular dichroism (CD) spectroscopy. This is the first study to show the detailed mass and CD spectral properties for the important cadmium-containing earthworm MT. We report that the 20-cysteine L. rubellus MT-2 binds seven Cd{sup 2+} ions. UV absorption and CD spectroscopy and ESI-MS pH titrations show a distinct biphasic demetalation reaction, which we propose results from the presence of two metal-thiolate binding domains. We propose stoichiometries of Cd{sub 3}Cys{sub 9} and Cd{sub 4}Cys{sub 11} based on the presence of 20 cysteines split into two isolated regions of the sequence with 11 cysteines in the N-terminal and 9 cysteines in the C-terminal. The CD spectrum reported is distinctly different from any other metallothionein known suggesting quite different binding site structure for the peptide.

  13. Functional phosphoproteomic mass spectrometry-based approaches

    PubMed Central

    2012-01-01

    Mass Spectrometry (MS)-based phosphoproteomics tools are crucial for understanding the structure and dynamics of signaling networks. Approaches such as affinity purification followed by MS have also been used to elucidate relevant biological questions in health and disease. The study of proteomes and phosphoproteomes as linked systems, rather than research studies of individual proteins, are necessary to understand the functions of phosphorylated and un-phosphorylated proteins under spatial and temporal conditions. Phosphoproteome studies also facilitate drug target protein identification which may be clinically useful in the near future. Here, we provide an overview of general principles of signaling pathways versus phosphorylation. Likewise, we detail chemical phosphoproteomic tools, including pros and cons with examples where these methods have been applied. In addition, basic clues of electrospray ionization and collision induced dissociation fragmentation are detailed in a simple manner for successful phosphoproteomic clinical studies. PMID:23369623

  14. Non-targeted metabolomics study for the analysis of chemical compositions in three types of tea by using gas chromatograph-mass spectrometry and liquid chromatography-mass spectrometry.

    PubMed

    Zhang, Lei; Zeng, Zhongda; Ye, Guozhu; Zhao, Chunxia; Lu, Xin; Xu, Guowang

    2014-08-01

    Tea is one of the most widely consumed beverages in the world for its benefits to daily life and health. To discover the difference and correlation of chemical compositions in the three typical types of tea, a non-targeted metabolomics method was developed. After the optimization of extraction methods, gas chromatography-time-of-flight mass spectrometry and liquid chromatography-quadrupole time-of-flight mass spectrometry were applied for metabolomics analysis, 1,812 and 2,608 features were obtained, respectively. By comparing with the known compounds in public and/or commercial databases, 173 compounds were tentatively identified, and 109 of them were experimentally confirmed by standards. Totally, 33 tea samples including 12, 12 and 9 samples of green, oolong and black tea, respectively, were analyzed by using the above two methods. Multivatiate analysis, Mann-Whitney U test and hierarchical cluster analysis were used to find and visualize the differential components in the three types of tea. Finally, 90 compounds, which contain catechins, amino acids, organic acids, flavonol glycosides, alkaloids, carbohydrates, lipids, etc, were found with a significant difference among them. This study demonstrates the potentials and power of metabolomics methods to understand the chemical secrets of tea. This should help a lot to optimize the processes of agriculture, storage, preparation and consumption.

  15. New cascarosides from Rhamnus purshiana and fragmentation studies of the class by ion trap mass spectrometry.

    PubMed

    Demarque, Daniel P; Pinho, Danielle R; Callejon, Daniel R; de Oliveira, Gibson G; Silva, Denise B; Carollo, Carlos A; Lopes, Norberto P

    2017-07-30

    Anthrone and oxanthrone are important anthraquinone derivatives present in medicinal plants which are used in therapeutics as laxatives. Some of these plants need to be stored at least one year before they can be used in order to oxidize anthrones into oxanthrones, so to avoid severe diarrhea and dehydration. Therefore, this work aimed to characterize fragmentation reactions between these anthraquinones to provide an easy way to differentiate between the two classes, since it is necessary and important to discriminate and identify these derivatives in laxative plants and phytotherapic drugs. Anthrone (cascarosides A-D) and oxanthrone (10-hydroxycascaroside A and B) derivatives were isolated and identified by NMR ((1) H, (13) C, DEPT, NOESY) and used for fragmentation study by direct infusion on an electrospray ionization (ESI) ion trap mass spectrometer (AmazonSL, Bruker) in positive and negative mode. The additional hydroxyl at C-10 in oxanthrones allowed McLafferty-type rearrangements to form the quinone group in positive mode, while in negative mode the second sugar loss infringed the odd-electron rule and formed a radical fragment. No differences in fragmentation reactions were found between diastereoisomeric pairs, although the additional oxygen at C-10 of oxanthrones allowed a different fragmentation pattern. The proposed fragmentation patterns can be used to differentiate anthrones from oxanthrones in both ion modes. In addition, they can be applied to differentiate these compounds in anthraquinone-rich plants and phytotherapic drugs. Finally, herein, the strategy applied allowed us to identify new natural products. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  16. A Mass Spectrometry and DFT study of pyrithione complexes with transition metals in the gas phase.

    PubMed

    Butler, Matias; Cabrera, Gabriela M

    2017-07-24

    2-mercaptopyridine N-oxide (pyrithione, PTOH) along with several transition metal ions forms coordination compounds displaying notable biological activities. Gas-phase complexes formed between pyrithione and Manganese (II), Cobalt (II), Nickel (II), Copper (II) and Zinc (II) were investigated by infusion in the electrospray source of a quadrupole-time of flight mass spectrometer. Remarkably, positive ion mode spectra displayed the singly charged metal adduct ion [C10 H8 MN2 O2 S2 ](2+) ([M(PTO)2 ](+•) or [M(DPTO)](+•) ), where DPTO is dipyrithione, 2,2'-dithiobis(pyridine N-oxide), among the most abundant peaks, implying a change in the oxidation state of whether the metal ion or the ligands. In addition, doubly charged ions were recognized as metal adduct ions containing DPTO ligands, [M(DPTO)n ](2+) . Generation of [M(PTO)2 ](+•) / [M(DPTO)](+•) could be traced by CID of [M(DPTO)2 ](2+) , by observation of the sequential losses of a charged (PTO(+) ) and a radical (PTO(•) ) deprotonated pyrithione ligand. The fragmentation pathways of [M(PTO)2 ](+•) / [M(DPTO)](+•) were compared among the different metal ions, and some common features were noticed. Density functional theory (DFT) calculations were employed to study the structures of the observed adduct ions, and especially, to decide in the adduct ion [M(PTO)2 ](+•) / [M(DPTO)](+•) whether the ligands are two deprotonated pyrithiones or a single dipyrithione as well as the oxidation state of the metal ion in the complex. Characterization of gas-phase pyrithione metal ion complexes becomes important, especially taking into account the presence of a redox-active ligand in the complexes, since redox state changes that produce new species can have a marked effect on the overall toxicological/biological response elicited by the metal system. This article is protected by copyright. All rights reserved.

  17. Electrospray mass spectrometry studies of non-heme iron-containing proteins.

    PubMed

    Lei, Q P; Cui, X; Kurtz, D M; Amster, I J; Chernushevich, I V; Standing, K G

    1998-05-01

    The oligomeric state and the metal atom stoichiometry of a series of non-heme iron-containing, multimeric proteins have been measured using electrospray ionization (ESI) in a time-of-flight (TOF) mass spectrometer. The proteins were obtained both from natural sources and by overexpression of recombinant DNA in Escherichia coli. ESI-TOF mass spectra of the metalloproteins present in nondenaturing solutions exhibit peaks corresponding to the multimeric forms of the holoproteins containing the expected number of metal atoms. Capillary-skimmer dissociation of the holoproteins produces a series of ions, which allows an exact count of the number of metal atoms present in each subunit, and also provides an indication of the oxidation state of the metal atoms. Two recombinant proteins, Phascolopsis gouldii hemerythrin (Pg-Hr) and Desulfovibrio vulgaris rubrerythrin (Dv-Rr), have been examined as well as hemerythrin isolated from Lingula reevii (Lr-Hr). ESI-TOF measurements of the aqueous solution of Pg-Hr at pH 6 yields ions of mass 108,783 Da, in close agreement with the calculated average molecular mass of an intact octameric holoprotein. Capillary-skimmer dissociation of the ions of the holoprotein produces a mass spectrum that contains peaks corresponding to a low m/z monomer and a high m/z heptamer. The masses of the monomer ions produced in this manner are assigned to the aposubunit, [subunit + Fe - 3H]+, and [subunit + 2Fe - 6 H]+. Naturally occurring Lr-Hr is composed of two subunits with average molecular masses measured under denaturing conditions by ESI-TOF to be 13,877.0 Da for the alpha-subunit and 13,517.5 Da for the beta-subunit. Under nondenaturing conditions, a multimeric species with a molecular weight of 110,663 Da is measured by ESI-TOF, corresponding to an alpha 4 beta 4 octamer. Capillary-skimmer dissociation of the alpha 4 beta 4 oligomer produces ions corresponding to both types of monomers (alpha and beta) and the corresponding heptamers (alpha 3

  18. Microbial proteomics using mass spectrometry.

    PubMed

    Hines, Harry B

    2012-01-01

    Proteomic analyses involve a series of intricate, interdependent steps involving approaches and technical issues that must be fully coordinated to obtain the optimal amount of required information about the test subject. Fortunately, many of these steps are common to most test subjects, requiring only modifications to or, in some cases, substitution of some of the steps to ensure they are relevant to the desired objective of a study. This fortunate occurrence creates an essential core of proteomic approaches and techniques that are consistently available for most studies, regardless of test subject. In this chapter, an overview of some of these core approaches, techniques, and mass spectrometric instrumentation is given, while indicating how such steps are useful for and applied to bacterial investigations. To exemplify how such proteomic concepts and techniques are applicable to bacterial investigations, a practical, quantitative method useful for bacterial proteomic analysis is presented with a discussion of possibilities, pitfalls, and some emerging technology to provide a compilation of information from the diverse literature that is intermingled with experimental experience.

  19. Capillary electrophoresis electrospray ionization mass spectrometry interface

    DOEpatents

    Smith, Richard D.; Severs, Joanne C.

    1999-01-01

    The present invention is an interface between a capillary electrophoresis separation capillary end and an electrospray ionization mass spectrometry emitter capillary end, for transporting an anolyte sample from a capillary electrophoresis separation capillary to a electrospray ionization mass spectrometry emitter capillary. The interface of the present invention has: (a) a charge transfer fitting enclosing both of the capillary electrophoresis capillary end and the electrospray ionization mass spectrometry emitter capillary end; (b) a reservoir containing an electrolyte surrounding the charge transfer fitting; and (c) an electrode immersed into the electrolyte, the electrode closing a capillary electrophoresis circuit and providing charge transfer across the charge transfer fitting while avoiding substantial bulk fluid transfer across the charge transfer fitting. Advantages of the present invention have been demonstrated as effective in providing high sensitivity and efficient analyses.

  20. Isotope ratio analysis by Orbitrap mass spectrometry

    NASA Astrophysics Data System (ADS)

    Eiler, J. M.; Chimiak, L. M.; Dallas, B.; Griep-Raming, J.; Juchelka, D.; Makarov, A.; Schwieters, J. B.

    2016-12-01

    Several technologies are being developed to examine the intramolecular isotopic structures of molecules (i.e., site-specific and multiple substitution), but various limitations in sample size and type or (for IRMS) resolution have so far prevented the creation of a truly general technique. We will discuss the initial findings of a technique based on Fourier transform mass spectrometry, using the Thermo Scientific Q Exactive GC — an instrument that contains an Orbitrap mass analyzer. Fourier transform mass spectrometry is marked by exceptionally high mass resolutions (the Orbitrap reaches M/∆M in the range 250,000-1M in the mass range of greatest interest, 50-200 amu). This allows for resolution of a large range of nearly isobaric interferences for isotopologues of volatile and semi-volatile compounds (i.e., involving isotopes of H, C, N, O and S). It also provides potential to solve very challenging mass resolution problems for isotopic analysis of other, heavier elements. Both internal and external experimental reproducibilities of isotope ratio analyses using the Orbitrap typically conform to shot-noise limits down to levels of 0.2 ‰ (1SE), and routinely in the range 0.5-1.0 ‰, with similar accuracy when standardized to concurrently run reference materials. Such measurements can be made without modifications to the ion optics of the Q Exactive GC, but do require specially designed sample introduction devices to permit sample/standard comparison and long integration times. The sensitivity of the Q Exactive GC permits analysis of sub-nanomolar samples and quantification of multiply-substituted species. The site-specific capability of this instrument arises from the fact that mass spectra of molecular analytes commonly contain diverse fragment ion species, each of which samples a specific sub-set of molecular sites. We will present applications of this technique to the biological and abiological chemistry of amino acids, forensic identification of

  1. Molecular Characterization of Organic Aerosol Using Nanospray Desorption/Electrospray Ionization Mass Spectrometry: CalNex 2010 field study

    SciTech Connect

    O'Brien, Rachel E.; Laskin, Alexander; Laskin, Julia; Liu, Shang; Weber, Robin; Russell, Lynn; Goldstein, Allen H.

    2013-04-01

    Aerosol samples from the CalNex 2010 field study were analyzed using high resolution mass spectrometry (HR-MS) coupled to a nanospray-desorption/electrospray ionization (nano-DESI) source. The samples were collected in Bakersfield, CA on June 22-23, 2010. The chemical formulas of over 1300 unique molecular species were detected in the mass range of 50-800 m/z. Our analysis focused on identification of two main groups: compounds containing only carbon, hydrogen, and oxygen (CHO only), and nitrogen-containing organic compounds (NOC). The NOC accounted for 35% (by number) of the compounds observed in the afternoon, and for 59% in the early morning samples. By comparing plausible reactant-product pairs, we propose that over 50% of the NOC in each sample could have been formed through reactions transforming carbonyls into imines. The CHO only compounds were dominant in the afternoon suggesting a photochemical source. The average O:C ratios of all observed compounds were fairly consistent throughout the day, ranging from 0.34 in the early morning to 0.37 at night. We conclude that both photooxidation and ammonia chemistry play important roles in forming the compounds observed in this mixed urban-rural environment.

  2. Online study on the co-pyrolysis of coal and corn with vacuum ultraviolet photoionization mass spectrometry.

    PubMed

    Weng, Jun-Jie; Liu, Yue-Xi; Zhu, Ya-Nan; Pan, Yang; Tian, Zhen-Yu

    2017-11-01

    With the aim to support the experimental tests in a circulating fluidized bed pilot plant, the pyrolysis processes of coal, corn, and coal-corn blend have been studied with an online pyrolysis photoionization time-of-flight mass spectrometry (Py-PI-TOFMS). The mass spectra at different temperatures (300-800°C) as well as time-evolved profiles of selected species were measured. The pyrolysis products such as alkanes, alkenes, phenols, aromatics, as well as nitrogen- and sulfur-containing species were detected. As temperature rises, the relative ion intensities of high molecular weight products tend to decrease, while those of aromatics increase significantly. During the co-pyrolysis, coal can promote the reaction temperature of cellulose in corn. Time-evolved profiles demonstrate that coal can affect pyrolysis rate of cellulose, hemicellulose, and lignin of corn in blend. This work shows that Py-PI-TOFMS is a powerful approach to permit a better understanding of the mechanisms underlying the co-pyrolysis of coal and biomass. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Determination of dexmedetomidine in children's plasma by ultra-performance liquid chromatography tandem mass spectrometry and application to pharmacokinetic study.

    PubMed

    Liu, Hua-Cheng; Sun, Wei; Wang, Cheng-Yu; Ying, Wei-Yang; Zheng, Li-Dan; Zeng, Rui-Feng; Wang, Zhe; Ge, Ren-Shan

    2016-06-15

    A rapid, sensitive, and selective ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of dexmedetomidine in children's plasma. Sample preparation was accomplished through a simple one-step deproteinization procedure with 0.2mL of acetonitrile to a 0.1mL plasma sample. Plasma samples were separated by UPLC on an Acquity UPLC BEH C18 column using a mobile phase consisting of acetonitrile-0.1% formic acid in water with gradient elution. The total run time was 3.1min and the elution of dexmedetomidine was at 1.24min. The detection was performed on a triple quadrupole tandem mass spectrometer in the multiple reaction-monitoring mode using the respective transitions m/z 201.3→95.1 for dexmedetomidine and m/z 204.2→98.0 for the internal standard, respectively. The calibration curve was linear over the range of 0.05-10ng/mL with a lower limit of quantitation of 0.05ng/mL. Mean recovery rate of dexmedetomidine in plasma was in the range of 86.7-89.1%. Intra-day and inter-day precision were both <11.6%. This method was successfully applied in pharmacokinetic study after commencement of 1.0μg/kg dexmedetomidine infusion in children.

  4. Simultaneous determination of decitabine and vorinostat (Suberoylanalide hydroxamic acid, SAHA) by liquid chromatography tandem mass spectrometry for clinical studies.

    PubMed

    Patel, Katan; Guichard, Sylvie M; Jodrell, Duncan I

    2008-02-15

    A reverse-phase high-performance liquid chromatography method with electrospray ionization and detection by tandem mass spectrometry is described for the simultaneous quantitative determination of decitabine (5-aza-2'-deoxycytidine) and vorinostat (Suberoylanalide hydroxamic acid, SAHA) in human plasma. The method involves a simple acetonitrile precipitation step and centrifugation followed by injection of the supernatant onto a C18 150mmx2.1mm I.D., 3microm HPLC column at 36 degrees C. Separation of decitabine, SAHA and their respective internal standards was achieved with a gradient elution and detection was via the mass spectrometer operated in selected reaction monitoring mode. The method was within the defined validation parameters for linearity, repeatability, reproducibility and stability. The limit of detection was determined as 1.0 and 0.125ngml(-1) and lower limits of quantitation were 10 and 1ngml(-1) for decitabine and SAHA, respectively. Effects of sample preparation on stability were also evaluated in human plasma. For clinical sample handling tetrahydrouridine, an inhibitor of cytidine deaminase was found to help prevent decitabine degradation. The method is currently being used in clinical pharmacokinetic studies for the evaluation of decitabine and SAHA combination therapies.

  5. Determination of dimenhydrinate in human plasma by liquid chromatography-electrospray tandem mass spectrometry: application to a relative bioavailability study.

    PubMed

    Tavares, V; Macedo, C C; Montanhez, L; Barros, F A P; Meurer, E C; Campos, D R; Coelho, E C; Calaffati, S A; Pedrazzoli, J

    2007-06-15

    Here we present a sensitive and specific liquid chromatography-tandem mass spectrometric method for the quantification of dimenhydrinate (I) in human plasma. Sample preparation is conducted using citalopram (II) addition as an internal standard (IS), liquid-liquid extraction with basified plasma using a mixture hexane/acetate (1:1, v/v) as the extracting solvent, and the final extract reconstituted in the mobile phase. I and II (IS) were injected in a C8 column with the mobile phase composed of methanol:isopropanol:water:formic acid (78.00:19.92:2.00:0.08, v/v/v/v) and monitored using a positive electrospray source with tandem mass spectrometry analyses. The selected reaction monitoring (SRM) was set using precursor ion and product ion combinations of m/z 256.0>167.0 and m/z 325.0>109.0 for I and II, respectively. The limit of quantification (LOQ) was 0.4 ng/mL, the dynamic range being 0.4-200 ng/mL. Validation results on linearity, specificity, accuracy, precision and stability, as well as on application to the analysis of plasma samples taken up to 24 h after oral administration of 100 mg of dimenhydrinate in healthy volunteers demonstrated its applicability to bioavailability studies.

  6. Determination of levocetirizine in human plasma by liquid chromatography-electrospray tandem mass spectrometry: application to a bioequivalence study.

    PubMed

    Morita, M R; Berton, D; Boldin, R; Barros, F A P; Meurer, E C; Amarante, A R; Campos, D R; Calafatti, S A; Pereira, R; Abib, E; Pedrazolli, J

    2008-02-01

    We describe a liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for levocetirizine quantification (I) in human plasma. Sample preparation was made using a fexofenadine (II) addition as internal standard (IS), liquid-liquid extraction using cold dichloromethane, and dissolving the final extract in acetonitrile. I and II (IS) were injected in a C18 column and the mobile phase composed of acetonitrile:water:formic acid (80.00:19.90:0.10, v/v/v) and monitored using positive electrospray source with tandem mass spectrometry analyses. The selected reaction monitoring (SRM) was set using precursor ion and product ion combinations of m/z 389>201 for I and m/z 502>467 for II. The limit of quantification and the dynamic range achieved were 0.5ng/mL and 0.5-500.0ng/mL. Validation results on linearity, specificity, accuracy, precision and stability, as well as its application to the analysis of plasma samples taken up to 48h after oral administration of 5mg of levocetirizine dichloridrate in healthy volunteers demonstrate its applicability to bioavailability studies.

  7. [Development of a gas chromatography-mass spectrometry method for the metabolomic study of rice (Oryza sativa L.) grain].

    PubMed

    Zhou, Jia; Wang, Shuangyuan; Chang, Yuwei; Zhao, Yanni; Lu, Xin; Zhao, Chunxia; Xu, Guowang

    2012-10-01

    An analytical strategy for the metabolic profiling of rice grain was developed based on gas chromatography-mass spectrometry (GC-MS). For the purpose of obtaining abundant metabolite information, sample preparation step prior to instrumental analysis is necessary to be optimized. D-optimal experimental design was applied to optimize the extraction solvent. Four solvents, including water, methanol, isopropanol and acetonitrile, and their combinations were evaluated for the extraction efficiency using multivariate statistical analysis (partial least square regression). The count of resolved peaks and the sum of peak areas were taken as the evaluation indexes. Methanol/water (80:20, v/v) mixture was highly efficient for rice metabolites and was selected as the suitable solvent formulation. Then, the analytical characteristics of the method were measured. More than 90% of the metabolites had satisfactory precisions, reproducibilities and stabilities (relative standard deviations (RSDs) < 30%). Most of the detected metabolites (about 88.0% of total peak area) showed good linear responses. With the optimized analytical protocol, 315 metabolites were detected in rice and 86 of which were structurally identified by searching in the NIST 08/Wiley standard mass spectral library, covering carbohydrates, amino acids, organic acids, steroids and so on which showed a broad coverage of metabolite data. The established method is expected to be useful for the metabolomic studies of rice.

  8. Interfacing membrane mimetics with mass spectrometry

    PubMed Central

    Marty, Michael T.; Hoi, Kin Kuan; Robinson, Carol V.

    2017-01-01

    Conspectus Membrane proteins play critical physiological roles and make up the majority of drug targets. Due to their generally low expression levels and amphipathic nature, membrane proteins represent challenging molecular entities for biophysical study. Mass spectrometry offers several sensitive approaches to study the biophysics of membrane proteins. By preserving noncovalent interactions in the gas phase and using collisional activation to remove solubilization agents inside the mass spectrometer, native mass spectrometry (MS) is capable of studying isolated assemblies that would be insoluble in aqueous solution, such as membrane protein oligomers and protein-lipid complexes. Conventional methods use detergent to solubilize the protein prior to electrospray ionization. Gas-phase activation inside the mass spectrometer removes the detergent to yield the isolated proteins with bound ligands. This approach has proven highly successful for ionizing membrane proteins. With the appropriate choice of detergents, membrane proteins with bound lipid species can be observed, which allows characterization of protein-lipid interactions. However, detergents have several limitations. They do not necessarily replicate the native lipid bilayer environment, and only a small number of protein-lipid interactions can be resolved. In this Account, we summarize the development of different membrane mimetics as cassettes for MS analysis of membrane proteins. Examples include amphipols, bicelles, and picodiscs with a special emphasis on lipoprotein Nanodiscs. Polydispersity and heterogeneity of the membrane mimetic cassette is a critical issue for study by MS. Ever more complex datasets consisting of overlapping protein charge states and multiple lipid-bound entities have required development of new computational, theoretical, and experimental approaches to interpret both mass and ion mobility spectra. We will present the rationale and limitations of these approaches. Starting with the

  9. Solid-phase N-terminal peptide enrichment study by optimizing trypsin proteolysis on homoarginine modified proteins by mass spectrometry

    PubMed Central

    Chowdhury, Saiful M.; Munske, Gerhard R.; Yang, Jonathon; Zhukova, Daria; Nguen, Hamilton; Bruce, James E.

    2014-01-01

    Rationale Proteolytic cleavages generate active precursor proteins by creating new N-termini in the proteins. A number of strategies recently published regarding the enrichment of original or newly formed N-terminal peptides using guanidination of lysine residues and amine reactive reagents. For effective enrichment of N-terminal peptides, the efficiency of trypsin proteolysis on homoarginine (guanidinated) modified proteins must be understood and simple and versatile solid-phase N-terminal capture strategies should be developed. Methods We present here a mass spectrometry-based study to evaluate and optimize the trypsin proteolysis on a guanidinated modified protein. Trypsin proteolysis was studied using different amount of trypsin to modified protein ratios. To capture the original N-termini, after guanidination of proteins, original N-termini were acetylated and the proteins were digested with trypsin. The newly formed N-terminal tryptic peptides were captured with a new amine reactive acid-cleavable solid-phase reagent. The original N-terminal peptides were then collected from the supernatant of the solution. Results We demonstrated a detailed study of the efficiency of enzyme trypsin on homoarginine modified proteins. We observed that the rate of hydrolysis of homoarginine residues compared to their lysine/arginine counter parts were slower but generally cleaved after an overnight digestion period depending on the protein to protease concentration ratios. Selectivity of the solid-phase N-terminal reagent was studied by enrichment of original N-terminal peptides from two standard proteins, ubiquitin and RNaseS. Conclusion We found enzyme trypsin is active in guanidinated form of protein depending on enzyme to protein concentrations, time and the proximity of arginine residues in the sequence. The novel solid-phase capture reagent also successfully enriched N-terminal peptides from the standard protein mixtures. We believe this trypsin proteolysis study on

  10. Mass Spectrometry Methodology in Lipid Analysis

    PubMed Central

    Li, Lin; Han, Juanjuan; Wang, Zhenpeng; Liu, Jian’an; Wei, Jinchao; Xiong, Shaoxiang; Zhao, Zhenwen

    2014-01-01

    Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However, because of the diversity and complexity of lipids, lipid analysis is still full of challenges. The recent development of methods for lipid extraction and analysis and the combination with bioinformatics technology greatly push forward the study of lipidomics. Among them, mass spectrometry (MS) is the most important technology for lipid analysis. In this review, the methodology based on MS for lipid analysis was introduced. It is believed that along with the rapid development of MS and its further applications to lipid analysis, more functional lipids will be identified as biomarkers and therapeutic targets and for the study of the mechanisms of disease. PMID:24921707

  11. Mass spectrometry methodology in lipid analysis.

    PubMed

    Li, Lin; Han, Juanjuan; Wang, Zhenpeng; Liu, Jian'an; Wei, Jinchao; Xiong, Shaoxiang; Zhao, Zhenwen

    2014-06-11

    Lipidomics is an emerging field, where the structures, functions and dynamic changes of lipids in cells, tissues or body fluids are investigated. Due to the vital roles of lipids in human physiological and pathological processes, lipidomics is attracting more and more attentions. However, because of the diversity and complexity of lipids, lipid analysis is still full of challenges. The recent development of methods for lipid extraction and analysis and the combination with bioinformatics technology greatly push forward the study of lipidomics. Among them, mass spectrometry (MS) is the most important technology for lipid analysis. In this review, the methodology based on MS for lipid analysis was introduced. It is believed that along with the rapid development of MS and its further applications to lipid analysis, more functional lipids will be identified as biomarkers and therapeutic targets and for the study of the mechanisms of disease.

  12. Characterization of candidate reference materials for bone lead via interlaboratory study and double isotope dilution mass spectrometry

    PubMed Central

    Bellis, David J.; Hetter, Katherine M.; Verostek, Mary Frances; Parsons, Patrick J.

    2012-01-01

    Summary Four candidate ground bone reference materials (NYS RMs 05-01 through 04), were produced from lead-dosed bovine and caprine sources, and characterized by interlaboratory study. The consensus value ( X ) and expanded standard uncertainty (UX ) were determined from the robust average and standard deviation of the participants’ data for each NYS RM 05-01 through 04. The values were 1.08 ±0.04, 15.3 ±0.5, 12.4 ±0.5, and 29.9 ±1.1 μg g−1 Pb, respectively. Youden plots of z-scores showed a statistically significant correlation between the results for pairs of NYS RM 05-02 through 04, indicating common sources of between-laboratory variation affecting reproducibility. NYS RM 05-01 exhibited more random variability affecting repeatability at low concentration. Some participants using electrothermal atomic absorption spectrometry (ETAAS) exhibited a negative bias compared to the all-method consensus value. Other methods used included inductively coupled plasma mass spectrometry (ICP-MS), isotope dilution (ID-) ICP-MS, and ICP atomic (optical) emission spectroscopy (-OES). The NYS RMs 05-01 through 04 were subsequently re-analyzed in house using double ID-ICP-MS to assign certified reference values (C ) and expanded uncertainty (UC ) of 1.09 ± 0.03, 16.1 ± 0.3, 13.2 ± 0.3 and 31.5 ± 0.7, respectively, indicating a low bias in the interlaboratory data. SRM 1486 Bone Meal was analyzed for measurement quality assessment obtaining results in agreement with the certified values within the stated uncertainty. Analysis using a primary reference method based on ID-ICP-MS with full quantification of uncertainty calculated according to ISO guidelines provided traceability to SI units. PMID:23087531

  13. Gas phase ion - molecule reactions studied by Fourier transform ion cyclotron resonance mass spectrometry

    SciTech Connect

    Ross, C.W. III.

    1993-01-01

    Intrinsic thermodynamic information of molecules can easily be determined in the low pressure FT/ICR mass spectrometer. The gas phase basicity of two carbenes were measured by isolating the protonated carbene ion and reacting it with neutral reference compounds by the bracketing method. A fundamentally new-dimensional FT/ICR/MS experiment, SWIM (stored waveform ion modulation) 2D-FT/ICR MS/MS, is described. Prior encodement of the second dimension by use of two identical excitation waveforms separated by a variable delay period is replaced by a new encodement in which each row of the two-dimensional data array is obtained by use of a single stored excitation waveform whose frequency-domain magnitude spectrum is a sinusoid whose frequency increases from one row to the next. In the two-dimensional mass spectrum, the conventional one-dimensional FT/ICR mass spectrum appears along the diagonal, and each off-diagonal peak corresponds to an ion-neutral reaction whose ionic components may be identified by horizontal and vertical projections to the diagonal spectrum. All ion-molecule reactions in a gaseous mixture may be identified from a single 2D-FT/ICR MS/MS experiment, without any prior knowledge of the system. In some endoergic reactions there is a minimum energy threshold that must overcome for a reaction to occur. Hence, a simple sinusoidal modulation of parent ion cyclotron radius leads to a clipped sinusoidal signal of the product ion abundance in the second dimension, which upon Fourier transformation produces signals with harmonic and combination ion cyclotron resonance frequencies. Moreover, ion-molecule reaction rates may vary directly within kinetic energy rather than cyclotron radius. With SWIM, it is possible to tailor the excitation profile so as to produce a sinusoidal modulation of ion kinetic energy as a function of cyclotron frequency.

  14. Study of Saiga Horn Using High-Performance Liquid Chromatography with Mass Spectrometry

    PubMed Central

    Mikulíková, Kateřina; Romanov, Oleg; Miksik, Ivan; Eckhardt, Adam; Pataridis, Statis; Sedláková, Pavla

    2012-01-01

    The saiga horns have been investigated the using of modern analytic methods. High-performance liquid chromatography (HPLC) with mass-spectrometric (MS and MS/MS) detection and polyacrylamide gel electrophoresis (PAGE) were used. It could be concluded that basic proteins of the saiga horns are keratins and collagen. The basic representation protein in all samples is keratin type I microfibrillar (from sheep), keratin type II microfibrillar (from sheep), collagen type I (α1) (from bovine) and collagen type I (α2) (from bovine). Free amino acids we determined in all samples are nontreated by enzyme. PMID:22629195

  15. High levels of heavy metal accumulation in dental calculus of smokers: a pilot inductively coupled plasma mass spectrometry study.

    PubMed

    Yaprak, E; Yolcubal, I; Sinanoğlu, A; Doğrul-Demiray, A; Guzeldemir-Akcakanat, E; Marakoğlu, I

    2017-02-01

    Various trace elements, including toxic heavy metals, may exist in dental calculus. However, the effect of environmental factors on heavy metal composition of dental calculus is unknown. Smoking is a major environmental source for chronic toxic heavy metal exposition. The aim of this study is to compare toxic heavy metal accumulation levels in supragingival dental calculus of smokers and non-smokers. A total of 29 supragingival dental calculus samples were obtained from non-smoker (n = 14) and smoker (n = 15) individuals. Subjects with a probability of occupational exposure were excluded from the study. Samples were analyzed by inductively coupled plasma mass spectrometry in terms of 26 metals and metalloids, including toxic heavy metals. Toxic heavy metals, arsenic (p < 0.05), cadmium (p < 0.05), lead (p < 0.01), manganese (p < 0.01) and vanadium (p < 0.01) levels were significantly higher in smokers than non-smokers. The levels of other examined elements were similar in both groups (p > 0.05). Within the limitations of this study, it can be concluded that the elementary composition of dental calculus may be affected by environmental factors such as tobacco smoke. Therefore, dental calculus may be utilized as a non-invasive diagnostic biological material for monitoring chronic oral heavy metal exposition. However, further studies are required to evaluate its diagnostic potential. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Soil carbon content and character in an old-growth forest in northwestern Pennsylvania: a case study introducing pyrolysis molecular beam mass spectrometry (py-MBMS)

    Treesearch

    C.M. Hoover; K.A. Magrini; R.J. Evans

    2002-01-01

    This study was conducted to: (1) test the utility of a new and rapid analytical method, pyrolysis molecular beam mass spectrometry (py-MBMS), for the measurement and characterization of carbon in forest soils, and (2) examine the effects of natural disturbance on soil carbon dynamics. An additional objective was to test the ability of py-MBMS to distinguish recent from...

  17. Applying the tools of chemistry (mass spectrometry and covalent modification by small molecule reagents) to the detection of prions and the study of their structure

    USDA-ARS?s Scientific Manuscript database

    Prions are molecular pathogens, able to convert a normal cellular prion protein PrPC into a prion PrPSc. The information necessary for this conversion is contained in the conformation of PrPSc. Mass spectrometry and small-molecule covalent reactions have recently been used to study prions. This w...

  18. Tandem mass spectrometry of peptides using hybrid and four-sector instruments: a comparative study.

    PubMed

    Bean, M F; Carr, S A; Thorne, G C; Reilly, M H; Gaskell, S J

    1991-07-15

    Product-ion spectra produced by high- and low-energy collisionally activated dissociation (CAD) of [M + H]+ ions of a series of peptides (Mr 550-2500) have been compared on four-sector and hybrid tandem mass spectrometers, respectively. The fast atom bombardment product-ion spectra obtained for the smallest peptide analyzed (methionine-enkephalin) were remarkably similar, but substantial differences in fragmentation were observed for the heavier analytes. For peptides with Mr greater than 1000, more complete sequence information was obtained from high-energy CAD on the four-sector instrument. Nevertheless, low-energy CAD on the hybrid mass spectrometer was able to produce partial sequence information even for the largest of the peptides compared. Limits of analysis, defined as the least quantities of analyte for which product-ion spectra of essentially uncompromised quality could be obtained, were similar (ca. 15 pmol) for small peptides, but lower limits were achieved for larger peptides (Mr greater than 1000) with the four-sector instrument. High-energy CAD spectra were found to be highly reproducible, with qualitatively similar spectra obtained over a wide range of operating conditions. In contrast, it was necessary to carefully control collision gas pressures and collision energies in order to obtain good reproducible data for low-energy CAD. Experimental procedures for obtaining reproducible spectra with good sensitivity for peptides on the hybrid instrument are presented.

  19. The allure of mass spectrometry: From an earlyday chemist's perspective

    PubMed Central

    2016-01-01

    1 This reminiscing review article is an account of the author's fascination and involvements with mass spectrometry from the perspective of an organic chemist with an interest in natural product chemistry. It covers a period from 1961 through the mid 1990s as mass spectrometry evolved form a novelty technique to become a most widely used analytical technique. Following a brief synopsis of my pathway to mass spectrometry, my research efforts in this field are presented with a focus mainly on evolving principles and technologies which I had personal involvements with. To provide historical perspectives, discussions of these developments are accompanied by brief outlines of the relevant state‐of‐the‐art, shedding light on the technical and conceptual challenges encountered during those early days in mass spectrometry. Examples are presented of my involvements with basic and applied research in mass spectrometry during graduate studies at Stanford University and close to three decade tenure in pharmaceutical research at Syntex Research. My basic research interests focused mainly on principles of electron ionization induced fragmentation mechanisms, with an emphasis on steroids and other model compounds. Extensive deuterium labeling evidence was used to determine the fragmentation mechanisms of the diagnostically significant ions in the spectra of numerous model compounds, uncovering examples of wide‐ranging hydrogen transfers, skeletal rearrangements, methyl and phenyl migrations, stereoselective fragmentations and low and high energy fragmentation processes. Depiction of the industrial research phase of my career includes comments on the pivotal role mass spectrometry played on advancing modern pharmaceutical research. Examples are presented of involvements with instrumental developments and a few select cases of applied research, including studies of bile mechanisms in vertebrates, identification of bisphenol‐A leaching from sterilized polycarbonate

  20. Fast Atom Bombardment Mass Spectrometry.

    ERIC Educational Resources Information Center

    Rinehart, Kenneth L., Jr.

    1982-01-01

    Discusses reactions and characteristics of fast atom bombardment (FAB) mass spectroscopy in which samples are ionized in a condensed state by bombardment with xenon or argon atoms, yielding positive/negative secondary ions. Includes applications of FAB to structural problems and considers future developments using the technique. (Author/JN)

  1. Fast Atom Bombardment Mass Spectrometry.

    ERIC Educational Resources Information Center

    Rinehart, Kenneth L., Jr.

    1982-01-01

    Discusses reactions and characteristics of fast atom bombardment (FAB) mass spectroscopy in which samples are ionized in a condensed state by bombardment with xenon or argon atoms, yielding positive/negative secondary ions. Includes applications of FAB to structural problems and considers future developments using the technique. (Author/JN)

  2. Fourier transform ion cyclotron resonance mass spectrometry

    NASA Astrophysics Data System (ADS)

    Marshall, Alan G.

    1998-06-01

    As for Fourier transform infrared (FT-IR) interferometry and nuclear magnetic resonance (NMR) spectroscopy, the introduction of pulsed Fourier transform techniques revolutionized ion cyclotron resonance mass spectrometry: increased speed (factor of 10,000), increased sensitivity (factor of 100), increased mass resolution (factor of 10,000-an improvement not shared by the introduction of FT techniques to IR or NMR spectroscopy), increased mass range (factor of 500), and automated operation. FT-ICR mass spectrometry is the most versatile technique for unscrambling and quantifying ion-molecule reaction kinetics and equilibria in the absence of solvent (i.e., the gas phase). In addition, FT-ICR MS has the following analytically important features: speed (~1 second per spectrum); ultrahigh mass resolution and ultrahigh mass accuracy for analysis of mixtures and polymers; attomole sensitivity; MSn with one spectrometer, including two-dimensional FT/FT-ICR/MS; positive and/or negative ions; multiple ion sources (especially MALDI and electrospray); biomolecular molecular weight and sequencing; LC/MS; and single-molecule detection up to 108 Dalton. Here, some basic features and recent developments of FT-ICR mass spectrometry are reviewed, with applications ranging from crude oil to molecular biology.

  3. Mass spectrometry imaging and profiling of single cells

    PubMed Central

    Lanni, Eric J.; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2012-01-01

    Mass spectrometry imaging and profiling of individual cells and subcellular structures provide unique analytical capabilities for biological and biomedical research, including determination of the biochemical heterogeneity of cellular populations and intracellular localization of pharmaceuticals. Two mass spectrometry technologies—secondary ion mass spectrometry (SIMS) and matrix assisted laser desorption ionization mass spectrometry (MALDI MS)—are most often used in micro-bioanalytical investigations. Recent advances in ion probe technologies have increased the dynamic range and sensitivity of analyte detection by SIMS, allowing two- and three-dimensional localization of analytes in a variety of cells. SIMS operating in the mass spectrometry imaging (MSI) mode can routinely reach spatial resolutions at the submicron level; therefore, it is frequently used in studies of the chemical composition of subcellular structures. MALDI MS offers a large mass range and high sensitivity of analyte detection. It has been successfully applied in a variety of single-cell and organelle profiling studies. Innovative instrumentation such as scanning microprobe MALDI and mass microscope spectrometers enable new subcellular MSI measurements. Other approaches for MS-based chemical imaging and profiling include those based on near-field laser ablation and inductively-coupled plasma MS analysis, which offer complementary capabilities for subcellular chemical imaging and profiling. PMID:22498881

  4. Recent trends in inorganic mass spectrometry

    SciTech Connect

    Smith, D.H.; Barshick, C.M.; Duckworth, D.C.; Riciputi, L.R.

    1996-10-01

    The field of inorganic mass spectrometry has seen substantial change in the author`s professional lifetime (over 30 years). Techniques in their infancy 30 years ago have matured; some have almost disappeared. New and previously unthought of techniques have come into being; some of these, such as ICP-MS, are reasonably mature now, while others have some distance to go before they can be so considered. Most of these new areas provide fertile fields for researchers, both in the development of new analytical techniques and by allowing fundamental studies to be undertaken that were previously difficult, impossible, or completely unforeseen. As full coverage of the field is manifestly impossible within the framework of this paper, only those areas with which the author has personal contact will be discussed. Most of the work originated in his own laboratory, but that of other laboratories is covered where it seemed appropriate.

  5. Accelerator mass spectrometry (AMS) in plutonium analysis.

    PubMed

    Strumińska-Parulska, Dagmara I

    The paper summarizes the results of the (240)Pu/(239)Pu atomic ratio studies in atmospheric fallout samples collected in 1986 over Gdynia (Poland) as well as three Baltic fish species collected in 1997 using the accelerator mass spectrometry. A new generation of AMS has been developed during last years and this method is an efficient and good technique to measure long-lived radioisotopes in the environment and provides the most accurate determination of the atomic ratios between (240)Pu and (239)Pu. The nuclide compositions of plutonium in filter samples correspond to their means of production. AMS measurements of atmospheric fallout collected in April showed sufficient increase of the (240)Pu/(239)Pu atomic ratio from 0.28 from March to 0.47. Also such high increase of (240)Pu/(239)Pu atomic ratio, close to reactor core (240)Pu/(239)Pu atomic ratio, was observed in September and equaled 0.47.

  6. In situ secondary ion mass spectrometry analysis

    SciTech Connect

    Groenewold, G.S.; Applehans, A.D.; Ingram, J.C.; Delmore, J.E.; Dahl, D.A.

    1993-01-01

    The direct detection of tributyl phosphate (TBP) on rocks using molecular beam surface analysis [MBSA or in situ secondary ion mass spectrometry (SIMS)] is demonstrated. Quantities as low as 250 ng were detected on basalt and sandstone with little or no sample preparation. Detection of TBP on soil has proven to be more problematic and requires further study. Ethylenediaminetetraacetic acid (EDTA) is more difficult to detect because it is very reactive with surfaces of interest. Nevertheless, it is possible to detect EDTA if the acidity of the surface is controlled. The detection of EDTA-metal complexes is currently an open question, but evidence is presented for the detection of ions arising from a EDTA-lead complex. Carboxylic acids (i.e., citric, ascorbic, malic, succinic, malonic, and oxalic) give characteristic SIM spectra, but their detection on sample surfaces awaits evaluation.

  7. Multiplex mass spectrometry imaging for latent fingerprints.

    PubMed

    Yagnik, Gargey B; Korte, Andrew R; Lee, Young Jin

    2013-01-01

    We have previously developed in-parallel data acquisition of orbitrap mass spectrometry (MS) and ion trap MS and/or MS/MS scans for matrix-assisted laser desorption/ionization MS imaging (MSI) to obtain rich chemical information in less data acquisition time. In the present study, we demonstrate a novel application of this multiplex MSI methodology for latent fingerprints. In a single imaging experiment, we could obtain chemical images of various endogenous and exogenous compounds, along with simultaneous MS/MS images of a few selected compounds. This work confirms the usefulness of multiplex MSI to explore chemical markers when the sample specimen is very limited. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Laser Ablation Inductively Coupled Plasma Mass Spectrometry

    PubMed Central

    Hutchinson, Robert W.; McLachlin, Katherine M.; Riquelme, Paloma; Haarer, Jan; Broichhausen, Christiane; Ritter, Uwe; Geissler, Edward K.; Hutchinson, James A.

    2015-01-01

    ABSTRACT New analytical techniques for multiparametric characterisation of individual cells are likely to reveal important information about the heterogeneity of immunological responses at the single-cell level. In this proof-of-principle study, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was applied to the problem of concurrently detecting 24 lineage and activation markers expressed by human leucocytes. This approach was sufficiently sensitive and specific to identify subpopulations of isolated T, B, and natural killer cells. Leucocyte subsets were also accurately detected within unfractionated peripheral blood mononuclear cells preparations. Accordingly, we judge LA-ICP-MS to be a suitable method for assessing expression of multiple tissue antigens in solid-phase biological specimens, such as tissue sections, cytospins, or cells grown on slides. These results augur well for future development of LA-ICP-MS–based bioimaging instruments for general users. PMID:27500232

  9. Nanospray ion mobility mass spectrometry of selected high mass species.

    PubMed

    Campuzano, Iain; Giles, Kevin

    2011-01-01

    The introduction of electrospray ionization (ESI) and in particular nano-electrospray (nESI) has enabled the routine mass spectrometric (MS) analysis of large protein complexes in native aqueous buffers. Time-of-flight (ToF) mass spectrometers, in particular the hybrid quadrupole time-of-flight (Q-ToF) instruments, are well suited to the analysis of large protein complexes. When ionized under native-MS conditions, protein complexes routinely exhibit multiple charge states in excess of m/z 6,000, well above the standard mass range of many quadrupole or ion cyclotron-based instruments. The research area of native MS has expanded considerably in the last decade and has shown particular relevance in the area of protein structure determination. Researchers are now able to routinely measure intact MS spectra of protein complexes above 1 MDa in mass. The advent of ion mobility mass spectrometry (IM-MS), in combination with molecular dynamics (MD) studies, is now allowing researchers to infer the shape of the protein complex being analyzed. Herein, we describe how to acquire IM-MS data that ranges from inorganic salt clusters of caesium iodide (CsI) to large biomolecular complexes such as the chaperone protein GroEL.

  10. Study of acidified ignitable liquid residues in fire debris by solid-phase microextraction with gas chromatography and mass spectrometry.

    PubMed

    Martín-Alberca, Carlos; García-Ruiz, Carmen; Delémont, Olivier

    2015-07-14

    The detection and identification of ignitable liquid residues in fire debris can be meaningful in fire investigations. However, background pyrolysis products and weathering hinder the identification and classification steps. In addition to those processes, the acidification of the ignitable liquids before the combustion process could make those tasks even more difficult. Nevertheless, there are no systematic studies assessing the extraction, analysis and composition of acidified ignitable liquid residues obtained from fire debris. In this work, a methodology for the study of acidified ignitable liquid residues in fire debris by solid-phase microextraction with gas chromatography and mass spectrometry is proposed. This methodology has been evaluated, first with simulated solutions (gasoline-sulphuric acid mixtures set on fire under controlled conditions), and then with analysis of samples from real fire debris obtained from 18 chemical ignition Molotov cocktails made with sulfuric acid and three different ignitable liquids (two types of gasoline and diesel fuel). In addition, the extensive modifications observed in chromatograms of acidified ignitable liquid residues regarding neat and weathered samples were studied. These alterations were produced by the combustion and acidification processes. As a consequence, tert-butylated compounds are proposed as diagnostic indicators for the identification of acidified gasoline in fire debris, even in strongly weathered samples. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. Preliminary study of 10Be/7Be in rainwater from Xi’an by Accelerator Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Zhang, Li; Fu, Yun-Chong

    2017-01-01

    The 10Be/7Be ratio is a sensitive tracer for the study of atmospheric transport, particularly with regard to stratosphere-troposphere exchange. Measurements with high accuracy and efficiency are crucial to 7Be and 10Be tracer studies. This article describes sample preparation procedures and analytical benchmarks for 7Be and 10Be measurements at the Xi’an Accelerator Mass Spectrometry (Xi’an-AMS) laboratory for the study of rainwater samples. We describe a sample preparation procedure to fabricate beryllium oxide (BeO) AMS targets that includes co-precipitation, anion exchange column separation and purification. We then provide details for the AMS measurement of 7Be and 10Be following the sequence BeO-→Be2+→Be4+ in the Xi’an- AMS. The 10Be/7Be ratio of rainwater collected in Xi’an is shown to be about 1.3 at the time of rainfall. The virtue of the method described here is that both 7Be and 10Be are measured in the same sample, and it is suitable for routine analysis of large numbers of rainwater samples by AMS. Supported by National Natural Science Foundation of China (11205161) and CAS Key Technology Talent Program

  12. [Studies on the occurrence of furan in food for infants by gas chromatography with mass spectrometry method].

    PubMed

    Minorczyk, Maria; Starski, Andrzej; Jedra, Małgorzata; Gawarska, Halina; Sawilska-Rautenstrauch, Dorota

    2011-01-01

    Furan is an organic compound formed during heat treatment. It has been shown to be carcinogenic in animal laboratory studies. The aim of this study was to determine the content of furan in vegetables and vegetable-meat products intended for infants. The testing system used during this study was gas chromatography coupled with mass spectrometry (GC/MS). The content of furan in 48 samples of processed food ready to eat has been determined. In all samples furan was detected within the range from 13.2 to 91.1 microg/kg, and its average value was 43.3 microg/kg. The paper estimate the exposure assessment of infants to furan found in food. The calculated exposure ranged from 0.23 to 1.77 microg/kg bw/day with the average content of furan in ready to eat products ranged from 35.3 to 52.2 microg/kg. Exposure did not exceed the ADI value 2 microg/kg bw/day.

  13. Neurochemical study of amino acids in rodent brain structures using an improved gas chromatography-mass spectrometry method.

    PubMed

    Pinto, Mauro Cunha Xavier; de Paiva, Maria José Nunes; Oliveira-Lima, Onésia Cristina; Menezes, Helvécio Costa; Cardeal, Zenilda de Lourdes; Gomez, Marcus Vinícius; Resende, Rodrigo Ribeiro; Gomez, Renato Santiago

    2014-01-01

    The analysis of amino acid levels is crucial for neuroscience studies because of the roles of these molecules as neurotransmitters and their influence on behavior. The present study describes the distribution and levels of 16 amino acids (alanine, asparagine, aspartic acid, cysteine, glycine, glutamic acid, isoleucine, leucine, lysine, methionine, phenylalanine, proline, sarcosine, serine, valine, and threonine) in brain tissues (prefrontal cortex, striatum, hippocampus and cerebellum) and the serum. Neurochemical analysis was performed on Wistar rats and C57BL/6 mice using an efficient method for extraction, a fast microwave-assisted derivatization and gas chromatography-mass spectrometry analysis. The amino acid concentration varied across brain regions for 14 of the 16 analyzed molecules, with detection limits ranging from 0.02±0.005μmolL(-1) to 7.07±0.05μmolL(-1). In rats, the concentrations of alanine, glycine, methionine, serine and threonine were higher in prefrontal cortex than in other areas, whereas in mice, the concentrations of glutamic acid, leucine and proline were highest in the hippocampus. In conclusion, this study provides a cerebral profile of amino acids in brain regions and the serum of rats and mice. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Pilot study of newborn screening of inborn error of metabolism using tandem mass spectrometry in Malaysia: outcome and challenges.

    PubMed

    Yunus, Zabedah Md; Rahman, Salina Abdul; Choy, Yew Sing; Keng, Wee Teik; Ngu, Lock Hock

    2016-09-01

    The aim of this study was to determine the feasibility of performing newborn screening (NBS) of inborn errors of metabolism (IEMs) using tandem mass spectrometry (TMS) and the impact on its detection rate in Malaysia. During the study period between June 2006 and December 2008, 30,247 newborns from 11 major public hospitals in Malaysia were screened for 27 inborn errors of amino acid, organic acid and fatty acid metabolism by TMS. Dried blood spot (DBS) samples were collected between 24 h and 7 days with parental consent. Samples with abnormal results were repeated and the babies were recalled to confirm the diagnosis with follow-up testing. Cut-off values for amino acids and acylcarnitines were established. Eight newborns were confirmed to have IEM: two newborns with Maple syrup urine disease (MSUD), two with methylmalonic aciduria (MMA) one with ethylmalonic aciduria, two with argininosuccinic aciduria and one with isovaleric aciduria. Diagnosis was missed in two newborns. The detection rate of IEMs in this study was one in 2916 newborns. The sensitivity and specificity of TMS were 80% and 99%, respectively. IEMs are common in Malaysia. NBS of IEMs by TMS is a valuable preventive strategy by enabling the diagnosis and early treatment of IEM before the onset of symptoms aiming at prevention of mental retardation and physical handicap. A number of shortcomings warrant further solution so that in near future NBS for IEMs will become a standard of care for all babies in Malaysia in tandem with the developed world.

  15. A provenance study of iron archaeological artefacts by Inductively Coupled Plasma-Mass Spectrometry multi-elemental analysis

    NASA Astrophysics Data System (ADS)

    Desaulty, Anne-Marie; Mariet, Clarisse; Dillmann, Philippe; Joron, Jean Louis; Fluzin, Philippe

    2008-11-01

    Raw materials and wastes (i.e. ore, slag and laitier) from ironmaking archaeological sites have been analyzed in order to understand the behavior of the trace elements in the ancient ironmaking processes and to find the significant-most elements to characterize an iron making region. The ICP-MS (Inductively Coupled Plasma Mass Spectrometry) appears to be an excellent technique for this type of studies. The comparison between the ICP-MS results obtained with the Standard Addition method and the INAA (Instrumental Neutron Activation Analyses) results proved that Sc, Co, (Ni), Rb, Cs, Ba, La, Ce, Sm, Eu, Yb, Hf, Th, U contents in the ores, slag and laitiers, and Co and Ni contents in the cast iron can be successfully determined by ICP-MS after wet acid digestion (low detection limits, good sensitivity and precision). By using significant trace element pairs (Yb/Ce, Ce/Th, La/Sc, U/Th, Nb/Y) present in the ores, laitiers and slag, it is possible to discriminate different French ironmaking regions as the Pays de Bray, Lorraine and Pays d'Ouche. These results open the way to further studies on the provenance of iron objects. The comparison between the ICP-MS results obtained with the Standard Calibration Curves method and the INAA results shows that matrices rich in iron, affect the ICP-MS analyses by suppressing the analytes signal. Further studies are necessary to improve understanding matrix effects.

  16. NCBI Peptidome: a new repository for mass spectrometry proteomics data.

    PubMed

    Ji, Li; Barrett, Tanya; Ayanbule, Oluwabukunmi; Troup, Dennis B; Rudnev, Dmitry; Muertter, Rolf N; Tomashevsky, Maxim; Soboleva, Alexandra; Slotta, Douglas J

    2010-01-01

    Peptidome is a public repository that archives and freely distributes tandem mass spectrometry peptide and protein identification data generated by the scientific community. Data from all stages of a mass spectrometry experiment are captured, including original mass spectra files, experimental metadata and conclusion-level results. The submission process is facilitated through acceptance of data in commonly used open formats, and all submissions undergo syntactic validation and curation in an effort to uphold data integrity and quality. Peptidome is not restricted to specific organisms, instruments or experiment types; data from any tandem mass spectrometry experiment from any species are accepted. In addition to data storage, web-based interfaces are available to help users query, browse and explore individual peptides, proteins or entire Samples and Studies. Results are integrated and linked with other NCBI resources to ensure dissemination of the information beyond the mass spectroscopy proteomics community. Peptidome is freely accessible at http://www.ncbi.nlm.nih.gov/peptidome.

  17. Aging effects on macadamia nut oil studied by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Proschogo, Nicholas W; Albertson, Peter L; Bursle, Johanna; McConchie, Cameron A; Turner, Athol G; Willett, Gary D

    2012-02-29

    High-resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry is successfully used in the detailed molecular analysis of aged macadamia nut oils. The results are consistent with peroxide values, the current industry measure for rancidity, and provide detailed molecular information on the oxidative and hydrolytic degeneration of such oils. Mass analysis of macadamia oil samples stored for extended periods at 6 °C revealed that oils obtained by the cold press method are more susceptible to aging than those obtained using modified Soxhlet or accelerated solvent extraction methods.

  18. Targeted Quantitation of Proteins by Mass Spectrometry

    PubMed Central

    2013-01-01

    Quantitative measurement of proteins is one of the most fundamental analytical tasks in a biochemistry laboratory, but widely used immunochemical methods often have limited specificity and high measurement variation. In this review, we discuss applications of multiple-reaction monitoring (MRM) mass spectrometry, which allows sensitive, precise quantitative analyses of peptides and the proteins from which they are derived. Systematic development of MRM assays is permitted by databases of peptide mass spectra and sequences, software tools for analysis design and data analysis, and rapid evolution of tandem mass spectrometer technology. Key advantages of MRM assays are the ability to target specific peptide sequences, including variants and modified forms, and the capacity for multiplexing that allows analysis of dozens to hundreds of peptides. Different quantitative standardization methods provide options that balance precision, sensitivity, and assay cost. Targeted protein quantitation by MRM and related mass spectrometry methods can advance biochemistry by transforming approaches to protein measurement. PMID:23517332

  19. Absorption mode FTICR mass spectrometry imaging.

    PubMed

    Smith, Donald F; Kilgour, David P A; Konijnenburg, Marco; O'Connor, Peter B; Heeren, Ron M A

    2013-12-03

    Fourier transform ion cyclotron resonance mass spectrometry offers the highest mass resolving power for molecular imaging experiments. This high mass resolving power ensures that closely spaced peaks at the same nominal mass are resolved for proper image generation. Typically higher magnetic fields are used to increase mass resolving power. However, a gain in mass resolving power can also be realized by phase correction of the data for absorption mode display. In addition to mass resolving power, absorption mode offers higher mass accuracy and signal-to-noise ratio over the conventional magnitude mode. Here, we present the first use of absorption mode for Fourier transform ion cyclotron resonance mass spectrometry imaging. The Autophaser algorithm is used to phase correct each spectrum (pixel) in the image, and then, these parameters are used by the Chameleon work-flow based data processing software to generate absorption mode "Datacubes" for image and spectral viewing. Absorption mode reveals new mass and spatial features that are not resolved in magnitude mode and results in improved selected ion image contrast.

  20. Characterisation of DEFB107 by mass spectrometry

    NASA Astrophysics Data System (ADS)

    McCullough, Bryan J.; Eastwood, Hayden; Clark, Dave J.; Polfer, Nick C.; Campopiano, Dominic J.; Dorin, Julia A.; Maxwell, Alison; Langley, Ross J.; Govan, John R. W.; Bernstein, Summer L.; Bowers, Michael T.; Barran, Perdita E.

    2006-05-01

    Mammalian defensins are small endogenous cationic proteins which form a class of antimicrobial peptides that is part of the innate immune response of all mammalian species [R. Lehrer, Nat. Rev. Microbiol. 2 (9) (2004) 727; T. Ganz, R.I. Lehrer, Curr. Opin. Immunol. 6 (4) (1994) 584] [1] and [2]. We have developed mass spectrometry based strategies for characterising the structure-activity relationship of defensins [D.J. Campopiano, D.J. Clarke, N.C. Polfer, P.E. Barran, R.J. Langley, J.R.W. Govan, A. Maxwell, J.R. Dorin, J. Biol. Chem. 279 (47) (2004) 48671; P.E. Barran, N.C. Polfer, D.J. Campopiano, D.J. Clarke, P.R.R. Langridge-Smith, R.J. Langley, J.R.W. Govan, A. Maxwell, J.R. Dorin, R.P. Millar, M.T. Bowers, Int. J. Mass Spectrom. 240 (2005) 273] [3] and [4], and here we present data obtained from a five cysteine containing [beta]-defensin, DEFB107. The synthetic product of this human defensin exists with a glutathione capping group, its oxidation state and disulphide connectivity have been determined via accurate mass measurements and peptide mass mapping respectively, and despite possessing three disulphide bridges, it does not fit the [beta]-defensin canonical motif. With the use of molecular modelling, we have generated candidate geometries to discern the influence of disulphide bridging on the overall tertiary structure of DEFB107. These are compared with experimental results from ion mobility measurements. Defensins display activity against a wide variety of pathogens including both gram-negative and gram-positive bacteria. Their mechanism of mode of action is unknown, but is believed to involve defensin aggregation at cell surfaces, followed by cell permeabilisation and hence deathE To probe this mechanism, the localisation of DEFB107 in synthetic vesicles was studied using H/D exchange and mass spectrometry. The results obtained are used to analyse the antimicrobial activity of DEFB107.

  1. Deciphering the histone code using mass spectrometry

    NASA Astrophysics Data System (ADS)

    Ueberheide, Beatrix M.; Mollah, Sahana

    2007-01-01

    During the past decade, studies surrounding chromatin research have grown exponentially. A major focus of chromatin biology is centered on understanding of how histone modifications alter chromatin structure at the molecular and mechanistic levels. Discoveries are being made at a rapid pace due to the advent of new and innovative techniques. Mass spectrometry has emerged as a powerful tool in the field of histone research due to its speed, sensitivity, and ease of use. This has resulted in the identification of a number of novel histone modification sites. In consequence, new roles in biological processes have been discovered and hypothetical models, such as the `histone code' have been reaffirmed or refined. One significant advantage to using mass spectrometric techniques is that the combinations of modifications on different sites can be determined which is crucial to deciphering the `histone code'. In this manuscript, the mass spectrometric approaches developed over the past decade for both qualitative and quantitative analysis of histone post-translational modifications (PTMs) are discussed.

  2. Atmospheric-pressure Penning ionization mass spectrometry.

    PubMed

    Hiraoka, Kenzo; Fujimaki, Susumu; Kambara, Shizuka; Furuya, Hiroko; Okazaki, Shigemitsu

    2004-01-01

    A preliminary study on the atmospheric-pressure Penning ionization (APP(e)I) of gaseous organic compounds with Ar* has been made. The metastable argon atoms (Ar*: 11.55 eV for (3)P(2) and 11.72 eV for (3)P(0)) were generated by the negative-mode corona discharge of atmospheric-pressure argon gas. By applying a high positive voltage (+500 to +1000 V) to the stainless steel capillary for the sample introduction (0.1 mm i.d., 0.3 mm o.d.), strong ion signals could be obtained. The ions formed were sampled through an orifice into the vacuum and mass-analyzed by an orthogonal time-of-flight mass spectrometer. The major ions formed by APP(e)I are found to be molecular-related ions for alkanes, aromatics, and oxygen-containing compounds. Because only the molecules with ionization energies less than the internal energy of Ar* are ionized, the present method will be a selective and highly sensitive interface for gas chromatography/mass spectrometry.

  3. Molecular recognition of T:G mismatched base pairs in DNA as studied by electrospray ionization mass spectrometry.

    PubMed

    Riccardi Sirtori, Federico; Aldini, Giancarlo; Colombo, Maristella; Colombo, Nicoletta; Malyszko, Jan; Vistoli, Giulio; D'Alessio, Roberto

    2012-06-01

    Postreplicative mismatch repair (MMR) is a cellular system involved in the recognition and correction of DNA polymerase errors that escape detection in proofreading. Of the various mismatched bases, T:G pairing in DNA is one of the more common mutations leading to the formation of tumors in humans. In addition, the absence of the MMR system can generate resistance to several chemotherapeutic agents, particularly DNA-damaging substances. The main purpose of this study was the setup and validation of an electrospray ionization (ESI) mass spectrometry method for the identification of small molecules that are able to recognize T:G mismatches in DNA targets. These findings could be useful for the discovery of new antitumor drugs. The analytical method is based on the ability of electrospray to preserve the noncovalent adducts present in solution and transfer them to the gas phase. Lexitropsin derivatives (polyimidazole compounds) have been previously described as selective for T:G mismatch binding by NMR and ITC studies. We synthesized and tested various polyimidazole derivatives, one of which in particular (NMS-057) showed a higher affinity for an oligonucleotide DNA sequence containing a T:G mismatched base pair. To rationalize these findings, molecular docking studies were performed using available NMR structures. Moreover, ESI-MS experiments, performed on an orbitrap mass spectrometer, highlighted the formation of heterodimeric complexes between DNA sequences, distamycin A, and polyimidazole compounds. Our results confirm that this ESI method could be a valuable tool for the identification of new molecules able to specifically recognize T:G mismatched base pairs.

  4. Laser desorption mass spectrometry for molecular diagnosis

    NASA Astrophysics Data System (ADS)

    Chen, C. H. Winston; Taranenko, N. I.; Zhu, Y. F.; Allman, S. L.; Tang, K.; Matteson, K. J.; Chang, L. Y.; Chung, C. N.; Martin, Steve; Haff, Lawrence

    1996-04-01

    Laser desorption mass spectrometry has been used for molecular diagnosis of cystic fibrosis. Both 3-base deletion and single-base point mutation have been successfully detected by clinical samples. This new detection method can possibly speed up the diagnosis by one order of magnitude in the future. It may become a new biotechnology technique for population screening of genetic disease.

  5. Pyrolysis Mass Spectrometry of Complex Organic Materials.

    ERIC Educational Resources Information Center

    Meuzelaar, Henk L. C.; And Others

    1984-01-01

    Illustrates the state of the art in pyrolysis mass spectrometry techniques through applications in: (1) structural determination and quality control of synthetic polymers; (2) quantitative analysis of polymer mixtures; (3) classification and structural characterization of fossil organic matter; and (4) nonsupervised numerical extraction of…

  6. Pyrolysis Mass Spectrometry of Complex Organic Materials.

    ERIC Educational Resources Information Center

    Meuzelaar, Henk L. C.; And Others

    1984-01-01

    Illustrates the state of the art in pyrolysis mass spectrometry techniques through applications in: (1) structural determination and quality control of synthetic polymers; (2) quantitative analysis of polymer mixtures; (3) classification and structural characterization of fossil organic matter; and (4) nonsupervised numerical extraction of…

  7. Nanostructure-initiator mass spectrometry biometrics

    DOEpatents

    Leclerc, Marion; Bowen, Benjamin; Northen, Trent

    2015-09-08

    Several embodiments described herein are drawn to methods of identifying an analyte on a subject's skin, methods of generating a fingerprint, methods of determining a physiological change in a subject, methods of diagnosing health status of a subject, and assay systems for detecting an analyte and generating a fingerprint, by nanostructure-initiator mass spectrometry (NIMS).

  8. Optimization Of A Mass Spectrometry Process

    SciTech Connect

    Lopes, Jose; Alegria, F. Correa; Redondo, Luis; Barradas, N. P.; Alves, E.; Rocha, Jorge

    2011-06-01

    In this paper we present and discuss a system developed in order to optimize the mass spectrometry process of an ion implanter. The system uses a PC to control and display the mass spectrum. The operator interacts with the I/O board, that interfaces with the computer and the ion implanter by a LabVIEW code. Experimental results are shown and the capabilities of the system are discussed.

  9. Fundamental studies with a monodisperse aerosol-based liquid chromatography/mass spectrometry interface (MAGIC-LC/MS)

    SciTech Connect

    Browner, R.F.

    1990-10-01

    Accomplishments on the fundamental studies with a monodisperse aerosol-based liquid chromatography/mass spectrometry (LC/MS) interface during the period 1 December 1989 to 30 November 1990 are summarized. In order to determine the influence of temperature on the vaporization and decomposition properties of molecules, test have been carried out on both thermally stable and thermally labile molecules. The test compounds used were a series of polynuclear aromatic (PAH) compounds covering a wide range of molecular weights from two-ring naphthalene to twelve-ring perylene. The less thermally stable species examined were aldicarb, a highly thermally labile pesticide, and cholesterol, which readily loses water when subjected to high temperatures. A new, externally heated probe, which can be raised to temperatures as high as 500{degree}C was also used. Matrix loading effects for a range of surface active and non-surface active compounds in three different matrices: glycerol, 3-nitrobenzyl alcohol, and thioglycerol for fast atom bombardment (FAB) particle beam LC/MS have been studied. The time dependence of FAB spectra generation in the particle beam system has been examined and contrasted with ion generation in normal probe FAB work. Future FAB LC/MS research is outlined. 3 refs. (BM)

  10. Analytical Approaches Based on Gas Chromatography Mass Spectrometry (GC/MS) to Study Organic Materials in Artworks and Archaeological Objects.

    PubMed

    Bonaduce, Ilaria; Ribechini, Erika; Modugno, Francesca; Colombini, Maria Perla

    2016-02-01

    Gas chromatography/mass spectrometry (GC/MS), after appropriate wet chemical sample pre-treatments or pyrolysis, is one of the most commonly adopted analytical techniques in the study of organic materials from cultural heritage objects. Organic materials in archaeological contexts, in classical art objects, or in modern and contemporary works of art may be the same or belong to the same classes, but can also vary considerably, often presenting different ageing pathways and chemical environments. This paper provides an overview of the literature published in the last 10 years on the research based on the use of GC/MS for the analysis of organic materials in artworks and archaeological objects. The latest progresses in advancing analytical approaches, characterising materials and understanding their degradation, and developing methods for monitoring their stability are discussed. Case studies from the literature are presented to examine how the choice of the working conditions and the analytical approaches is driven by the analytical and technical question to be answered, as well as the nature of the object from which the samples are collected.

  11. A gas chromatography-mass spectrometry based study on urine metabolomics in rats chronically poisoned with hydrogen sulfide.

    PubMed

    Deng, Mingjie; Zhang, Meiling; Sun, Fa; Ma, Jianshe; Hu, Lufeng; Yang, Xuezhi; Lin, Guanyang; Wang, Xianqin

    2015-01-01

    Gas chromatography-mass spectrometry (GS-MS) in combination with multivariate statistical analysis was applied to explore the metabolic variability in urine of chronically hydrogen sulfide- (H2S-) poisoned rats relative to control ones. The changes in endogenous metabolites were studied by partial least squares-discriminate analysis (PLS-DA) and independent-samples t-test. The metabolic patterns of H2S-poisoned group are separated from the control, suggesting that the metabolic profiles of H2S-poisoned rats were markedly different from the controls. Moreover, compared to the control group, the level of alanine, d-ribose, tetradecanoic acid, L-aspartic acid, pentanedioic acid, cholesterol, acetate, and oleic acid in rat urine of the poisoning group decreased, while the level of glycine, d-mannose, arabinofuranose, and propanoic acid increased. These metabolites are related to amino acid metabolism as well as energy and lipid metabolism in vivo. Studying metabolomics using GC-MS allows for a comprehensive overview of the metabolism of the living body. This technique can be employed to decipher the mechanism of chronic H2S poisoning, thus promoting the use of metabolomics in clinical toxicology.

  12. Fluoroacetylation/fluoroethylesterification as a derivatization approach for gas chromatography-mass spectrometry in metabolomics: preliminary study of lymphohyperplastic diseases.

    PubMed

    Karamani, Anna A; Fiamegos, Yiannis Ch; Vartholomatos, George; Stalikas, Constantine D

    2013-08-09

    Metabolic fingerprinting in combination with gas chromatography and multivariate analysis is being extensively employed for the improved understanding of biological changes induced by endogenous or exogenous factors. Chemical derivatization increases the sensitivity and specificity of gas chromatography-mass spectrometry (GC-MS) for polar or thermally labile biological compounds, which bear derivatizable groups. Thus, there is a constant demand for simple methods of derivatization and separation that satisfy the need for metabolite analysis, identifying as many chemical classes of compounds as possible. In this study, an optimized protocol of extraction and derivatization is established as a generally applicable method for the analysis of a wide range of classes of metabolites in urine, whole blood and saliva. Compounds of biological relevance bearing hydroxyl- carboxyl- and amino-groups are derivatized using single-step fluoroacetylation/fluoroethylesterification after proper optimization of the protocol. Subsequently, the developed derivatization procedure is engaged in finding blood metabolic biomarkers, induced by lymphohyperplastic disease, through the metabolomic fingerprinting approach, the multivariate modeling (hierarchical cluster analysis) and GC-MS. Our preliminary, GC-MS-based metabolomic fingerprinting study underlines the contribution of certain metabolites to the discrimination of patients with lymphohyperplastic diseases.

  13. Using Hydrogen/Deuterium Exchange Mass Spectrometry to Study Conformational Changes in Granulocyte Colony Stimulating Factor upon PEGylation

    NASA Astrophysics Data System (ADS)

    Wei, Hui; Ahn, Joomi; Yu, Ying Qing; Tymiak, Adrienne; Engen, John R.; Chen, Guodong

    2012-03-01

    PEGylation is the covalent attachment of polyethylene glycol to proteins, and it can be used to alter immunogenicity, circulating half life and other properties of therapeutic proteins. To determine the impact of PEGylation on protein conformation, we applied hydrogen/deuterium exchange mass spectrometry (HDX MS) to analyze granulocyte colony stimulating factor (G-CSF) upon PEGylation as a model system. The combined use of HDX automation technology and data analysis software allowed reproducible and robust measurements of the deuterium incorporation levels for peptic peptides of both PEGylated and non-PEGylated G-CSF. The results indicated that significant differences in deuterium incorporation were induced by PEGylation of G-CSF, although the overall changes observed were quite small. PEGylation did not result in gross conformational rearrangement of G-CSF. The data complexity often encountered in HDX MS measurements was greatly reduced through a data processing and presentation format designed to facilitate the comparison process. This study demonstrates the practical utility of HDX MS for comparability studies, process monitoring, and protein therapeutic characterization in the biopharmaceutical industry.

  14. A hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) based metabolomics study on colour stability of ovine meat.

    PubMed

    Subbaraj, Arvind K; Kim, Yuan H Brad; Fraser, Karl; Farouk, Mustafa M

    2016-07-01

    Meat colour is one of the cues available to the consumer to gauge overall meat quality and wholesomeness. Colour stability of meat is determined by several factors both inherent to the animal and post-slaughter conditions, including ageing, storage/packaging and display times. A hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) based metabolomics study was undertaken to identify and compare polar metabolites between ovine meat samples that were exposed to different durations of ageing, storage conditions, and display times. Primary metabolites comprising amino acids, sugars, nucleotides, nucleosides, organic acids and their breakdown products were mainly identified as discriminating factors. For the first time, boron complexes of sugar and malic acid were also tentatively identified. As expected, most compounds identified were related to myoglobin chemistry, and compounds with antioxidant properties were found in higher levels in colour stable samples. Supplementary studies identifying semi-polar, non-polar and volatile compounds will provide a holistic understanding of the chemical basis of colour stability in ovine meat.

  15. Determination of salbutamol in human plasma and urine using liquid chromatography coupled to tandem mass spectrometry and its pharmacokinetic study.

    PubMed

    Zhang, Dujuan; Teng, Yanni; Chen, Keguang; Liu, Sha; Wei, Chunmin; Wang, Benjie; Yuan, Guiyan; Zhang, Rui; Liu, Xiaoyan; Guo, Ruichen

    2012-10-01

    A sensitive and selective liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of salbutamol in human plasma and urine, and successfully applied to the pharmacokinetic study of salbutamol in Chinese healthy volunteers after inhalation of salbutamol sulfate aerosol. Salbutamol and the internal standard (IS) acetaminophen in plasma and urine were extracted with ethyl acetate, separated on a C(18) reversed-phase column, eluted with mobile phase of acetonitrile-ammonium acetate (5 m m; 30:70, v/v), ionized by positive ion pneumatically assisted electrospray and detected in the multi-reaction monitoring mode using precursor → product ions of m/z 240.2 → 148.1 for salbutamol and 152 → 110 for the IS. The lower limits of quantitation of salbutamol in human plasma and urine by this method were 0.02 and 1 ng/mL, respectively. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision and several stabilities were validated for salbutamol in human plasma and urine. In conclusion, the validation results showed that this method is robust, specific and sensitive, and can successfully fulfill the requirement of clinical pharmacokinetic study of salbutamol in healthy Chinese volunteers.

  16. Pharmacokinetics, tissue distribution, and excretion studies of l-isocorypalmine using ultra high performance liquid chromatography with tandem mass spectrometry.

    PubMed

    Wang, Weihui; Liu, Jing; Zhao, Xiaoning; Peng, Yan; Wang, Nannan; Lee, David Y W; Dai, Ronghua

    2017-03-01

    l-Isocorypalmine is a newly identified metabolite of l-tetrahydropalmatine with a unique dual pharmacological profile as a partial dopamine receptor 1 agonist and dopamine receptor 2 antagonist properties for treating cocaine use disorder. The purpose of this study was to explore the pharmacokinetic profiles, tissue distribution, and excretion of l-isocorypalmine in Sprague-Dawley rats. A sensitive and reliable ultra high performance liquid chromatography with tandem mass spectrometry method was developed and validated for determination of l-isocorypalmine in biological samples. The biological samples were extracted by liquid-liquid extraction and separated on a Bonshell ASB C18 column (2.1 × 100 mm, 2.7 μm, Agela) with gradient mobile phase at the flow rate of 0.2 mL/min. The detection was performed by positive electrospray ionization with multiple reaction monitoring mode. Satisfactory linearity, precision, accuracy, extraction recovery, and acceptable matrix effect were achieved. The quantitative method was successfully applied to the pharmacokinetics, tissue distribution, and excretion study of l-isocorypalmine. The results showed that l-isocorypalmine was rapidly distributed, and eliminated from rat plasma and manifested linear dynamics in a dose range of 7.5-15 mg/kg. In addition, the results would be helpful for further clinical reference of l-isocorypalmine as a potential candidate drug for the treatment of cocaine addiction.

  17. Study of Grape Polyphenols by Liquid Chromatography-High-Resolution Mass Spectrometry (UHPLC/QTOF) and Suspect Screening Analysis

    PubMed Central

    Flamini, Riccardo; De Rosso, Mirko; Bavaresco, Luigi

    2015-01-01

    Suspect screening analysis is a targeted metabolomics method in which the identification of compounds relies on specific available information, such as their molecular formula and isotopic pattern. This method, coupled to liquid chromatography-high-resolution mass spectrometry, is effective in the study of grape metabolomics, in particular for characterization of flavonols, stilbene derivatives, and anthocyanins. For identification of compounds expected in the samples, a new database of putative compounds was expressly constructed by using the molecular information on potential metabolites of grape and wine from the literature and other electronic databases. Currently, this database contains around 1,100 compounds. The method allows identification of several hundred grape metabolites with two analyses (positive and negative ionization modes), and performing of data reprocessing using “untargeted” algorithms also provided the identification of some flavonols and resveratrol trimers and tetramers in grape for the first time. This approach can be potentially used in the study of metabolomics of varieties of other plant species. PMID:25734021

  18. Matrix-Free UV-Laser Desorption Ionization Mass Spectrometry as a Versatile Approach for Accelerating Dereplication Studies on Lichens.

    PubMed

    Le Pogam, Pierre; Schinkovitz, Andreas; Legouin, Béatrice; Le Lamer, Anne-Cécile; Boustie, Joël; Richomme, Pascal

    2015-10-20

    The present study examined the suitability of laser desorption/ionization time-of-flight mass spectrometry (LDI-MS) for the rapid chemical fingerprinting of lichen extracts. Lichens are known to produce a wide array of secondary metabolites. Most of these compounds are unique to the symbiotic condition but some can be found in many species. Therefore, dereplication, that is, the rapid identification of known compounds within a complex mixture is crucial in the search for novel natural products. Over the past decade, significant advances were made in analytical techniques and profiling methods specifically adapted to crude lichen extracts, but LDI-MS has never been applied in this context. However, most classes of lichen metabolites have UV chromophores, which are quite similar to commercial matrix molecules used in matrix-assisted laser desorption ionization (MALDI). It is consequently postulated that these molecules could be directly detectable by matrix-free LDI-MS. The present study evaluated the versatility of this technique by investigating the LDI properties of a vast array of single lichen metabolites as well as lichen extracts of known chemical composition. Results from the LDI experiments were compared with those obtained by direct ESI-MS detection as well as LC-ESI-MS. It was shown that LDI ionization leads to strong molecular ion formation with little fragmentation, thus, facilitating straightforward spectra interpretation and representing a valuable alternative to time-consuming LC-MS analysis.

  19. Analyzing slowly exchanging protein conformations by ion mobility mass spectrometry: study of the dynamic equilibrium of prolyl oligopeptidase.

    PubMed

    López, Abraham; Vilaseca, Marta; Madurga, Sergio; Varese, Monica; Tarragó, Teresa; Giralt, Ernest

    2016-07-01

    Ion mobility mass spectrometry (IMMS) is a biophysical technique that allows the separation of isobaric species on the basis of their size and shape. The high separation capacity, sensitivity and relatively fast time scale measurements confer IMMS great potential for the study of proteins in slow (µs-ms) conformational equilibrium in solution. However, the use of this technique for examining dynamic proteins is still not generalized. One of the major limitations is the instability of protein ions in the gas phase, which raises the question as to what extent the structures detected reflect those in solution. Here, we addressed this issue by analyzing the conformational landscape of prolyl oligopeptidase (POP) - a model of a large dynamic enzyme in the µs-ms range - by native IMMS and compared the results obtained in the gas phase with those obtained in solution. In order to interpret the experimental results, we used theoretical simulations. In addition, the stability of POP gaseous ions was explored by charge reduction and collision-induced unfolding experiments. Our experiments disclosed two species of POP in the gas phase, which correlated well with the open and closed conformations in equilibrium in solution; moreover, a gas-phase collapsed form of POP was also detected. Therefore, our findings not only support the potential of IMMS for the study of multiple co-existing conformations of large proteins in slow dynamic equilibrium in solution but also stress the need for careful data analysis to avoid artifacts. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Metabonomics study of liver cancer based on ultra performance liquid chromatography coupled to mass spectrometry with HILIC and RPLC separations.

    PubMed

    Chen, Jing; Wang, Wenzhao; Lv, Shen; Yin, Peiyuan; Zhao, Xinjie; Lu, Xin; Zhang, Fengxia; Xu, Guowang

    2009-09-14

    In this study, urinary metabolites from liver cancer patients and healthy volunteers were studied by a metabonomic method based on ultra performance liquid chromatography coupled to mass spectrometry. Both hydrophilic interaction chromatography (HILIC) and reversed-phase liquid chromatography (RPLC) were used to separate the urinary metabolites. Principle component analysis (PCA) and partial least squares to latent structure-discriminant analysis (PLS-DA) models were built to separate the healthy volunteers from the liver cancer patients and to find compounds that are expressed in significantly different amounts between the two populations. 21 metabolite ions were considered as potential biomarkers according to the Variable importance in the Project (VIP) value and S-plot. Compared with RPLC, a more sensitive and stable response can be recorded in HILIC mode due to the high content of organic solvent used. Moreover, the liver cancer group and the healthy volunteers can be better separated based on the data from the HILIC separation, which indicates that HILIC is suitable for urinary metabonomic analysis. In HILIC mode, several polar compounds related to arginine and proline metabolism, alanine and aspartate metabolism, lysine degradation, nicotinate and nicotinamide metabolism were found to be significantly changed in the concentrations of the two different populations: healthy and cancer. In contrast, in RPLC mode, these changed compounds are related to fatty acids oxidation.

  1. Mass Spectrometry-Based Tissue Imaging of Small Molecules

    PubMed Central

    Ferguson, Carly N.; Fowler, Joseph W.M.; Waxer, Jonathan F.; Gatti, Richard A.; Loo, Joseph A.

    2014-01-01

    Mass spectrometry imaging (MSI) of tissue samples is a promising analytical tool that has quickly become associated with biomedical and pharmacokinetic studies. It eliminates several labor-intensive protocols associated with more classical imaging techniques, and provides accurate, histological data at a rapid pace. Because mass spectrometry is used as the readout, MSI can be applied to almost any molecule, especially those that are biologically relevant. Many examples of its utility in the study of peptides and proteins have been reported; here we discuss its value in the mass range of small molecules. We explore its success and potential in the analysis of lipids, medicinals, and metal-based compounds by featuring representative studies from mass spectrometry imaging laboratories around the globe. PMID:24952187

  2. Fragmentation studies and electrospray ionization mass spectrometry of lapachol: protonated, deprotonated and cationized species.

    PubMed

    Vessecchi, Ricardo; Emery, Flavio S; Galembeck, Sérgio E; Lopes, Norberto P

    2010-07-30

    Electrospray ionization mass spectrometric analysis of lapachol (2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone) was accomplished in order to elucidate the gas-phase dissociation reactions of this important biologically active natural product. The occurrence of protonated and cationized species in the positive mode and of deprotonated species in the negative mode was explored by means of collision-induced dissociation (CID) experiments. For the protonated molecule, the H(2)O and C(4)H(8) losses occur by two competitive channels. For the deprotonated molecule, the even-electron rule is not conserved, and the radicalar species are eliminated by formation of distonic anions. The fragmentation mechanism for each ion was suggested on the basis of computational thermochemistry. Atomic charges, relative energies, and frontier orbitals were employed aiming at a better understanding of the gas-phase reactivity of lapachol. Potential energy surfaces for fragmentation reactions were obtained by the B3LYP/6-31+G(d,p) model.

  3. NEGATIVE-ION MASS SPECTROMETRY OF SULFONYLUREA HERBICIDES

    EPA Science Inventory

    Sulfonylurea herbicides have been studied using neg-ion desorption chem.-ionization (DCI) mass spectrometry (MS) and DCI-MS/MS techniques. Both {M-H]- and M.- ions were obsd. in the DCI mass spectra. The collisonally activated dissocn. (CAD) spectra were characteristic of the str...

  4. NEGATIVE-ION MASS SPECTROMETRY OF SULFONYLUREA HERBICIDES

    EPA Science Inventory

    Sulfonylurea herbicides have been studied using neg-ion desorption chem.-ionization (DCI) mass spectrometry (MS) and DCI-MS/MS techniques. Both {M-H]- and M.- ions were obsd. in the DCI mass spectra. The collisonally activated dissocn. (CAD) spectra were characteristic of the str...

  5. Preliminary studies on identification of inorganic species in complex mixtures by electrospray mass spectrometry in the counter ion mode

    SciTech Connect

    Mollah, Sahana

    1999-11-08

    Suppression of mass spectral peaks due to matrix problem is a major hurdle to overcome during identification work. So far, preliminary studies have been done in investigating solutions containing various percentages of nitric and hydrochloric acid. Since other anions would also be present in real samples, also needed to be examined is how the extent of suppression of metal complexes by Cl- compares with suppression by other anions such as PO43- or SO42-. If suppression of other anions is as severe as that of the chloride ion, then it would be virtually impossible to analyze unknown samples containing large amount of such anions by direct infusion electrospray mass spectrometry. It seems like a separation step is needed to separate these matrix anions from the metal complexes prior to putting the solution through the electrospray. However, separation of inorganic complexes can be difficult and has not been studied thoroughly as LC separation of bioorganic compounds. Both zinc and copper chloro complexes have been observed to be more tolerant to higher amount of chloride ion present in a solution compared to the group I and II metal chloro complexes. Other transition metals including the lanthanide complexes need to be examined more intensively to see how they fare against other transition metal complexes. So far, only preliminary work has been done in identifying inorganic species in solutions using both ICP-MS and ES-MS. The solution contained a number of metals but only one major anion, NO3-. Therefore, complex solutions containing a number of anions and metals can be examined to see if identification is still feasible. This identification work can be continued on into investigating real samples.

  6. Photochemistry of limonene secondary organic aerosol studied with chemical ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Pan, Xiang

    Limonene is one of the most abundant monoterpenes in the atmosphere. Limonene easily reacts with gas-phase oxidants in air such as NO3, ozone and OH. Secondary organic aerosol (SOA) is formed when low vapor pressure products condense into particles. Chemicals in SOA particles can undergo further reactions with oxidants and with solar radiation that significantly change SOA composition over the course of several days. The goal of this work was to characterize radiation induced reaction in SOA. To perform experiments, we have designed and constructed an Atmospheric Pressure Chemical Ionization Mass Spectrometer (APCIMS) coupled to a photochemical cell containing SOA samples. In APCIMS, (H2O)nH 3O+ clusters are generated in a 63Ni source and react with gaseous organic analytes. Most organic chemicals are not fragmented by the ionization process. We have focused our attention on limonene SOA prepared in two different ways. The first type of SOA is produced by oxidation of limonene by ozone; and the second type of SOA is formed by the NO3-induced oxidation of limonene. They model the SOA formed under daytime and nighttime conditions, respectively. Ozone initiated oxidation is the most important chemical sink for limonene both indoors, where it is used for cleaning purposes, and outdoors. Terpenes are primarily oxidized by reactions with NO3 at night time. We generated limonene SOA under different ozone and limonene concentrations. The resulting SOA samples were exposed to wavelength-tunable radiation in the UV-Visible range between 270 nm and 630 nm. The results show that the photodegradation rates strongly depend on radiation wavelengths. Gas phase photodegradation products such as acetone, formaldehyde, acetaldehyde, and acetic acid were shown to have different production rates for SOA formed in different concentration conditions. Even for SOA prepared under the lowest concentrations, the SOA photodegradation was efficient. The conclusion is that exposure of SOA to

  7. Analysis of omnoponum by surface-ionization mass spectrometry and liquid chromatography tandem mass spectrometry methods.

    PubMed

    Usmanov, Dilshadbek; Khasanov, Usman; Pantsirev, Aleksey; Van Bocxlaer, Jan

    2010-12-01

    This paper provides the development of analytical capabilities of surface-ionization mass spectrometry (SI/MS) and high performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS) for narcotic analgesic omnoponum, which perfectly exemplifies a mixture of opium alkaloids. It has been revealed that the investigated opiates solution, omnoponum, is ionized by the surface ionization (SI) method with high sensitivity. In the SI mass spectrum, M+, (M-H)+, (M-H-2nH)+, (M-R)+ and (M-R-2nH)+ ion lines, where M is a molecule, H is the hydrogen atom and R is a radical, were observed. These ion lines consist of combined omnoponum mixture SI mass spectra, i.e. morphine, codeine, thebaine, papaverine, and narcotine. Moreover, while the study of omnoponum by HPLC/MS/MS methods has attested that the mixture really consists of 5 components, it has been demonstrated that the SI/MS method can be utilized for the analysis of this mixture without the necessity of its chromatographic separation. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  8. Pharmacokinetic and pharmacometabolomic study of pirfenidone in normal mouse tissues using high mass resolution MALDI-FTICR-mass spectrometry imaging.

    PubMed

    Sun, Na; Fernandez, Isis E; Wei, Mian; Wu, Yin; Aichler, Michaela; Eickelberg, Oliver; Walch, Axel

    2016-02-01

    Given the importance of pirfenidone as the first worldwide-approved drug for idiopathic pulmonary fibrosis treatment, its pharmacodynamic properties and the metabolic response to pirfenidone treatment have not been fully elucidated. The aim of the present study was to get molecular insights of pirfenidone-related pharmacometabolomic response using MALDI-FTICR-MSI. Quantitative MALDI-FTICR-MSI was carried out for determining the pharmacokinetic properties of pirfenidone and its related metabolites 5-hydroxymethyl pirfenidone and 5-carboxy pirfenidone in lung, liver and kidney. To monitor the effect of pirfenidone administration on endogenous cell metabolism, additional in situ endogenous metabolite imaging was performed in lung tissue sections. While pirfenidone is highly abundant and delocalized across the whole micro-regions of lung, kidney and liver, 5-hydroxymethyl pirfenidone and 5-carboxy pirfenidone demonstrate heterogeneous distribution patterns in lung and kidney. In situ endogenous metabolite imaging study of lung tissue indicates no significant effects of pirfenidone on metabolic pathways. Remarkably, we found 129 discriminative m/z values which represent clear differences between control and treated lungs, the majority of which are currently unknown. PCA analysis and heatmap view can accurately distinguish control and treated groups. This is the first pharmacokinetic study to investigate the tissue distribution of orally administered pirfenidone and its related metabolites simultaneously in organs without labeling. The combination of pharmametabolome with histological features provides detailed mapping of drug effects on metabolism as response of healthy lung tissue to pirfenidone treatment.

  9. Tracking traces of transition metals present in concrete mixtures by inductively-coupled plasma mass spectrometry studies.

    PubMed

    Bassioni, Ghada; Pillay, Alvin E; El Kadi, Mirella; Fegali, Fadi; Fok, Sai Cheong; Stephen, Sasi

    2010-01-01

    Transition metals can have a significant impact in research related to the dosage optimization of superplasticizers. It is known that the presence of transition metals can influence such doses, and the application of a contemporary instrumental method to obtain the profiles of subsisting transition elements in concrete mixtures would be useful. In this work, inductively-coupled plasma mass spectrometry (ICP-MS) is investigated as a possible tool to track traces of transition metals in concrete mixtures. Depth profiling using ICP-MS on proofed and unproofed concrete shows the presence of Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu and Zn at trace intensities in the bulk of the samples under investigation. The study demonstrates that the transition metals present in the concrete sample are largely a part of the cement composition and, to a minor degree, a result of exposure to the seawater after curing. The coated concrete samples have a metal distribution pattern similar to the uncoated samples, but slight differences in intensity bear testimony to the very low levels that originate from the exposure to seawater. While X-ray diffraction fails to detect these traces of metals, ICP-MS is successful in detecting ultra-trace intensities to parts per trillion. This method is not only a useful application to track traces of transition metals in concrete, but also provides information to estimate the pore size distribution in a given sample by very simple means.

  10. Stereoselective pharmacokinetic study of rhynchophylline and isorhynchophylline epimers in rat plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Wang, Xin; Zheng, Mei; Liu, Jia; Qiao, Zhou; Liu, Wenyuan; Feng, Feng

    2017-06-01

    1. In this study, the stereoselective pharmacokinetics of rhynchophylline (RIN) and isorhynchophylline (IRN) in rat plasma were investigated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). 2. A rapid, robust and sensitive LC-MS/MS method for simultaneous quantification of RIN and IRN in rat plasma was established and validated. Chromatographic separation was performed on a Poroshell 120 EC-C18 column under a gradient elution with methanol and water containing 0.01% ammonia as mobile phase. Calibration curve was linear over a concentration range of 1-2000 ng/mL for both epimers. 3. After intravenous administration, there was no apparent difference in pharmacokinetic parameters between two epimers. However, after oral administration, RIN showed remarkable higher plasma exposure than IRN. The bioavailability, Cmax and AUC0-t of RIN were about 9.2-fold, 6.4-fold and 9.1-fold higher than those of IRN at 10 mg/kg, and 7.8-fold, 4.3-fold and 7.7-fold at 20 mg/kg, respectively. Additionally, with dosage enhanced from 10 mg/kg to 20 mg/kg, the plasma concentrations of RIN or IRN increased significantly and the bioavailability enhanced about three times. 4. In conclusion, the results of this work demonstrated for the first time that the pharmacokinetics of RIN and IRN have stereoselectivity.

  11. Structure and dynamics of a protein-surfactant assembly studied by ion-mobility mass spectrometry and molecular dynamics simulations.

    PubMed

    Borysik, Antoni J

    2015-09-01

    The structure and dynamics of a protein-surfactant assembly studied by ion-mobility mass spectrometry (IMS) and vacuum molecular dynamics (MD) simulations is reported. Direct evidence is provided for the ability of the surfactant dodecyl-β-D-maltoside (DDM) to prevent charge-induced unfolding of the membrane protein (PagP) in the gas-phase. Restraints obtained by IMS are used to map the surfactant positions onto the protein surface. Surfactants occupying more exposed positions at the apexes of the β-barrel structure are most in-line with the experimental observations. MD simulations provide additional evidence for this assembly organization through surfactant inversion and migration on the protein structure in the absence of solvent. Surfactant migration entails a net shift from apolar membrane spanning regions to more polar regions of the protein structure with the DDM molecule remaining attached to the protein via headgroup interactions. These data provide evidence for the role of protein-DDM headgroup interactions in stabilizing membrane protein structure from gas-phase unfolding.

  12. Photodegradation of secondary organic aerosol generated from limonene oxidation by ozone studied with chemical ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Pan, X.; Underwood, J. S.; Xing, J.-H.; Mang, S. A.; Nizkorodov, S. A.

    2009-06-01

    Photodegradation of secondary organic aerosol (SOA) prepared by ozone-initiated oxidation of D-limonene is studied with an action spectroscopy approach, which relies on detection of volatile photoproducts with chemical ionization mass-spectrometry as a function of the UV irradiation wavelength. Efficient photodegradation is observed for a broad range of ozone (0.1-300 ppm) and D-limonene (0.02-3 ppm) concentrations used in the preparation of SOA. The observed photoproducts are dominated by oxygenated C1-C3 compounds such as methanol, formic acid, acetaldehyde, acetic acid, and acetone. The irradiation wavelength dependence of the combined yield of the photoproducts closely tracks the absorption spectrum of the SOA material suggesting that photodegradation is not limited to the UV wavelengths. Kinetic simulations suggest that RO2+HO2/RO2 reactions represent the dominant route to photochemically active carbonyl and peroxide species in the limonene SOA prepared in these experiments. Similar photodegradation processes are likely to occur in realistic SOA produced by OH- or O3-initiated oxidation of biogenic volatile organic compounds in clean air.

  13. Photodegradation of secondary organic aerosol generated from limonene oxidation by ozone studied with chemical ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Pan, X.; Underwood, J. S.; Xing, J.-H.; Mang, S. A.; Nizkorodov, S. A.

    2009-02-01

    Photodegradation of secondary organic aerosol (SOA) prepared by ozone-initiated oxidation of D-limonene is studied with an action spectroscopy approach, which relies on detection of volatile photoproducts with chemical ionization mass-spectrometry as a function of the UV irradiation wavelength. Efficient photodegradation is observed for a broad range of ozone and D-limonene concentrations (0.1-300 ppm) used in the preparation of SOA. The observed photoproducts are dominated by oxygenated C1-C3 compounds such as methanol, formic acid, acetaldehyde, acetic acid, and acetone. The irradiation wavelength dependence of the combined yield of the photoproducts closely tracks the absorption spectrum of the SOA material suggesting that photodegradation is not limited to the UV wavelengths. Kinetic simulations suggest that RO2+HO2/RO2 reactions represent the dominant route to photochemically active carbonyl and peroxide species in the limonene SOA material. Similar photodegradation processes are likely to occur in realistic SOA produced by OH- or O3-initiated oxidation of biogenic volatile organic compounds in clean air.

  14. Interactions of nucleosides with CrO(4) (2-) and Cr(3+) as studied by electrospray ionization mass spectrometry.

    PubMed

    Frańska, Magdalena; Gierczyk, Karolina

    2008-06-01

    The interactions of CrO(4) (2-) and Cr(3+) with nucleosides studied by electrospray ionization mass spectrometry (ESI-MS) are reported. In water, the nucleosides which do not contain the NH(2) group form the unstable [M+HCrO(4)](-) anion. In the presence of a reducing agent, namely methanol, chromate anion forms stable complexes with nucleosides, [M+CH(3)CrO(4)](-) anions. The fragmentation of [M+CH(3)CrO(4)](-) anions involve elimination of the methanol molecule. Chromium cation-nucleoside complexes were not observed in water. In methanol solutions, adenosine and cytidine form [(M-H)+CrOCH(3)](+) and [(M-H)(2)+Cr](+) ions. Most probably, deprotonated imine tautomers form complexes in which a metal cation is simultaneously coordinated by two nitrogen atoms. Complexes containing chloride anions and a few methanol molecules were observed for other nucleosides. Guanosine and inosine form doubly charged ions of the type [M(2)+CrOCH(3)](2+) that probably contain a bond between the oxygen atom and the chromium cation, (HN(1)--C(6)==O)(2) (....)Cr(3+)).

  15. Nuclear magnetic resonance- and mass spectrometry-based metabolomics to study maleic acid toxicity from repeated dose exposure in rats.

    PubMed

    Wu, Charlene; Chen, Chi-Hung; Chen, Hsin-Chang; Liang, Hao-Jan; Chen, Shu-Ting; Lin, Wan-Yu; Wu, Kuen-Yuh; Chiang, Su-Yin; Lin, Ching-Yu

    2017-07-10

    Maleic acid (MA), a chemical intermediate used in many consumer and industrial products, was intentionally adulterated in a variety of starch-based foods and instigated food safety incidents in Asia. We aim to elucidate possible mechanisms of MA toxicity after repeated exposure by (1) determining the changes of metabolic profile using (1) H nuclear magnetic resonance spectroscopy and multivariate analysis, and (2) investigating the occurrence of oxidative stress using liquid chromatography tandem mass spectrometry by using Sprague-Dawley rat urine samples. Adult male rats were subjected to a 28 day subchronic study (0, 6, 20 and 60 mg kg(-1) ) via oral gavage. Urine was collected twice a day on days 0, 7, 14, 21 and 28; organs underwent histopathological examination. Changes in body weight and relative kidney weights in medium- and high-dose groups were significantly different compared to controls. Morphological alterations were evident in the kidneys and liver. Metabolomic results demonstrated that MA exposure increases the urinary concentrations of 8-hydroxy-2'-deoxyguanosine, 8-nitroguanine and 8-iso-prostaglandin F2α ; levels of acetoacetate, hippurate, alanine and acetate demonstrated time- and dose-dependent variations in the treatment groups. Findings suggest that MA consumption escalates oxidative damage, membrane lipid destruction and disrupt energy metabolism. These aforementioned changes in biomarkers and endogenous metabolites elucidate and assist in characterizing the possible mechanisms by which MA induces nephro- and hepatotoxicity. Copyright © 2017 John Wiley & Sons, Ltd.

  16. A study of resveratrol-copper complexes by electrospray ionization mass spectrometry and density functional theory calculations.

    PubMed

    Tamboli, Vajir; Defant, Andrea; Mancini, Ines; Tosi, Paolo

    2011-02-28

    Resveratrol is a polyphenolic compound found in plants and human foods which has shown biological activities including chemoprevention, acting through a mechanism which involves the reduction of Cu(II) species. By electrospray ionization (ESI) mass spectrometry we have produced and detected the resveratrol-copper complexes [Resv+Cu](+), [Resv+Cu+H(2)O](+) and [2Resv+Cu](+) by using a resveratrol/CuSO(4) solution in CH(3)CN/H(2)O. The most stable structures of the detected complexes have been calculated at the B3LYP/6-311G(d) level of theory. Resveratrol interacts with the copper ion through nucleophilic carbon atoms on the aromatic ring and the alkenyl group. The fact that only singly charged ions were observed implies that Cu(II) is reduced to Cu(I) in the ESI process. For investigating the structure-reactivity correlation, we have carried out a similar study on the synthetic analogue dihydroresveratrol (DHResv). For the latter only the [DHResv+Cu](+) complex has been detected. Copyright © 2011 John Wiley & Sons, Ltd.

  17. Zwitterionic hydrophilic interaction solid-phase extraction and multi-dimensional mass spectrometry for shotgun lipidomic study of Hypophthalmichthys nobilis.

    PubMed

    Jin, Renyao; Li, Linqiu; Feng, Junli; Dai, Zhiyuan; Huang, Yao-Wen; Shen, Qing

    2017-02-01

    Zwitterionic hydrophilic interaction liquid chromatography (ZIC-HILIC) material was used as solid-phase extraction sorbent for purification of phospholipids from Hypophthalmichthys nobilis. The conditions were optimized to be pH 6, flow rate 2.0mL·min(-1), loading breakthrough volume ⩽5mL, and eluting solvent 5mL. Afterwards, the extracts were analyzed by multi-dimensional mass spectrometry (MDMS) based shotgun lipidomics; 20 species of phosphatidylcholine (PC), 22 species of phosphatidylethanoamine (PE), 15 species of phosphatidylserine (PS), and 5 species of phosphatidylinositol (PI) were identified, with content 224.1, 124.1, 27.4, and 34.7μg·g(-1), respectively. The MDMS method was validated in terms of linearity (0.9963-0.9988), LOD (3.7ng·mL(-1)), LOQ (9.8ng·mL(-1)), intra-day precision (<3.64%), inter-day precision (<5.31%), and recovery (78.8-85.6%). ZIC-HILIC and MDMS shotgun lipidomics are efficient for studying phospholipids in H. nobilis.

  18. Determination of domperidone in human plasma using liquid chromatography coupled to tandem mass spectrometry and its pharmacokinetic study.

    PubMed

    Zhang, D; Chen, K; Teng, Y; Zhang, J; Liu, S; Wei, C; Wang, B; Liu, X; Yuan, G; Zhang, R; Guo, R

    2012-03-01

    A sensitive and selective liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of domperidone (CAS number: 57808-66-9) in human plasma using paracetamol (CAS number: 103-90-2) as an internal standard (IS). Domperidone and paracetamol in plasma were extracted with ethyl acetate, separated on a C18 reversed phase column, eluted with mobile phase of acetonitrile-glacial acetic acid (0.3%) (40:60, v/v), ionized by positive ion pneumatically assisted electrospray and detected in the multi-reaction monitoring mode using precursor→product ions of m/z 426.2→175.1 for domperidone and 152→110 for the IS, respectively. The calibration curve was linear (r2≥0.99, n=5) over the concentration range of 0.2-80 ng/mL and with lower limit of detection and quantitation of 0.05 and 0.2 ng/mL. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision, and stabilities were validated for domperidone in human plasma. In conclusion, the validation results showed that this method was sensitive, economical and less toxic and it can successfully fulfill the requirement of clinical pharmacokinetic study of domperidone oral preparation in Chinese healthy volunteers. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Complexation studies with lanthanides and humic acid analyzed by ultrafiltration and capillary electrophoresis-inductively coupled plasma mass spectrometry.

    PubMed

    Kautenburger, Ralf; Beck, Horst Philipp

    2007-08-03

    For the long-term storage of radioactive waste, detailed information about geo-chemical behavior of radioactive and toxic metal ions under environmental conditions is necessary. Humic acid (HA) can play an important role in the immobilisation or mobilisation of metal ions due to complexation and colloid formation. Therefore, we investigate the complexation behavior of HA and its influence on the migration or retardation of selected lanthanides (europium and gadolinium as homologues of the actinides americium and curium). Two independent speciation techniques, ultrafiltration and capillary electrophoresis coupled with inductively coupled plasma mass spectrometry (CE-ICP-MS) have been compared for the study of Eu and Gd interaction with (purified Aldrich) HA. The degree of complexation of Eu and Gd in 25 mg l(-1) Aldrich HA solutions was determined with a broad range of metal loading (Eu and Gd total concentration between 10(-6) and 10(-4) mol l(-1)), ionic strength of 10 mM (NaClO4) and different pH-values. From the CE-ICP-MS electropherograms, additional information on the charge of the Eu species was obtained by the use of 1-bromopropane as neutral marker. To detect HA in the ICP-MS and separate between HA complexed and non complexed metal ions in the CE-ICP-MS, we have halogenated the HA with iodine as ICP-MS marker.

  20. Activation processes and polyethylene formation on a phillips model catalyst studied by laser ablation, laser desorption, and static secondary ion mass spectrometry.

    PubMed

    Aubriet, Frédéric; Muller, Jean-François; Poleunis, Claude; Bertrand, Patrick; Di Croce, Pascal G; Grange, Paul

    2006-03-01

    Since the discovery of the Phillips catalysts, there still is much uncertainty concerning their activation, their molecular structure, the nature of the active chromium sites, and the polymerization mechanisms. Surface techniques are not easy to be used for such study according to the nonconductive behavior of the support. Therefore, model Phillips catalyst is elaborated by spin coating a trivalent chromium precursor on a silicon wafer. The surface characterization of this model catalyst is conducted by laser ablation mass spectrometry (LA-MS), laser desorption/ionization mass spectrometry (LDI-MS), and static secondary ion mass spectrometry (s-SIMS), at different steps of its preparation. To validate our approach, a comparison is also made between the model and the real Philips catalyst. Moreover, the model catalyst efficiency for polyethylene synthesis is evaluated and allows us to discuss the validity of the mechanisms previously proposed to explain the catalytic process. The characterization of Phillips model catalyst by mass spectrometry allows us to better understand the activation processes of such catalyst. Depending on the activation temperature, chromium oxide species are formed and anchored at the support surface. They consist mainly in mono-chromium sites at high temperature. The chromium valence is hexavalent. This model catalyst is active for the polymerization of ethylene. A pseudo-oligomer molecular weight distribution is observed by LA-MS, whereas s-SIMS allows us to elucidate the anchorage of the polymer at activate chromium surface sites.

  1. Tandem ion mobility-mass spectrometry (IMS-MS) study of ion evaporation from ionic liquid-acetonitrile nanodrops.

    PubMed

    Hogan, Christopher J; Fernández de la Mora, Juan

    2009-09-28

    Ion evaporation is an essential step in the formation of charged ions from electrosprays, yet many aspects of the process are poorly understood. The ion evaporation kinetics of the 1-ethyl-3-methyl-imidazolium+ (EMI+) based ionic liquids (ILs) EMI-BF4, EMI-bis(perfluoroethylsulfonyl)imide, EMI-bis(trifluoromethylsulfonyl)imide and EMI-tris(trifluoromethylsulfonyl)methide (EMI-Methide) are studied by tandem ion mobility-mass spectrometry (IMS-MS) of IL nanodrop residues from positive and negative electrosprays of IL-acetonitrile solutions. Two-dimensional (2D) IMS-MS spectra are obtained using a differential mobility analyzer (DMA) coupled to a commercial quadrupole-time-of-flight mass spectrometer. Nanodrops of different charge states (z=1,2,...,10,...) are separated into distinct bands in 2D DMA-MS spectra, allowing for determination of both nanodrop size (radius) and charge. With the exception of negatively charged EMI-BF4, all clusters observed are charged below the Rayleigh limit of both the ILs and acetonitrile, showing that the charge loss mechanism is ion evaporation. Solvation energies, DeltaG, of evaporating ions from acetonitrile are inferred from radius and charge state data. With the exclusion of EMI-BF4 in negative mode (DeltaG>1.84 eV), all are in the 1.54-1.65 eV range, considerably lower than previously reported for tetra-alkyl ammonium salts in formamide. Measured size distributions of EMI-Methide nanodrops agree with those predicted by ion evaporation theory, though with narrower widths observed for doubly and singly charged nanodrops.

  2. Uptake of Ra during the recrystallization of barite: a microscopic and time of flight-secondary ion mass spectrometry study.

    PubMed

    Klinkenberg, Martina; Brandt, Felix; Breuer, Uwe; Bosbach, Dirk

    2014-06-17

    A combined macroscopic and microanalytical approach was applied on two distinct barite samples from Ra uptake batch experiments using time of flight-secondary ion mass spectrometry (ToF-SIMS) and detailed scanning electron microscopy (SEM) investigations. The experiments were set up at near to equilibrium conditions to distinguish between two possible scenarios for the uptake of Ra by already existent barite: (1) formation of a Ba1-xRaxSO4 solid solution surface layer on the barite or (2) a complete recrystallization, leading to homogeneous Ba1-xRaxSO4 crystals. It could be clearly shown that Ra uptake in all barite particles analyzed within this study is not limited to the surface but extends to the entire solid. For most grains a homogeneous distribution of Ra could be determined, indicating a complete recrystallization of barite into a Ba1-xRaxSO4 solid solution. The maxima of the Ra/Ba intensity ratio distribution histograms calculated from ToF-SIMS are identical with the expected Ra/Ba ratios calculated from mass balance assuming a complete recrystallization. In addition, the role of Ra during the recrystallization of barite was examined via detailed SEM investigations. Depending on the type of barite used, an additional coarsening effect or a strong formation of oriented aggregates was observed compared to blank samples without Ra. In conclusion, the addition of Ra to a barite at close to equilibrium conditions has a major impact on the system leading to a fast re-equilibration of the solid to a Ba1-xRaxSO4 solid solution and visible effects on the particle size distribution, even at room temperature.

  3. Study on Mass Discrimination Effect of Resonance Ionization Mass Spectrometry Using an Inductively Coupled Plasma as an Atomic Source (ICP-RIMS)

    SciTech Connect

    Higuchi, Y.; Watanabe, K.; Tomita, H.; Kawarabayashi, J.; Iguchi, T.

    2009-03-17

    We have proposed a novel concept of Resonance Ionization Mass Spectrometry using an Inductively Coupled Plasma as an Atomic Source (ICP-RIMS). Isotope ratio analysis using ICP-RIMS is expected to be a convenient and precise technique with high throughput. However, the mass discrimination effect caused from difference in kinetic energy of neutral atoms in ICP-RIMS is crucial for precise isotope analysis. We, therefore, investigated the atom kinetic energy distribution introduced into the laser ionization region. The mass-dependent kinetic energy was confirmed in the initial kinetic energy distributions. We preliminary estimated a mass discrimination effect caused by mass-dependent kinetic energy in ICP-RIMS for various detector sizes. We proposed that this effect can be suppressed by selecting the appropriate detector size and adopting the scanning mode of the deflecting voltage.

  4. Protein structure change studied by hydrogen-deuterium exchange, functional labeling, and mass spectrometry

    PubMed Central

    Englander, Joan J.; Del Mar, Charyl; Li, Will; Englander, S. Walter; Kim, Jack S.; Stranz, David D.; Hamuro, Yoshitomo; Woods, Virgil L.

    2003-01-01

    An automated high-throughput, high-resolution deuterium exchange HPLC-MS method (DXMS) was used to extend previous hydrogen exchange studies on the position and energetic role of regulatory structure changes in hemoglobin. The results match earlier highly accurate but much more limited tritium exchange results, extend the analysis to the entire sequence of both hemoglobin subunits, and identify some energetically important changes. Allosterically sensitive amide hydrogens located at near amino acid resolution help to confirm the reality of local unfolding reactions and their use to evaluate resolved structure changes in terms of allosteric free energy. PMID:12773622

  5. Brain stem cell division and maintenance studied using multi-isotope imaging mass spectrometry (MIMS).

    PubMed

    Enikolopov, G; Guillermier, C; Wang, M; Trakimas, L; Steinhauser, M; Lechene, C

    2014-11-01

    New neurons are continuously produced from neural stem cells in specific regions of the adult brain of animals and humans. In the hippocampus, a region crucial for cognitive function, neurogenesis responds to a multitude of extrinsic stimuli; emerging evidence indicates that it may be important for behavior, pathophysiology, brain repair, and response to drugs. We have developed an approach to identify and quantify the cellular targets of pro- and anti-neurogenic stimuli, based on reporter transgenic mouse lines in which neural stem and progenitor cells or their progeny are marked by fluorescent proteins. Here, we demonstrate the feasibility of using MIMS for studying adult neurogenesis.

  6. Gas chromatography-mass spectrometry study of sterols from Pinus elliotti tissues.

    NASA Technical Reports Server (NTRS)

    Laseter, J. L.; Evans, R.; Weete, J. D.; Walkinshaw, C. H.

    1973-01-01

    A comparative study of the sterol components of slash pine (Pinus elliotti) callus tissue cultures, seeds, and seedlings was carried out using GC-MS techniques. Cholesterol, desmosterol, campesterol, stigmasterol, sitosterol and cycloeucalenol were identified in all tissues while lophenol and 24-methylenelophenol were identified in only the seed and seedlings. 24-Ethylidenelophenol was detected in trace concentrations in only the seedlings. Sitosterol was the predominant sterol component, i.e., 80.8, 38.1 and 47.8% of the tissue culture, seed and seedling sterols, respectively.

  7. Protein structure change studied by hydrogen-deuterium exchange, functional labeling, and mass spectrometry.

    PubMed

    Englander, Joan J; Del Mar, Charyl; Li, Will; Englander, S Walter; Kim, Jack S; Stranz, David D; Hamuro, Yoshitomo; Woods, Virgil L

    2003-06-10

    An automated high-throughput, high-resolution deuterium exchange HPLC-MS method (DXMS) was used to extend previous hydrogen exchange studies on the position and energetic role of regulatory structure changes in hemoglobin. The results match earlier highly accurate but much more limited tritium exchange results, extend the analysis to the entire sequence of both hemoglobin subunits, and identify some energetically important changes. Allosterically sensitive amide hydrogens located at near amino acid resolution help to confirm the reality of local unfolding reactions and their use to evaluate resolved structure changes in terms of allosteric free energy.

  8. Liquid chromatography tandem mass spectrometry analysis of photodegradation of a diazo compound: a mechanistic study.

    PubMed

    Meetani, M A; Hisaindee, S M; Abdullah, F; Ashraf, S S; Rauf, M A

    2010-06-01

    The photolytic degradation of the diazo dye, Amido Black, using UV/H(2)O(2) has been carried out experimentally and parameters for most efficient dye degradation have been determined. The degradation of the dye was followed by UV-Vis spectroscopy, HPLC, and LC-MS and is proposed to be initiated by ()OH radicals formed by the photolysis of H(2)O(2). A detailed study was also carried out using LC-MS and LC-MS/MS to determine the degradation pathway of the dye as well as to identify some of the intermediate products formed. Our results suggest that Amido Black degradation occurs preferentially by ()OH radical attack at the more electron rich diazo functionality of the molecule. Furthermore, evidence is presented that subsequent steps in this diazo dye degradation pathway include radical denitration, radical desulfonation and radical diazotization. This report is one of the very few studies that have proposed possible mechanistic pathways for the degradation pathways of a diazo compound.

  9. Peptide Immunoaffinity Enrichment and Targeted Mass Spectrometry Enables Multiplex, Quantitative Pharmacodynamic Studies of Phospho-Signaling*

    PubMed Central

    Whiteaker, Jeffrey R.; Zhao, Lei; Yan, Ping; Ivey, Richard G.; Voytovich, Uliana J.; Moore, Heather D.; Lin, Chenwei; Paulovich, Amanda G.

    2015-01-01

    In most cell signaling experiments, analytes are measured one Western blot lane at a time in a semiquantitative and often poorly specific manner, limiting our understanding of network biology and hindering the translation of novel therapeutics and diagnostics. We show the feasibility of using multiplex immuno-MRM for phospho-pharmacodynamic measurements, establishing the potential for rapid and precise quantification of cell signaling networks. A 69-plex immuno-MRM assay targeting the DNA damage response network was developed and characterized by response curves and determinations of intra- and inter-assay repeatability. The linear range was ≥3 orders of magnitude, the median limit of quantification was 2.0 fmol/mg, the median intra-assay variability was 10% CV, and the median interassay variability was 16% CV. The assay was applied in proof-of-concept studies to immortalized and primary human cells and surgically excised cancer tissues to quantify exposure–response relationships and the effects of a genomic variant (ATM kinase mutation) or pharmacologic (kinase) inhibitor. The study shows the utility of multiplex immuno-MRM for simultaneous quantification of phosphorylated and nonmodified peptides, showing feasibility for development of targeted assay panels to cell signaling networks. PMID:25987412

  10. Development of a Postcolumn Infused-Internal Standard Liquid Chromatography Mass Spectrometry Method for Quantitative Metabolomics Studies.

    PubMed

    Liao, Hsiao-Wei; Chen, Guan-Yuan; Wu, Ming-Shiang; Liao, Wei-Chih; Lin, Ching-Hung; Kuo, Ching-Hua

    2017-02-03

    Quantitative metabolomics has become much more important in clinical research in recent years. Individual differences in matrix effects (MEs) and the injection order effect are two major factors that reduce the quantification accuracy in liquid chromatography-electrospray ionization-mass spectrometry-based (LC-ESI-MS) metabolomics studies. This study proposed a postcolumn infused-internal standard (PCI-IS) combined with a matrix normalization factor (MNF) strategy to improve the analytical accuracy of quantitative metabolomics. The PCI-IS combined with the MNF method was applied for a targeted metabolomics study of amino acids (AAs). D8-Phenylalanine was used as the PCI-IS, and it was postcolumn-infused into the ESI interface for calibration purposes. The MNF was used to bridge the AA response in a standard solution with the plasma samples. The MEs caused signal changes that were corrected by dividing the AA signal intensities by the PCI-IS intensities after adjustment with the MNF. After the method validation, we evaluated the method applicability for breast cancer research using 100 plasma samples. The quantification results revealed that the 11 tested AAs exhibit an accuracy between 88.2 and 110.7%. The principal component analysis score plot revealed that the injection order effect can be successfully removed, and most of the within-group variation of the tested AAs decreased after the PCI-IS correction. Finally, targeted metabolomics studies on the AAs showed that tryptophan was expressed more in malignant patients than in the benign group. We anticipate that a similar approach can be applied to other endogenous metabolites to facilitate quantitative metabolomics studies.

  11. Space Applications of Mass Spectrometry. Chapter 31

    NASA Technical Reports Server (NTRS)

    Hoffman, John H.; Griffin, Timothy P.; Limero, Thomas; Arkin, C. Richard

    2010-01-01

    Mass spectrometers have been involved in essentially all aspects of space exploration. This chapter outlines some of these many uses. Mass spectrometers have not only helped to expand our knowledge and understanding of the world and solar system around us, they have helped to put man safely in space and expand our frontier. Mass spectrometry continues to prove to be a very reliable, robust, and flexible analytical instrument, ensuring that its use will continue to help aid our investigation of the universe and this small planet that we call home.

  12. Mass Spectrometry of Acoustically Levitated Droplets

    PubMed Central

    Westphall, Michael S.; Jorabchi, Kaveh; Smith, Lloyd M.

    2008-01-01

    Containerless sample handling techniques such as acoustic levitation offer potential advantages for mass spectrometry, by eliminating surfaces where undesired adsorption/desorption processes can occur. In addition, they provide a unique opportunity to study fundamental aspects of the ionization process as well as phenomena occurring at the air–droplet interface. Realizing these advantages is contingent, however, upon being able to effectively interface levitated droplets with a mass spectrometer, a challenging task that is addressed in this report. We have employed a newly developed charge and matrix-assisted laser desorption/ionization (CALDI) technique to obtain mass spectra from a 5-μL acoustically levitated droplet containing peptides and an ionic matrix. A four-ring electrostatic lens is used in conjunction with a corona needle to produce bursts of corona ions and to direct those ions toward the droplet, resulting in droplet charging. Analyte ions are produced from the droplet by a 337-nm laser pulse and detected by an atmospheric sampling mass spectrometer. The ion generation and extraction cycle is repeated at 20 Hz, the maximum operating frequency of the laser employed. It is shown in delayed ion extraction experiments that both positive and negative ions are produced, behavior similar to that observed for atmospheric pressure matrix-assisted laser absorption/ionization. No ion signal is observed in the absence of droplet charging. It is likely, although not yet proven, that the role of the droplet charging is to increase the strength of the electric field at the surface of the droplet, reducing chargere combination after ion desorption. PMID:18582090

  13. Mass spectrometry of acoustically levitated droplets.

    PubMed

    Westphall, Michael S; Jorabchi, Kaveh; Smith, Lloyd M

    2008-08-01

    Containerless sample handling techniques such as acoustic levitation offer potential advantages for mass spectrometry, by eliminating surfaces where undesired adsorption/desorption processes can occur. In addition, they provide a unique opportunity to study fundamental aspects of the ionization process as well as phenomena occurring at the air-droplet interface. Realizing these advantages is contingent, however, upon being able to effectively interface levitated droplets with a mass spectrometer, a challenging task that is addressed in this report. We have employed a newly developed charge and matrix-assisted laser desorption/ionization (CALDI) technique to obtain mass spectra from a 5-microL acoustically levitated droplet containing peptides and an ionic matrix. A four-ring electrostatic lens is used in conjunction with a corona needle to produce bursts of corona ions and to direct those ions toward the droplet, resulting in droplet charging. Analyte ions are produced from the droplet by a 337-nm laser pulse and detected by an atmospheric sampling mass spectrometer. The ion generation and extraction cycle is repeated at 20 Hz, the maximum operating frequency of the laser employed. It is shown in delayed ion extraction experiments that both positive and negative ions are produced, behavior similar to that observed for atmospheric pressure matrix-assisted laser absorption/ionization. No ion signal is observed in the absence of droplet charging. It is likely, although not yet proven, that the role of the droplet charging is to increase the strength of the electric field at the surface of the droplet, reducing charge recombination after ion desorption.

  14. Study of protein and RNA in dendritic spines using multi-isotope imaging mass spectrometry (MIMS).

    PubMed

    Brismar, H; Aperia, A; Westin, L; Moy, J; Wang, M; Guillermier, C; Poczatek, C; Lechene, C

    2014-11-01

    The classical view of neuronal protein synthesis is that proteins are made in the cell body and then transported to their functional sites in the dendrites and the dendritic spines. Indirect evidence, however, suggests that protein synthesis can directly occur in the distal dendrites, far from the cell body. We are developing protocols for dual labeling of RNA and proteins using (15)N-uridine and (18)O- or (13)C-leucine pulse chase in cultured neurons to identify and localize both protein synthesis and fate of newly synthesized proteins. Pilot experiments show discrete localization of both RNA and newly synthesized proteins in dendrites, close to dendritic spines. We have for the first time directly imaged and measured the production of proteins at the subcellular level in the neuronal dendrites, close to the functional sites, the dendritic spines. This will open a powerful way to study neural growth and synapse plasticity in health and disease.

  15. Impact of APCI ionization source in liquid chromatography tandem mass spectrometry based tissue distribution studies.

    PubMed

    Khatal, Laxman; Gaur, Ashwani; Naphade, Ashish; Kandikere, Vishwottam; Mookhtiar, Kasim

    2016-10-01

    Measurement of test article concentration in tissue samples has been an important part of pharmacokinetic study and has helped to co-relate pharmacokinetic/pharmacodynamic relationships since the 1950s. Bioanalysis of tissue samples using LC-MS/MS comes with unique challenges in terms of sample handling and inconsistent analyte response owing to nonvolatile matrix components. Matrix effect is a phenomenon where the target analyte response is either suppressed or enhanced in the presence of matrix components. Based on previous reports electrospray ionization (ESI) mode of ionization is believed to be more affected by matrix components than atmospheric pressure chemical ionization (APCI) or atmospheric pressure photoionization. To explore the impact of ionization source with respect to bioanalysis of tissue samples, five structurally diverse compounds - atenolol, verapamil, diclofenac, propranolol and flufenamic acid - were selected. Quality control standards were spiked into 10 different biological matrices like whole blood, liver, heart, brain, spleen, kidney, skeletal muscle, eye and skin tissue and were quantified against calibration standards prepared in rat plasma. Quantitative bioanalysis was performed utilizing both APCI and ESI mode and results were compared. Quality control standards when analyzed with APCI mode were found to be more consistent in terms of accuracy and precision as compared with ESI mode. Additionally, for some instances, up to 20-fold broader dynamic linearity range was observed with APCI mode as compared with ESI mode. As phospholid interferences have poor response in APCI mode, protein precipitation extraction technique can be used for multimatrix quantitation, which is more amenable to automation. The approach of multiple biological matrix quantitation against a single calibration curve helps bioanalysts to reduce turnaround time. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Lycopene bioavailability and metabolism in humans: an accelerator mass spectrometry study.

    PubMed

    Ross, Alastair B; Vuong, Le Thuy; Ruckle, Jon; Synal, Hans Arno; Schulze-König, Tim; Wertz, Karin; Rümbeli, Robert; Liberman, Rosa G; Skipper, Paul L; Tannenbaum, Steven R; Bourgeois, Alexandre; Guy, Philippe A; Enslen, Marc; Nielsen, Inge Lise F; Kochhar, Sunil; Richelle, Myriam; Fay, Laurent B; Williamson, Gary

    2011-06-01

    To our knowledge, there is no direct information on lycopene metabolism in humans. The objective of this study was to quantify the long-term human bioavailability of lycopene in plasma and skin after a single dose of (14)C-lycopene and to profile the metabolites formed. We preselected 2 male subjects as lycopene absorbers and gave them an oral dose of 10 mg synthetic lycopene combined with ≈6 μg [6,6',7,7'-(14)C]lycopene (≈30,000 Bq; 92% trans lycopene). The appearance of (14)C in plasma, plasma triacylglycerol-rich lipoprotein (TRL) fraction, urine, expired breath carbon dioxide, and skin biopsies was measured over 42 d. The (14)C in lycopene-isomer fractions from plasma and TRL fraction was measured to assess the isomerization of lycopene in vivo. We quantified (14)C from (14)C-lycopene in plasma, the plasma TRL fraction, expired carbon dioxide, urine, and skin. The time to maximum concentration (t(max)) of total (14)C-lycopene in plasma was 6 h, and the elimination half-life (t(1/2)) was 5 d, which were different from the t(max) and t(1/2) of unlabeled lycopene (0.5 and 48 d, respectively). (14)C-Lycopene was extensively isomerized after dosing as a 92% all-trans isomer at dosing but changed to 50% trans, 38% 5 cis, 1% 9 cis, and 11% other cis isomers after 24 h. A similar pattern of isomerization was seen in plasma TRL fractions. Lycopene was extensively isomerized after dosing and rapidly metabolized into polar metabolites excreted into urine with the rapid peak of (14)CO(2) after dosing, which implies that β-oxidation was involved in the lycopene metabolism. Lycopene or its metabolites were detected in skin for up to 42 d.

  17. Fluxomics: mass spectrometry versus quantitative imaging

    PubMed Central

    Wiechert, Wolfgang; Schweissgut, Oliver; Takanaga, Hitomi; Frommer, Wolf B

    2010-01-01

    The recent development of analytic high-throughput technologies enables us to take a bird’s view of how metabolism is regulated in real time. We have known for a long time that metabolism is highly regulated at all levels, including transcriptional, posttranslational and allosteric controls. Flux through a metabolic or signaling pathway is determined by the activity of its individual components. Fluxomics aims to define the genes involved in regulation by following the flux. Two technologies are used to monitor fluxes. Pulse labeling of the organism or cell with a tracer, such as 13C, followed by mass spectrometric analysis of the partitioning of label into different compounds provides an efficient tool to study flux and to compare the effect of mutations on flux. The second approach is based on the use of flux sensors, proteins that respond with a conformational change to ligand binding. Fluorescence resonance energy transfer (FRET) detects the conformational change and serves as a proxy for ligand concentration. In contrast to the mass spectrometry assays, FRET nanosensors monitor only a single compound. Both methods provide high time resolution. The major advantages of FRET nanosensors are that they yield data with cellular and subcellular resolution and the method is minimally invasive. PMID:17481942

  18. Fluxomics: mass spectrometry versus quantitative imaging.

    PubMed

    Wiechert, Wolfgang; Schweissgut, Oliver; Takanaga, Hitomi; Frommer, Wolf B

    2007-06-01

    The recent development of analytic high-throughput technologies enables us to take a bird's view of how metabolism is regulated in real time. We have known for a long time that metabolism is highly regulated at all levels, including transcriptional, posttranslational and allosteric controls. Flux through a metabolic or signaling pathway is determined by the activity of its individual components. Fluxomics aims to define the genes involved in regulation by following the flux. Two technologies are used to monitor fluxes. Pulse labeling of the organism or cell with a tracer, such as 13C, followed by mass spectrometric analysis of the partitioning of label into different compounds provides an efficient tool to study flux and to compare the effect of mutations on flux. The second approach is based on the use of flux sensors, proteins that respond with a conformational change to ligand binding. Fluorescence resonance energy transfer (FRET) detects the conformational change and serves as a proxy for ligand concentration. In contrast to the mass spectrometry assays, FRET nanosensors monitor only a single compound. Both methods provide high time resolution. The major advantages of FRET nanosensors are that they yield data with cellular and subcellular resolution and the method is minimally invasive.

  19. Mass spectrometry in bioinorganic analytical chemistry.

    PubMed

    Lobiński, Ryszard; Schaumlöffel, Dirk; Szpunar, Joanna

    2006-01-01

    A considerable momentum has recently been gained by in vitro and in vivo studies of interactions of trace elements in biomolecules due to advances in inductively coupled plasma mass spectrometry (ICP MS) used as a detector in chromatography and capillary and planar electrophoresis. The multi-isotopic (including non-metals such as S, P, or Se) detection capability, high sensitivity, tolerance to matrix, and large linearity range regardless of the chemical environment of an analyte make ICP MS a valuable complementary technique to electrospray MS and MALDI MS. This review covers different facets of the recent progress in metal speciation in biochemistry, including probing in vitro interactions between metals and biomolecules, detection, determination, and structural characterization of heteroatom-containing molecules in biological tissues, and protein monitoring and quantification via a heteroelement (S, Se, or P) signal. The application areas include environmental chemistry, plant and animal biochemistry, nutrition, and medicine. (c) 2005 Wiley Periodicals, Inc. Mass Spec Rev 25:255-289, 2006.

  20. Linking Mass Spectrometry with Toxicology for Emerging Water Contaminants

    EPA Science Inventory

    This overview presentation will discuss the benefits of combining mass spectrometry with toxicology. These benefits will be described for 3 main areas: (1) Toxicity assays used to test new environmental contaminants previously identified using mass spectrometry, such that furth...

  1. Linking Mass Spectrometry with Toxicology for Emerging Water Contaminants

    EPA Science Inventory

    This overview presentation will discuss the benefits of combining mass spectrometry with toxicology. These benefits will be described for 3 main areas: (1) Toxicity assays used to test new environmental contaminants previously identified using mass spectrometry, such that furth...

  2. Mass Spectrometry Imaging under Ambient Conditions

    PubMed Central

    Wu, Chunping; Dill, Allison L.; Eberlin, Livia S.; Cooks, R. Graham; Ifa, Demian R.

    2012-01-01

    Mass spectrometry imaging (MSI) has emerged as an important tool in the last decade and it is beginning to show potential to provide new information in many fields owing to its unique ability to acquire molecularly specific images and to provide multiplexed information, without the need for labeling or staining. In MSI, the chemical identity of molecules present on a surface is investigated as a function of spatial distribution. In addition to now standard methods involving MSI in vacuum, recently developed ambient ionization techniques allow MSI to be performed under atmospheric pressure on untreated samples outside the mass spectrometer. Here we review recent developments and applications of MSI emphasizing the ambient ionization techniques of desorption electrospray ionization (DESI), laser ablation electrospray ionization (LAESI), probe electrospray ionization (PESI), desorption atmospheric pressure photoionization (DAPPI), femtosecond laser desorption ionization (fs-LDI), laser electrospray mass spectrometry (LEMS), infrared laser ablation metastable-induced chemical ionization (IR-LAMICI), liquid microjunction surface sampling probe mass spectrometry (LMJ-SSP MS), nanospray desorption electrospray ionization (nano-DESI), and plasma sources such as the low temperature plasma (LTP) probe and laser ablation coupled to flowing atmospheric-pressure afterglow (LA-FAPA). Included are discussions of some of the features of ambient MSI including the ability to implement chemical reactions with the goal of providing high abundance ions characteristic of specific compounds of interest and the use of tandem mass spectrometry to either map the distribution of targeted molecules with high specificity or to provide additional MS information in the structural identification of compounds. We also describe the role of bioinformatics in acquiring and interpreting the chemical and spatial information obtained through MSI, especially in biological applications for tissue

  3. Evaluation of automated sample preparation, retention time locked gas chromatography-mass spectrometry and data analysis methods for the metabolomic study of Arabidopsis species.

    PubMed

    Gu, Qun; David, Frank; Lynen, Frédéric; Rumpel, Klaus; Dugardeyn, Jasper; Van Der Straeten, Dominique; Xu, Guowang; Sandra, Pat

    2011-05-27

    In this paper, automated sample preparation, retention time locked gas chromatography-mass spectrometry (GC-MS) and data analysis methods for the metabolomics study were evaluated. A miniaturized and automated derivatisation method using sequential oximation and silylation was applied to a polar extract of 4 types (2 types×2 ages) of Arabidopsis thaliana, a popular model organism often used in plant sciences and genetics. Automation of the derivatisation process offers excellent repeatability, and the time between sample preparation and analysis was short and constant, reducing artifact formation. Retention time locked (RTL) gas chromatography-mass spectrometry was used, resulting in reproducible retention times and GC-MS profiles. Two approaches were used for data analysis. XCMS followed by principal component analysis (approach 1) and AMDIS deconvolution combined with a commercially available program (Mass Profiler Professional) followed by principal component analysis (approach 2) were compared. Several features that were up- or down-regulated in the different types were detected.

  4. Comparisons of Immunoassay and Mass Spectrometry Measurements of Serum Estradiol Levels and Their Influence on Clinical Association Studies in Men

    PubMed Central

    Nilsson, Maria E.; Tivesten, Åsa; Ryberg, Henrik; Mellström, Dan; Karlsson, Magnus K.; Ljunggren, Östen; Labrie, Fernand; Orwoll, Eric S.; Lee, David M.; Pye, Stephen R.; O'Neill, Terence W.; Finn, Joseph D.; Adams, Judith E.; Ward, Kate A.; Boonen, Steven; Bartfai, Gyorgy; Casanueva, Felipe F.; Forti, Gianni; Giwercman, Aleksander; Han, Thang S.; Huhtaniemi, Ilpo T.; Kula, Krzysztof; Lean, Michael E. J.; Pendleton, Neil; Punab, Margus; Vanderschueren, Dirk; Wu, Frederick C. W.; Vandenput, Liesbeth

    2013-01-01

    Context: Immunoassay-based techniques, routinely used to measure serum estradiol (E2), are known to have reduced specificity, especially at lower concentrations, when compared with the gold standard technique of mass spectrometry (MS). Different measurement techniques may be responsible for the conflicting results of associations between serum E2 and clinical phenotypes in men. Objective: Our objective was to compare immunoassay and MS measurements of E2 levels in men and evaluate associations with clinical phenotypes. Design and Setting: Middle-aged and older male subjects participating in the population-based Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2599), MrOS US (n = 688), and the European Male Aging Study (n = 2908) were included. Main Outcome Measures: Immunoassay and MS measurements of serum E2 were compared and related to bone mineral density (BMD; measured by dual energy x-ray absorptiometry) and ankle-brachial index. Results: Within each cohort, serum E2 levels obtained by immunoassay and MS correlated moderately (Spearman rank correlation coefficient rS 0.53–0.76). Serum C-reactive protein (CRP) levels associated significantly (albeit to a low extent, rS = 0.29) with immunoassay E2 but not with MS E2 levels. Similar associations of immunoassay E2 and MS E2 were seen with lumbar spine and total hip BMD, independent of serum CRP. However, immunoassay E2, but not MS E2, associated inversely with ankle-brachial index, and this correlation was lost after adjustment for CRP. Conclusions: Our findings suggest interference in the immunoassay E2 analyses, possibly by CRP or a CRP-associated factor. Although associations with BMD remain unaffected, this might imply for a reevaluation of previous association studies between immunoassay E2 levels and inflammation-related outcomes. PMID:23633197

  5. Aerosol Composition in Los Angeles During the 2010 CalNex Campaign Studied by High Resolution Aerosol Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Hayes, P. L.; Ortega, A. M.; Cubison, M.; Hu, W.; Toohey, D. W.; Flynn, J. H.; Grossberg, N.; Lefer, B. L.; Alvarez, S.; Rappenglueck, B.; Allan, J. D.; McKeen, S. A.; Holloway, J. S.; Gilman, J. B.; Kuster, W. C.; Graus, M.; Warneke, C.; de Gouw, J. A.; Richter, R.; Hofer, J.; Prevot, A. S.; Jimenez, J. L.

    2010-12-01

    Submicron atmospheric aerosols impact climate and human health, but their sources and composition are poorly understood. To address this knowledge gap, high-resolution time-of-flight aerosol mass spectrometry (AMS) [DeCarlo et al. Anal. Chem. 2006] and other advanced instrumentation were deployed during the CalNex field campaign in May and June 2010 for 4 weeks to characterize the composition of aerosols in the Los Angeles area. Utilizing AMS, the concentrations for both organic and non-refractory inorganic (sulfate, nitrate, ammonium, chloride) submicron aerosols were quantified at the Caltech/Pasadena ground site 15 km NE of downtown Los Angeles. The total submicron mass concentration as well as the species concentrations measured by AMS compare well with other instruments. Nitrate aerosols appear to dominate in the cooler mornings, but their concentration is reduced in the afternoon when organic aerosols (OA) increase and dominate. The diurnal variations in concentration are strongly influenced by vertical dilution from the rising planetary boundary layer in the afternoon. Secondary organic aerosols (SOA) are an important fraction of submicron aerosols. To assess the concentrations of different OA components present at the site, positive matrix factorization (PMF) is used to analyze the field data. The major OA classes are oxygenated OA (OOA, a surrogate for total SOA), and hydrocarbon-like OA (HOA, a surrogate for primary combustion OA). Preliminary PMF analysis finds that OOA is consistently the largest type of OA present (~75% of the total OA concentration). This result suggests that the air mass over the site has undergone substantial chemical aging. The correlations between OOA and Ox (O3 + NO2) concentrations, as well as between HOA, CO and black carbon concentrations are strong and consistent with previous studies. AMS and 14C measurements are combined to determine the fractions of HOA and OOA from non-fossil vs. fossil sources. Using measurements of SOA

  6. Mercapturic acids: recent advances in their determination by liquid chromatography/mass spectrometry and their use in toxicant metabolism studies and in occupational and environmental exposure studies

    PubMed Central

    Mathias, Patricia I.; B’Hymer, Clayton

    2016-01-01

    This review describes recent selected HPLC/MS methods for the determination of urinary mercapturates that are useful as non-invasive biomarkers in characterizing human exposure to electrophilic industrial chemicals in occupational and environmental studies. High performance liquid chromatography/mass spectrometry is a sensitive and specific method for analysis of small molecules found in biological fluids. In this review, recent selected mercapturate quantification methods are summarized and specific cases are presented. The biological formation of mercapturates is introduced and their use indicators of metabolic processing of reactive toxicants is discussed, as well as future trends and limitations in this area of research. PMID:26900903

  7. The Area Between Exchange Curves as a Measure of Conformational Differences in Hydrogen-Deuterium Exchange Mass Spectrometry Studies

    NASA Astrophysics Data System (ADS)

    Mazur, Sharlyn J.; Weber, Daniel P.

    2017-02-01

    Hydrogen-deuterium exchange mass spectrometry (HDX-MS) provides information about protein conformational mobility under native conditions. The area between exchange curves, A bec , a functional data analysis concept, was adapted to the interpretation of HDX-MS data and provides a useful measure of exchange curve dissimilarity for tests of significance. Importantly, for most globular proteins under native conditions, A bec values provide an estimate of the log ratio of exchange-competent fractions in the two states, and thus are related to differences in the free energy of microdomain unfolding.

  8. Methods in the Study of PTEN Structure: X-Ray Crystallography and Hydrogen Deuterium Exchange Mass Spectrometry.

    PubMed

    Masson, Glenn R; Burke, John E; Williams, Roger L

    2016-01-01

    Despite its small size and deceptively simple domain organization, PTEN remains a challenging structural target due to its N- and C-terminal intrinsically disordered segments, and the conformational heterogeneity caused by phosphorylation of its C terminus. Using hydrogen/deuterium exchange mass spectrometry (HDX-MS), it is possible to probe the conformational dynamics of the disordered termini, and also to determine how PTEN binds to lipid membranes. Here, we describe how to purify recombinant, homogenously dephosphorylated PTEN from a eukaryotic system for subsequent investigation with HDX-MS or crystallography.

  9. Ultrahigh-Mass Mass Spectrometry of Single Biomolecules and Bioparticles

    NASA Astrophysics Data System (ADS)

    Chang, Huan-Cheng

    2009-07-01

    Since the advent of soft ionization methods, mass spectrometry (MS) has found widespread application in the life sciences. Mass is now known to be a critical parameter for characterization of biomolecules and their complexes; it is also a useful parameter to characterize bioparticles such as viruses and cells. However, because of the genetic diversity of these entities, it is necessary to measure their masses individually and to obtain the corresponding mean masses and mass distributions. Here, I review recent technological developments that enable mass measurement of ultrahigh-mass biomolecules and bioparticles at the single-ion level. Some representative examples include cryodetection time-of-flight MS of single-megadalton protein ions, Millikan-type mass measurements of single viruses in a cylindrical ion trap, and charge-detection quadrupole ion trap MS of single whole cells. I also discuss the promises and challenges of these new technologies in real-world applications.

  10. Determination of mesoridazine by liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic study in rats.

    PubMed

    Im, So Hee; Park, Myoung Joo; Seo, Hyewon; Choi, Sung Heum; Kim, Sang Kyum; Ahn, Sung-Hoon

    2014-05-01

    The object of the present study was to develop and validate an assay method of mesoridazine in rat plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma samples from rats were prepared by simple protein precipitation and injected onto the LC-MS/MS system for quantification. Mesoridazine and chlorpromazine as an internal standard (IS) were separated by a reversed phase C18 column. A mobile phase was composed of 10mM ammonium formate in water and acetonitrile (ACN) (v/v) by a linear gradient system, increasing the percentage of ACN from 2% at 0.4min to 98% at 2.5min with 4min total run time. The ion transitions monitored in positive-ion mode [M+H](+) of multiple-reaction monitoring (MRM) were m/z 387>126 for mesoridazine and m/z 319>86 for IS. The detector response was specific and linear for mesoridazine at concentrations within the range 0.001-4μg/ml and the correlation coefficient (R(2)) was greater than 0.999 and the signal-to-noise ratios for the samples were ≥10. The intra- and inter-day precision and accuracy of the method were determined to be within the acceptance criteria for assay validation guidelines. The matrix effects were approximately 101 and 99.5% from rat plasma for mesoridazine and chlorpromazine, respectively. Mesoridazine was stable under various processing and/or handling conditions. Mesoridazine concentrations were readily measured in rat plasma samples after intravenous and oral administration. This assay method can be practically useful to the pharmacokinetic and/or toxicokinetic studies of mesoridazine.

  11. Biological particle analysis by mass spectrometry

    NASA Technical Reports Server (NTRS)

    Vilker, V. L.; Platz, R. M.

    1983-01-01

    An instrument that analyzes the chemical composition of biological particles in aerosol or hydrosol form was developed. Efforts were directed toward the acquisition of mass spectra from aerosols of biomolecules and bacteria. The filament ion source was installed on the particle analysis by mass spectrometry system. Modifications of the vacuum system improved the sensitivity of the mass spectrometer. After the modifications were incorporated, detailed mass spectra of simple compounds from the three major classes of biomolecules, proteins, nucleic acids, and carbohydrates were obtained. A method of generating bacterial aerosols was developed. The aerosols generated were collected and examined in the scanning electron microscope to insure that the bacteria delivered to the mass spectrometer were intact and free from debris.

  12. Laser-Cooling-Assisted Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Schneider, Christian; Schowalter, Steven J.; Chen, Kuang; Sullivan, Scott T.; Hudson, Eric R.

    2014-09-01

    Mass spectrometry is used in a wide range of scientific disciplines including proteomics, pharmaceutics, forensics, and fundamental physics and chemistry. Given this ubiquity, there is a worldwide effort to improve the efficiency and resolution of mass spectrometers. However, the performance of all techniques is ultimately limited by the initial phase-space distribution of the molecules being analyzed. Here, we dramatically reduce the width of this initial phase-space distribution by sympathetically cooling the input molecules with laser-cooled, cotrapped atomic ions, improving both the mass resolution and detection efficiency of a time-of-flight mass spectrometer by over an order of magnitude. Detailed molecular-dynamics simulations verify the technique and aid with evaluating its effectiveness. This technique appears to be applicable to other types of mass spectrometers.

  13. Mass spectrometry in Chronic Kidney Disease research

    PubMed Central

    Merchant, Michael L.

    2010-01-01

    Proteomics has evolved into an invaluable tool for biomedical research and for research on renal diseases. A central player in the proteomic revolution is the mass spectrometer and its application to analyze biological samples. Our need to understand both the identity of proteins and their abundance has led to improvements in mass spectrometers and their ability to analyze complex tryptic peptide mixtures with high sensitivity and high mass accuracy in a high throughput fashion (such as the LTQ-Orbitrap). It should not be surprising that this occurred coincident with dramatic improvements in our understanding chronic kidney disease (CKD), the mechanisms through which CKD progresses and the development of candidate CKD biomarkers. This review attempts to present a basic framework for the operational components of mass spectrometers, basic insight into how they are used in renal research and a discussion of CKD research that was driven by mass spectrometry. PMID:21044768

  14. Single-Cell Imaging Mass Spectrometry

    PubMed Central

    Passarelli, Melissa K.; Ewing, Andrew G.

    2013-01-01

    Single-cell imaging mass spectrometry (IMS) is a powerful technique used to map the distributions of endogenous biomolecules with sub-cellular resolution. Currently, secondary ion mass spectrometry is the predominant technique for single-cell IMS, thanks to its sub-micron lateral resolution and surface sensitivity. However, recent methodological and technological developments aimed at improving the spatial resolution of matrix assisted laser desorption ionization (MALDI) have made this technique a potential platform of single-cell IMS. MALDI opens the field of single-cell IMS to new possibilities, including single cell proteomic imaging and atmospheric pressure analyses; however, sensitivity is a challenge. In this report, we estimate the availability of proteins and lipids in a single cell and discuss strategies employed to improve sensitivity at the single-cell level. PMID:23948695

  15. Impact of automation on mass spectrometry.

    PubMed

    Zhang, Yan Victoria; Rockwood, Alan

    2015-10-23

    Mass spectrometry coupled to liquid chromatography (LC-MS and LC-MS/MS) is an analytical technique that has rapidly grown in popularity in clinical practice. In contrast to traditional technology, mass spectrometry is superior in many respects including resolution, specificity, multiplex capability and has the ability to measure analytes in various matrices. Despite these advantages, LC-MS/MS remains high cost, labor intensive and has limited throughput. This specialized technology requires highly trained personnel and therefore has largely been limited to large institutions, academic organizations and reference laboratories. Advances in automation will be paramount to break through this bottleneck and increase its appeal for routine use. This article reviews these challenges, shares perspectives on essential features for LC-MS/MS total automation and proposes a step-wise and incremental approach to achieve total automation through reducing human intervention, increasing throughput and eventually integrating the LC-MS/MS system into the automated clinical laboratory operations.

  16. Accelerator mass spectrometry - from DNA to astrophysics

    NASA Astrophysics Data System (ADS)

    Kutschera, Walter

    2013-12-01

    A brief review of accelerator mass spectrometry (AMS) is presented. The present work touches on a few technical aspects and recent developments of AMS, and describes two specific applications of AMS, the dating of human DNA with the 14C bomb peak and the search for superheavy elements in nature. Since two extended general reviews on technical developments in AMS [1] and applications of AMS [2] will appear in 2013, frequent reference to these reviews is made.

  17. Monolithic multinozzle emitters for nanoelectrospray mass spectrometry

    DOEpatents

    Wang, Daojing; Yang, Peidong; Kim, Woong; Fan, Rong

    2011-09-20

    Novel and significantly simplified procedures for fabrication of fully integrated nanoelectrospray emitters have been described. For nanofabricated monolithic multinozzle emitters (NM.sup.2 emitters), a bottom up approach using silicon nanowires on a silicon sliver is used. For microfabricated monolithic multinozzle emitters (M.sup.3 emitters), a top down approach using MEMS techniques on silicon wafers is used. The emitters have performance comparable to that of commercially-available silica capillary emitters for nanoelectrospray mass spectrometry.

  18. Radiation Biomarker Research Using Mass Spectrometry

    DTIC Science & Technology

    2007-07-01

    The data was of insufficient quality to obtain definitive biomarkers. Trips were also made to AFRL/HEDR at Brooks City Base to assist with their...sample analysis using the Finnigan LTQ located there. Mr. Mullens and Ms. Nagore assisted with training personnel at AFRL/HEDR and when necessary...techniques with saliva samples and matrix- assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), we have been able to

  19. [Photon burst mass spectrometry technique.] Final report

    SciTech Connect

    Fairbank, W.M. Jr

    1996-04-01

    The basic tools have been developed and demonstrated for selective detection of Kr isotopes in the Photon Burst Mass Spectrometry technique. The effort is divided into: photon burst measurements on Mg{sup +} demonstrating high isotopic selectivity, charge exchange of Kr{sup +} with Cs and Rb to produce metastable Kr atoms, development of a diode laser system for photon burst detection of Kr{sup +}, and measurements of photon bursts detection of Kr.

  20. High-resolution mass spectrometry applied to the study of metabolome modifications in various chicken tissues after amoxicillin administration.

    PubMed

    Hermo, M P; Saurina, J; Barbosa, J; Barrón, D

    2014-06-15

    The performance of high resolution accurate mass spectrometry (HRMS) operating in full scan MS mode was investigated for the quantitative determination of amoxicillin (AMX) as well as qualitative analysis of metabolomic profiles in tissues of medicated chickens. The metabolomic approach was exploited to compile analytical information on changes in the metabolome of muscle, kidney and liver from chickens subjected to a pharmacological program with AMX. Data consisting of m/z features taken throughout the entire chromatogram were extracted and filtered to be treated by Principal Component Analysis. As a result, it was found that medicated and non-treated animals were clearly clustered in distinct groups. Besides, the multivariate analysis revealed some relevant mass features contributing to this separation. In this context, recognizing those potential markers of each chicken class was a priority research for both metabolite identification and, obviously, evaluation of food quality and health effects associated to food consumption.

  1. Seized cannabis seeds cultivated in greenhouse: A chemical study by gas chromatography-mass spectrometry and chemometric analysis.

    PubMed

    Mariotti, Kristiane de Cássia; Marcelo, Marcelo Caetano Alexandre; Ortiz, Rafael S; Borille, Bruna Tassi; Dos Reis, Monique; Fett, Mauro Sander; Ferrão, Marco Flôres; Limberger, Renata Pereira

    2016-01-01

    Cannabis sativa L. is cultivated in most regions of the world. In 2013, the Brazilian Federal Police (BFP) reported 220 tons of marijuana seized and about 800,000 cannabis plants eradicated. Efforts to eradicate cannabis production may have contributed to the development of a new form of international drug trafficking in Brazil: the sending of cannabis seeds in small amounts to urban centers by logistics postal. This new and increasing panorama of cannabis trafficking in Brazil, encouraged the chemical study of cannabis seeds cultivated in greenhouses by gas-chromatography coupled with mass spectrometry (GC-MS) associated with exploratory and discriminant analysis. Fifty cannabis seeds of different varieties and brands, seized by the BFP were cultivated under predefined conditions for a period of 4.5 weeks, 5.5 weeks, 7.5 weeks, 10 weeks and 12 weeks. Aerial parts were analyzed and cannabigerol, cannabinol, cannabidiol, cannabichromene Δ9-tetrahydrocannabinol (THC) and other terpenoids were detected. The chromatographic chemical profiles of the samples were significantly different, probably due to different variety, light exposition and age. THC content increased with the age of the plant, however, for other cannabinoids, this correlation was not observed. The chromatograms were plotted in a matrix with 50 rows (samples) and 3886 columns (abundance in a retention time) and submitted to PCA, HCA and PLS-DA after pretreatment (normalization, first derivative and autoscale). The PCA and HCA showed age separation between samples however it was not possible to verify the separation by varieties and brands. The PLS-DA classification provides a satisfactory prediction of plant age.

  2. Study of a noncovalent trp repressor: DNA operator complex by electrospray ionization time-of-flight mass spectrometry.

    PubMed

    Potier, N; Donald, L J; Chernushevich, I; Ayed, A; Ens, W; Arrowsmith, C H; Standing, K G; Duckworth, H W

    1998-06-01

    Electrospray ionization time-of-flight mass spectrometry (ESI-TOF MS) has been used to study noncovalent interactions between the trp apo-repressor (TrpR), its co-repressor tryptophan and its specific operator DNA. In 5 mM ammonium acetate, TrpR was detected as a partially unfolded monomer. In the presence of a 21-base-pair DNA possessing the two symmetrically arranged CTAG consensus sequences required for specific TrpR binding, a homodimer-dsDNA complex with a 1:1 stoichiometry was observed. Co-repressor was not needed for the complex to form under our experimental conditions. Collision induced dissociation (CID-MS) revealed that this complex was very stable in the gas phase since dissociation was achieved only at energies that also broke covalent bonds. We saw no evidence for the presence of the six water molecules that mediate the interaction between the protein and the DNA in the crystal structure. To check the binding specificity of the TrpR for its target DNA, a competitive experiment was undertaken: the protein was mixed with an equimolar amount of three different DNAs in which the two CTAG sequences were separated by 2, 4, and 6 bp, respectively. Only the DNA with the correct consensus spacing of 4 bp was able to form stable interactions with TrpR. This experiment demonstrates the potential of ESI-MS to test the sequence-specificity of protein-DNA complexes. The interactions between the TrpR-DNA complex and 5-methyl-, L- and D-tryptophan were also investigated. Two molecules of 5-methyl- or L-tryptophan were bound with high affinity to the TrpR-DNA complex. On the other hand, D-tryptophan appeared to bind to the complex with poor specificity and poor affinity.

  3. Study of a noncovalent trp repressor: DNA operator complex by electrospray ionization time-of-flight mass spectrometry.

    PubMed Central

    Potier, N.; Donald, L. J.; Chernushevich, I.; Ayed, A.; Ens, W.; Arrowsmith, C. H.; Standing, K. G.; Duckworth, H. W.

    1998-01-01

    Electrospray ionization time-of-flight mass spectrometry (ESI-TOF MS) has been used to study noncovalent interactions between the trp apo-repressor (TrpR), its co-repressor tryptophan and its specific operator DNA. In 5 mM ammonium acetate, TrpR was detected as a partially unfolded monomer. In the presence of a 21-base-pair DNA possessing the two symmetrically arranged CTAG consensus sequences required for specific TrpR binding, a homodimer-dsDNA complex with a 1:1 stoichiometry was observed. Co-repressor was not needed for the complex to form under our experimental conditions. Collision induced dissociation (CID-MS) revealed that this complex was very stable in the gas phase since dissociation was achieved only at energies that also broke covalent bonds. We saw no evidence for the presence of the six water molecules that mediate the interaction between the protein and the DNA in the crystal structure. To check the binding specificity of the TrpR for its target DNA, a competitive experiment was undertaken: the protein was mixed with an equimolar amount of three different DNAs in which the two CTAG sequences were separated by 2, 4, and 6 bp, respectively. Only the DNA with the correct consensus spacing of 4 bp was able to form stable interactions with TrpR. This experiment demonstrates the potential of ESI-MS to test the sequence-specificity of protein-DNA complexes. The interactions between the TrpR-DNA complex and 5-methyl-, L- and D-tryptophan were also investigated. Two molecules of 5-methyl- or L-tryptophan were bound with high affinity to the TrpR-DNA complex. On the other hand, D-tryptophan appeared to bind to the complex with poor specificity and poor affinity. PMID:9655343

  4. Pharmacokinetic study of ACT-132577 in rat plasma by ultra performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhang, Jin; Geng, Peiwu; Luo, Xinhua; Zhou, Genzhi; Lin, Yingying; Zhang, Lijing; Wang, Shuanghu; Wen, Congcong; Ma, Jianshe; Ding, Ting

    2015-01-01

    It was reported that macitentan was metabolized predominantly by cytochrome P450 3A4, and ACT-132577, its pharmacologically active metabolite, is fivefold less potent at blocking ET receptors than macitentan. In this work, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of ACT-132577 in rat plasma was developed and validated. After addition of diazepam as an internal standard (IS), protein precipitation by acetonitrile was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) with 0.2% formic acid and methanol as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 546.9→200.6 for ACT-132577, and m/z 285.1→193.1 for IS. Calibration plots were linear throughout the range 10-4000 ng/mL for ACT-132577 in rat plasma. Mean recovery of ACT-132577 in rat plasma ranged from 82.6% to 90.6%, matrix effect of ACT-132577 in rat plasma ranged from 101.4% to 115.2%. RSD of intra-day and inter-day precision were both less than 11%. The accuracy of the method ranged from 96.1% to 103.5%. The method was successfully applied to pharmacokinetic study of ACT-132577 after oral and intravenous administration of macitentan.

  5. Preliminary study to characterize plastic polymers using elemental analyser/isotope ratio mass spectrometry (EA/IRMS).

    PubMed

    Berto, Daniela; Rampazzo, Federico; Gion, Claudia; Noventa, Seta; Ronchi, Francesca; Traldi, Umberto; Giorgi, Giordano; Cicero, Anna Maria; Giovanardi, Otello

    2017-06-01

    Plastic waste is a growing global environmental problem, particularly in the marine ecosystems, in consideration of its persistence. The monitoring of the plastic waste has become a global issue, as reported by several surveillance guidelines proposed by Regional Sea Conventions (OSPAR, UNEP) and appointed by the EU Marine Strategy Framework Directive. Policy responses to plastic waste vary at many levels, ranging from beach clean-up to bans on the commercialization of plastic bags and to Regional Plans for waste management and recycling. Moreover, in recent years, the production of plant-derived biodegradable plastic polymers has assumed increasing importance. This study reports the first preliminary characterization of carbon stable isotopes (δ(13)C) of different plastic polymers (petroleum- and plant-derived) in order to increase the dataset of isotopic values as a tool for further investigation in different fields of polymers research as well as in the marine environment surveillance. The δ(13)C values determined in different packaging for food uses reflect the plant origin of "BIO" materials, whereas the recycled plastic materials displayed a δ(13)C signatures between plant- and petroleum-derived polymers source. In a preliminary estimation, the different colours of plastic did not affect the variability of δ(13)C values, whereas the abiotic and biotic degradation processes that occurred in the plastic materials collected on beaches and in seawater, showed less negative δ(13)C values. A preliminary experimental field test confirmed these results. The advantages offered by isotope ratio mass spectrometry with respect to other analytical methods used to characterize the composition of plastic polymers are: high sensitivity, small amount of material required, rapidity of analysis, low cost and no limitation in black/dark samples compared with spectroscopic analysis.

  6. Human urinary metabolic patterns of the designer benzodiazepines flubromazolam and pyrazolam studied by liquid chromatography-high resolution mass spectrometry.

    PubMed

    Pettersson Bergstrand, Madeleine; Meyer, Markus R; Beck, Olof; Helander, Anders

    2017-07-05

    Over the past ~8 years, hundreds of unregulated new psychoactive substances (NPS) of various chemical categories have been introduced as recreational drugs through mainly open online trade. This study was performed to further investigate the human metabolic pattern of the NPS, or designer benzodiazepines flubromazolam and pyrazolam, and to propose analytical targets for urine drug testing of these substances. The urine samples originated from patient samples confirmed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) analysis to contain flubromazolam or pyrazolam. The LC-HRMS/MS system consisted of a YMC-UltraHT Hydrosphere C18 column (YMC, Dinslaken, Germany) coupled to a Thermo Scientific (Waltham, MA, USA) Q Exactive Orbitrap MS operating in positive electrospray mode. The samples were analyzed both with and without enzymatic hydrolysis using β-glucuronidase. Besides the parent compounds, the main urinary excretion products were parent glucuronides, mono-hydroxy metabolites, and mono-hydroxy glucuronides. In samples prepared without hydrolysis, the most common flubromazolam metabolites were 1 of the mono-hydroxy glucuronides and 1 of the parent glucuronides. For pyrazolam, a parent glucuronide was the most common metabolite. These 3 metabolites were detected in all samples and were considered the primary targets for urine drug testing and confirmation of intake. After enzymatic hydrolysis of the urine samples, a 2-19-fold increase in the concentration of flubromazolam was found, highlighting the value of hydrolysis for this analyte. With hydrolysis, the flubromazolam hydroxy metabolites should be used as target metabolites. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Sorption-desorption behavior of phenanthrene elucidated by pyrolysis-gas chromatography-mass spectrometry studies of soil organic matter

    SciTech Connect

    Schultz, L.F.; Young, T.M.; Higashi, R.M.

    1999-08-01

    Commonly used partitioning models of hydrophobic organic contaminant sorption in soil, which treat all soil organic matter (SOM) as having identical structure, are unable to explain differences in organic carbon-normalized sorption coefficients (K{sub OC}) among sorbents, isotherm nonlinearity, and sorption-desorption hysteresis. This study relates one index of SOM composition, structural fragments quantified by pyrolysis-gas chromatography-mass spectrometry, to aqueous and supercritical carbon dioxide (SC CO{sub 2}) sorption-desorption parameters. Results show positive correlations between aqueous K{sub OC}s and hydrocarbon fragment peak areas and negative correlation to N- and O-containing peaks, which is consistent with hypotheses attributing sorption of phenanthrene to hydrophobic sorbent domains. Positive correlation between Freundlich n values in SC CO{sub 2} and hydrocarbon fragments with negative correlation to N- and O-containing fragments suggests that energetic heterogeneity of polar environments controls nonlinearity in this solvent of limited polarity. Aqueous sorption-desorption hysteresis appears to be suppressed by N- and O-containing moieties and correlates with decreased thermal desorption of phenanthrene at 800 C. The SC CO{sub 2} extraction efficiency and, to a lesser degree, the desorption response when methanol is added as a cosolvent indicate that polar functional groups play a role in retarding phenanthrene desorption during SC CO{sub 2} extraction. Organic matter pyrolysis under varying time and temperature conditions indicates that pyrolysis fragments that do not significantly correlated with functional trends likely evolve by a different pyrolytic mechanism and are generally poorly correlated with sorption-desorption properties. The level of structural detail utilized in structure-function correlations in this work exceeds previous efforts to relate sorption behavior to sorbent structure. However, the work reveals that certain sorption

  8. Determination of levetiracetam in human plasma by liquid chromatography/electrospray tandem mass spectrometry and its application to bioequivalence studies.

    PubMed

    Jain, Deepak S; Subbaiah, Gunta; Sanyal, Mallika; Pal, Usha; Shrivastav, Pranav S

    2006-01-01

    The first liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the determination of levetiracetam, an antiepileptic drug, in human plasma is described. The plasma filtrate obtained after solid-phase extraction (SPE), using a polymer-based, hydrophilic-lipophilic balanced (HLB) cartridge, was submitted directly to a short column LC/MS/MS assay. There was no significant matrix effect on the analysis. For validation of the method, the recovery of the free analytes was compared to that from an optimized extraction method, and the analyte stability was examined under conditions mimicking sample storage, handling, and analytical procedures. The extraction procedure yielded extremely clean extracts with a recovery of 79.95% and 89.02% for levetiracetam and the internal standard (IS), respectively. The intra-assay and inter-assay precision for the samples at the lower limit of quantitation (LLOQ) were 6.33 and 6.82%, respectively. The calibration curves were linear for the dynamic range of 0.5 to 50 microg/mL with a correlation coefficient r >/= 0.9971. The intra-assay accuracy at LLOQ, LQC, MQC, and HQC levels ranged from 81.60 to 95.40, 93.00 to 103.47, 95.97 to 104.09, and 91.15 to 95.18%, respectively, while the inter-assay accuracy at LLOQ, LQC, MQC and HQC levels varied from 80.20 to 95.40, 88.53 to 107.53, 95.97 to 108.45, and 91.15 to 112.70%, respectively. The method is rugged and fast with a total instrumental run time of 2 min. The method was successfully applied for bioequivalence studies in human subject samples after oral administration of 1000 mg immediate release (IR) formulations.

  9. Hypoxia-Responsive Cobalt Complexes in Tumor Spheroids: Laser Ablation Inductively Coupled Plasma Mass Spectrometry and Magnetic Resonance Imaging Studies.

    PubMed

    O'Neill, Edward S; Kaur, Amandeep; Bishop, David P; Shishmarev, Dmitry; Kuchel, Philip W; Grieve, Stuart M; Figtree, Gemma A; Renfrew, Anna K; Bonnitcha, Paul D; New, Elizabeth J

    2017-08-21

    Dense tumors are resistant to conventional chemotherapies due to the unique tumor microenvironment characterized by hypoxic regions that promote cellular dormancy. Bioreductive drugs that are activated in response to this hypoxic environment are an attractive strategy for therapy with anticipated lower harmful side effects in normoxic healthy tissue. Cobalt bioreductive pro-drugs that selectively release toxic payloads upon reduction in hypoxic cells have shown great promise as anticancer agents. However, the bioreductive response in the tumor microenvironment must be better understood, as current techniques for monitoring bioreduction to Co(II) such as X-ray absorption near-edge structure and extended X-ray absorption fine structure provide limited information on speciation and require synchrotron radiation sources. Here, we present magnetic resonance imaging (MRI) as an accessible and powerful technique to monitor bioreduction by treating the cobalt complex as an MRI contrast agent and monitoring the change in water signal induced by reduction from diamagnetic Co(III) to paramagnetic Co(II). Cobalt pro-drugs built upon the tris(2-pyridylmethyl)amine ligand scaffold with varying charge were investigated for distribution and activity in a 3D tumor spheroid model by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and MRI. In addition, paramagnetic (1)H NMR spectroscopy of spheroids enabled determination of the speciation of activated Co(II)TPAx complexes. This study demonstrates the utility of MRI and associated spectroscopy techniques for understanding bioreductive cobalt pro-drugs in the tumor microenvironment and has broader implications for monitoring paramagnetic metal-based therapies.

  10. Pharmacokinetic study of ACT-132577 in rat plasma by ultra performance liquid chromatography-tandem mass spectrometry

    PubMed Central

    Zhang, Jin; Geng, Peiwu; Luo, Xinhua; Zhou, Genzhi; Lin, Yingying; Zhang, Lijing; Wang, Shuanghu; Wen, Congcong; Ma, Jianshe; Ding, Ting

    2015-01-01

    It was reported that macitentan was metabolized predominantly by cytochrome P450 3A4, and ACT-132577, its pharmacologically active metabolite, is fivefold less potent at blocking ET receptors than macitentan. In this work, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of ACT-132577 in rat plasma was developed and validated. After addition of diazepam as an internal standard (IS), protein precipitation by acetonitrile was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) with 0.2% formic acid and methanol as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 546.9→200.6 for ACT-132577, and m/z 285.1→193.1 for IS. Calibration plots were linear throughout the range 10-4000 ng/mL for ACT-132577 in rat plasma. Mean recovery of ACT-132577 in rat plasma ranged from 82.6% to 90.6%, matrix effect of ACT-132577 in rat plasma ranged from 101.4% to 115.2%. RSD of intra-day and inter-day precision were both less than 11%. The accuracy of the method ranged from 96.1% to 103.5%. The method was successfully applied to pharmacokinetic study of ACT-132577 after oral and intravenous administration of macitentan. PMID:26770447

  11. [Sample preparation and bioanalysis in mass spectrometry].

    PubMed

    Bourgogne, Emmanuel; Wagner, Michel

    2015-01-01

    The quantitative analysis of compounds of clinical interest of low molecular weight (<1000 Da) in biological fluids is currently in most cases performed by liquid chromatography-mass spectrometry (LC-MS). Analysis of these compounds in biological fluids (plasma, urine, saliva, hair...) is a difficult task requiring a sample preparation. Sample preparation is a crucial part of chemical/biological analysis and in a sense is considered the bottleneck of the whole analytical process. The main objectives of sample preparation are the removal of potential interferences, analyte preconcentration, and converting (if needed) the analyte into a more suitable form for detection or separation. Without chromatographic separation, endogenous compounds, co-eluted products may affect a quantitative method in mass spectrometry performance. This work focuses on three distinct parts. First, quantitative bioanalysis will be defined, different matrices and sample preparation techniques currently used in bioanalysis by mass spectrometry of/for small molecules of clinical interest in biological fluids. In a second step the goals of sample preparation will be described. Finally, in a third step, sample preparation strategies will be made either directly ("dilute and shoot") or after precipitation.

  12. Broadband non-selective excitation of plutonium isotopes for isotope ratio measurements in resonance ionization mass spectrometry: a theoretical study.

    PubMed

    Sankari, M

    2012-10-15

    Making isotope ratio measurements with minimum isotope bias has always been a challenging task to mass spectrometrists, especially for the specific case of plutonium, owing to the strategic importance of the element. In order to use resonance ionization mass spectrometry (RIMS) as a tool for isotope ratio measurements, optimization of the various laser parameters and other atomic and system parameters is critical to minimize isotopic biases. Broadband simultaneous non-selective excitation of the isotopes of plutonium in the triple resonance excitation scheme with λ(1) = 420.77 nm, λ(2) = 847.28 nm, and λ(3) = 767.53 nm based on density matrix formalism has been theoretically computed for the determination of isotope ratios. The effects of the various laser parameters and other factors such as the atomization temperature and the dimensions of the atomic beam on the estimation of isotope ratios were studied. The effects of Doppler broadening, and time-dependent excitation parameters such as Rabi frequencies, ionization rate and the effect of non-Lorenztian lineshape have all been incorporated. The average laser powers and bandwidths for the three-excitation steps were evaluated for non-selective excitation. The laser intensity required to saturate the three-excitation steps were studied. The two-dimensional lineshape contour and its features were investigated, while the reversal of peak asymmetry of two-step and two-photon excitation peaks under these conditions is discussed. Optimized powers for the non-selective ionization of the three transitions were calculated as 545 mW, 150 mW and 545 mW and the laser bandwidth for all the three steps was ~20 GHz. The isotopic bias between the resonant and off-resonant isotope under the optimized conditions was no more than 9%, which is better than an earlier reported value. These optimized laser power and bandwidth conditions are better than in the earlier experimental work since these comprehensive calculations yield

  13. Stable compositions and geometrical structures of titanium oxide cluster cations and anions studied by ion mobility mass spectrometry

    NASA Astrophysics Data System (ADS)

    Ohshimo, Keijiro; Norimasa, Naoya; Moriyama, Ryoichi; Misaizu, Fuminori

    2016-05-01

    Geometrical structures of titanium oxide cluster cations and anions have been investigated by ion mobility mass spectrometry and quantum chemical calculations based on density functional theory. Stable cluster compositions with respect to collision induced dissociation were also determined by changing ion injection energy to an ion drift cell for mobility measurements. The TinO2n-1+ cations and TinO2n- anions were predominantly observed at high injection energies, in addition to TinO2n+ for cations and TinO2n+1- for anions. Collision cross sections of TinO2n+ and TinO2n+1- for n = 1-7, determined by ion mobility mass spectrometry, were compared with those obtained theoretically as orientation-averaged cross sections for the optimized structures by quantum chemical calculations. All of the geometrical structures thus assigned have three-dimensional structures, which are in marked contrast with other oxides of late transition metals. One-oxygen atom dissociation processes from TinO2n+ and TinO2n+1- by collisions were also explained by analysis of spin density distributions.

  14. Biological Mass Spectrometry and Shotgun Proteomics of Microbial Systems: Methods for studying microbial physiology from isolates to environmental communities

    SciTech Connect

    Dill, Brian; Young, Jacque C; Carey, Patricia A; Verberkmoes, Nathan C

    2010-01-01

    Microbial ecology is currently experiencing a renaissance spurred by the rapid development of molecular techniques and omics technologies in particular. As never before, these tools have allowed researchers in the field to produce a massive amount of information through in situ measurements and analysis of natural microbial communities, both vital approaches to the goal of unraveling the interactions of microbes with their environment and with one another. While genomics can provide information regarding the genetic potential of microbes, proteomics characterizes the primary end-stage product, proteins, thus conveying functional information concerning microbial activity. Advances in mass spectrometry instrumentation and methodologies, along with bioinformatic approaches, have brought this analytic chemistry technique to relevance in the biological realm due to its powerful applications in proteomics. Mass spectrometry-enabled proteomics, including bottom-up and top-down approaches, is capable of supplying a wealth of biologically-relevant information, from simple protein cataloging of the proteome of a microbial community to identifying post-translational modifications of individual proteins.

  15. Stable compositions and geometrical structures of titanium oxide cluster cations and anions studied by ion mobility mass spectrometry.

    PubMed

    Ohshimo, Keijiro; Norimasa, Naoya; Moriyama, Ryoichi; Misaizu, Fuminori

    2016-05-21

    Geometrical structures of titanium oxide cluster cations and anions have been investigated by ion mobility mass spectrometry and quantum chemical calculations based on density functional theory. Stable cluster compositions with respect to collision induced dissociation were also determined by changing ion injection energy to an ion drift cell for mobility measurements. The TinO2n-1 (+) cations and TinO2n (-) anions were predominantly observed at high injection energies, in addition to TinO2n (+) for cations and TinO2n+1 (-) for anions. Collision cross sections of TinO2n (+) and TinO2n+1 (-) for n = 1-7, determined by ion mobility mass spectrometry, were compared with those obtained theoretically as orientation-averaged cross sections for the optimized structures by quantum chemical calculations. All of the geometrical structures thus assigned have three-dimensional structures, which are in marked contrast with other oxides of late transition metals. One-oxygen atom dissociation processes from TinO2n (+) and TinO2n+1 (-) by collisions were also explained by analysis of spin density distributions.

  16. On-plate deposition of oxidized proteins to facilitate protein footprinting studies by radical probe mass spectrometry.

    PubMed

    Maleknia, Simin D; Downard, Kevin M

    2012-10-15

    The on-plate deposition of oxidized proteins is described to advance footprinting applications by radical probe mass spectrometry (RP-MS). An electrospray ionization (ESI) needle assembly mounted vertically over a 384-target matrix-assisted laser desorption/ionization (MALDI) plate enabled the limited oxidation of proteins as they were released in the charged droplets ahead of their deposition on the plate. This method combined with on-plate proteolytic digestion protocols expedites the analysis of proteins oxidized by RP-MS, and avoids the need to collect and reconstitute samples prior to analysis by MALDI mass spectrometry. Oxidation of peptides from solutions in water as well as an ammonium bicarbonate solution was investigated to test the optimal conditions required for on-plate oxidation of proteins. These comprised of peptides with a wide range of reactive amino acids including Phe, Tyr, Pro, His, Leu, Met and Lys that were previously shown to oxidize in both electrospray discharge and synchrotron radiolysis based footprinting experiments. The on-plate deposition of lysozyme oxidized at electrospray needle voltages of 6 and 9 kV were carried out to demonstrate conditions suitable for footprinting experiments as well as those that induce the onset of protein damage.

  17. Mass Spectrometry Analysis of Pseudomonas aeruginosa Treated with Azithromycin

    NASA Astrophysics Data System (ADS)

    Phelan, Vanessa V.; Fang, Jinshu; Dorrestein, Pieter C.

    2015-06-01

    In microbiology, changes in specialized metabolite production (cell-to-cell signaling metabolites, virulence factors, and natural products) are measured using phenotypic assays. However, advances in mass spectrometry-based techniques including imaging mass spectrometry (IMS) now allow researchers to directly visualize the production of specialized metabolites from microbial colony biofilms. In this study, a combination of IMS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to visualize the effect of the macrolide antibiotic azithromycin (AZM) on colony biofilms of Pseudomonas aeruginosa. Although previous research suggested that AZM may inhibit cell-to-cell signaling of P. aeruginosa and thereby reduce pathogenicity, we observed no clear decrease in specialized metabolite production.

  18. Mass Spectrometry Analysis of Pseudomonas aeruginosa Treated With Azithromycin

    PubMed Central

    Phelan, Vanessa V.; Fang, Jinshu; Dorrestein, Pieter C.

    2015-01-01

    In microbiology, changes in specialized metabolite production (cell-to-cell signaling metabolites, virulence factors and natural products) are measured using phenotypic assays. However, advances in mass spectrometry based techniques including imaging mass spectrometry (IMS) now allow researchers to directly visualize the production of specialized metabolites from microbial colony biofilms. In this study, a combination of IMS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to visualize the effect of the macrolide antibiotic azithromycin (AZM) on colony biofilms of Pseudomonas aeruginosa. While previous research suggested that AZM may inhibit cell-to-cell signaling of P. aeruginosa and thereby reducing pathogenicity, we observed no clear decrease in specialized metabolite production. PMID:25801585

  19. Toward Single-Molecule Nanomechanical Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Roukes, Michael

    2009-03-01

    Mass spectrometry (MS) has become a preeminent methodology of proteomics since it provides rapid and quantitative identification of protein species with relatively low sample consumption. Yet with the trend toward biological analysis at increasingly smaller scales, ultimately down to the volume of an individual cell, MS with few-to-single molecule resolution will be required. We report the first realization of MS based on single-biological-molecule detection with nanoelectromechanical systems (NEMS). NEMS provide unparalleled mass resolution, now sufficient for detection of individual molecular species in real time. However, high sensitivity is only one of several components required for MS. We demonstrate a first complete prototype NEMS-MS system for single-molecule mass spectrometry providing proof-of-principle for this new technique. Nanoparticles and protein species are introduced by electrospray injection from the fluid phase in ambient conditions into vacuum and subsequently delivered to the NEMS detector by hexapole ion optics . Mass measurements are then recorded in real-time as analytes adsorb, one-by-one, onto a phase-locked, ultrahigh frequency (UHF) NEMS resonator. These first NEMS-MS spectra, obtained with modest resolution from only several hundred mass adsorption events, presage the future capabilities of this methodology. We outline the substantial improvements feasible in near term, through recent advances and technological avenues that are unique to NEMS-MS.

  20. Distribution study of cisplatin in rat kidney and liver cancer tissues by using liquid chromatography electrospray ionization tandem mass spectrometry.

    PubMed

    Bandu, Raju; Ahn, Hyun Soo; Lee, Joon Won; Kim, Yong Woo; Choi, Seon Hee; Kim, Hak Jin; Kim, Kwang Pyo

    2015-06-01

    A sensitive and rapid liquid chromatography positive ion electrospray ionization tandem mass spectrometric (LC/ESI-MS/MS) method has been developed and validated for the quantitative determination and distribution of cisplatin (CP) in kidney and liver tissues after intravenous administration of drug to adult male Sprague Dawley rats. Oxaliplatin (OXP) was used as an internal standard. The tissue samples were homogenized and extracted using conventional liquid-liquid extraction method with phosphate buffer containing ethyl acetate and then subjected to LC-MS analysis. The chromatographic separation was achieved on an Agilent ZORBAX SB C-18 column (50 × 2.1 mm, 1.8 µm) using the mobile phase consisting of 0.1% formic acid in water (Solvent A) : methanol (Solvent B) (40 : 60; v/v) in an isocratic elution followed by detection with positive ion electrospray ionization tandem mass spectrometry using the transitions of m/z 301 > 265 for CP and m/z 398 > 310 for OXP in multiple reaction monitoring mode. The calibration curve was linear in the range of 5.0-7000 and 10.0-6000 ng/ml for kidney and liver tissue homogenates, respectively. The method revealed good performances in terms of within-batch, between-batch precision (1.31-5.70%) and accuracy (97.0-102.24%) for CP in both kidney and liver tissue homogenates including lower and upper limits of quantification. The recoveries from spiked control samples were >81.0% and >87.0 % for CP and OXP, respectively. Matrix effect was found to be negligible, and the stability data were within the acceptable limits. Further, the validated LC/ES-MS/MS method was successfully applied to investigate the distribution of CP in kidney and liver tissues after intravenous administration of CP to male Sprague Dawley rats. The results showed that the higher amount of CP was distributed in kidney followed by liver, which indicated that CP mainly accumulated in kidney tissues and renal excretion might be a primary and

  1. Fast Single-Cell Patterning for Study of Drug-Induced Phenotypic Alterations of HeLa Cells Using Time-of-Flight Secondary Ion Mass Spectrometry.

    PubMed

    Huang, Lu; Chen, Yin; Weng, Lu-Tao; Leung, Mark; Xing, Xiaoxing; Fan, Zhiyong; Wu, Hongkai

    2016-12-20

    A facile single-cell patterning (ScP) method was developed and integrated with time-of-flight secondary ion mass spectrometry (TOF-SIMS) for the study of drug-induced cellular phenotypic alterations. Micropatterned poly(dimethylsiloxane) (PDMS) stencil film and centrifugation-assisted cell trapping were combined for the preparation of on-surface single-cell microarrays, which exhibited both high site occupancy (>90%) and single-cell resolution (>97%). TOF-SIMS is a surface-sensitive mass spectrometry and is increasingly utilized in biological studies. Here we demonstrated, for the first time, its successful application in high-throughput single-cell analysis. Drug-induced phenotypic alterations of HeLa cells in the early stage of apoptosis were investigated using TOF-SIMS. The major molecular sources of variations were analyzed by principle component analysis (PCA).

  2. A comparative study of 129I content in environmental standard materials IAEA-375, NIST SRM 4354 and NIST SRM 4357 by Thermal Ionization Mass Spectrometry and Accelerator Mass Spectrometry

    SciTech Connect

    Olson, John; Adamic, Mary; Snyder, Darin; Brookhart, Jacob; Hahn, Paula; Watrous, Matthew

    2016-11-01

    Iodine environmental measurements have consistently been backed up in the literature by standard materials like IAEA-375, Chernobyl Soil. There are not many other sources of a certified reference material for 129I content for mass spectrometry measurements. Some that have been found in the literature include NIST-4354 and NIST-4357. They are still available at the time of this writing. They don’t have certified content or isotopic values. There has been some work in the literature to show that iodine is present, but there hasn’t been enough to establish a consensus value. These materials have been analyzed at INL through two separate mass spectrometry techniques. They involve a combustion method of the starting material in oxygen, followed by TIMS analysis and a leaching preparation analyzed by accelerator mass spectrometry. Combustion/TIMS preparation of NIST SRM-4354 resulted in a 129I/127I ratio of 1.92 x 10-6 which agrees with AMS measurements which measured the 129I/127I ratio to be 1.93 x 10-6.

  3. Mass spectrometry with direct supercritical fluid injection

    SciTech Connect

    Smith, R.D.; Udseth, H.R.

    1983-12-01

    Direct fluid injection mass spectrometry utilizes supercritical fluids for solvation and transfer of materials to a mass spectrometer chemical ionization (CI) source. Available data suggest that any material soluble in a supercritical fluid is transferred efficiently to the ionization region. Mass spectra are presented for mycotoxins of the trichothecene group obtained by use of supercritical carbon dioxide with isobutane as the CI reagent gas. Direct fluid injection MS/MS is also illustrated for major ions in the isobutane chemical ionization of T-2 toxin. The effect of pressure and temperature upon solubility in supercritical fluids is described and illustrated for diacetoxycirpenol. A potential method is also demonstrated for on-line fraction during MS analysis using pressure to control supercritical fluid solubility. Mass spectra are also presented for polar compounds, using supercritical ammonia, and the extension to complex mixtures is described. The fundamental basis and experimental requirements of the direct fluid injection process are discussed. 34 references, 11 figures, 1 table.

  4. Mass spectrometry with direct supercritical fluid injection

    SciTech Connect

    Smith, R.D.; Udseth, H.R.

    1983-12-01

    Direct fluid injection mass spectrometry utilizes supercritical fluids for solvation and transfer of materials to a mass spectrometer chemical ionization (CI) source. Available data suggest that any material soluble in a supercritical fluid is transferred efficiently to the ionization region. Mass spectra are presented for mycotoxins of the trichothecene group obtained by use of supercritical carbon dioxide with isobutane as the CI reagent gas. Direct fluid injection MS/MS is also illustrated for major ions in the isobutane chemical ionization of T-2 toxin. The effect of pressure and temperature upon solubility in supercritical fluids is described and illustrated for diacetoxyscirpenol. A potential method is also demonstrated for ''on-line fractionation'' during MS analysis using pressure to control supercritical fluid solubility. Mass spectra are also presented for polar compounds, using supercritical ammonia, and the extension to complex mixtures is described. The fundamental basis and experimental requirements of the direct fluid injection process are discussed. 1 figure, 11 tables.

  5. Observational infant exploratory [14C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis

    PubMed Central

    Garner, Colin R; Park, Kevin B; French, Neil S; Earnshaw, Caroline; Schipani, Alessandro; Selby, Andrew M; Byrne, Lindsay; Siner, Sarah; Crawley, Francis P; Vaes, Wouter H J; van Duijn, Esther; deLigt, Rianne; Varendi, Heili; Lass, Jane; Grynkiewicz, Grzegorz; Maruszak, Wioletta; Turner, Mark A

    2015-01-01

    Aims The aims of the study were to compare [14C]-paracetamol ([14C]-PARA) paediatric pharmacokinetics (PK) after administration mixed in a therapeutic dose or an isolated microdose and to develop further and validate accelerator mass spectrometry (AMS) bioanalysis in the 0–2 year old age group. Methods [14C]-PARA concentrations in 10–15 µl plasma samples were measured after enteral or i.v. administration of a single [14C]-PARA microdose or mixed in with therapeutic dose in infants receiving PARA as part of their therapeutic regimen. Results Thirty-four infants were included in the PARA PK analysis for this study: oral microdose (n = 4), i.v. microdose (n = 6), oral therapeutic (n = 6) and i.v. therapeutic (n = 18). The respective mean clearance (CL) values (SDs in parentheses) for these dosed groups were 1.46 (1.00) l h–1, 1.76 (1.07) l h–1, 2.93 (2.08) l h–1 and 2.72 (3.10) l h–1, t1/2 values 2.65 h, 2.55 h, 8.36 h and 7.16 h and dose normalized AUC(0-t) (mg l–1 h) values were 0.90 (0.43), 0.84 (0.57), 0.7 (0.79) and 0.54 (0.26). Conclusions All necessary ethical, scientific, clinical and regulatory procedures were put in place to conduct PK studies using enteral and systemic microdosing in two European centres. The pharmacokinetics of a therapeutic dose (mg kg–1) and a microdose (ng kg–1) in babies between 35 to 127 weeks post-menstrual age. [14C]-PARA pharmacokinetic parameters were within a two-fold range after a therapeutic dose or a microdose. Exploratory studies using doses significantly less than therapeutic doses may offer ethical and safety advantages with increased bionalytical sensitivity in selected exploratory paediatric pharmacokinetic studies. PMID:25619398

  6. Ligand-binding mass spectrometry to study biotransformation of fusion protein drugs and guide immunoassay development: strategic approach and application to peptibodies targeting the thrombopoietin receptor.

    PubMed

    Hall, Michael P; Gegg, Colin; Walker, Kenneth; Spahr, Christopher; Ortiz, Robert; Patel, Vimal; Yu, Steven; Zhang, Liana; Lu, Hsieng; DeSilva, Binodh; Lee, Jean W

    2010-12-01

    The knowledge of in vivo biotransformation (e.g., proteolysis) of protein therapeutic candidates reveals structural liabilities that impact stability. This information aids the development and confirmation of ligand-binding assays with the required specificity for bioactive moieties (including intact molecule and metabolites) for appropriate PK profiling. Furthermore, the information can be used for re-engineering of constructs to remove in vivo liabilities in order to design the most stable candidates. We have developed a strategic approach of ligand-binding mass spectrometry (LBMS) to study biotransformation of fusion proteins of peptides fused to human Fc ("peptibodies") using anti-human Fc immunoaffinity capture followed by tiered mass spectrometric interrogation. LBMS offers the combined power of selectivity of ligand capture with the specificity and detailed molecular-level information of mass spectrometry. In this paper, we demonstrate the preclinical application of LBMS to three peptibodies, AMG531 (romiplostim), AMG195(linear), and AMG195(loop), that target the thrombopoietin receptor. The data show that ligand capture offers excellent sample cleanup and concentration of intact peptibodies and metabolites for subsequent query by matrix-assisted laser desorption ionization time-of-flight mass spectrometry for identification of in vivo proteolytic points. Additional higher-resolution analysis by nanoscale liquid chromatography interfaced with electrospray ionization mass spectrometry is required for identification of heterogeneous metabolites. Five proteolytic points are accurately identified for AMG531 and two for AMG195(linear), while AMG195(loop) is the most stable construct in rats. We recommend the use of LBMS to assess biotransformation and in vivo stability during early preclinical phase development for all novel fusion proteins.

  7. A case study of de novo sequence analysis of N-sulfonated peptides by MALDI TOF/TOF mass spectrometry.

    PubMed

    Samyn, Bart; Debyser, Griet; Sergeant, Kjell; Devreese, Bart; Van Beeumen, Jozef

    2004-12-01

    The simplicity and sensitivity of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry have increased its application in recent years. The most common method of "peptide mass fingerprint" analysis often does not provide robust identification. Additional sequence information, obtained by post-source decay or collision induced dissociation, provides additional constraints for database searches. However, de novo sequencing by mass spectrometry is not yet common practice, most likely because of the difficulties associated with the interpretation of high and low energy CID spectra. Success with this type of sequencing requires full sequence coverage and demands better quality spectra than those typically used for data base searching. In this report we show that full-length de novo sequencing is possible using MALDI TOF/TOF analysis. The interpretation of MS/MS data is facilitated by N-terminal sulfonation after protection of lysine side chains (Keough et al., Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 7131-7136). Reliable de novo sequence analysis has been obtained using sub-picomol quantities of peptides and peptide sequences of up to 16 amino acid residues in length have been determined. The simple, predictable fragmentation pattern allows routine de novo interpretation, either manually or using software. Characterization of the complete primary structure of a peptide is often hindered because of differences in fragmentation efficiencies and in specific fragmentation patterns for different peptides. These differences are controlled by various structural parameters including the nature of the residues present. The influence of the presence of internal Pro, acidic and basic residues on the TOF/TOF fragmentation pattern will be discussed, both for underivatized and guanidinated/sulfonated peptides.

  8. Accelerator Mass Spectrometry in Laboratory Nuclear Astrophysics

    NASA Astrophysics Data System (ADS)

    Nusair, O.; Bauder, W.; Gyürky, G.; Paul, M.; Collon, P.; Fülöp, Zs; Greene, J.; Kinoshita, N.; Palchan, T.; Pardo, R.; Rehm, K. E.; Scott, R.; Vondrasek, R.

    2016-01-01

    The extreme sensitivity and discrimination power of accelerator mass spectrometry (AMS) allows for the search and the detection of rare nuclides either in natural samples or produced in the laboratory. At Argonne National Laboratory, we are developing an AMS setup aimed in particular at the detection of medium and heavy nuclides, relying on the high ion energy achievable with the ATLAS superconducting linear accelerator and on gas-filled magnet isobaric separation. The setup was recently used for the detection of the 146Sm p-process nuclide and for a new determination of the 146Sm half-life (68.7 My). AMS plays an important role in the measurement of stellar nuclear reaction cross sections by the activation method, extending thus the technique to the study of production of long-lived radionuclides. Preliminary measurements of the 147Sm(γ,n)146Sm are described. A measurement of the 142Nd(α,γ)146Sm and 142Nd(α,n)145Sm reactions is in preparation. A new laser-ablation method for the feeding of the Electron Cyclotron Resonance (ECR) ion source is described.

  9. Accelerator mass spectrometry of small biological samples.

    PubMed

    Salehpour, Mehran; Forsgard, Niklas; Possnert, Göran

    2008-12-01

    Accelerator mass spectrometry (AMS) is an ultra-sensitive technique for isotopic ratio measurements. In the biomedical field, AMS can be used to measure femtomolar concentrations of labeled drugs in body fluids, with direct applications in early drug development such as Microdosing. Likewise, the regenerative properties of cells which are of fundamental significance in stem-cell research can be determined with an accuracy of a few years by AMS analysis of human DNA. However, AMS nominally requires about 1 mg of carbon per sample which is not always available when dealing with specific body substances such as localized, organ-specific DNA samples. Consequently, it is of analytical interest to develop methods for the routine analysis of small samples in the range of a few tens of microg. We have used a 5 MV Pelletron tandem accelerator to study small biological samples using AMS. Different methods are presented and compared. A (12)C-carrier sample preparation method is described which is potentially more sensitive and less susceptible to contamination than the standard procedures.

  10. Study of the chemical composition of particulate matter from the Rio de Janeiro metropolitan region, Brazil, by inductively coupled plasma-mass spectrometry and optical emission spectrometry

    NASA Astrophysics Data System (ADS)

    Mateus, Vinícius Lionel; Monteiro, Isabela Luizi Gonçalves; Rocha, Rafael Christian Chávez; Saint'Pierre, Tatiana Dillenburg; Gioda, Adriana

    2013-08-01

    Air quality in the metropolitan region of Rio de Janeiro was evaluated by analysis of particulate matter (PM) in industrial (Santa Cruz) and rural (Seropédica) areas. Total suspended particles (TSP) and fine particulate matter (PM2.5) collected in filters over 24 h were quantified and their chemical composition determined. TSP exceeded Brazilian guidelines (80 μg m- 3) in Santa Cruz, while PM2.5 levels exceeded the World Health Organization guidelines (10 μg m- 3) in both locations. Filters were extracted with water and/or HNO3, and the concentrations of 20 elements, mostly metals, were determined by inductively coupled plasma mass spectrometry (ICP-MS) and optical emission spectrometry (ICP OES). Water soluble inorganic anions were determined by ion chromatography (IC). To estimate the proportion of these elements extracted, a certified reference material (NIST SRM 1648a, Urban Dust) was subjected to the same extraction process. Concordant results were obtained by ICP-MS and ICP OES for most elements. Some elements could not be quantified by both techniques; the most appropriate technique was chosen in each case. The urban dust was also analyzed by the United States Environmental Protection Agency (US EPA) method, which employs a combination of hydrochloric and nitric acids for the extraction, but higher extraction efficiency was obtained when only nitric acid was employed. The US EPA method gave better results only for Sb. In the PM samples, the elements found in the highest average concentrations by ICP were Zn and Al (3-6 μg m- 3). The anions found in the highest average concentrations were SO42 - in PM2.5 (2-4 μg m- 3) and Cl- in TSP (2-6 μg m- 3). Principal component analysis (PCA) in combination with enrichment factors (EF) indicated industrial sources in PM2.5. Analysis of TSP suggested both anthropogenic and natural sources. In conclusion, this work contributes data on air quality, as well as a method for the analysis of PM samples by ICP-MS.

  11. Chemotaxonomic studies of nine Paris species from China based on ultra-high performance liquid chromatography tandem mass spectrometry and Fourier transform infrared spectroscopy.

    PubMed

    Wang, Yuanzhong; Liu, Ehu; Li, Ping

    2017-06-05

    Paris species, which contain steroid saponins, have been used as herb folk medicines in Asia. In the present study, a comprehensive strategy based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and Fourier transform infrared (FT-IR) spectroscopy was firstly proposed to evaluate the chemotaxonomic relationships of nine Paris species sampled from different geographical regions in China. Principle component analysis (PCA) based on FT-IR data revealed chemical similarities in term of the nine species and geographical regions, indicating the accumulation of metabolites affected by the combination of geographical factors and species. The chemotaxonomic relationships of four species supported the morphological taxonomy and implied ancestry from P. polyphylla. After high-efficiency chromatographic separation, ions trap/time-of-flight mass spectrometry (IT-TOFMS) and triple quadrupole mass spectrometry (QQQ-MS) were used to identify unknown metabolites and simultaneously determine six key compounds (polyphyllin I, II, V, VI, VII and gracillin) in Paris species, respectively. The tentative identification of 22 steroid saponins was indicative of a common biosynthetic pathway in Paris species. Phytoecdysones, gracillin and open-chain steroid saponins were considered as key precursors. According to Pearson's correlation analysis, an insignificant correlation was found between diosgenin-type and pennogenin-type saponins belonging to the same biosynthetic pathways in the current stage. Our results could provide a reasonable foundation for chemotaxonomy or further studies of Paris species. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Determination of flumazenil in serum by liquid chromatography-mass spectrometry: Application to kinetics study in acute diazepam overdose.

    PubMed

    Djordjević, Snezana; Jović-Stosić, Jasmina; Kilibarda, Vesna; Segrt, Zoran; Perković-Vukcević, Natasa

    2016-02-01

    Flumazenil is benzodiazepine receptor antagonist. It has been studied for a various indications, including reversal of sedation after surgery or diagnostic procedures, awakening of comatose patients in benzodiazepine overdose, or for symptomatic treatment of hepatic encephalopathy. Some drugs, like theophylline, may prolong its elimination half-life. Considering the long half-life of diazepam and its metabolites, concomitant use of theophylline may reduce the need for repeated dosing of flumazenil in patients with acute diazepam poisoning. The aim of this study was to introduce a reliable and accurate method for determining the concentration of flumazenil after therapeutic application in patients with acute poisoning, and using that method to assess whether the kinetics of flumazenil change in the presence of aminophylline (combination of theophylline and ethylenediamine in a 2:1 ratio) applied as concomitant therapy. Blood samples from patients with acute diazepam poisoning that received flumazenil at the dose of 0.5 mg, or the same dose with 3 mg/kg of body weight of aminophylline, were collected 1, 3, 10, 30, 60, 120 and 240 min after its intravenous administration. Samples were prepared by solid-phase extraction on Oasis HLB cartridges with ethylacetate as extracting agens. Flumazenil was determined by liquid chromatography with mass spectrometry (LC-MS) in single ionmonitoring mode at m/z 304. Separation of flumazenil from matrix compound was performed on Lichrospher RP-8 column usingthe mixture of acidic acetonitrile and 20 mM of ammonium acetatein water (55 : 45) as a mobile phase. The applied analitycal method showed excellent recovery (94.65%). The obtained extracts were much cleaner than the extracts obtained by the sameextractant in the process of liquid-liquid extraction. The limit ofdetection of the LC-MS method described in this paper was 0.5 ng/mL and the limit of quantitation was 1 ng/mL. In the patientstreated with both flumazenil and aminophylline

  13. Analysis of Glycosaminoglycans Using Mass Spectrometry

    PubMed Central

    Staples, Gregory O.; Zaia, Joseph

    2015-01-01

    The glycosaminoglycans (GAGs) are linear polysaccharides expressed on animal cell surfaces and in extracellular matrices. Their biosynthesis is under complex control and confers a domain structure that is essential to their ability to bind to protein partners. Key to understanding the functions of GAGs are methods to determine accurately and rapidly patterns of sulfation, acetylation and uronic acid epimerization that correlate with protein binding or other biological activities. Mass spectrometry (MS) is particularly suitable for the analysis of GAGs for biomedical purposes. Using modern ionization techniques it is possible to accurately determine molecular weights of GAG oligosaccharides and their distributions within a mixture. Methods for direct interfacing with liquid chromatography have been developed to permit online mass spectrometric analysis of GAGs. New tandem mass spectrometric methods for fine structure determination of GAGs are emerging. This review summarizes MS-based approaches for analysis of GAGs, including tissue extraction and chromatographic methods compatible with LC/MS and tandem MS. PMID:25705143

  14. Computational mass spectrometry for small molecules

    PubMed Central

    2013-01-01

    The identification of small molecules from mass spectrometry (MS) data remains a major challenge in the interpretation of MS data. This review covers the computational aspects of identifying small molecules, from the identification of a compound searching a reference spectral library, to the structural elucidation of unknowns. In detail, we describe the basic principles and pitfalls of searching mass spectral reference libraries. Determining the molecular formula of the compound can serve as a basis for subsequent structural elucidation; consequently, we cover different methods for molecular formula identification, focussing on isotope pattern analysis. We then discuss automated methods to deal with mass spectra of compounds that are not present in spectral libraries, and provide an insight into de novo analysis of fragmentation spectra using fragmentation trees. In addition, this review shortly covers the reconstruction of metabolic networks using MS data. Finally, we list available software for different steps of the analysis pipeline. PMID:23453222

  15. Computational mass spectrometry for small molecules.

    PubMed

    Scheubert, Kerstin; Hufsky, Franziska; Böcker, Sebastian

    2013-03-01

    : The identification of small molecules from mass spectrometry (MS) data remains a major challenge in the interpretation of MS data. This review covers the computational aspects of identifying small molecules, from the identification of a compound searching a reference spectral library, to the structural elucidation of unknowns. In detail, we describe the basic principles and pitfalls of searching mass spectral reference libraries. Determining the molecular formula of the compound can serve as a basis for subsequent structural elucidation; consequently, we cover different methods for molecular formula identification, focussing on isotope pattern analysis. We then discuss automated methods to deal with mass spectra of compounds that are not present in spectral libraries, and provide an insight into de novo analysis of fragmentation spectra using fragmentation trees. In addition, this review shortly covers the reconstruction of metabolic networks using MS data. Finally, we list available software for different steps of the analysis pipeline.

  16. Potato glycoalkaloids in soil-optimising liquid chromatography-time-of-flight mass spectrometry for quantitative studies.

    PubMed

    Jensen, Pia H; Juhler, René K; Nielsen, Nikoline J; Hansen, Thomas H; Strobel, Bjarne W; Jacobsen, Ole S; Nielsen, John; Hansen, Hans Christian B

    2008-02-22

    Potato glycoalkaloids are produced in high amounts in potato fields during the growth season and losses to soil potentially impact shallow groundwater and via tiles to fresh water ecosystems. A quantitative liquid chromatography-electrospray ionization time-of-flight mass spectrometry (LC-ESI-TOF-MS) method for determination and quantification of potato glycoalkaloids and their metabolites in aqueous soil extracts was developed. The LC-ESI-TOF-MS method had linearities up to 2000microg/L for alpha-solanine and alpha-chaconine and up to 760microg/L for solanidine. No matrix effect was observed, and the detection limits found were in the range 2.2-4.7microg/L. The method enabled quantification of the potato glycoalkaloids in environmental samples.

  17. A fatal case of trichlorofluoromethane (Freon 11) poisoning. Tissue distribution study by gas chromatography-mass spectrometry.

    PubMed

    Groppi, A; Polettini, A; Lunetta, P; Achille, G; Montagna, M

    1994-05-01

    A case of lethal poisoning due to trichlorofluoromethane (FC11) inhalation is described. The fluorocarbon was determined in biological tissues by headspace gas chromatography-mass spectrometry. FC11 was detected in all the examined tissues, with decreasing levels in heart, lung, brain, liver, blood, kidney, and spleen. The highest concentration measured in heart could be related to the mode of toxic action of fluorocarbons postulated by many authors, characterized by the sensitization of the myocardium to the catecholamines producing arrhythmia and cardiac arrest. Nevertheless the aspecific picture of the anatomo-pathological and histological findings does not exclude that the described accidental fatality may have been caused by the combination of direct from toxicity with hypoxemic asphyxiation, due to the saturation of the atmosphere by FC11 in the closed environment in which the intoxication occurred.

  18. INSTRUMENTS AND METHODS OF INVESTIGATION: Surface-ionization field mass-spectrometry studies of nonequilibrium surface ionization

    NASA Astrophysics Data System (ADS)

    Blashenkov, Nikolai M.; Lavrent'ev, Gennadii Ya

    2007-01-01

    The ionization of polyatomic molecules on tungsten and tungsten oxide surfaces is considered for quasiequilibrium or essentially nonequilibrium conditions (in the latter case, the term nonequilibrium surface ionization is used for adsorbate ionization). Heterogeneous reactions are supposed to proceed through monomolecular decay of polyatomic molecules or fragments of multimolecular complexes. The nonequilibrium nature of these reactions is established. The dependences of the current density of disordered ions on the surface temperature, electric field strength, and ionized particle energy distribution are obtained in analytical form. Heterogeneous dissociation energies, the ionization potentials of radicals, and the magnitude of reaction departure from equilibrium are determined from experimental data, as are energy exchange times between reaction products and surfaces, the number of molecules in molecular complexes, and the number of effective degrees of freedom in molecules and complexes. In collecting the data a new technique relying on surface-ionization field mass-spectrometry was applied.

  19. Combining combing and secondary ion mass spectrometry to study DNA on chips using 13C and 15N labeling

    PubMed Central

    Cabin-Flaman, Armelle; Monnier, Anne-Francoise; Coffinier, Yannick; Audinot, Jean-Nicolas; Gibouin, David; Wirtz, Tom; Boukherroub, Rabah; Migeon, Henri-Noël; Bensimon, Aaron; Jannière, Laurent; Ripoll, Camille; Norris, Victor

    2016-01-01

    Dynamic secondary ion mass spectrometry ( D-SIMS) imaging of combed DNA – the combing, imaging by SIMS or CIS method – has been developed previously using a standard NanoSIMS 50 to reveal, on the 50 nm scale, individual DNA fibers labeled with different, non-radioactive isotopes in vivo and to quantify these isotopes. This makes CIS especially suitable for determining the times, places and rates of DNA synthesis as well as the detection of the fine-scale re-arrangements of DNA and of molecules associated with combed DNA fibers. Here, we show how CIS may be extended to 13C-labeling via the detection and quantification of the 13C 14N - recombinant ion and the use of the 13C: 12C ratio, we discuss how CIS might permit three successive labels, and we suggest ideas that might be explored using CIS. PMID:27429742

  20. Liquid chromatography-high-resolution mass spectrometry for pesticide residue analysis in fruit and vegetables: screening and quantitative studies.

    PubMed

    Gómez-Ramos, M M; Ferrer, C; Malato, O; Agüera, A; Fernández-Alba, A R

    2013-04-26

    This work reviews the current state-of-the-art of liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) techniques applied to the analysis of pesticides in fruit-based and vegetable-based matrices. Nowadays, simultaneous trace analysis of hundreds of pesticides from different classes is required, preferably in just one run. The most commonly used QqQ-MS technology presents certain limitations in its application in a cost and effective way when analyzing a large number of pesticides. Thus, this review includes HRMS technology as a reliable complementary alternative allowing the analysis of a wide range of pesticides in food. Its capabilities and limitations in identifying, confirming and quantifying pesticides are discussed. HRMS instruments can adequately address such issues; however, the main drawbacks are as a result of insufficient prior optimization of the operational parameters during non-target analysis in full-scan mode and due to software shortcomings.

  1. Fast atom bombardment mass spectrometry of condensed tannin sulfonate derivatives

    Treesearch

    J.J. Karchesy; L.Y. Foo; Richard W. Hemingway; E. Barofsky; D.F. Barofsky

    1989-01-01

    Condensed tannin sulfonate derivatives were studied by fast atom bombardment mass spectrometry (FAB-MS) to assess the feasibility of using this technique for determining molecular weight and structural information about these compounds. Both positive- and negative-ion spectra provided useful data with regard to molecular weight, cation species present, and presence of...

  2. Precision and accuracy in the quantitative analysis of biological samples by accelerator mass spectrometry: application in microdose absolute bioavailability studies.

    PubMed

    Gao, Lan; Li, Jing; Kasserra, Claudia; Song, Qi; Arjomand, Ali; Hesk, David; Chowdhury, Swapan K

    2011-07-15

    Determination of the pharmacokinetics and absolute bioavailability of an experimental compound, SCH 900518, following a 89.7 nCi (100 μg) intravenous (iv) dose of (14)C-SCH 900518 2 h post 200 mg oral administration of nonradiolabeled SCH 900518 to six healthy male subjects has been described. The plasma concentration of SCH 900518 was measured using a validated LC-MS/MS system, and accelerator mass spectrometry (AMS) was used for quantitative plasma (14)C-SCH 900518 concentration determination. Calibration standards and quality controls were included for every batch of sample analysis by AMS to ensure acceptable quality of the assay. Plasma (14)C-SCH 900518 concentrations were derived from the regression function established from the calibration standards, rather than directly from isotopic ratios from AMS measurement. The precision and accuracy of quality controls and calibration standards met the requirements of bioanalytical guidance (U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, Center for Veterinary Medicine. Guidance for Industry: Bioanalytical Method Validation (ucm070107), May 2001. http://www.fda.gov/downloads/Drugs/GuidanceCompilanceRegulatoryInformation/Guidances/ucm070107.pdf ). The AMS measurement had a linear response range from 0.0159 to 9.07 dpm/mL for plasma (14)C-SCH 900158 concentrations. The CV and accuracy were 3.4-8.5% and 94-108% (82-119% for the lower limit of quantitation (LLOQ)), respectively, with a correlation coefficient of 0.9998. The absolute bioavailability was calculated from the dose-normalized area under the curve of iv and oral doses after the plasma concentrations were plotted vs the sampling time post oral dose. The mean absolute bioavailability of SCH 900518 was 40.8% (range 16.8-60.6%). The typical accuracy and standard deviation in AMS quantitative analysis of drugs from human plasma samples have been reported for the first time, and the impact of these

  3. The dissociation kinetics of NO on Rh(111) as studied by temperature programmed static secondary ion mass spectrometry and desorption

    NASA Astrophysics Data System (ADS)

    Borg, H. J.; Reijerse, J. F. C.-J. M.; van Santen, R. A.; Niemantsverdriet, J. W.

    1994-12-01

    Temperature programmed static secondary ion mass spectrometry (TPSSIMS) and temperature programmed desorption (TPD) have been used to study the kinetics of adsorption, dissociation, and desorption of NO on Rh(111). At 100 K, NO adsorption is molecular and proceeds via mobile precursor state kinetics with a high initial sticking probability. SSIMS indicates the presence of two distinct NO adsorption states, indicative of threefold adsorption at low coverage, and occupation of bridge sites at higher coverages. Three characteristic coverage regimes appear with respect to NO dissociation. At low coverages θNO<0.25 ML, NO dissociates completely at temperatures between 275 and 340 K. If we neglect lateral interactions and assume pure first order dissociation kinetics, we find effective values for the activation barrier and preexponential factor of 40±6 kJ/mol and 106±1 s-1 for the dissociation of 0.15-0.20 ML NO. However, if we assume that a NO molecule needs an ensemble of three to four vacant sites in order to dissociate, the preexponential factor and activation energy are ˜1011 s-1 and 65 kJ/mol, in better agreement with transition state theory expectations. The Nads and Oads dissociation products desorb as N2 and O2, respectively, with desorption parameters Edes=118±10 kJ/mol and νdes=1010.1±1.0 s-1 for N2 in the zero coverage limit. At higher coverages, the desorption kinetics of N2 is strongly influenced by the presence of coadsorbed oxygen. In the medium coverage range 0.25<θNO<0.50 ML, part of the NO desorbs molecularly, with an estimated desorption barrier of 113±10 kJ/mol and a preexponential of 1013.5±1.0 s-1. Dissociation of NO becomes progressively inhibited due to site blocking, the onset shifting from 275 K at 0.25 ML to 400 K, coinciding with the NO desorption temperature, at a coverage of 0.50 ML. The accumulation of nitrogen and oxygen atoms on the highly covered surface causes a destabilization of the nitrogen atoms, which results in an

  4. Improving gene annotation using peptide mass