Science.gov

Sample records for isotope mass spectrometry

  1. 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.

  2. Calibration graphs in isotope dilution mass spectrometry.

    PubMed

    Pagliano, Enea; Mester, Zoltn; Meija, Juris

    2015-10-01

    Isotope-based quantitation is routinely employed in chemical measurements. Whereas most analysts seek for methods with linear theoretical response functions, a unique feature that distinguishes isotope dilution from many other analytical methods is the inherent possibility for a nonlinear theoretical response curve. Most implementations of isotope dilution calibration today either eliminate the nonlinearity by employing internal standards with markedly different molecular weight or they employ empirical polynomial fits. Here we show that the exact curvature of any isotope dilution curve can be obtained from three-parameter rational function, y=f(q)=(a0+a1q)/(1+a2q), known as the Pad[1,1] approximant. The use of this function allows eliminating an unnecessary source of error in isotope dilution analysis when faced with nonlinear calibration curves. In addition, fitting with Pad model can be done using linear least squares. PMID:26481988

  3. Isotope ratio measurements using glow discharge mass spectrometry

    NASA Astrophysics Data System (ADS)

    Riciputi, Lee R.; Duckworth, D. C.; Barshick, C. M.; Smith, David H.

    1995-08-01

    Glow discharge mass spectrometry (GDMS) has been evaluated for its ability to measure isotope ratios in solids. Isotope ratios were measured for B, Cu, Sr, Ag, Sb, Re and Pb in concentrations ranging from 15 ppm to pure metal. External precision of better than 0.03% has been achieved for isotope ratios measured using pure solid elemental samples; typical precision is better than 0.1% for elements present in concentrations greater than 0.5 wt.%. For elements present in concentrations of 10-20 ppm, precision was about 1%. Isotopic bias was < 1%, and day-to-day variations in isotopic bias for a single element are as large as variations in isotopic bias between different elements, suggesting that most isotopic bias is dominated by instrumental parameters. Values of isotope ratios show a dependence on the pressure of the Ar discharge gas, suggesting that improvements in sample geometry and discharge stability have the potential to allow GDMS to achieve even better precision in the measurement of isotope ratios.

  4. 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.

  5. Using isotope dilution mass spectrometry to determine aqueous trichloroacetic acid

    SciTech Connect

    Norwood, D.L.; Christman, R.F.; Johnson, J.D.; Hass, J.R.

    1986-01-01

    The development, verification, and application of a method based on isotope-dilution gas chromatography-mass spectrometry to determine aqueous trichloroacetic acid (TCAA) at the micrograms per litre level are described. The simultaneous determination of aqueous chloroform is also demonstrated. Trichloroacetic acid is shown to be a significant by-product of the chlorination of raw waters in the laboratory and to constitute a large fraction of the total organic halide (TOX) formed. Analysis of finished-water samples indicated that TCAA, like trihalomethanes is ubiquitous. Positive correlations exist between the levels of TCAA in laboratory-chlorinated raw waters and in finished waters and measured TOX.

  6. Improved Isotopic Measurement of Plutonium by Thermal Ionization Mass Spectrometry

    SciTech Connect

    Shick, C. Jr.

    2002-02-07

    Thermal ionization mass spectrometry (TIMS) is accepted widely as the benchmark method for precise and accurate isotopic determination of plutonium. TIMS is one of the few analytical methods capable of determining Pu in bioassay samples at the level required for detecting a 50 yr committed dose of 100 mRem resulting from an inhalation exposure to highly insoluble forms of Pu. Typically, Pu is measured in bioassay samples by radiochemical separation, electrodeposition onto a planchet, and radiometric determination by alpha spectrometry. If, based on the alpha spectrometry results, a sample is deemed to need a more sensitive analysis (i.e. suspected uptake, borderline alpha spectrometry positive for Pu uptake, etc.), then the sample is prepared for analysis by TIMS. Part of the development process for establishing a program to determine Pu in bioassay samples by TIMS at the Savannah River Site involved a careful evaluation of the Pu blank value in the reagents used for sample preparation and in urine blanks. This exercise allowed for the evaluation of the newly developed radiochemical separation procedure, the resin bead loading procedure, and the detection limits of the thermal ionization mass spectrometer.

  7. Ion Mobility Mass Spectrometry Direct Isotope Abundance Analysis

    SciTech Connect

    Manuel J. Manard, Stephan Weeks, Kevin Kyle

    2010-05-27

    The nuclear forensics community is currently engaged in the analysis of illicit nuclear or radioactive material for the purposes of non-proliferations and attribution. One technique commonly employed for gathering nuclear forensics information is isotope analysis. At present, the state-of-the-art methodology for obtaining isotopic distributions is thermal ionization mass spectrometry (TIMS). Although TIMS is highly accurate at determining isotope distributions, the technique requires an elementally pure sample to perform the measurement. The required radiochemical separations give rise to sample preparation times that can be in excess of one to two weeks. Clearly, the nuclear forensics community is in need of instrumentation and methods that can expedite their decision making process in the event of a radiological release or nuclear detonation. Accordingly, we are developing instrumentation that couples a high resolution IM drift cell to the front end of a MS. The IM cell provides a means of separating ions based upon their collision cross-section and mass-to-charge ratio (m/z). Two analytes with the same m/z, but with different collision cross-sections (shapes) would exit the cell at different times, essentially enabling the cell to function in a similar manner to a gas chromatography (GC) column. Thus, molecular and atomic isobaric interferences can be effectively removed from the ion beam. The mobility selected chemical species could then be introduced to a MS for high-resolution mass analysis to generate isotopic distributions of the target analytes. The outcome would be an IM/MS system capable of accurately measuring isotopic distributions while concurrently eliminating isobaric interferences and laboratory radiochemical sample preparation. The overall objective of this project is developing instrumentation and methods to produce near real-time isotope distributions with a modular mass spectrometric system that performs the required gas-phase chemistry and separations. The system couples a high-resolution ion mobility (IM) drift cell to the front end of a mass spectrometer (MS) allowing for chemical separation prior to isotope distribution analyses. This will yield isotope ratio measurement capabilities with minimal sample preparation.

  8. Quantitation of DNA adducts by stable isotope dilution mass spectrometry

    PubMed Central

    Tretyakova, Natalia; Goggin, Melissa; Janis, Gregory

    2012-01-01

    Exposure to endogenous and exogenous chemicals can lead to the formation of structurally modified DNA bases (DNA adducts). If not repaired, these nucleobase lesions can cause polymerase errors during DNA replication, leading to heritable mutations potentially contributing to the development of cancer. Due to their critical role in cancer initiation, DNA adducts represent mechanism-based biomarkers of carcinogen exposure, and their quantitation is particularly useful for cancer risk assessment. DNA adducts are also valuable in mechanistic studies linking tumorigenic effects of environmental and industrial carcinogens to specific electrophilic species generated from their metabolism. While multiple experimental methodologies have been developed for DNA adduct analysis in biological samples – including immunoassay, HPLC, and 32P-postlabeling – isotope dilution high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) generally has superior selectivity, sensitivity, accuracy, and reproducibility. As typical DNA adducts concentrations in biological samples are between 0.01 – 10 adducts per 108 normal nucleotides, ultrasensitive HPLC-ESI-MS/MS methodologies are required for their analysis. Recent developments in analytical separations and biological mass spectrometry – especially nanoflow HPLC, nanospray ionization MS, chip-MS, and high resolution MS – have pushed the limits of analytical HPLC-ESI-MS/MS methodologies for DNA adducts, allowing researchers to accurately measure their concentrations in biological samples from patients treated with DNA alkylating drugs and in populations exposed to carcinogens from urban air, drinking water, cooked food, alcohol, and cigarette smoke. PMID:22827593

  9. Efficient Analysis of Mass Spectrometry Data Using the Isotope Wavelet

    NASA Astrophysics Data System (ADS)

    Hussong, Rene; Tholey, Andreas; Hildebrandt, Andreas

    2007-09-01

    Mass spectrometry (MS) has become today's de-facto standard for high-throughput analysis in proteomics research. Its applications range from toxicity analysis to MS-based diagnostics. Often, the time spent on the MS experiment itself is significantly less than the time necessary to interpret the measured signals, since the amount of data can easily exceed several gigabytes. In addition, automated analysis is hampered by baseline artifacts, chemical as well as electrical noise, and an irregular spacing of data points. Thus, filtering techniques originating from signal and image analysis are commonly employed to address these problems. Unfortunately, smoothing, base-line reduction, and in particular a resampling of data points can affect important characteristics of the experimental signal. To overcome these problems, we propose a new family of wavelet functions based on the isotope wavelet, which is hand-tailored for the analysis of mass spectrometry data. The resulting technique is theoretically well-founded and compares very well with standard peak picking tools, since it is highly robust against noise spoiling the data, but at the same time sufficiently sensitive to detect even low-abundant peptides.

  10. Efficient Analysis of Mass Spectrometry Data Using the Isotope Wavelet

    SciTech Connect

    Hussong, Rene; Hildebrandt, Andreas; Tholey, Andreas

    2007-09-18

    Mass spectrometry (MS) has become today's de-facto standard for high-throughput analysis in proteomics research. Its applications range from toxicity analysis to MS-based diagnostics. Often, the time spent on the MS experiment itself is significantly less than the time necessary to interpret the measured signals, since the amount of data can easily exceed several gigabytes. In addition, automated analysis is hampered by baseline artifacts, chemical as well as electrical noise, and an irregular spacing of data points. Thus, filtering techniques originating from signal and image analysis are commonly employed to address these problems. Unfortunately, smoothing, base-line reduction, and in particular a resampling of data points can affect important characteristics of the experimental signal. To overcome these problems, we propose a new family of wavelet functions based on the isotope wavelet, which is hand-tailored for the analysis of mass spectrometry data. The resulting technique is theoretically well-founded and compares very well with standard peak picking tools, since it is highly robust against noise spoiling the data, but at the same time sufficiently sensitive to detect even low-abundant peptides.

  11. Advances in Isotope Ratio Mass Spectrometry and Required Isotope Reference Materials

    PubMed Central

    Vogl, Jochen

    2013-01-01

    The article gives a condensed version of the keynote lecture held at the International Mass Spectrometry Conference 2012 in Kyoto. Starting with some examples for isotope research the key requirements for metrologically valid procedures enabling traceable and comparable isotope data are discussed. Of course multi-collector mass spectrometers are required which offer sufficiently high isotope ratio precision for the intended research work. Following this, corrections for mass fractionation/discrimination, validation of the analytical procedure including chemical sample preparation and complete uncertainty budgets are the most important issues for obtaining a metrologically valid procedure for isotope ratio determination. Only the application of such metrologically valid procedures enables the generation of traceable and comparable isotope data. To realize this suitable isotope and/or ?-reference materials are required, which currently are not sufficiently available for most isotope systems. Boron is given as an example, for which the situation regarding isotope and ?-reference materials is excellent. Boron may therefore serve as prototype for other isotope systems. PMID:24349939

  12. Isotope ratio monitoring gas chromatography/Mass spectrometry of D/H by high temperature conversion isotope ratio mass spectrometry.

    PubMed

    Hilkert; Douthitt; Schlter; Brand

    1999-07-01

    Of all the elements, hydrogen has the largest naturally occurring variations in the ratio of its stable isotopes (D/H). It is for this reason that there has been a strong desire to add hydrogen to the list of elements amenable to isotope ratio monitoring gas chromatography/mass spectrometry (irm-GC/MS). In irm-GC/MS the sample is entrained in helium as the carrier gas, which is also ionized and separated in the isotope ratio mass spectrometer (IRMS). Because of the low abundance of deuterium in nature, precise and accurate on-line monitoring of D/H ratios with an IRMS requires that low energy helium ions be kept out of the m/z 3 collector, which requires the use of an energy filter. A clean mass 3 (HD(+.)) signal which is independent of a large helium load in the electron impact ion source is essential in order to reach the sensitivity required for D/H analysis of capillary GC peaks. A new IRMS system, the DELTA(plus)XL(trade mark), has been designed for high precision, high accuracy measurements of transient signals of hydrogen gas. It incorporates a retardation lens integrated into the m/z 3 Faraday cup collector. Following GC separation, the hydrogen bound in organic compounds must be quantitatively converted into H(2) gas prior to analysis in the IRMS. Quantitative conversion is achieved by high temperature conversion (TC) at temperatures >1400 degrees C. Measurements of D/H ratios of individual organic compounds in complicated natural mixtures can now be made to a precision of 2 per thousand (delta notation) or, better, with typical sample amounts of approximately 200 ng per compound. Initial applications have focused on compounds of interest to petroleum research (biomarkers and natural gas components), food and flavor control (vanillin and ethanol), and metabolic studies (fatty acids and steroids). Copyright 1999 John Wiley & Sons, Ltd. PMID:10407302

  13. A novel isotope analysis of oxygen in uranium oxides: comparison of secondary ion mass spectrometry, glow discharge mass spectrometry and thermal ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Pajo, L.; Tamborini, G.; Rasmussen, G.; Mayer, K.; Koch, L.

    2001-05-01

    The natural variation of the oxygen isotopic composition is used among geologists to determine paleotemperatures and the origin of minerals. In recent studies, oxygen isotopic composition has been recognized as a possible tool for identification of the origin of seized uranium oxides in nuclear forensic science. In the last 10 years, great effort has been made to develop new direct and accurate n( 18O)/ n( 16O) measurements methods. Traditionally, n( 18O)/ n( 16O) analyses are performed by gas mass spectrometry. In this work, a novel oxygen isotope analysis by thermal ionization mass spectrometry (TIMS), using metal oxide ion species (UO +), is compared to the direct methods: glow discharge mass spectrometry (GDMS) and secondary ion mass spectrometry (SIMS). Because of the possible application of the n( 18O)/ n( 16O) ratio in nuclear forensics science, the samples were solid, pure UO 2 or U 3O 8 particles. The precision achieved using TIMS analysis was 0.04%, which is similar or even better than the one obtained using the SIMS technique (0.05%), and clearly better if compared to that of GDMS (0.5%). The samples used by TIMS are micrograms in size. The suitability of TIMS as a n( 18O)/ n( 16O) measurement method is verified by SIMS measurements. In addition, TIMS results have been confirmed by characterizing the n( 18O)/ n( 16O) ratio of UO 2 sample also by the traditional method of static vacuum mass spectrometry at the University of Chicago.

  14. The Role of Naturally Occurring Stable Isotopes in Mass Spectrometry, Part II: The Instrumentation

    PubMed Central

    Bluck, Les; Volmer, Dietrich A.

    2013-01-01

    In the second instalment of this tutorial, the authors explain the instrumentation for measuring naturally occurring stable isotopes, specifically the magnetic sector mass spectrometer. This type of instrument remains unrivalled in its performance for isotope ratio mass spectrometry (IRMS) and the reader is reminded of its operation and its technical advantages for isotope measurements. PMID:23772101

  15. Forensic applications of isotope ratio mass spectrometry--a review.

    PubMed

    Benson, Sarah; Lennard, Chris; Maynard, Philip; Roux, Claude

    2006-02-10

    The key role of a forensic scientist is to assist in determining whether a crime has been committed, and if so, assist in the identification of the offender. Many people hold the belief that a particular item can be conclusively linked to a specific person, place or object. Unfortunately, this is often not achievable in forensic science. In performing their role, scientists develop and test hypotheses. The significance of those hypotheses that cannot be rejected upon completion of all available examinations/analyses is then evaluated. Although one can generally identify the substances present using available techniques, it is generally not possible to distinguish one source of the same substance from another. In such circumstances, although a particular hypothesis cannot be rejected, it cannot be conclusively proven, i.e. the samples could still have originated from different sources. This limitation of not being able to distinguish between sources currently extends to the analysis of other forensic samples including, but not limited to, ignitable liquids, paints, adhesives, textile fibres, plastics, and illicit drugs. Stable isotope ratio mass spectrometry (IRMS) is an additional technique that can be utilised to test a given hypothesis. This technique shows the potential to be able to individualise a range of materials of forensic interest. This paper provides a brief description of the technique, followed by a review of the various applications of IRMS in different scientific fields. The focus of this summary is on forensic applications of IRMS, in particular the analysis of explosives, ignitable liquids and illicit drugs. PMID:15919168

  16. Isotope Dilution Mass Spectrometry for the Quantification of Sulfane Sulfurs

    PubMed Central

    Liu, Chunrong; Zhang, Faya; Munske, Gerhard; Zhang, Hui

    2014-01-01

    Sulfane sulfurs are one type of important reactive sulfur species. These molecules have unique reactivity that can attach reversibly to other sulfur atoms and exhibit regulatory effects in diverse biological systems. Recent studies have suggested that sulfane sulfurs are involved in signal transduction processes regulated by hydrogen sulfide (H2S). Accurate and reliable measurements of sulfane sulfurs in biological samples are thus needed to reveal their production and mechanisms of actions. Herein we report a convenient and accurate method for the determination of sulfane sulfurs concentrations. The method employs a triphenylphosphine derivative (P2) to capture sulfane sulfurs as a stable phosphine sulphide product PS2. The concentration of PS2 was then determined by isotope dilution mass spectrometry, using a 13C3-labelled phosphine sulfide PS1 as the internal standard. The specificity and efficiency of the method were proved by model reactions. It was also applied in the measurement of sulfane sulfurs in mice tissues including brain, kidney, lung, liver, heart, spleen, and blood. PMID:25152234

  17. Computer Analysis of Isotope Clusters in Mass Spectrometry

    ERIC Educational Resources Information Center

    Bell, Harold M.

    1974-01-01

    Describes the application of a computer program designed to produce a formula determination simultaneously accounting for both elemental composition and probable isotopic species for a measured ion mass. (SLH)

  18. Optical spectroscopy versus mass spectrometry: The race for fieldable isotopic analysis

    SciTech Connect

    Barshick, C.M.; Young, J.P.; Shaw, R.W.

    1995-12-31

    Several techniques have been developed to provide on-site isotopic analyses, including decay-counting and mass spectrometry, as well as methods that rely on the accessibility of optical transitions for isotopic selectivity (e.g., laser-induced fluorescence and optogalvanic spectroscopy). The authors have been investigating both mass spectrometry and optogalvanic spectroscopy for several years. Although others have considered these techniques for isotopic analysis, the authors have focussed on the use of a dc glow discharge for atomization and ionization, and a demountable discharge cell for rapid sample exchange. The authors` goal is a fieldable instrument that provides useful uranium isotope ratio information.

  19. Isotope Ratio Monitoring Gas Chromatography Mass Spectrometry (IRM-GCMS)

    NASA Technical Reports Server (NTRS)

    Freeman, K. H.; Ricci, S. A.; Studley, A.; Hayes, J. M.

    1989-01-01

    On Earth, the C-13 content of organic compounds is depleted by roughly 13 to 23 permil from atmospheric carbon dioxide. This difference is largely due to isotope effects associated with the fixation of inorganic carbon by photosynthetic organisms. If life once existed on Mars, then it is reasonable to expect to observe a similar fractionation. Although the strongly oxidizing conditions on the surface of Mars make preservation of ancient organic material unlikely, carbon-isotope evidence for the existence of life on Mars may still be preserved. Carbon depleted in C-13 could be preserved either in organic compounds within buried sediments, or in carbonate minerals produced by the oxidation of organic material. A technique is introduced for rapid and precise measurement of the C-13 contents of individual organic compounds. A gas chromatograph is coupled to an isotope-ratio mass spectrometer through a combustion interface, enabling on-line isotopic analysis of isolated compounds. The isotope ratios are determined by integration of ion currents over the course of each chromatographic peak. Software incorporates automatic peak determination, corrections for background, and deconvolution of overlapped peaks. Overall performance of the instrument was evaluated by the analysis of a mixture of high purity n-alkanes of know isotopic composition. Isotopic values measured via IRM-GCMS averaged withing 0.55 permil of their conventionally measured values.

  20. Determination of inorganic chlorine stable isotopes by continuous flow isotope ratio mass spectrometry.

    PubMed

    Shouakar-Stash, Orfan; Drimmie, Robert J; Frape, Shaun K

    2005-01-01

    Chlorine stable isotope analyses of inorganic samples were conducted using continuous flow isotope ratio mass spectrometry (CF-IRMS) coupled with gas chromatography (GC). Inorganic chloride was precipitated in the form of silver chloride (AgCl) by using silver nitrate in a standard methodology. Chlorine stable isotope analysis was carried out on methyl chloride (CH3Cl) after converting AgCl into CH3Cl by reacting it with methyl iodide (CH3I). The reaction between AgCl and CH3I took place in 20 mL size vials. Addition of CH3I was performed in a glove bag under helium flow. An Agilent 6890 gas chromatograph equipped with a CTC Analytics CombiPAL autosampler and a DB-5MS 60 m column was used to separate CH3Cl from CH3I. This new technique uses samples as small as 0.2 mg of AgCl (1.4 micromol of Cl-). The chlorine stable isotope analysis using continuous flow technology showed excellent precision and accuracy. The internal precision using pure CH3Cl gas is better than +/-0.04 per thousand (+/-STDV). The external precision using seawater standard is better than +/-0.07 per thousand (+/-STDV) for n=12. Moreover, the sample analysis time is much shorter and many more samples can be analyzed in one day than by using the conventional off-line techniques. PMID:15593067

  1. Cholesterol efflux analyses using stable isotopes and mass spectrometry.

    PubMed

    Brown, Robert J; Shao, Fei; Baldán, Angel; Albert, Carolyn J; Ford, David A

    2013-02-01

    Cholesterol efflux from macrophages and the vascular wall is the initial step of the cardiovascular protective reverse cholesterol transport process. This study demonstrates a mass spectrometry based assay to measure the cellular and medium content of [d(7)]cholesterol and unlabeled cholesterol that can be used to measure cholesterol efflux from cell lines. Using a triple-quadrupole electrospray ionization-MS instrument in direct infusion mode, product ion scanning for m/z 83, neutral loss (NL) 375.5 scanning, and NL 368.5 scanning were used to detect cholesterol (as an acetylated derivative), [d(7)]cholesteryl ester (CE), and unlabeled CE, respectively. The same mass of [d(7)]cholesterol was substituted for [(3)H]cholesterol under standard efflux assay conditions. At the end of [d(7)]cholesterol loading, the intracellular mass of [d(7)]cholesterol was twofold greater than that of unlabeled cholesterol, and the intracellular [d(7)]CE profile was similar to that of unlabeled CE. Efflux of cholesterol to apolipoprotein A-I and high-density lipoproteins was similar comparing efflux of either [d(7)]cholesterol or [(3)H]cholesterol as measured by following efflux of the tracers only. This technique also can be used to assess the efflux of unlabeled cholesterol to acceptors in medium that are initially cholesterol-free (e.g., apolipoprotein A-I). Taken together, this mass spectrometry-based assay provides new molecular detail to assess cholesterol efflux. PMID:23072980

  2. Attogram measurement of rare isotopes by CW resonance ionization mass spectrometry

    SciTech Connect

    Bushaw, B.A.

    1992-05-01

    Three-color double-resonance ionization mass spectrometry, using two single-frequency cw dye lasers and a cw carbon dioxide laser, has been applied to the detection of attogram quantities of rare radionuclides. {sup 210}Pb has been measured in human hair and brain tissue samples to assess indoor radon exposure. Measurements on {sup 90}Sr have shown overall isotopic selectivity of greater than 10{sup 9} despite unfavorable isotope shifts relative to the major stable isotope, {sup 88}Sr.

  3. Cooling of radioactive isotopes for Schottky mass spectrometry

    SciTech Connect

    Steck, M.; Beckert, K.; Eickhoff, H.; Franzke, B.; Nolden, F.; Reich, H.; Schlitt, B.; Winkler, T.

    1999-01-15

    Nuclear masses of radioactive isotopes can be determined by measurement of their revolution frequency relative to the revolution frequency of reference ions with well-known masses. The resolution of neighboring frequency lines and the accuracy of the mass measurement is dependent on the achievable minimum longitudinal momentum spread of the ion beam. Electron cooling allows an increase of the phase space density by several orders of magnitude. For high intensity beams Coulomb scattering in the dense ion beam limits the beam quality. For low intensity beams a regime exists in which the diffusion due to intrabeam scattering is not dominating any more. The minimum momentum spread {delta}p/p=5x10{sup -7} which is observed by Schottky noise analysis is considerably higher than the value expected from the longitudinal electron temperature. The measured frequency spread results from fluctuations of the magnetic field in the storage ring magnets. Systematic mass measurements have started and can be presently used for ions with half-lives of some ten seconds. For shorter-lived nuclei a stochastic precooling system is in preparation.

  4. Mass spectrometry and natural variations of iron isotopes.

    PubMed

    Dauphas, Nicolas; Rouxel, Olivier

    2006-01-01

    Although the processes that govern iron isotope variations in nature are just beginning to be understood, multiple studies attest of the virtue of this system to solve important problems in geosciences and biology. In this article, we review recent advances in the geochemistry, cosmochemistry, and biochemistry of iron isotopes. In Section 2, we briefly address the question of the nucleosynthesis of Fe isotopes. In Section 3, we describe the different methods for purifying Fe and analyzing its isotopic composition. The methods of SIMS, RIMS, and TIMS are presented but more weight is given to measurements by MC-ICPMS. In Section 4, the isotope anomalies measured in extraterrestrial material are briefly discussed. In Section 5, we show how high temperature processes like evaporation, condensation, diffusion, reduction, and phase partitioning can affect Fe isotopic composition. In Section 6, the various low temperature processes causing Fe isotopic fractionation are presented. These involve aqueous and biologic systems. PMID:16463281

  5. DETERMINATION OF NIACIN IN FOOD MATERIALS BY ISOTOPE DILUTION MASS SPECTROMETRY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The availability of deuterium-labeled nicotinic acid makes stable isotope dilution mass spectrometry (SIDMS) coupled with liquid chromatography (LC) an attractive option for the determination of the water-soluble B-vitamin, niacin, in food samples. We present a method based on acid digestion, solid ...

  6. Protein N- and C-Termini Identification Using Mass Spectrometry and Isotopic Labeling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A new method for protein N- and C-terminal analysis using mass spectrometry is introduced. A novel stable isotopic labeling scheme has been developed to identify terminal peptides generated from an enzyme digestion for the determination of both N- and C-termini of the protein. This method works dire...

  7. Isotopic abundance measurements on solid nuclear-type samples by glow discharge mass spectrometry.

    PubMed

    Betti, M; Rasmussen, G; Koch, L

    1996-07-01

    A double-focusing Glow Discharge Mass Spectrometer (GDMS) installed in a glovebox for nuclear sample screening has been employed for isotopic measurements. Isotopic compositions of zirconium, silicon, lithium, boron, uranium and plutonium which are elements of nuclear concern have been determined. Interferences arising from the matrix sample and the discharge gas (Ar) for each of these elements are discussed. The GDMS results are compared with those from Thermal Ionization Mass Spectrometry (TIMS). For boron and lithium at microg/g-ng/g levels, the two methods gave results in good agreement. In samples containing uranium the isotopic composition obtained by GDMS was in agreement with those from TIMS independently of the enrichment. Attempts for the determination of plutonium isotopic composition were also made. In this case, due to the interferences of uranium at mass 238 and americium at mass 241, the GDMS raw data are complementary with those values obtained from physical non-destructive techniques. PMID:15045270

  8. A new series of uranium isotope reference materials for investigating the linearity of secondary electron multipliers in isotope mass spectrometry

    NASA Astrophysics Data System (ADS)

    Richter, S.; Alonso, A.; Aregbe, Y.; Eykens, R.; Kehoe, F.; Khn, He; Kivel, N.; Verbruggen, A.; Wellum, R.; Taylor, P. D. P.

    2009-04-01

    A new series of gravimetrically prepared uranium isotope reference materials, the so-called IRMM-074 series, with the n(235U)/n(238U) isotope ratio held constant at unity and the n(233U)/n(238U) isotope ratios varying from 1.0 to 10-6 has been prepared and certified. This series is suited for calibration of secondary electron multipliers used widely in isotope mass spectrometry, in particular for techniques such as thermal ionization mass spectrometry (TIMS), inductively coupled plasma mass spectrometry (ICPMS), accelerator mass spectrometry (AMS) and resonance ionization mass spectrometry (RIMS). The new IRMM-074 was prepared as a replacement for the already exhausted IRMM-072 predecessor series. Uranium materials with high isotopic enrichments of 233U, 235U and 238U were purified using identical methods involving separation on anion and cation column followed by a precipitation as peroxide. The oxides were calcined to convert them to U3O8 simultaneously, in an oven installed in a glove-box that provided a controlled low-humidity environment. The oxides of 235U and 238U were weighed and mixed with a mole ratio n(235U)/n(238U) = 1.0 and then dissolved. The 233U oxide was dissolved to form a separate solution with the same concentration and 6rom this primary solution three dilutions were made by weighing. A weighed amount of the n(235U)/n(238U) solution and weighed amounts of the 233U solutions were mixed in various proportions in order to achieve n(233U)/n(238U) isotope ratios varying from 1.0 to 10-6. The methods for the preparation, the mixing and the mixing calculations are described. The expanded uncertainties (coverage factor k = 2) of the certified isotope ratios for the IRMM-074 series are 0.015% for the n(235U)/n(238U) ratio and 0.025% for the n(233U)/n(238U) ratios, which constitutes an improvement compared to those of the predecessor IRMM-072 series. In addition, recent observations regarding the linearity response of secondary electron multipliers (SEMs) and suitable reference materials for investigating detector linearity are reviewed. Two measurement procedures for applying the IRMM-072 and IRMM-073 (diluted from the remaining fraction of IRMM-072) series as well as the new IRMM-074 series for assessing SEM linearity are suggested. The procedures are tailor-made for the specific instrumental characteristics of thermal ionization mass spectrometers (TIMS) and multiple-collector inductively coupled plasma mass spectrometers (MC-ICPMS) but can be adapted also for further types of isotope ratio mass spectrometers.

  9. On the Fine Isotopic Distribution and Limits to Resolution in Mass Spectrometry.

    PubMed

    Dittwald, Piotr; Valkenborg, Dirk; Claesen, Jrgen; Rockwood, Alan L; Gambin, Anna

    2015-10-01

    Mass spectrometry enables the study of increasingly larger biomolecules with increasingly higher resolution, which is able to distinguish between fine isotopic variants having the same additional nucleon count, but slightly different masses. Therefore, the analysis of the fine isotopic distribution becomes an interesting research topic with important practical applications. In this paper, we propose the comprehensive methodology for studying the basic characteristics of the fine isotopic distribution. Our approach uses a broad spectrum of methods ranging from generating functions--that allow us to estimate the variance and the information theory entropy of the distribution--to the theory of thermal energy fluctuations. Having characterized the variance, spread, shape, and size of the fine isotopic distribution, we are able to indicate limitations to high resolution mass spectrometry. Moreover, the analysis of "thermorelativistic" effects (i.e., mass uncertainty attributable to relativistic effects coupled with the statistical mechanical uncertainty of the energy of an isolated ion), in turn, gives us an estimate of impassable limits of isotopic resolution (understood as the ability to distinguish fine structure peaks), which can be moved further only by cooling the ions. The presented approach highlights the potential of theoretical analysis of the fine isotopic distribution, which allows modeling the data more accurately, aiming to support the successful experimental measurements. PMID:26265039

  10. On the Fine Isotopic Distribution and Limits to Resolution in Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Dittwald, Piotr; Valkenborg, Dirk; Claesen, Jrgen; Rockwood, Alan L.; Gambin, Anna

    2015-08-01

    Mass spectrometry enables the study of increasingly larger biomolecules with increasingly higher resolution, which is able to distinguish between fine isotopic variants having the same additional nucleon count, but slightly different masses. Therefore, the analysis of the fine isotopic distribution becomes an interesting research topic with important practical applications. In this paper, we propose the comprehensive methodology for studying the basic characteristics of the fine isotopic distribution. Our approach uses a broad spectrum of methods ranging from generating functionsthat allow us to estimate the variance and the information theory entropy of the distributionto the theory of thermal energy fluctuations. Having characterized the variance, spread, shape, and size of the fine isotopic distribution, we are able to indicate limitations to high resolution mass spectrometry. Moreover, the analysis of "thermorelativistic" effects (i.e., mass uncertainty attributable to relativistic effects coupled with the statistical mechanical uncertainty of the energy of an isolated ion), in turn, gives us an estimate of impassable limits of isotopic resolution (understood as the ability to distinguish fine structure peaks), which can be moved further only by cooling the ions. The presented approach highlights the potential of theoretical analysis of the fine isotopic distribution, which allows modeling the data more accurately, aiming to support the successful experimental measurements.

  11. Illustrating the Concepts of Isotopes and Mass Spectrometry in Introductory Courses: A MALDI-TOF Mass Spectrometry Laboratory Experiment

    ERIC Educational Resources Information Center

    Dopke, Nancy Carter; Lovett, Timothy Neal

    2007-01-01

    Mass spectrometry is a widely used and versatile tool for scientists in many different fields. Soft ionization techniques such as matrix-assisted laser desorption/ionization (MALDI) allow for the analysis of biomolecules, polymers, and clusters. This article describes a MALDI mass spectrometry experiment designed for students in introductory

  12. Illustrating the Concepts of Isotopes and Mass Spectrometry in Introductory Courses: A MALDI-TOF Mass Spectrometry Laboratory Experiment

    ERIC Educational Resources Information Center

    Dopke, Nancy Carter; Lovett, Timothy Neal

    2007-01-01

    Mass spectrometry is a widely used and versatile tool for scientists in many different fields. Soft ionization techniques such as matrix-assisted laser desorption/ionization (MALDI) allow for the analysis of biomolecules, polymers, and clusters. This article describes a MALDI mass spectrometry experiment designed for students in introductory…

  13. Profiling of thiol-containing compounds by stable isotope labeling double precursor ion scan mass spectrometry.

    PubMed

    Liu, Ping; Huang, Yun-Qing; Cai, Wen-Jing; Yuan, Bi-Feng; Feng, Yu-Qi

    2014-10-01

    Here we developed a novel strategy of isotope labeling in combination with high-performance liquid chromatography-double precursor ion scan mass spectrometry (IL-LC-DPIS-MS) analysis for nontargeted profiling of thiol-containing compounds. In this strategy, we synthesized a pair of isotope labeling reagents (?-bromoacetonylquinolinium bromide, BQB; ?-bromoacetonylquinolinium-d7 bromide, BQB-d7) that contain a reactive group, an isotopically labeled moiety, and an ionizable group to selectively label thiol-containing compounds. The BQB and BQB-d7 labeled compounds can generate two characteristic product ions m/z 218 and 225, which contain an isotope tag and therefore were used for double precursor ion scans in mass spectrometry analysis. The peak pairs with characteristic mass differences can be readily extracted from the two precursor ion scan (PIS) spectra and assigned as potential thiol-containing candidates, which facilitates the identification of analytes. BQB and BQB-d7 labeled thiol-containing compounds can be clearly distinguished by generating two individual ion chromatograms. Thus, thiol-containing compounds from two samples labeled with different isotope reagents are ionized at the same time but recorded separately by mass spectrometry, offering good identification and accurate quantification by eliminating the MS response fluctuation and mutual interference from the two labeled samples. Using the IL-LC-DPIS-MS strategy, we profiled the thiol-containing compounds in beer and human urine, and 21 and 103 thiol candidates were discovered in beer and human urine, respectively. In addition, 9 and 17 thiol candidates in beer and human urine were successfully identified by further comparison with thiol standards or tandem mass spectrometry analysis. Taken together, the IL-LC-DPIS-MS method is demonstrated to be a promising strategy in the profiling of compounds with identical groups in metabolomics study. PMID:25222826

  14. In-Vivo Zinc Metabolism by Isotope Ratio Mass Spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this chapter is to highlight some of the methodological and technical issues surrounding the in vivo use of stable isotopes and to provide examples of how such studies have advanced our knowledge of human zinc metabolism. The advantages and disadvantages of the currently available in...

  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 plume, this study has developed a mass spectrometry characterization technique that may be useful for investigating chemical reactions during laser ablation.

  16. Performance and limits of liquid chromatography isotope ratio mass spectrometry system for halogenated compounds

    NASA Astrophysics Data System (ADS)

    Gilevska, Tetyana; Gehre, Matthias; Richnow, Hans

    2014-05-01

    Compound Specific Isotope Analysis (CSIA) has been an important step for the assessment of the origin and fate of compounds in environmental science.[1] Biologically or pharmaceutically important compounds often are not amenable for gas chromatographic separation because of high polarity and lacking volatility, thermostability. In 2004 liquid chromatography isotope ratio mass spectrometry (LC-IRMS) became commercially available. LC-IRMS system intent a quantitative conversion of analytes separation into CO2 via wet oxidation with sodium persulfate in the presence of phosphoric acid while analytes are still dissolved in the aqueous liquid phase.[2] The aim of this study is to analyze the oxidation capacity of the interface of the LC-IRMS system and determine which parameters could improve oxidation of compounds which are resistant to persulfate oxidation. Oxidation capacity of the liquid chromatography isotope ratio mass spectrometry system was tested with halogenated acetic acid and a set of aromatic compounds with different substitutes. Acetic acid (AA) was taken as a model compound for complete oxidation and compared to the oxidation of other analytes on a molar basis. Correct values were obtained for di- and mono chlorinated and fluorinated and also for tribrominated acetic acid and for all studied aromatic compounds. Incomplete oxidation for trichloroacetic (TCAA) and trifluoroacetic (TFAA) acid was revealed with lower recovery compared to acetic acid and isotope fractionation leading to depleted carbon isotope composition compared to values obtained with an elementary analyzer connected to an isotope mass spectrometer Several optimization steps were tried in order to improve the oxidation of TCAA and TFAA: (i) increasing the concentration of the oxidizing agent, (ii) variation of flow rate of the oxidizing and acid solution, (iii) variation of flow rate of liquid chromatography pump (iv) addition of a catalyzer. These modifications lead to longer reaction time in the coil and increase in the concentration of radical but complete combustion of highly chlorinated or fluorinated compounds was not achieved. Due to these findings the limit for a LC-IRMS system for similar structure compounds can be predicted. 1. Elsner, M., et al., Current challenges in compound-specific stable isotope analysis of environmental organic contaminants. Analytical and Bioanalytical Chemistry, 2012. 403(9): p. 2471-2491. 2. Krummen, M., et al., A new concept for isotope ratio monitoring liquid chromatography/mass spectrometry. Rapid Communications in Mass Spectrometry, 2004. 18(19): p. 2260-2266.

  17. Accelerator mass spectrometry for heavy isotopes at Oxford (OSIRIS)

    NASA Astrophysics Data System (ADS)

    Chew, S. H.; Greenway, T. J. L.; Allen, K. W.

    1984-11-01

    The isotopic ratios 194Pt/195Pt/196Pt and 193Ir/194Pt/195Pt have been measured for samples from the Cretaceous-Tertiary boundary at Stevns Klint, Dania, Nye Klv in Denmark and at Hor Har Har in Israel, for iron meteorites Odessa and Buenaventura and for the carbonaceous chondrite Allende. Determination of the indium ratio 193/191 in a standard and in a sample from the Cretaceous-Tertiary boundary at Stevns Klint has also been made. Preliminary measurements of the ratio 188Os/189Os in laboratory prepared Os samples (abundance approximately 10 ppm), in the Odessa and Allende meteorites and in the Stevns Klint Cretaceous-Tertiary boundary have been carried out. An anomalous abundance of 193Ir, 194Pt, 195Pt and 189Os at the Cretaceous-Tertiary boundary at Stevns Klint has also been established.

  18. Improving precision in resonance ionization mass spectrometry : influence of laser bandwidth in uranium isotope ratio measurements.

    SciTech Connect

    Isselhardt, B. H.; Savina, M. R.; Knight, K. B.; Pellin, M. J.; Hutcheon, I. D.; Prussin, S. G.

    2011-03-01

    The use of broad bandwidth lasers with automated feedback control of wavelength was applied to the measurement of {sup 235}U/{sup 238}U ratios by resonance ionization mass spectrometry (RIMS) to decrease laser-induced isotopic fractionation. By broadening the bandwidth of the first laser in a three-color, three-photon ionization process from a bandwidth of 1.8 GHz to about 10 GHz, the variation in sequential relative isotope abundance measurements decreased from 10% to less than 0.5%. This procedure was demonstrated for the direct interrogation of uranium oxide targets with essentially no sample preparation.

  19. Analysis of 18O enrichment in biological fluids by continuous flow-isotope ratio mass spectrometry.

    PubMed

    McMillan, D C; Preston, T; Taggart, D P

    1989-08-01

    A novel method is described for the analysis of 18O in urine by continuous flow-isotope ratio mass spectrometry (CF-IRMS), after sample equilibration with CO2. The method is shown to be fast, precise and accurate and therefore facilitates studies of total body water and water turnover in the clinical field. The method uses existing CF-IRMS instrumentation with minor hardware modification which does not compromise routine analysis of 13C and 15N. This method emphasizes the versatility of CF-IRMS and thus its economy for the biomedical research group using stable isotope tracers. PMID:2804440

  20. RAPID DETERMINATION OF 237 NP AND PU ISOTOPES IN WATER BY INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY AND ALPHA SPECTROMETRY

    SciTech Connect

    Maxwell, S.; Jones, V.; Culligan, B.; Nichols, S.; Noyes, G.

    2010-06-23

    A new method that allows rapid preconcentration and separation of plutonium and neptunium in water samples was developed for the measurement of {sup 237}Np and Pu isotopes by inductively-coupled plasma mass spectrometry (ICP-MS) and alpha spectrometry; a hybrid approach. {sup 238}U can interfere with {sup 239}Pu measurement by ICP-MS as {sup 238}UH{sup +} mass overlap and {sup 237}Np via peak tailing. The method provide enhanced removal of uranium by separating Pu and Np initially on TEVA Resin, then moving Pu to DGA resin for additional removal of uranium. The decontamination factor for uranium from Pu is almost 100,000 and the decontamination factor for U from Np is greater than 10,000. This method uses stacked extraction chromatography cartridges and vacuum box technology to facilitate rapid separations. Preconcentration is performed using a streamlined calcium phosphate precipitation method. Purified solutions are split between ICP-MS and alpha spectrometry so that long and short-lived Pu isotopes can be measured successfully. The method allows for simultaneous extraction of 20 samples (including QC samples) in 4 to 6 hours, and can also be used for emergency response. {sup 239}Pu, {sup 242}Pu and {sup 237}Np were measured by ICP-MS, while {sup 236}Pu, {sup 238}Pu, and {sup 239}Pu were measured by alpha spectrometry.

  1. Determination of phthalate esters in Chinese spirits using isotope dilution gas chromatography with tandem mass spectrometry.

    PubMed

    Wang, Jing; Li, Xiaomin; Zhang, Qinghe; Xiong, Jinping; Li, Hongmei

    2015-05-01

    Phthalate esters are additives used in polyvinylchloride and are found as contaminants in many food products. An isotope dilution mass spectrometry technique has been developed for accurate analysis of 16 phthalate esters in Chinese spirits by adopting the 16 corresponding isotope-labeled phthalate esters. The ethanol in the spirit sample was first removed by heating with a water bath at 100C with a stream of nitrogen, after which the residue was extracted with n-hexane twice. The phthalates collected were identified and quantified by gas chromatography with tandem mass spectrometry in multiple reaction monitoring mode. The spiking recoveries of 16 analytes ranged from 94.3 to 105.3% with relative standard deviation values of <6.5%. The detection limits for 16 analytes were <10.0 ng/g. The expanded relative uncertainties were from 3.0 to 14%. A survey was performed on Chinese spirits from the market. Six of the nine analyzed samples were contaminated by phthalates. Di-n-butyl phthalate and di-2-ethylhexyl phthalate showed higher detection frequency and concentrations. This isotope dilution gas chromatography with tandem mass spectrometry method is simple, rapid, accurate, and highly sensitive, which qualifies as a candidate reference method for the determination of phthalates in spirits. PMID:25755215

  2. Application of Uranium Isotope Dilution Mass Spectrometry in the preparation of New Certified Reference Materials

    NASA Astrophysics Data System (ADS)

    Hasözbek, A.; Mathew, K. J.; Orlowicz, G.; Srinivasan, B.; Narayanan, U.

    2012-04-01

    Proven measurement techniques play a critical role in the preparation of Certified Reference Materials (CRMs) - those requiring high accuracy and precision in the measurement results. Isotope Dilution Mass Spectrometry (IDMS) is one such measurement method commonly used in the quantitative analysis of uranium in nuclear safeguards and isotope geology applications. In this project, we evaluated the possibility of using some of the uranium isotopic and assay CRMs made earlier by the New Brunswick laboratory as IDMS spikes to define the uranium mass fraction in future preparations of CRMs. Uranium solutions prepared from CRM 112-A (a highly pure uranium metal assay standard) and CRM 115 (a highly pure uranium oxide isotopic and assay standard) were used as spikes in the determination of uranium. Two different thermal ionization mass spectrometer instruments (MAT 261 and TRITON) were used for the isotopic measurements. Standard IDMS equation was used for data reduction to yield results for uranium mass fraction along with uncertainties, the latter calculated according to GUM. The results show that uranium mass fraction measurements can be made with the required accuracy and precision for defining the uranium concentration in new CRMs as well as in routine samples analyses.

  3. Determination of perchlorate in infant formula by isotope dilution ion chromatography/tandem mass spectrometry

    PubMed Central

    Wang, Z.; Lau, B.P.-Y.; Tague, B.; Sparling, M.; Forsyth, D.

    2011-01-01

    A sensitive and selective isotope dilution ion chromatography/tandem mass spectrometry (ID IC-MS/MS) method was developed and validated for the determination of perchlorate in infant formula. The perchlorate was extracted from infant formula by using 20 ml of methanol and 5 ml of 1% acetic acid. All samples were spiked with 18O4 isotope-labelled perchlorate internal standard prior to extraction. After purification on a graphitised carbon solid-phase extraction column, the extracts were injected into an ion chromatography system equipped with an Ionpac AS20 column for separation of perchlorate from other anions. The presence of perchlorate in samples was quantified by isotope dilution mass spectrometry. Analysis of both perchlorate and its isotope-labelled internal standard was carried out on a Waters Quattro Ultima triple quadrupole mass spectrometer operating in a multiple reaction monitoring (MRM) negative ionisation mode. The method was validated for linearity and range, accuracy, precision, sensitivity, and matrix effects. The limit of quantification (LOQ) was 0.4 ?g 1?1 for liquid infant formula and 0.95 ?g kg?1 for powdered infant formula. The recovery ranged from 94% to 110% with an average of 98%. This method was used to analyse 39 infant formula, and perchlorate concentrations ranging from

  4. High-precision measurements of seawater Pb isotope compositions by double spike thermal ionization mass spectrometry.

    PubMed

    Paul, Maxence; Bridgestock, Luke; Rehkmper, Mark; van DeFlierdt, Tina; Weiss, Dominik

    2015-03-10

    A new method for the determination of seawater Pb isotope compositions and concentrations was developed, which combines and optimizes previously published protocols for the separation and isotopic analysis of this element. For isotopic analysis, the procedure involves initial separation of Pb from 1 to 2L of seawater by co-precipitation with Mg hydroxide and further purification by a two stage anion exchange procedure. The Pb isotope measurements are subsequently carried out by thermal ionization mass spectrometry using a (207)Pb-(204)Pb double spike for correction of instrumental mass fractionation. These methods are associated with a total procedural Pb blank of 2821 pg (1sd) and typical Pb recoveries of 40-60%. The Pb concentrations are determined by isotope dilution (ID) on 50 mL of seawater, using a simplified version of above methods. Analyses of multiple aliquots of six seawater samples yield a reproducibility of about 1 to 10% (1sd) for Pb concentrations of between 7 and 50 pmol/kg, where precision was primarily limited by the uncertainty of the blank correction (124 pg; 1sd). For the Pb isotope analyses, typical reproducibilities (2sd) of 700-1500 ppm and 1000-2000 ppm were achieved for (207)Pb/(206)Pb, (208)Pb/(206)Pb and (206)Pb/(204)Pb, (207)Pb/(204)Pb, (208)Pb/(204)Pb, respectively. These results are superior to literature data that were obtained using plasma source mass spectrometry and they are at least a factor of five more precise for ratios involving the minor (204)Pb isotope. Both Pb concentration and isotope data, furthermore, show good agreement with published results for two seawater intercomparison samples of the GEOTRACES program. Finally, the new methods were applied to a seawater depth profile from the eastern South Atlantic. Both Pb contents and isotope compositions display a smooth evolution with depth, and no obvious outliers. Compared to previous Pb isotope data for seawater, the (206)Pb/(204)Pb ratios are well correlated with (207)Pb/(206)Pb, underlining the significant improvement achieved in the measurement of the minor (204)Pb isotope. PMID:25732313

  5. Ultratrace analysis of calcium with high isotopic selectivity by diode laser resonance ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Wendt, Karen M.; Blaum, K.; Bushaw, Bruce A.; Mueller, P.; Noertershaeuser, W.; Schmitt, A.; Trautmann, N.; Wiche, B.

    1998-07-01

    A refined diode laser based resonance ionization mass spectrometer for highly selective ultratrace analysis is presented, which combines coherent narrow-band multistep resonance excitation and ionization with a compact quadruple mass spectrometer. The widespread analytical potential and applicability of this system is demonstrated in the determination of calcium trace and ultratrace isotopes for cosmochemical studies, medical investigations and radiodating. For a detailed theoretical understanding of the coherent high resolution multistep excitation process a description in the density matrix formalism was worked out. For calcium optical isotopic selectivities of more than 1010 and efficiencies of up to 5 percent are predicted, which compare well to the analytical requirements for 41Ca-determination, which reach a maximum isotopic selectivity of more than 1015. Experimentally different ionization schemes, including single-, double- and triple- resonance excitation of calcium, have been investigated. The first-step excitation at 422,7 nm requires frequency doubling of a diode laser, while second and third steps are directly excited with extended cavity diode lasers. Analytical measurements cover meteorite and blood samples and demonstrate the feasibility of the predicted specifications. Continuing work will focus towards the application of the full triple-resonance scheme for ultra low-level measurements of 41Ca and shall establish resonance ionization mass spectrometry as a competitive technology to accelerator mass spectrometry.

  6. Multi-isotope imaging mass spectrometry quantifies stem cell division and metabolism.

    PubMed

    Steinhauser, Matthew L; Bailey, Andrew P; Senyo, Samuel E; Guillermier, Christelle; Perlstein, Todd S; Gould, Alex P; Lee, Richard T; Lechene, Claude P

    2012-01-26

    Mass spectrometry with stable isotope labels has been seminal in discovering the dynamic state of living matter, but is limited to bulk tissues or cells. We developed multi-isotope imaging mass spectrometry (MIMS) that allowed us to view and measure stable isotope incorporation with submicrometre resolution. Here we apply MIMS to diverse organisms, including Drosophila, mice and humans. We test the 'immortal strand hypothesis', which predicts that during asymmetric stem cell division chromosomes containing older template DNA are segregated to the daughter destined to remain a stem cell, thus insuring lifetime genetic stability. After labelling mice with (15)N-thymidine from gestation until post-natal week 8, we find no (15)N label retention by dividing small intestinal crypt cells after a four-week chase. In adult mice administered (15)N-thymidine pulse-chase, we find that proliferating crypt cells dilute the (15)N label, consistent with random strand segregation. We demonstrate the broad utility of MIMS with proof-of-principle studies of lipid turnover in Drosophila and translation to the human haematopoietic system. These studies show that MIMS provides high-resolution quantification of stable isotope labels that cannot be obtained using other techniques and that is broadly applicable to biological and medical research. PMID:22246326

  7. Elemental and isotopic analysis of inorganic salts by laser desorption ionization mass spectrometry

    SciTech Connect

    Jayasekharan, T.; Sahoo, N. K.

    2013-02-05

    Laser desorption ionization mass spectrometry is applied for the analysis of elements as well as their isotopic composition in different inorganic salts. At very low laser energies the inorganic ions are desorbed and ionized from the thin layer of the sample surface. The naturally occurring isotopes of alkali and silver ions are resolved using time of flight mass spectrometer. Further increase in laser energy shows the appearance of Al, Cr, and Fe ions in the mass spectra. This indicates the penetration laser beam beyond the sample surface leading to the ablation of sample target at higher energies. The simultaneous appearance of atomic ions from the sample target at relatively higher laser energies hampers the unambiguous identification of amino acid residues from the biomolecular ions in MALDI-MS.

  8. Separation and Analysis of Boron Isotope in High Plant by Thermal Ionization Mass Spectrometry

    PubMed Central

    Xu, Qingcai; Dong, Yuliang; Zhu, Huayu; Sun, Aide

    2015-01-01

    Knowledge of boron and its isotope in plants is useful to better understand the transposition and translocation of boron within plant, the geochemical behavior in the interface between soil and plant, and the biogeochemical cycle of boron. It is critical to develop a useful method to separate boron from the plant for the geochemical application of boron and its isotope. A method was developed for the extraction of boron in plant sample, whose isotope was determined by thermal ionization mass spectrometry. The results indicated that this method of dry ashing coupled with two-step ion-exchange chromatography is powerful for the separation of boron in plant sample with large amounts of organic matters completely. The ratios of boron isotope composition in those plant tissue samples ranged from −19.45‰ to +28.13‰ (total range: 47.58‰) with a mean value of 2.61 ± 11.76‰ SD. The stem and root isotopic compositions were lower than those in flower and leaf. The molecular mechanism of boron isotope may be responsible for the observed variation of boron isotopic composition and are considered as a useful tool for the better understanding of boron cycling process in the environment and for the signature of living systems. PMID:26819618

  9. Applications of Structural Mass Spectrometry to Metabolomics: Clarifying Bond Specific Spectral Signatures with Isotope Edited Spectroscopy

    NASA Astrophysics Data System (ADS)

    Gorlova, Olga; Wolke, Conrad T.; Fournier, Joseph; Colvin, Sean; Johnson, Mark; Miller, Scott

    2015-06-01

    Comprehensive FTIR, MS/MS and NMR of pharmaceuticals are generally readily available but characterization of their metabolites has been an obstacle. Atorvastatin is a statin drug responsible for the maintenance of cholesterol in the body. Diovan is an angiostensin receptor antagonist used to treat high blood pressure and congestive heart failure. The field of metabolomics, however, is struggling to obtain the identity of their structures. We implement mass spectrometry with cryogenic ion spectroscopy to study gaseous ions of the desired metabolites which, in combination, not only identify the mass of the metabolite but also elucidate their structures through isotope-specific infrared spectroscopy.

  10. Determination of complex isotopomer patterns in isotopically labeled compounds by mass spectrometry.

    PubMed

    Jennings, Mark E; Matthews, Dwight E

    2005-10-01

    A classic problem in analytical chemistry has been determination of individual components in a mixture without availability of the pure individual components. Measurement of the distribution of isotopomers in a labeled compound or mixture of labeled compounds is an example of this problem that is commonly encountered when stable isotopically labeled metabolites are used to determine in vivo kinetics and metabolism. We present a method that uses the measured mass spectral data of the unlabeled material to represent any and all combinations of isotopomer variations of that material and to determine abundances of these isotopomers. Although examples of the method are presented for gas chromatography/mass spectrometry, the method is applicable to any type of mass spectrometry data. The method also accounts for errors induced by mass spectrometer ionization and resolution effects. To demonstrate this method, we determined the isotopomer distributions of samples of 13C-labeled leucine and glucose for both highly enriched isotopomers and labeled isotopomers present in low abundance against a natural isotopic abundance background. The method accurately and precisely determined isotopomer identity and abundance in the labeled materials without adding noise or error that was not inherent in the original mass spectral data. In examples shown here, isotopomer uncertainties were calculated with relative standard errors of <1% from good quality mass spectral data. PMID:16194110

  11. Chlorine isotope effects from isotope ratio mass spectrometry suggest intramolecular C-Cl bond competition in trichloroethene (TCE) reductive dehalogenation.

    PubMed

    Cretnik, Stefan; Bernstein, Anat; Shouakar-Stash, Orfan; Lffler, Frank; Elsner, Martin

    2014-01-01

    Chlorinated ethenes are prevalent groundwater contaminants. To better constrain (bio)chemical reaction mechanisms of reductive dechlorination, the position-specificity of reductive trichloroethene (TCE) dehalogenation was investigated. Selective biotransformation reactions (i) of tetrachloroethene (PCE) to TCE in cultures of Desulfitobacterium sp. strain Viet1; and (ii) of TCE to cis-1,2-dichloroethene (cis-DCE) in cultures of Geobacter lovleyi strain SZ were investigated. Compound-average carbon isotope effects were -19.0 0.9 (PCE) and -12.2 1.0 (TCE) (95% confidence intervals). Using instrumental advances in chlorine isotope analysis by continuous flow isotope ratio mass spectrometry, compound-average chorine isotope effects were measured for PCE (-5.0 0.1) and TCE (-3.6 0.2). In addition, position-specific kinetic chlorine isotope effects were determined from fits of reactant and product isotope ratios. In PCE biodegradation, primary chlorine isotope effects were substantially larger (by -16.3 1.4 (standard error)) than secondary. In TCE biodegradation, in contrast, the product cis-DCE reflected an average isotope effect of -2.4 0.3 and the product chloride an isotope effect of -6.5 2.5, in the original positions of TCE from which the products were formed (95% confidence intervals). A greater difference would be expected for a position-specific reaction (chloride would exclusively reflect a primary isotope effect). These results therefore suggest that both vicinal chlorine substituents of TCE were reactive (intramolecular competition). This finding puts new constraints on mechanistic scenarios and favours either nucleophilic addition by Co(I) or single electron transfer as reductive dehalogenation mechanisms. PMID:24853618

  12. Stable isotope dilution analysis of hydrologic samples by inductively coupled plasma mass spectrometry

    USGS Publications Warehouse

    Garbarino, J.R.; Taylor, H.E.

    1987-01-01

    Inductively coupled plasma mass spectrometry is employed in the determination of Ni, Cu, Sr, Cd, Ba, Ti, and Pb in nonsaline, natural water samples by stable isotope dilution analysis. Hydrologic samples were directly analyzed without any unusual pretreatment. Interference effects related to overlapping isobars, formation of metal oxide and multiply charged ions, and matrix composition were identified and suitable methods of correction evaluated. A comparability study snowed that single-element isotope dilution analysis was only marginally better than sequential multielement isotope dilution analysis. Accuracy and precision of the single-element method were determined on the basis of results obtained for standard reference materials. The instrumental technique was shown to be ideally suited for programs associated with certification of standard reference materials.

  13. High-resolution quantitative imaging of mammalian and bacterial cells using stable isotope mass spectrometry

    PubMed Central

    Lechene, Claude; Hillion, Francois; McMahon, Greg; Benson, Douglas; Kleinfeld, Alan M; Kampf, J Patrick; Distel, Daniel; Luyten, Yvette; Bonventre, Joseph; Hentschel, Dirk; Park, Kwon Moo; Ito, Susumu; Schwartz, Martin; Benichou, Gilles; Slodzian, Georges

    2006-01-01

    Background Secondary-ion mass spectrometry (SIMS) is an important tool for investigating isotopic composition in the chemical and materials sciences, but its use in biology has been limited by technical considerations. Multi-isotope imaging mass spectrometry (MIMS), which combines a new generation of SIMS instrument with sophisticated ion optics, labeling with stable isotopes, and quantitative image-analysis software, was developed to study biological materials. Results The new instrument allows the production of mass images of high lateral resolution (down to 33 nm), as well as the counting or imaging of several isotopes simultaneously. As MIMS can distinguish between ions of very similar mass, such as 12C15N- and 13C14N-, it enables the precise and reproducible measurement of isotope ratios, and thus of the levels of enrichment in specific isotopic labels, within volumes of less than a cubic micrometer. The sensitivity of MIMS is at least 1,000 times that of 14C autoradiography. The depth resolution can be smaller than 1 nm because only a few atomic layers are needed to create an atomic mass image. We illustrate the use of MIMS to image unlabeled mammalian cultured cells and tissue sections; to analyze fatty-acid transport in adipocyte lipid droplets using 13C-oleic acid; to examine nitrogen fixation in bacteria using 15N gaseous nitrogen; to measure levels of protein renewal in the cochlea and in post-ischemic kidney cells using 15N-leucine; to study DNA and RNA co-distribution and uridine incorporation in the nucleolus using 15N-uridine and 81Br of bromodeoxyuridine or 14C-thymidine; to reveal domains in cultured endothelial cells using the native isotopes 12C, 16O, 14N and 31P; and to track a few 15N-labeled donor spleen cells in the lymph nodes of the host mouse. Conclusion MIMS makes it possible for the first time to both image and quantify molecules labeled with stable or radioactive isotopes within subcellular compartments. PMID:17010211

  14. Stable isotope ratio mass spectrometry of nanogram quantities of boron and sulfur

    NASA Astrophysics Data System (ADS)

    Wieser, Michael Eugene

    1998-09-01

    Instrumentation and analytical techniques were developed to measure isotope abundances from nanograms of sulfur and boron. Sulfur isotope compositions were determined employing continuous flow isotope ratio mass spectroscopy (CF-IRMS) procedures and AsS+ thermal ionization mass spectrometry techniques (AsS+-TIMS). Boron isotope abundances were determined by BO2/sp--TIMS. CF-IRMS measurements realized δ34S values from 10 μg sulfur with precisions of ±0.3/perthous. To extend sulfur isotope measurements to much smaller samples, a TIMS procedure was developed to measure 75As32S+ and 75As34S+ at masses 108 and 109 from 200 ng S on a Finnigan MAT 262 with an ion counter. This is possibly the smallest amount of sulfur which has been successfully analyzed isotopically. The internal precision of 32S/34S ratios measured by AsS+-TIMS was better than ±0.15 percent. δ34S-values calculated relative to the measured 32S/34S value of an IAEA AG2S standard (S-1) agreed with those determined by CF-IRMS to within ±3/perthous. The increasing sensitivity of S-isotope analyses permits hiterto impossible investigations e.g. sulfur in tree rings and ice cores. Boron isotope abundances were measured as BO2/sp- from 50 ng B using an older thermal ionization mass spectrometer which had been extensively upgraded including the addition of computer control electronics, sensitive ion current amplification and fiber optic data bus. The internal precisions of the measured 11B/10B ratios were ±0.15 percent and the precisions of δ11B values calculated relative to the accepted international standard (SRM-951) were ±3/perthous. Two applications of boron isotope abundance variations were initiated (1) ground waters of Northern Alberta and (2) coffee beans in different regions of the world. In the first it was demonstrated that boron isotopes could be used to trace boron released during steam injection of oil sands into the surrounding environment. Data from the second study suggest that boron isotopes can be used to improve cultivation of coffee particularly in regions where 'organically grown' coffee had markedly different δ11B values than beans grown with boron- containing fertilizers in neighbouring regions. A regional dependence on the δ11B values of the coffee allow the sources of commercial coffee blends to be identified.

  15. High precision Penning trap mass spectrometry of rare isotopes produced by projectile fragmentation

    NASA Astrophysics Data System (ADS)

    Kwiatkowski, A. A.; Barquest, B. R.; Block, M.; Bollen, G.; Campbell, C. M.; Ferrer, R.; Lincoln, D. L.; Morrissey, D. J.; Pang, G. K.; Redshaw, M.; Ringle, R.; Schwarz, S.; Savory, J.

    2011-09-01

    The Low Energy Beam and Ion Trap (LEBIT) is the only present facility to combine high precision Penning trap mass spectrometry with fast beam projectile fragmentation. Located at the National Superconducting Cyclotron Laboratory (NSCL), LEBIT is able to measure radionuclides produced in a chemically independent process with minimal decay losses. Recent exotic mass measurements include 66As, 63-66Fe, and 32Si. 66As is a new candidate to test the Conserved Vector Current (CVC) hypothesis. The masses of the neutron-rich iron isotopes provide additional information about the mass surface and the subshell closure at N = 40. 32Si is a member of the A = 32, T = 2 quintet; its measurement permits the most stringent test of the validity of the isobaric multiplet mass equation (IMME). An overview of some recent measurements will be presented as well as advanced techniques for ion manipulation.

  16. Quantifying proteomes and their post-translational modifications by stable isotope label-based mass spectrometry

    PubMed Central

    Merrill, Anna E.; Coon, Joshua J.

    2013-01-01

    Stable isotope labeling coupled with mass spectrometry has revolutionized the scope and impact of protein expression studies. Label incorporation can occur metabolically or chemically, and each method bears specific strengths and weaknesses. Quantitative proteomics confidently identifies specific interactions between proteins and other biological species, such as nucleic acids and metabolites. Extending label-based methods to phosphorylation-modified forms of proteins enables the construction of signaling networks and their temporal responses to stimuli. The integration of multiple data types offers systems-level insight on coordinated biological processes. Finally, the development of methods applicable to tissue quantification suggests the emerging role of label-based, quantitative mass spectrometry in translational science. PMID:23835517

  17. Improving boron isotope ratio measurement precision with quadrupole inductively coupled plasma-mass spectrometry

    NASA Astrophysics Data System (ADS)

    Al-Ammar, Assad; Reitznerová, Eva; Barnes, Ramon M.

    2000-12-01

    A method was developed to improve the precision of inductively coupled plasma quadrupole mass spectrometry (ICP-QMS) for the determination of boron isotope ratios ( 11B/ 10B) in various environmental materials including seawater. This approach is based on the common analyte internal standardization (CAIS) chemometric algorithm. The sample solution obtained after digestion is spiked with lithium, and both 7Li/ 6Li and 11B/ 10B values are measured using long-counting periods (20 min). The CAIS algorithm corrects the measured 11B/ 10B values for (a) statistical fluctuations resulting from short-term noise; (b) drift in 11B-to- 10B ratio as a result of long-term deviation in instrumental parameters likely to occur during long counting times; (c) change in 11B-to- 10B ratio caused by variation in matrix elements concentrations; and (d) drift in mass bias correction factor. Comparing boron isotopic ratios in seawater measured by conventional and the new isotope ratio methods validates the procedure. A synthetic isotopic mixture of boron SRM 951 and enriched 10B SRM 952 also was examined. The CAIS method provided a measured boron isotopic ratio precision of 0.05% R.S.D. while eliminating 5.1% matrix concentration error and 0.25% instrumental drift error.

  18. Accurate analysis of trace pentachlorophenol in textiles by isotope dilution liquid chromatography-mass spectrometry.

    PubMed

    Su, FuHai; Zhang, Pan

    2011-03-01

    A highly accurate method for measuring pentachlorophenol (PCP) concentrations in textile samples was developed. This highly accurate method for the analysis of textile samples is valuable, given the inherent challenges associated with the complexity of the sample matrix. This method can be applied to certify the concentration of pentachlorophenol in textile CRMs. A measurement procedure based on isotope dilution liquid chromatography-isotope dilution mass spectrometry (LC-IDMS) was developed. Samples were pretreated with acid and then with n-hexane. Excellent precision was obtained. The validated concentration ranges for the method were 1.0-50 ng/g, the LOD was 1.0 ng/g, and the LOQ was 5.0 ng/g. The precision of this method is in the range of 0.80-1.40%. The method can trace to mass. PMID:21259431

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

    SciTech Connect

    Luong, E.

    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 {beta}-cyclodextrin are chosen for the study, initial observation of spectral interference of {sup 13}C{sup +} with {sup 12}C{sup 1}H{sup +} comes from the incomplete dissociation of myoglobin and/or {beta}-cyclodextrin.

  20. Isolation and derivatization of plasma taurine for stable isotope analysis by gas chromatography-mass spectrometry

    SciTech Connect

    Irving, C.S.; Klein, P.D.

    1980-09-01

    A method for the isolation and derivatization of plasma taurine is described that allows stable isotope determinations of taurine to be made by gas chromatography-mass spectrometry. The isolation procedure can be applied to 0.1 ml of plasma; the recovery of plasma taurine was 70 to 80%. For gc separation, taurine was converted to its dimethylaminomethylene methyl ester derivative which could not be detected by hydrogen flame ionization, but could be monitored readily by NH/sub 3/ chemical ionization mass spectrometry. The derivatization reaction occurred partially on-column and required optimization of injection conditions. Using stable isotope ratiometry multiple ion detection, (M + 2 + H)/sup +//(M + H)/sup +/ ion ratio of natural abundance taurine was determined with a standard deviation of less than +-0.07% of the ratio. The (1,2-/sup 13/C)taurine/taurine mole ratios of standard mixtures could be accurately determined to 0.001. This stable isotope gc-ms method is suitable for studying the plasma kinetics of (1,2-/sup 13/C)taurine in infants who are at risk with respect to taurine depletion.

  1. Lead concentrations and isotope ratios in street dust determined by electrothermal atomic absorption spectrometry and inductively coupled plasma mass spectrometry.

    PubMed

    Nageotte, S M; Day, J P

    1998-01-01

    A major source of environmental lead, particularly in urban areas, has been from the combustion of leaded petrol. Street dust has previously been used to assess urban lead contamination, and the dust itself can also be a potential source of lead ingestion, particularly to children. The progressive reduction of lead in petrol, in recent years, would be expected to have been reflected in a reduction of lead in urban dust. We have tested this hypothesis by repeating an earlier survey of Manchester street dust and carrying out a comparable survey in Paris. Samples were collected from streets and parks, lead was extracted by digestion with concentrated nitric acid and determined by electrothermal atomic absorption spectrometry. Lead isotope ratios were measured by inductively coupled plasma mass spectrometry. Results for Manchester show that lead concentrations have fallen by about 40% (street dust averages, 941 micrograms g-1 (ppm) in 1975 down to 569 ppm in 1997). In Paris, the lead levels in street dust are much higher and significant differences were observed between types of street (not seen in Manchester). Additionally, lead levels in parks were much lower than in Manchester. Samples collected under the Eiffel Tower had very high concentrations and lead isotope ratios showed that this was unlikely to be fallout from motor vehicles but could be due to the paint used on the tower. Isotope ratios measurements also revealed that lead additives used in France and the UK come from different sources. PMID:9581021

  2. Essentials of iron, chromium, and calcium isotope analysis of natural materials by thermal ionization mass spectrometry

    USGS Publications Warehouse

    Fantle, M.S.; Bullen, T.D.

    2009-01-01

    The use of isotopes to understand the behavior of metals in geological, hydrological, and biological systems has rapidly expanded in recent years. One of the mass spectrometric techniques used to analyze metal isotopes is thermal ionization mass spectrometry, or TIMS. While TIMS has been a useful analytical technique for the measurement of isotopic composition for decades and TIMS instruments are widely distributed, there are significant difficulties associated with using TIMS to analyze isotopes of the lighter alkaline earth elements and transition metals. Overcoming these difficulties to produce relatively long-lived and stable ion beams from microgram-sized samples is a non-trivial task. We focus here on TIMS analysis of three geologically and environmentally important elements (Fe, Cr, and Ca) and present an in-depth look at several key aspects that we feel have the greatest potential to trouble new users. Our discussion includes accessible descriptions of different analytical approaches and issues, including filament loading procedures, collector cup configurations, peak shapes and interferences, and the use of isotopic double spikes and related error estimation. Building on previous work, we present quantitative simulations, applied specifically in this study to Fe and Ca, that explore the effects of (1) time-variable evaporation of isotopically homogeneous spots from a filament and (2) interferences on the isotope ratios derived from a double spike subtraction routine. We discuss how and to what extent interferences at spike masses, as well as at other measured masses, affect the double spike-subtracted isotope ratio of interest (44Ca/40Ca in the case presented, though a similar analysis can be used to evaluate 56Fe/54Fe and 53Cr/52Cr). The conclusions of these simulations are neither intuitive nor immediately obvious, making this examination useful for those who are developing new methodologies. While all simulations are carried out in the context of a specific isotope system, it should be noted that the same methods can be used to evaluate any isotope system of interest. ?? 2008 Elsevier B.V.

  3. Analytical Validation of Accelerator Mass Spectrometry for Pharmaceutical Development: the Measurement of Carbon-14 Isotope Ratio.

    SciTech Connect

    Keck, B D; Ognibene, T; Vogel, J S

    2010-02-05

    Accelerator mass spectrometry (AMS) is an isotope based measurement technology that utilizes carbon-14 labeled compounds in the pharmaceutical development process to measure compounds at very low concentrations, empowers microdosing as an investigational tool, and extends the utility of {sup 14}C labeled compounds to dramatically lower levels. It is a form of isotope ratio mass spectrometry that can provide either measurements of total compound equivalents or, when coupled to separation technology such as chromatography, quantitation of specific compounds. The properties of AMS as a measurement technique are investigated here, and the parameters of method validation are shown. AMS, independent of any separation technique to which it may be coupled, is shown to be accurate, linear, precise, and robust. As the sensitivity and universality of AMS is constantly being explored and expanded, this work underpins many areas of pharmaceutical development including drug metabolism as well as absorption, distribution and excretion of pharmaceutical compounds as a fundamental step in drug development. The validation parameters for pharmaceutical analyses were examined for the accelerator mass spectrometry measurement of {sup 14}C/C ratio, independent of chemical separation procedures. The isotope ratio measurement was specific (owing to the {sup 14}C label), stable across samples storage conditions for at least one year, linear over 4 orders of magnitude with an analytical range from one tenth Modern to at least 2000 Modern (instrument specific). Further, accuracy was excellent between 1 and 3 percent while precision expressed as coefficient of variation is between 1 and 6% determined primarily by radiocarbon content and the time spent analyzing a sample. Sensitivity, expressed as LOD and LLOQ was 1 and 10 attomoles of carbon-14 (which can be expressed as compound equivalents) and for a typical small molecule labeled at 10% incorporated with {sup 14}C corresponds to 30 fg equivalents. AMS provides an sensitive, accurate and precise method of measuring drug compounds in biological matrices.

  4. Isotope-selective laser photodetachment for 129I accelerator mass spectrometry

    NASA Astrophysics Data System (ADS)

    Takahashi, Tone; Tomita, Hideki; Nakayama, Motoi; Adachi, Yoshitaka; Sonnenschein, Volker; Iguchi, Tetsuo; Wendt, Klaus

    2013-04-01

    A pulsed injection-locked Ti:Sapphire laser and a negative ion laser ablation source are developed for compact accelerator mass spectrometry assisted by isotope-selective laser photodetachment. An output of about 60 mW at a repetition rate of 1 kHz is available using intracavity second-harmonic generation with a bandwidth of 20 MHz. A negative iodine ion pulse with a width of 100 ns is obtained by laser ablation of a NH4I sample. The negative ion source and the injection-locked Ti:Sapphire laser are suitable for trace analysis of 129I.

  5. GasBench/isotope ratio mass spectrometry: a carbon isotope approach to detect exogenous CO(2) in sparkling drinks.

    PubMed

    Cabaero, Ana I; San-Hiplito, Tamar; Ruprez, Mercedes

    2007-01-01

    A new procedure for the determination of carbon dioxide (CO(2)) (13)C/(12)C isotope ratios, using direct injection into a GasBench/isotope ratio mass spectrometry (GasBench/IRMS) system, has been developed to improve isotopic methods devoted to the study of the authenticity of sparkling drinks. Thirty-nine commercial sparkling drink samples from various origins were analyzed. Values of delta(13)C(cava) ranged from -20.30 per thousand to -23.63 per thousand, when C3 sugar addition was performed for a second alcoholic fermentation. Values of delta(13)C(water) ranged from -5.59 per thousand to -6.87 per thousand in the case of naturally carbonated water or water fortified with gas from the spring, and delta(13)C(water) ranged from -29.36 per thousand to -42.09 per thousand when industrial CO(2) was added. It has been demonstrated that the addition of C4 sugar to semi-sparkling wine (aguja) and industrial CO(2) addition to sparkling wine (cava) or water can be detected. The new procedure has advantages over existing methods in terms of analysis time and sample treatment. In addition, it is the first isotopic method developed that allows (13)C/(12)C determination directly from a liquid sample without previous CO(2) extraction. No significant isotopic fractionation was observed nor any influence by secondary compounds present in the liquid phase. PMID:17879391

  6. Nitrogen isotopic analyses by isotope-ratio-monitoring gas chromatography/mass spectrometry

    NASA Technical Reports Server (NTRS)

    Merritt, D. A.; Hayes, J. M.

    1994-01-01

    Amino acids containing natural-abundance levels of 15N were derivatized and analyzed isotopically using a technique in which individual compounds are separated by gas chromatography, combusted on-line, and the product stream sent directly to an isotope-ratio mass spectrometer. For samples of N2 gas, standard deviations of ratio measurement were better than 0.1% (Units for delta are parts per thousand or per million (%).) for samples larger than 400 pmol and better than 0.5% for samples larger than 25 pmol (0.1% 15N is equivalent to 0.00004 atom % 15N). Results duplicated those of conventional, batchwise analyses to within 0.05%. For combustion of organic compounds yielding CO2/N2 ratios between 14 and 28, in particular for N-acetyl n-propyl derivatives of amino acids, delta values were within 0.25% of results obtained using conventional techniques and standard deviations were better than 0.35%. Pooled data for measurements of all amino acids produced an accuracy and precision of 0.04 and 0.23%, respectively, when 2 nmol of each amino acid was injected on column and 20% of the stream of combustion products was delivered to the mass spectrometer.

  7. Recent developments in the use of isotope ratio mass spectrometry in sports drug testing.

    PubMed

    Piper, Thomas; Emery, Caroline; Saugy, Martial

    2011-08-01

    According to the annual report of the World Anti-Doping Agency, steroids are the most frequently detected class of doping agents. Detecting the misuse of endogenously occurring steroids, i.e. steroids such as testosterone that are produced naturally by humans, is one of the most challenging issues in doping control analysis. The established thresholds for urinary concentrations or concentration ratios such as the testosterone/epitestosterone quotient are sometimes inconclusive owing to the large biological variation in these parameters.For more than 15 years, doping control laboratories focused on the carbon isotope ratios of endogenous steroids to distinguish between naturally elevated steroid profile parameters and illicit administration of steroids. A variety of different methods has been developed throughout the last decade and the number of different steroids under investigation by isotope ratio mass spectrometry has recently grown considerably. Besides norandrosterone, boldenone was found to occur endogenously in rare cases and the misuse of corticosteroids or epitestosterone can now be detected with the aid of carbon isotope ratios as well. In addition, steroids excreted as sulfoconjugates were investigated, and the first results regarding hydrogen isotope ratios recently became available.All of these will be presented in detail within this review together with some considerations on validation issues and on identification of parameters influencing steroidal isotope ratios in urine. PMID:21448602

  8. Isolation and Puification of Uranium Isotopes for Measurement by Mass-Spectrometry (233, 234, 235, 236, 238U) and Alpha Spectrometry (232U)

    SciTech Connect

    Marinelli, R; Hamilton, T; Brown, T; Marchetti, A; Williams, R; Tumey, S

    2006-05-30

    This report describes a standardized methodology used by researchers from the Center for Accelerator Mass Spectrometry (CAMS) (Energy and Environment Directorate) and the Environmental Radiochemistry Group (Chemistry and Materials Science Directorate) at the Lawrence Livermore National Laboratory (LLNL) for the full isotopic analysis of uranium from solution. The methodology has largely been developed for use in characterizing the uranium composition of selected nuclear materials but may also be applicable to environmental studies and assessments of public, military or occupational exposures to uranium using in-vitro bioassay monitoring techniques. Uranium isotope concentrations and isotopic ratios are measured using a combination of Multi Collector Inductively Coupled Plasma Mass Spectrometry (MC ICP-MS), Accelerator Mass Spectrometry (AMS) and Alpha Spectrometry.

  9. Carbon isotopic analysis of atmospheric methane by isotope-ratio-monitoring gas chromatography-mass spectrometry

    NASA Technical Reports Server (NTRS)

    Merritt, Dawn A.; Hayes, J. M.; Des Marais, David J.

    1995-01-01

    Less than 15 min are required for the determination of delta C(sub PDB)-13 with a precision of 0.2 ppt(1 sigma, single measurement) in 5-mL samples of air containing CH4 at natural levels (1.7 ppm). An analytical system including a sample-introduction unit incorporating a preparative gas chromatograph (GC) column for separation of CH4 from N2, O2, and Ar is described. The 15-min procedure includes time for operation of that system, high-resolution chromatographic separation of the CH4, on-line combustion and purification of the products, and isotopic calibration. Analyses of standards demonstrate that systematic errors are absent and that there is no dependence of observed values of delta on sample size. For samples containing 100 ppm or more CH4, preconcentration is not required and the analysis time is less than 5 min. The system utilizes a commercially available, high-sensitivity isotope-ratio mass spectrometer. For optimal conditions of smaple handling and combustion, performance of the system is within a factor of 2 of the shot-noise limit. The potential exists therefore for analysis of samples as small as 15 pmol CH4 with a standard deviation of less than 1 ppt.

  10. Temperature-programmed high-performance liquid chromatography coupled to isotope ratio mass spectrometry.

    PubMed

    Godin, Jean-Philippe; Hopfgartner, Grard; Fay, Laurent

    2008-09-15

    The utility of liquid chromatography coupled to the isotope ratio mass spectrometry technique (LC-IRMS) has already been established through a variety of successful applications. However, the analytical constraint related to the use of aqueous mobile phases limits the LC separation mechanism. We report here a new strategy for high-precision (13)C isotopic analyses based on temperature-programmed LC-IRMS using aqueous mobile phases. Under these conditions, the isotopic precision and accuracy were studied. On one hand, experiments were carried out with phenolic acids using isothermal LC conditions at high temperature (170 degrees C); on the other hand, several experiments were performed by ramping the temperature, as conventionally used in a gas chromatography-based method with hydrosoluble fatty acids and pulses of CO 2 reference gas. In isothermal conditions at 170 degrees C, despite the increase of the CO 2 background, p-coumaric acid and its glucuronide conjugate gave reliable isotopic ratios compared to flow injection analysis-isotopic ratio mass spectrometry (FIA-IRMS) analyses (isotopic precision and accuracy are lower than 0.3 per thousand). On the opposite, for its sulfate conjugate, the isotopic accuracy is affected by its coelution with p-coumaric acid. Not surprisingly, this study also demonstrates that at high temperature (170 degrees C), a compound eluting with long residence time (i.e., ferulic acid) is degraded, affecting thus the delta (13)C (drift of 3 per thousand) and the peak area (compared to FIA-IRMS analysis at room temperature). Quantitation is also reported in isothermal conditions for p-coumaric acid in the range of 10-400 ng/mL and with benzoic acid as an internal standard. For temperature gradient LC-IRMS, in the area of the LC gradient (set up at 20 degrees C/min), the drift of the background observed produces a nonlinearity of SD (delta (13)C) approximately 0.01 per thousand/mV. To circumvent this drift, which impacts severely the precision and accuracy, an alternative approach, i.e., eluting the compound on the plateau of temperature studied was reported here. Other experiments with temperature-programmed LC-IRMS experiments are also reported with the presence of methanol in the injected solution to mimic residual solvent originating from the sample preparation or to slightly increase the solubility of the targeted compound for high-precision measurement. PMID:18690698

  11. Using Theoretical Protein Isotopic Distributions to Parse Small-Mass-Difference Post-Translational Modifications via Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Rhoads, Timothy W.; Williams, Jared R.; Lopez, Nathan I.; Morré, Jeffrey T.; Bradford, C. Samuel; Beckman, Joseph S.

    2013-01-01

    Small-mass-difference modifications to proteins are obscured in mass spectrometry by the natural abundance of stable isotopes such as 13C that broaden the isotopic distribution of an intact protein. Using a ZipTip (Millipore, Billerica, MA, USA) to remove salt from proteins in preparation for high-resolution mass spectrometry, the theoretical isotopic distribution intensities calculated from the protein's empirical formula could be fit to experimentally acquired data and used to differentiate between multiple low-mass modifications to proteins. We could readily distinguish copper from zinc bound to a single-metal superoxide dismutase (SOD1) species; copper and zinc only differ by an average mass of 1.8 Da and have overlapping stable isotope patterns. In addition, proteins could be directly modified while bound to the ZipTip. For example, washing 11 mM S-methyl methanethiosulfonate over the ZipTip allowed the number of free cysteines on proteins to be detected as S-methyl adducts. Alternatively, washing with the sulfhydryl oxidant diamide could quickly reestablish disulfide bridges. Using these methods, we could resolve the relative contributions of copper and zinc binding, as well as disulfide reduction to intact SOD1 protein present from <100 μg of the lumbar spinal cord of a transgenic, SOD1 overexpressing mouse. Although techniques like ICP-MS can measure total metal in solution, this is the first method able to assess the metal-binding and sulfhydryl reduction of SOD1 at the individual subunit level and is applicable to many other proteins.

  12. Isolation of Pu-isotopes from environmental samples using ion chromatography for accelerator mass spectrometry and alpha spectrometry.

    PubMed

    Chamizo, E; Jiménez-Ramos, M C; Wacker, L; Vioque, I; Calleja, A; García-León, M; García-Tenorio, R

    2008-01-14

    A radiochemical method for the isolation of plutonium-isotopes from environmental samples, based on the use of specific extraction chromatography resins for actinides (TEVA), Eichrom Industries, Inc.), has been set up in our laboratory and optimised for their posterior determination by alpha spectrometry (AS) or accelerator mass spectrometry (AMS). The proposed radiochemical method has replaced in our lab a well-established one based on the use of a relatively un-specific anion-exchange resin (AG) 1X8, Bio-rad Laboratories, Inc.), because it is clearly less time consuming, reduces the amounts and molarities of acid wastes produced, and reproducibly gives high radiochemical yields. In order to check the reliability of the proposed radiochemical method for the determination of plutonium-isotopes in different environmental matrixes, twin aliquots of a set of samples were prepared with TEVA and with AG 1X8 resins and measured by AS. Some samples prepared with TEVA resins were measured as well by AMS. As it is shown in the text, there is a comfortable agreement between AS and AMS, which adequately validates the method. PMID:18082656

  13. Carbon Stable Isotope Analysis of Methylmercury Toxin in Biological Materials by Gas Chromatography Isotope Ratio Mass Spectrometry.

    PubMed

    Masbou, Jeremy; Point, David; Guillou, Gal; Sonke, Jeroen E; Lebreton, Benoit; Richard, Pierre

    2015-12-01

    A critical component of the biogeochemical cycle of mercury (Hg) is the transformation of inorganic Hg to neurotoxic monomethylmercury (CH3Hg). Humans are exposed to CH3Hg by consuming marine fish, yet the origin of CH3Hg in fish is a topic of debate. The carbon stable isotopic composition (?(13)C) embedded in the methyl group of CH3Hg remains unexplored. This new isotopic information at the molecular level is thought to represent a new proxy to trace the carbon source at the origin of CH3Hg. Here, we present a compound-specific stable isotope analysis (CSIA) technique for the determination of the ?(13)C value of CH3Hg in biological samples by gas chromatography combustion isotope ratio mass spectrometry analysis (GC-C-IRMS). The method consists first of calibrating a CH3Hg standard solution for ?(13)C CSIA. This was achieved by comparing three independent approaches consisting of the derivatization and halogenation of the CH3Hg standard solution. The determination of ?(13)CCH3Hg values on natural biological samples was performed by combining a CH3Hg selective extraction, purification, and halogenation followed by GC-C-IRMS analysis. Reference ?(13)C values were established for a tuna fish certified material (ERM-CE464) originating from the Adriatic Sea (?(13)CCH3Hg = -22.1 1.5, 2 SD). This value is similar to the ?(13)C value of marine algal-derived particulate organic carbon (?(13)CPOC = -21). PMID:26511394

  14. Approaches to increasing analytical throughput of human samples with multi-isotope imaging mass spectrometry

    PubMed Central

    Steinhauser, Matthew L.; Guillermier, Christelle; Wang, Mei; Lechene, Claude P.

    2015-01-01

    Multi-isotope imaging mass spectrometry (MIMS) combines stable isotope tracers with the quantitative imaging of NanoSIMS ion microscopy. With extensive safety precedent, use of stable isotopes in MIMS applications opens the possibility of studying a wide array of biological questions in humans[1]. Here we describe a series of approaches to increase the effective analytical throughput for detecting rare nuclear labeling events with MIMS. At the level of sample preparation, cells in suspension were either smeared at high density or pelleted cells were embedded and sectioned to reach nuclear depth. Presputtering conditions were optimized for each cell type to ensure the reproducible sampling of nuclei. Adipose tissue posed a different challenge as the large volume of adipocytes results in an obligatorily low density of nuclei in any given plane. Before introducing samples to the NanoSIMS instrument, all nuclei were fluorescently stained, imaged, and their coordinates recorded, allowing automated analysis of fields that contained at least one nucleus and therefore minimizing analysis of dead space. These data emphasize unique challenges posed by human studies, where both ethical and practical issues may limit the administration of stable isotope labels for prolonged periods of time as may be necessary to achieve high labeling frequencies in cells that divide infrequently. PMID:26379341

  15. Calibration and Data Processing in Gas Chromatography Combustion Isotope Ratio Mass Spectrometry

    PubMed Central

    Zhang, Ying; Tobias, Herbert J.; Sacks, Gavin L.; Brenna, J. Thomas

    2013-01-01

    Compound-specific isotope analysis (CSIA) by gas chromatography combustion isotope ratio mass spectrometry (GCC-IRMS) is a powerful technique for the sourcing of substances, such as determination of the geographic or chemical origin of drugs and food adulteration, and it is especially invaluable as a confirmatory tool for detection of the use of synthetic steroids in competitive sport. We review here principles and practices for data processing and calibration of GCC-IRMS data with consideration to anti-doping analyses, with a focus on carbon isotopic analysis (13C/12C). After a brief review of peak definition, the isotopologue signal reduction methods of summation, curve-fitting, and linear regression are described and reviewed. Principles for isotopic calibration are considered in the context of the Δ13C = δ13CM – δ13CE difference measurements required for establishing adverse analytical findings for metabolites relative to endogenous reference compounds. Considerations for the anti-doping analyst are reviewed. PMID:22362612

  16. Carbon isotope determination for separate components of heterogeneous materials using coupled thermogravimetric analysis/isotope ratio mass spectrometry.

    PubMed

    Manning, David A C; Lopez-Capel, Elisa; White, Maggie L; Barker, Sam

    2008-04-01

    A gas-tight thermal analysis system (Netzsch STA 449C Jupiter) has been connected to an isotope ratio mass spectrometer (PDZ Europa 20-20) via an interface containing an oxidizing furnace, water trap, and gas-sampling valve. Using this system, delta(13)C has been measured for CO(2) derived from the thermal decomposition of carbonate and oxalate minerals and organic materials at temperatures that correspond to different decomposition events. There is close agreement between measured and published delta(13)C values for carbonate and oxalate minerals, which have simple decarbonation reactions on heating. Cellulose and lignin-rich materials show much more complex thermal decomposition, reflecting differences in their purity and structure, and measured delta(13)C values vary with the temperature of gas sampling. Provided that measurements are made at temperatures that correspond to the decomposition of cellulose and lignin (indicated by maximum weight loss), internally consistent data can be obtained. However, measurements for cellulose and lignin are systematically enriched in delta(13)C (by up to 1.4 per thousand) with respect to those reported for reference materials, possibly due to the slower combustion kinetics (compared with EA-IRMS). Thermogravimetric analysis/isotope ratio mass spectrometry (TG-IRMS) is ideal for materials and samples for which it is not possible to use other isotopic measurement techniques, for example because of sample heterogeneity. PMID:18348223

  17. 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.

  18. Light Isotopes and Trace Organics Analysis of Mars Samples with Mass Spectrometry

    NASA Technical Reports Server (NTRS)

    Mahaffy, P.; Niemann, Hasso (Technical Monitor)

    2001-01-01

    Precision measurement of light isotopes in Mars surface minerals and comparison of this isotopic composition with atmospheric gas and other, well-mixed reservoirs such as surface dust are necessary to understand the history of atmospheric evolution from a possibly warmer and wetter Martian surface to the present state. Atmospheric sources and sinks that set these ratios are volcanism, solar wind sputtering, photochemical processes, and weathering. Measurement of a range of trace organic species with a particular focus on species such as amino acids that are the building blocks of terrestrial life are likewise important to address the questions of prebiotic and present or past biological activity on Mars. The workshop topics "isotopic mineralogy" and "biology and pre-biotic chemistry" will be addressed from the point of view of the capabilities and limitations of insitu mass spectrometry (MS) techniques such as thermally evolved gas analysis (TEGA) and gas chromatography (GC) surface experiments using MS, in both cases, as a final chemical and isotopic composition detector. Insitu experiments using straightforward adaptations of existing space proven hardware can provide a substantial improvement in the precision and accuracy of our present knowledge of isotopic composition both in molecular and atomic species in the atmosphere and those chemically bound in rocks and soils. Likewise, detection of trace organic species with greatly improved sensitivity from the Viking GCMS experiment is possible using gas enrichment techniques. The limits to precision and accuracy of presently feasible insitu techniques compared to laboratory analysis of returned samples will be explored. The insitu techniques are sufficiently powerful that they can provide a high fidelity method of screening samples obtained from a diverse set of surface locations such as the subsurface or the interior of rocks for selection of those that are the most interesting for return to Earth.

  19. Assessment of Non-traditional Isotopic Ratios by Mass Spectrometry for Analysis of Nuclear Activities: Annual Report Year 2

    SciTech Connect

    Biegalski, S; Buchholz, B

    2009-08-26

    The objective of this work is to identify isotopic ratios suitable for analysis via mass spectrometry that distinguish between commercial nuclear reactor fuel cycles, fuel cycles for weapons grade plutonium, and products from nuclear weapons explosions. Methods will also be determined to distinguish the above from medical and industrial radionuclide sources. Mass spectrometry systems will be identified that are suitable for field measurement of such isotopes in an expedient manner. Significant progress has been made with this project within the past year: (1) Isotope production from commercial nuclear fuel cycles and nuclear weapons fuel cycles have been modeled with the ORIGEN and MCNPX codes. (2) MCNPX has been utilized to calculate isotopic inventories produced in a short burst fast bare sphere reactor (to approximate the signature of a nuclear weapon). (3) Isotopic ratios have been identified that are good for distinguishing between commercial and military fuel cycles as well as between nuclear weapons and commercial nuclear fuel cycles. (4) Mass spectrometry systems have been assessed for analysis of the fission products of interest. (5) A short-list of forensic ratios have been identified that are well suited for use in portable mass spectrometry systems.

  20. High-accuracy gas analysis via isotope dilution mass spectrometry: Carbon dioxide in air

    SciTech Connect

    Verkouteren, R.M.; Dorko, W.D. )

    1989-11-01

    An absolute method, based on isotope dilution mass spectrometry, is described for the determination of atmospheric concentrations of carbon dioxide (CO{sub 2}) in dry air. In this study, the relative amounts of sample and spike gases are measured manometrically under temperature control before blending. The spike CO{sub 2} composition is approximately 0.1 atom % {sup 13}C while the oxygen isotopic composition is normal. Exhaustive assessment of potential error sources leads to accountability of observed imprecision and determination of accuracy confidence intervals (CI). The imprecision interval (95% CI) about the mean is smaller than {plus minus} 0.1% ({plus minus}0.4 {mu}mol/mol) while the accuracy interval (95% CI) is {plus minus}0.15% ({plus minus}0.52 {mu}mol/mol) for air having a CO{sub 2} concentration of about 350 {mu}mol/mol. Calculated concentrations of CO{sub 2} are statistically indistinguishable from those generated by gravimetry, an independent method of analysis. In this study, the major contributors to uncertainty and imprecision are the predetermination of the gas volume ratio and the measurement of the isotopic composition of the blended CO{sub 2}, respectively.

  1. A Stable-Isotope Mass Spectrometry-Based Metabolic Footprinting Approach to Analyze Exudates from Phytoplankton

    PubMed Central

    Weber, Ralf J. M.; Selander, Erik; Sommer, Ulf; Viant, Mark R.

    2013-01-01

    Phytoplankton exudates play an important role in pelagic ecology and biogeochemical cycles of elements. Exuded compounds fuel the microbial food web and often encompass bioactive secondary metabolites like sex pheromones, allelochemicals, antibiotics, or feeding attractants that mediate biological interactions. Despite this importance, little is known about the bioactive compounds present in phytoplankton exudates. We report a stable-isotope metabolic footprinting method to characterise exudates from aquatic autotrophs. Exudates from 13C-enriched alga were concentrated by solid phase extraction and analysed by high-resolution Fourier transform ion cyclotron resonance mass spectrometry. We used the harmful algal bloom forming dinoflagellate Alexandrium tamarense to prove the method. An algorithm was developed to automatically pinpoint just those metabolites with highly 13C-enriched isotope signatures, allowing us to discover algal exudates from the complex seawater background. The stable-isotope pattern (SIP) of the detected metabolites then allowed for more accurate assignment to an empirical formula, a critical first step in their identification. This automated workflow provides an effective way to explore the chemical nature of the solutes exuded from phytoplankton cells and will facilitate the discovery of novel dissolved bioactive compounds. PMID:24172212

  2. Using Punnett Squares to Facilitate Students' Understanding of Isotopic Distributions in Mass Spectrometry

    ERIC Educational Resources Information Center

    Sein, Lawrence T., Jr.

    2006-01-01

    The isotopic distribution in mass spectroscopy is described for identifying pure compounds, being able to distinguish molecular fragments by masses. Punnett squares are familiar, easy to compute, and often graphical which makes helpful to students and the relative distribution of isotopic combination is easily generated for even isotopic

  3. Advancement and application of gas chromatography isotope ratio mass spectrometry techniques for atmospheric trace gas analysis

    NASA Astrophysics Data System (ADS)

    Giebel, Brian M.

    2011-12-01

    The use of gas chromatography isotope ratio mass spectrometry (GC-IRMS) for compound specific stable isotope analysis is an underutilized technique because of the complexity of the instrumentation and high analytical costs. However stable isotopic data, when coupled with concentration measurements, can provide additional information on a compounds production, transformation, loss, and cycling within the biosphere and atmosphere. A GC-IRMS system was developed to accurately and precisely measure delta13C values for numerous oxygenated volatile organic compounds having natural and anthropogenic sources. The OVOCs include methanol, ethanol, acetone, methyl ethyl ketone, 2-pentanone, and 3-pentanone. Guided by the requirements for analysis of trace components in air, the GC-IRMS system was developed with the goals of increasing sensitivity, reducing dead-volume and peak band broadening, optimizing combustion and water removal, and decreasing the split ratio to the IRMS. The technique relied on a two-stage preconcentration system, a low-volume capillary reactor and water trap, and a balanced reference gas delivery system. Measurements were performed on samples collected from two distinct sources (i.e. biogenic and vehicle emissions) and ambient air collected from downtown Miami and Everglades National Park. However, the instrumentation and the method have the capability to analyze a variety of source and ambient samples. The measured isotopic signatures that were obtained from source and ambient samples provide a new isotopic constraint for atmospheric chemists and can serve as a new way to evaluate their models and budgets for many OVOCs. In almost all cases, OVOCs emitted from fuel combustion were enriched in 13C when compared to the natural emissions of plants. This was particularly true for ethanol gas emitted in vehicle exhaust, which was observed to have a uniquely enriched isotopic signature that was attributed to ethanol's corn origin and use as an alternative fuel or fuel additive. Results from this effort show that ethanol's unique isotopic signature can be incorporated into air chemistry models for fingerprinting and source apportionment purposes and can be used as a stable isotopic tracer for biofuel inputs to the atmosphere on local to regional scales.

  4. Stable oxygen and hydrogen isotopes of brines - comparing isotope ratio mass spectrometry and isotope ratio infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Ahrens, Christian; Koeniger, Paul; van Geldern, Robert; Stadler, Susanne

    2013-04-01

    Today's standard analytical methods for high precision stable isotope analysis of fluids are gas-water equilibration and high temperature pyrolysis coupled to isotope ratio mass spectrometers (IRMS). In recent years, relatively new laser-based analytical instruments entered the market that are said to allow high isotope precision data on nearly every media. This optical technique is referred to as isotope ratio infrared spectroscopy (IRIS). The objective of this study is to evaluate the capability of this new instrument type for highly saline solutions and a comparison of the analytical results with traditional IRMS analysis. It has been shown for the equilibration method that the presence of salts influences the measured isotope values depending on the salt concentration (see Lcuyer et al, 2009; Martineau, 2012). This so-called 'isotope salt effect' depends on the salt type and salt concentration. These factors change the activity in the fluid and therefore shift the isotope ratios measured by the equilibration method. Consequently, correction factors have to be applied to these analytical data. Direct conversion techniques like pyrolysis or the new laser instruments allow the measurement of the water molecule from the sample directly and should therefore not suffer from the salt effect, i.e. no corrections of raw values are necessary. However, due to high salt concentrations this might cause technical problems with the analytical hardware and may require labor-intensive sample preparation (e.g. vacuum distillation). This study evaluates the salt isotope effect for the IRMS equilibration technique (Thermo Gasbench II coupled to Delta Plus XP) and the laser-based IRIS instruments with liquid injection (Picarro L2120-i). Synthetic salt solutions (NaCl, KCl, CaCl2, MgCl2, MgSO4, CaSO4) and natural brines collected from the Stassfurt Salt Anticline (Germany; Stadler et al., 2012) were analysed with both techniques. Salt concentrations ranged from seawater salinity up to full saturation. References Lcuyer, C. et al. (2009). Chem. Geol., 264, 122-126. [doi:10.1016/j.chemgeo.2009.02.017] Martineau, F. et al. (2012). Chem. Geol., 291, 236-240. [doi:10.1016/j.chemgeo.2011.10.017] Stadler, S. et al. (2012). Chem. Geol., 294-295, 226-242. [doi:10.1016/j.chemgeo.2011.12.006

  5. Sulfur-based absolute quantification of proteins using isotope dilution inductively coupled plasma mass spectrometry

    NASA Astrophysics Data System (ADS)

    Lee, Hyun-Seok; Heun Kim, Sook; Jeong, Ji-Seon; Lee, Yong-Moon; Yim, Yong-Hyeon

    2015-10-01

    An element-based reductive approach provides an effective means of realizing International System of Units (SI) traceability for high-purity biological standards. Here, we develop an absolute protein quantification method using double isotope dilution (ID) inductively coupled plasma mass spectrometry (ICP-MS) combined with microwave-assisted acid digestion for the first time. We validated the method and applied it to certify the candidate protein certified reference material (CRM) of human growth hormone (hGH). The concentration of hGH was determined by analysing the total amount of sulfur in hGH. Next, the size-exclusion chromatography method was used with ICP-MS to characterize and quantify sulfur-containing impurities. By subtracting the contribution of sulfur-containing impurities from the total sulfur content in the hGH CRM, we obtained a SI-traceable certification value. The quantification result obtained with the present method based on sulfur analysis was in excellent agreement with the result determined via a well-established protein quantification method based on amino acid analysis using conventional acid hydrolysis combined with an ID liquid chromatography-tandem mass spectrometry. The element-based protein quantification method developed here can be generally used for SI-traceable absolute quantification of proteins, especially pure-protein standards.

  6. Determination of iodine in oyster tissue by isotope dilution laser resonance ionization mass spectrometry

    SciTech Connect

    Fassett, J.D.; Murphy, T.J. )

    1990-02-15

    The technique of laser resonance ionization mass spectrometry has been combined with isotope dilution analysis to determine iodine in oyster tissue. The long-lived radioisotope, 129I, was used to spike the samples. Samples were equilibrated with the 129I, wet ashed under controlled conditions, and iodine separated by coprecipitation with silver chloride. The analyte was dried as silver ammonium iodide upon a tantalum filament from which iodine was thermally desorbed in the resonance ionization mass spectrometry instrument. A single-color, two-photon resonant plus one-photon ionization scheme was used to form positive iodine ions. Long-lived iodine signals were achieved from 100 ng of iodine. The precision of 127I/129I measurement has been evaluated by replicate determinations of the spike, the spike calibration samples, and the oyster tissue samples and was 1.0%. Measurement precision among samples was 1.9% for the spike calibration and 1.4% for the oyster tissue. The concentration of iodine determined in SRM 1566a, Oyster Tissue, was 4.44 micrograms/g with an estimate of the overall uncertainty for the analysis of +/- 0.12 microgram/g.

  7. Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry

    SciTech Connect

    Esteban, N.V.; Loughlin, T.; Yergey, A.L.; Zawadzki, J.K.; Booth, J.D.; Winterer, J.C.; Loriaux, D.L. )

    1991-01-01

    Growth retardation as well as the development of Cushingoid features in adrenally insufficient patients treated with the currently accepted replacement dose of cortisol (33-41 mumol/day.m2; 12-15 mg/m2.day) prompted us to reevaluate the cortisol production rate (FPR) in normal subjects and patients with Cushing's syndrome, using a recently developed thermospray liquid chromatography-mass spectrometry method. The stable isotope (9,12,12-2H3)cortisol was infused continuously for 31 h at about 5% of the anticipated FPR. Blood samples were obtained at 20-min intervals for 24 h, spun, and pooled in 4-h groups. Tracer dilution in plasma was determined by liquid chromatography/mass spectrometry. The method was validated with controlled infusions in 6 patients with adrenal insufficiency. Results from 12 normal volunteers revealed a FPR of 27.3 +/- 7.5 mumol/day (9.9 +/- 2.7 mg/day) or 15.7 mumol/day.m2; 5.7 mg/m2. day. A previously unreported circadian variation in FPR was observed. Patients with Cushing's syndrome demonstrated unequivocal elevation of FPR and cortisol concentration correlated during each sample period in normal volunteers, indicating that cortisol secretion, rather than metabolism, is mainly responsible for changes in plasma cortisol. Our data suggest that the FPR in normal subjects may be lower than previously believed.

  8. Hydroponic isotope labeling of entire plants and high-performance mass spectrometry for quantitative plant proteomics.

    PubMed

    Bindschedler, Laurence V; Mills, Davinia J S; Cramer, Rainer

    2012-01-01

    Hydroponic isotope labeling of entire plants (HILEP) combines hydroponic plant cultivation and metabolic labeling with stable isotopes using (15)N-containing inorganic salts to label whole and mature plants. Employing (15)N salts as the sole nitrogen source for HILEP leads to the production of healthy-looking plants which contain (15)N proteins labeled to nearly 100%. Therefore, HILEP is suitable for quantitative plant proteomic analysis, where plants are grown in either (14)N- or (15)N-hydroponic media and pooled when the biological samples are collected for relative proteome quantitation. The pooled (14)N-/(15)N-protein extracts can be fractionated in any suitable way and digested with a protease for shotgun proteomics, using typically reverse phase liquid chromatography nanoelectrospray ionization tandem mass spectrometry (RPLC-nESI-MS/MS). Best results were obtained with a hybrid ion trap/FT-MS mass spectrometer, combining high mass accuracy and sensitivity for the MS data acquisition with speed and high-throughput MS/MS data acquisition, increasing the number of proteins identified and quantified and improving protein quantitation. Peak processing and picking from raw MS data files, protein identification, and quantitation were performed in a highly automated way using integrated MS data analysis software with minimum manual intervention, thus easing the analytical workflow. In this methodology paper, we describe how to grow Arabidopsis plants hydroponically for isotope labeling using (15)N salts and how to quantitate the resulting proteomes using a convenient workflow that does not require extensive bioinformatics skills. PMID:22665301

  9. Quantification of four artificial sweeteners in Finnish surface waters with isotope-dilution mass spectrometry.

    PubMed

    Perkola, Noora; Sainio, Pirjo

    2014-01-01

    The artificial sweeteners sucralose (SCL), acesulfame (ACS), saccharin (SAC), and cyclamate (CYC) have been detected in environmental waters in Europe and North America. Higher environmental levels are expected in view of the increasing consumption of these food additives. In this study, an isotope-dilution mass spectrometry (IDMS) LC-MS/MS method was developed and validated for quantifying the four artificial sweeteners in boreal lakes (n=3) and rivers (n=12). The highest concentrations of ACS, SAC, CYC and SCL were 9,600, 490, 210 and 1000ng/L, respectively. ACS and SAC were detected in all studied samples, and CYC and SCL in 98% and 56% of the samples. Seasonal trends of ACS and SAC were observed in some rivers. ACS and SCL concentrations in rivers correlated linearly with population equivalents of the wastewater treatment plants in the catchment areas, whereas SAC and CYC concentrations depend more on the source. PMID:24100049

  10. Determination of dithiocarbamate fungicide residues by liquid chromatography/mass spectrometry and stable isotope dilution assay.

    PubMed

    Crnogorac, Goranka; Schwack, Wolfgang

    2007-01-01

    A rapid and very sensitive high-performance liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) method for the simultaneous determination of dithiocarbamate (DTC) fungicide residues in fruits and vegetables was developed. The surface extraction of samples used an alkaline buffer consisting of sodium hydrogen carbonate and DL-penicillamine. The three DTC subclasses, i.e. dimethyldithiocarbamates (DMDs), ethylenebis(dithiocarbamates) (EBDs), and propylenebis(dithiocarbamates) (PBDs), were separated on a Sequant ZIC-pHILIC column using an acetonitrile/10 mM ammonia gradient. Because of the instability of DTC residues extracted from plant samples, a stable isotope dilution assay was applied. For each DTC subclass, the limits of detection and quantification were approximately 0.03 mg kg(-1) and 0.05 mg kg(-1), respectively. Recoveries from grapes, cucumbers, tomatoes, and rucola, spiked in the range of 0.01-0.9 mg kg(-1), averaged between 90 and 100%. PMID:18000839

  11. Quantification of ferritin bound iron in human serum using species-specific isotope dilution mass spectrometry.

    PubMed

    Ren, Yao; Walczyk, Thomas

    2014-09-01

    Ferritin is a hollow sphere protein composed of 24 subunits that can store up to 4500 iron atoms in its inner cavity. It is mainly found in the liver and spleen but also in serum at trace levels. Serum ferritin is considered as the best single indicator in assessing body iron stores except liver or bone marrow biopsy. However, it is confounded by other disease conditions. Ferritin bound iron (FBI) and ferritin saturation have been suggested as more robust biomarkers. The current techniques for FBI determination are limited by low antibody specificity, low instrument sensitivity and possible analyte losses during sample preparation. The need for a highly sensitive and reliable method is widely recognized. Here we describe a novel technique to detect serum FBI using species-specific isotope dilution mass spectrometry (SS-IDMS). [(57)Fe]-ferritin was produced by biosynthesis and in vitro labeling with the (57)Fe spike in the form of [(57)Fe]-citrate after cell lysis and heat treatment. [(57)Fe]-ferritin for sample spiking was further purified by fast liquid protein chromatography. Serum ferritin and added [(57)Fe]-ferritin were separated from other iron species by ultrafiltration followed by isotopic analysis of FBI using negative thermal ionization mass spectrometry. Repeatability of our assay is 8% with an absolute detection limit of 18 ng FBI in the sample. As compared to other speciation techniques, SS-IDMS offers maximum control over sample losses and species conversion during analysis. The described technique may therefore serve as a reference technique for clinical applications of FBI as a new biomarker for assessing body iron status. PMID:25008269

  12. Spatially tracking 13C labeled substrate (bicarbonate) accumulation in microbial communities using laser ablation isotope ratio mass spectrometry

    SciTech Connect

    Moran, James J.; Doll, Charles G.; Bernstein, Hans C.; Renslow, Ryan S.; Cory, Alexandra B.; Hutchison, Janine R.; Lindemann, Stephen R.; Fredrickson, Jim K.

    2014-08-25

    This is a manuscript we would like to submit for publication in Environmental Microbiology Reports. This manuscript contains a description of a laser ablation isotope ratio mass spectrometry methodology developed at PNNL and applied to a microbial system at a PNNL project location – Hot Lake, Washington. I will submit a word document containing the entire manuscript with this Erica input request form.

  13. High-resolution multi-isotope imaging mass spectrometry enables visualisation of stem cell division and metabolism.

    PubMed

    Goto, Kensuke; Waki, Michihiko; Takahashi, Tsukasa; Kadowaki, Makoto; Setou, Mitsutoshi

    2012-05-29

    MIMS visualises metabolism: A recent publication by Steinhauser and co-workers presents a novel application of multi-isotope mass spectrometry (MIMS) to visualise physiological metabolism in live mammalian organisms, and validate the "immortal strand hypothesis" of asymmetric chromosomal division of stem cells in the small intestine. PMID:22619149

  14. The Determination of the Natural Abundance of the Isotopes of Chlorine: An Introductory Experiment in Mass Spectrometry.

    ERIC Educational Resources Information Center

    O'Malley, Rebecca M.

    1982-01-01

    Describes a laboratory experiment which introduces basic principles and experimental techniques of mass spectrometry for fourth year undergraduate (B.Sc.) students. Laboratory procedures, background information, and discussion of results are provided for the experiment in which the natural isotopic abundance of chlorine is determined. (Author/JN)

  15. Applications of stable isotope ratio mass spectrometry in cattle dung carbon cycling studies.

    PubMed

    Dungait, Jennifer A J; Bol, Roland; Lopez-Capel, Elisa; Bull, Ian D; Chadwick, David; Amelung, Wulf; Granger, Steven J; Manning, David A C; Evershed, Richard P

    2010-03-15

    Understanding the fate of dung carbon (C) in soils is challenging due to the ubiquitous presence of the plant-derived organic matter (OM), the source material from which both dung-derived OM and soil organic matter (SOM) predominantly originate. A better understanding of the fate of specific components of this substantial source of OM, and thereby its contribution to C cycling in terrestrial ecosystems, can only be achieved through the use of labelled dung treatments. In this short review, we consider analytical approaches using bulk and compound-specific stable carbon isotope analysis that have been utilised to explore the fate of dung-derived C in soils. Bulk stable carbon isotope analyses are now used routinely to explore OM matter cycling in soils, and have shown that up to 20% of applied dung C may be incorporated into the surface soil horizons several weeks after application, with up to 8% remaining in the soil profile after one year. However, whole soil delta(13)C values represent the average of a wide range of organic components with varying delta(13)C values and mean residence times in soils. Several stable (13)C isotope ratio mass spectrometric methods have been developed to qualify and quantify different fractions of OM in soils and other complex matrices. In particular, thermogravimetry-differential scanning calorimetry-isotope ratio mass spectrometry (TG-DSC-IRMS) and gas chromatography-combustion-IRMS (GC-C-IRMS) analyses have been applied to determine the incorporation and turnover of polymeric plant cell wall materials from C(4) dung into C(3) grassland soils using natural abundance (13)C isotope labelling. Both approaches showed that fluxes of C derived from polysaccharides, i.e. as cellulose or monosaccharide components, were more similar to the behaviour of bulk dung C in soil than lignin. However, lignin and its 4-hydroxypropanoid monomers were unexpectedly dynamic in soil. These findings provide further evidence for emerging themes in biogeochemical investigations of soil OM dynamics that challenge perceived concepts of recalcitrance of C pools in soils, which may have profound implications for the assessment of the potential of agricultural soils to influence terrestrial C sinks. PMID:20112271

  16. Flow injection analysis-isotope ratio mass spectrometry for bulk carbon stable isotope analysis of alcoholic beverages.

    PubMed

    Jochmann, Maik A; Steinmann, Dirk; Stephan, Manuel; Schmidt, Torsten C

    2009-11-25

    A new method for bulk carbon isotope ratio determination of water-soluble samples is presented that is based on flow injection analysis-isotope ratio mass spectrometry (FIA-IRMS) using an LC IsoLink interface. Advantages of the method are that (i) only very small amounts of sample are required (2-5 microL of the sample for up to 200 possible injections), (ii) it avoids complex sample preparation procedures such as needed for EA-IRMS analysis (only sample dilution and injection,) and (iii) high throughput due to short analysis times is possible (approximately 15 min for five replicates). The method was first tested and evaluated as a fast screening method with industrially produced ethanol samples, and additionally the applicability was tested by the measurement of 81 alcoholic beverages, for example, whiskey, brandy, vodka, tequila, and others. The minimal sample concentration required for precise and reproducible measurements was around 50 microL L(-1) ethanol/water (1.71 mM carbon). The limit of repeatability was determined to be r=0.49%. FIA-IRMS represents a fast screening method for beverage authenticity control. Due to this, samples can be prescreened as a decisive criterion for more detailed investigations by HPLC-IRMS or multielement GC-IRMS measurements for a verification of adulteration. PMID:19856915

  17. Precise determination of seawater calcium using isotope dilution inductively coupled plasma mass spectrometry.

    PubMed

    Liu, Hou-Chun; You, Chen-Feng; Cai, Wei-Jun; Chung, Chuan-Hsiung; Huang, Kuo-Fang; Chen, Bao-Shan; Li, Yen

    2014-02-21

    We describe a method for rapid, precise and accurate determination of calcium ion (Ca(2+)) concentration in seawater using isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS). A 10 ?L aliquot of seawater was spiked with an appropriate (43)Ca enriched solution for (44)Ca/(43)Ca ID-ICP-MS analyses, using an Element XR (Thermo Fisher Scientific), operated at low resolution in E-scan acquisition mode. A standard-sample bracketing technique was applied to correct for potential mass discrimination and ratio drift at every 5 samples. A precision of better than 0.05% for within-run and 0.10% for duplicate measurements of the IAPSO seawater standard was achieved using 10 ?L solutions with a measuring time less than 3 minutes. Depth profiles of seawater samples collected from the Arctic Ocean basin were processed and compared with results obtained by the classic ethylene glycol tetra-acetic acid (EGTA) titration. Our new ID-ICP-MS data agreed closely with the conventional EGTA data, with the latter consistently displaying 1.5% excess Ca(2+) values, possibly due to a contribution of interference from Mg(2+) and Sr(2+) in the EGTA titration. The newly obtained Sr/Ca profiles reveal sensitive water mass mixing in the upper oceanic column to reflect ice melting in the Arctic region. This novel technique provides a tool for seawater Ca(2+) determination with small sample size, high throughput, excellent internal precision and external reproducibility. PMID:24434804

  18. 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.

  19. 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. PMID:26070716

  20. Stable isotope labeling - Liquid chromatography/mass spectrometry for quantitative analysis of androgenic and progestagenic steroids.

    PubMed

    Guo, Ning; Liu, Ping; Ding, Jun; Zheng, Shu-Jian; Yuan, Bi-Feng; Feng, Yu-Qi

    2016-01-28

    Steroid hormones play important roles in mammal at very low concentrations and are associated with numerous endocrinology and oncology diseases. Therefore, quantitative analysis of steroid hormones can provide crucial information for uncovering underlying mechanisms of steroid hormones related diseases. In the current study, we developed a sensitive method for the detection of steroid hormones (progesterone, dehydroepiandrosterone, testosterone, pregnenolone, 17-hydroxyprogesterone, androstenedione and 17α-hydroxypregnenolone) in body fluids by stable isotope labeling coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. In this respect, a pair of isotopes labeling reagents, Girard reagent P (GP) and d5-Girard reagent P (d5-GP), were synthesized and utilized to label steroid hormones in follicular fluid samples and steroid hormone standards, respectively. The heavy labeled standards were used as internal standards for quantification to minimize quantitation deviation in MS analysis due to the matrix and ion suppression effects. The ionization efficiencies of steroid hormones were greatly improved by 4-504 folds through the introduction of a permanent charged moiety of quaternary ammonium from GP. Using the developed method, we successfully quantified steroid hormones in human follicular fluid. We found that the contents of testosterone and androstenedione exhibited significant increase while the content of pregnenolone had significant decrease in follicular fluid of polycystic ovarian syndrome (PCOS) patients compared with healthy controls, indicating that these steroid hormones with significant change may contribute to the pathogenesis of PCOS. Taken together, the developed stable isotope labeling coupled LC-ESI-MS/MS analysis demonstrated to be a promising method for the sensitive and accurate determination of steroid hormones, which may facilitate the in-depth investigation of steroid hormones related diseases. PMID:26755144

  1. Simultaneous Quantification of Steroids in Rat Intratesticular Fluid by HPLCIsotope Dilution Tandem Mass Spectrometry

    PubMed Central

    RENNE, ALISSA; LUO, LINDI; JAROW, JONATHAN; WRIGHT, WILLIAM W.; BROWN, TERRY R.; CHEN, HAOLIN; ZIRKIN, BARRY R.; FRIESEN, MARLIN D.

    2014-01-01

    An isotope dilution mass spectrometry method has been developed for the simultaneous measurement of picolinoyl derivatives of testosterone (T), dihydrotestosterone (DHT), 17?-estradiol (E2), and 5?-androstan-3?,17?-diol (3?-diol) in rat intratesticular fluid. The method uses reversed-phase high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry. Following derivatization of 10-?L samples of testicular fluid with picolinoyl chloride hydrochloride, the samples were purified by solid phase extraction before analysis. The accuracy of the method was satisfactory for the 4 analytes at 3 concentrations, and both inter- and intraday reproducibility were satisfactory for T, DHT, and E2. Measurements of intratesticular T concentrations in a group of 8 untreated adult rats by this method correlated well with measurements of the same samples by radioimmunoassay. As in men, there was considerable rat-to-rat variability in T concentration, despite the fact that the rats were inbred. Although its levels were more than an order of magnitude lower than those of T, DHT was measured reliably in all 8 intratesticular fluid samples. DHT concentration also varied from rat to rat and was highly correlated with T levels. The levels of E2 and 3?-diol also were measurable. The availability of a sensitive method by which to measure steroids accurately and rapidly in the small volumes of intratesticular fluid obtainable from individual rats will make it possible to examine the effects, over time, of such perturbations as hormone and drug administration and environmental toxicant exposures on the intratesticular hormonal environment of exposed individual males and thereby to begin to understand differences in response between individuals. PMID:22016356

  2. Investigation of bn-44 peptide fragments using high resolution mass spectrometry and isotope labeling.

    PubMed

    Wang, Bing; Yu, Jiayi; Wang, Huixin; Wei, Zhonglin; Guo, Xinhua; Xiao, Zhaohui; Zeng, Zhoufang; Kong, Wei

    2014-12-01

    An N-terminal deuterohemin-containing hexapeptide (DhHP-6) was designed as a short peptide cytochrome c (Cyt c) mimetic to study the effect of N-terminal charge on peptide fragmentation pathways. This peptide gave different dissociation patterns than normal tryptic peptides. Upon collision-induced dissociation (CID) with an ion trap mass spectrometer, the singly charged peptide ion containing no added proton generated abundant and characteristic bn-44 ions instead of bn-28 (an) ions. Studies by high resolution mass spectrometry (HRMS) and isotope labeling indicate that elimination of 44 Da fragments from b ions occurs via two different pathways: (1) loss of CH3CHO (44.0262) from a Thr side chain; (2) loss of CO2 (43.9898) from the oxazolone structure in the C-terminus. A series of analogues were designed and analyzed. The experimental results combined with Density Functional Theory (DFT) calculations on the proton affinity of the deuteroporphyrin demonstrate that the production of these novel bn-44 ions is related to the N-terminal charge via a charge-remote rather than radical-directed fragmentation pathway. PMID:25280401

  3. Isotope-ratio-monitoring gas chromatography-mass spectrometry: methods for isotopic calibration

    NASA Technical Reports Server (NTRS)

    Merritt, D. A.; Brand, W. A.; Hayes, J. M.

    1994-01-01

    In trial analyses of a series of n-alkanes, precise determinations of 13C contents were based on isotopic standards introduced by five different techniques and results were compared. Specifically, organic-compound standards were coinjected with the analytes and carried through chromatography and combustion with them; or CO2 was supplied from a conventional inlet and mixed with the analyte in the ion source, or CO2 was supplied from an auxiliary mixing volume and transmitted to the source without interruption of the analyte stream. Additionally, two techniques were investigated in which the analyte stream was diverted and CO2 standards were placed on a near-zero background. All methods provided accurate results. Where applicable, methods not involving interruption of the analyte stream provided the highest performance (sigma = 0.00006 at.% 13C or 0.06% for 250 pmol C as CO2 reaching the ion source), but great care was required. Techniques involving diversion of the analyte stream were immune to interference from coeluting sample components and still provided high precision (0.0001 < or = sigma < or = 0.0002 at.% or 0.1 < or = sigma < or = 0.2%).

  4. Sulfur Isotope Variation in Melt Inclusions From Arc Basalts Revealed By Secondary Ion Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Mandeville, C. W.; Shimizu, N.; Kelley, K. A.

    2009-12-01

    Subduction zones are sites where elements once at the Earths surface are recycled back to the mantle. Arc volcanoes return volatiles and hydrous melts to the surface. Understanding of sulfur recycling in magmatic arcs is hampered by insufficient data on net sulfur isotopic composition of slab inputs, that range from ?34S of seawater (21) to negative ?34S of -70 for secondary sulfides, to values of 0 3 in relict magmatic sulfides. We lack sufficient knowledge of the sulfur concentration and isotopic composition of the mantle wedge. Degassing and assimilation of crustal sulfur may produce changes to initial sulfur isotope ratios of magmas. To preclude degassing effects, we measured S isotope ratios in mafic melt inclusions by secondary ionization mass spectrometry (SIMS) from three arc volcanoes, Galunggung, and Krakatau in Indonesia, and Augustine, in Alaska. These data provide a view of the variability of initial sulfur isotope ratios of mafic arc magmas and are being evaluated for correlations with sulfur and iron oxidation state, dissolved volatiles, trace elements, and degassing effects in order to determine the origin(s) of dissolved S. Olivine-hosted melt inclusions from a basaltic bomb from the 1982-1983 Galunggung eruption represent the relatively dry adiabatic decompression melting end member of primary arc magma genesis (Sisson and Bronto,1998). New SIMS ?34S measurements of Galunggung melt inclusions yield ratios from -3.0 to +5.0 with S concentrations of 1950 ppm - 990 ppm. A few Galunggung inclusions have ?34S between 0.5 and 1.4 with S conc.'s of 1690 - 1760 ppm, that are within the mantle range, and have low water contents of 0.25 to 0.30 wt.% (Kelley et al. 2005). A subgroup of inclusions yield ?34S of 2.8 to 5.0 and 990 - 1920 ppm S. Pre-1883 basaltic scoria from Krakatau volcano contain olivine-hosted melt inclusions with water and CO2 concentrations from 1.8 - 4.1 wt.% and 79 - 1017 ppm, respectively. Dissolved S conc. in these inclusions ranges from 620-2400 ppm. SIMS isotope measurements yield ?34S ranging from 1.6 to 8.7 with no obvious correlation with S concentration, but inclusions with greater than 1400 ppm S have ?34S of 3.0 to 5.5. Tentative positive correlations in ?34S versus dissolved CO2 and H2O may indicate a H2O - and 34S-enriched component entering into the magma source region. A Pleistocene basaltic pyroclastic deposit from Augustine volcano contains olivine-hosted melt inclusions with some of the highest dissolved water (up to 7.5 wt.%), sulfur (6600 ppm) and chlorine (6500 ppm) for mafic magmas worldwide (Plank et al. 2006). SIMS isotope measurements yield ?34S values of 1.5 to 14.9 for inclusions with 2624 to 4650 ppm S. Most melt inclusion data form a cluster with ?34S ranging from 6.7 to 12.7. Extreme volatile enrichment coupled with elevated ?34S values indicate a 34S-enriched component in the magma source region. Kelley K A,et al.(2005)Geochim. Cosmochim. Acta, 10S, A743. Plank T, et al. (2006) EOS Trans., AGU, 87(52), Fall Meet. Suppl., Abstract V42B-06. Sisson T, and Bronto S (1998) Nature, 391, 883-886.

  5. Isotope Ratio Mass Spectrometry and Shale Gas - What Is Possible with Current Technology?

    NASA Astrophysics Data System (ADS)

    Barrie, C. D.; Kasson, A.

    2014-12-01

    With ever increasing exploration and exploitation of 'unconventional' hydrocarbon resources, the drive to understand the origins, history and importance of these resources and their effects on the surrounding environment (i.e. ground waters) has never been more important. High-throughput, high-precision isotopic measurements are therefore a key tool in this industry to both understand the gas generated and monitor the development and stability of wells through time. With the advent of cavity ringdown spectroscopy (CRDS) instrumentation, there has been a push in some applications - environmental & atmospheric - to gather more and more data directly at the location of collection or at dedicated field stations. Furthermore, CRDS has resulted in users seeking greater autonomy of instrumentation and so-called black box technology. Traditionally IRMS technology has not met any of these demands, requiring very specific and extensive footprint, power and environmental requirements. This has meant that the 'Oil & Gas' sector, which for natural gases measurements requires GC-IRMS technology - not possible via CRDS - loses time, money and manpower as samples get sent to central facility or contract labs with potentially long lee times. However, recent developments in technology mean that IRMS systems exist which are benchtop, have much lower power requirements, standard power connections and as long as housed in a temperature controlled field stations can be deployed anywhere. Furthermore, with advances in electronics and software IRMS systems are approaching the black box level of newer instrumentation while maintaining the flexibility and abilities of isotope ratio mass spectrometry. This presentation will outline changes in IRMS technology applicable to the Oil & Gas industry, discuss the feasibility of true 'field' deployability and present results from a range of Oil & Gas samples.

  6. 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

  7. Measurement of trimethylamine-N-oxide by stable isotope dilution liquid chromatography tandem mass spectrometry

    PubMed Central

    Wang, Zeneng; Levison, Bruce S.; Hazen, Jennie E.; Donahue, Lillian; Li, Xin-Min; Hazen, Stanley L.

    2014-01-01

    Trimethylamine-N-oxide (TMAO) levels in blood predict future risk for major adverse cardiac events including myocardial infarction, stroke and death. Thus, the rapid determination of circulating TMAO concentration is of clinical interest. Here we report a method to measure TMAO in biological matrices by stable isotope dilution liquid chromatography tandem mass spectrometry (LC/MS/MS) with lower and upper limits of quantification of 0.05 and >200 M, respectively. Spike and recovery studies demonstrate an accuracy at low (0.5 M), mid (5 M) and high (100 M) levels of 98.2%, 97.3% and 101.6%, respectively. Additional assay performance metrics include intra-day and inter-day coefficients of variance of < 6.4% and < 9.9%, respectively, across the range of TMAO levels. Stability studies reveal TMAO in plasma is stable both during storage at ?80 C for 5 years and to multiple freeze thaw cycles. Fasting plasma normal range studies among apparently healthy subjects (n=349) shows a range of 0.73 126 M, median (interquartile range) levels of 3.45 (2.255.79) M, and increasing values with age. The LC/MS/MS based assay reported should be of value for further studies evaluating TMAO as a risk marker and for examining the effect of dietary, pharmacologic and environmental factors on TMAO levels. PMID:24704102

  8. Quantitation of Thioprolines in Grape Wine by Isotope Dilution-Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Liu, Jingjing; Meng, Xiangpeng; Chan, Wan

    2016-02-17

    Cysteine reacts with reactive carbonyls to form thioprolines, which have been demonstrated to possess various pharmaceutical properties. Therefore, thioproline formation is considered as a major detoxification pathway for carcinogenic reactive carbonyls. In this study, we report the initial identification of thiazolidine-4-carboxylic acid (1) and 2-methylthiazolidine-4-carboxylic acid (2), two very common thioprolines, formed by reacting formaldehyde and acetaldehyde with cysteine in grape wine samples. We have developed an isotope dilution-liquid chromatography-tandem mass spectrometry method featuring high sensitivity (limit of detection of ?1.5 ng/mL) and selectivity to quantitate compounds 1 and 2. The method after validated to be highly accurate (recovery of ?92%) and precise [intraday relative standard deviation (RSD) of ?4.1% and interday RSD of ?9.7%] was applied to determine the varying compound 1 and 2 contents in grape wine samples. Results revealed the grape type and storage duration-dependent formation of thioprolines in grape wines. Overall, the results are expected to facilitate compound-dependent investigations of the health benefits of grape wine, and our findings could be adopted to predict the age of grape wine. PMID:26806197

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

    PubMed

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

    2011-06-01

    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-[(13)C(20)]-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

  10. Measurement of trimethylamine-N-oxide by stable isotope dilution liquid chromatography tandem mass spectrometry.

    PubMed

    Wang, Zeneng; Levison, Bruce S; Hazen, Jennie E; Donahue, Lillian; Li, Xin-Min; Hazen, Stanley L

    2014-06-15

    Trimethylamine-N-oxide (TMAO) levels in blood predict future risk for major adverse cardiac events including myocardial infarction, stroke, and death. Thus, the rapid determination of circulating TMAO concentration is of clinical interest. Here we report a method to measure TMAO in biological matrices by stable isotope dilution liquid chromatography tandem mass spectrometry (LC/MS/MS) with lower and upper limits of quantification of 0.05 and >200?M, respectively. Spike and recovery studies demonstrate an accuracy at low (0.5?M), mid (5?M), and high (100?M) levels of 98.2, 97.3, and 101.6%, respectively. Additional assay performance metrics include intraday and interday coefficients of variance of <6.4 and <9.9%, respectively, across the range of TMAO levels. Stability studies reveal that TMAO in plasma is stable both during storage at -80C for 5years and to multiple freeze thaw cycles. Fasting plasma normal range studies among apparently healthy subjects (n=349) show a range of 0.73-126?M, median (interquartile range) levels of 3.45 (2.25-5.79)?M, and increasing values with age. The LC/MS/MS-based assay reported should be of value for further studies evaluating TMAO as a risk marker and for examining the effect of dietary, pharmacologic, and environmental factors on TMAO levels. PMID:24704102

  11. Chemical and isotopic measurements of micrometeoroids by secondary ion mass spectrometry (A0187-2)

    NASA Technical Reports Server (NTRS)

    Foote, J. H.; Swan, P. D.; Walker, R. M.; Zinner, E. K.; Bahr, D.; Fechtig, H.; Jessberger, E.; Igenbergs, E.; Kreitmayr, U.; Kuczera, H.

    1984-01-01

    The objective of this experiment is to measure the chemical and isotopic composition of interplanetary dust particles of mass greater than 10 to the minus 10 power G for most of thermator elements expected to be present.

  12. PALOMA : an isotope analyzer using static mass spectrometry, coupled with cryogenic and chemical trapping, for the MSL mission to Mars

    NASA Astrophysics Data System (ADS)

    Chassefiere, E.; Jambon, A.; Berthelier, J.-J.; Goulpeau, G.; Leblanc, F.; Montmessin, F.; Sarda, P.; Agrinier, P.; Fouchet, T.; Waite, H.

    The technique of GCMS analysis has to be completed by static mass spectrometry for precise in-situ measurements of the isotopic composition of planetary atmospheres (noble gases, stable isotopes), and volatile outgassed products from solid sample pyrolysis. Static mass spectrometry, coupled with gas separation by cryo-separation and gettering, is commonly used in the laboratory to study volatiles extracted from terrestrial and meteoritic samples. Such an instrument (PALOMA) is presently developed in our laboratories, and it will be coupled with a Pyr-GCMS analyzer (MACE), built by a US consortium of science laboratories and industrials (University of Michigan, Southwest Research Institute, JPL, Ball Aerospace). The MACE/PALOMA experiment will be proposed on the NASA Mars Science Laboratory mission, planned to be launched in 2009. The scientific objectives of PALOMA, coupled with MACE, may be listed as follows : (i) search for isotopic signatures of past life in atmosphere, rock, dust and ice samples, with emphasis on carbon, nitrogen and hydrogen; (ii) accurately measure isotopic composition of atmospheric noble gases, and stable isotopes, in order to better constrain past escape, surface interaction, outgassing history and climate evolution; (iii) precisely measure diurnal/ seasonal variations of isotopic ratios of H2O, CO2, and N2, for improving our understanding of present and past climate, and of the role of water cycle. Main measurement objectives are : (i) C, H, O, N isotopic composition in both organic evolved samples (provided by MACE pyrolysis system) and atmosphere with high accuracy (a few per mil at 1-s level); (ii) noble gas (He, Ne, Ar, Kr, Xe) and stable (C, H, O, N) isotope composition in atmosphere with high accuracy (a few per mil at 1-s level); (iii) molecular and isotopic composition of inorganic evolved samples (salts, hydrates, nitrates, {ldots}), including ices; (iv) diurnal and seasonal monitoring of D/H in water vapor, and water ice.

  13. Cd Isotopic Composition Measured by Plasma Source Mass Spectrometry on Natural and Anthropogenic Materials. A Preliminary Outline of Cd Isotope Systematics

    NASA Astrophysics Data System (ADS)

    Innocent, C.

    2004-05-01

    Cadmium is a trace metal that is used as a geochemical tracer of natural processes, like biological productivity and paleoproductivity, and also of anthropogenic pollution, as Cd is known to be a toxic heavy metal that has become a major environmental and health concern. For these purposes, an outstanding issue is to determine whether Cd, like a number of metallic elements (e.g. Fe, Cu, Zn, Mo, Tl), may display variable isotopic compositions in natural and/or industrial compounds. It is known that Cd may display variable isotopic composition. Indeed, isotopic fractionation processes have been documented in some meteorites and in lunar soils. Consequently, due to its relatively low boiling point (767\\deg C) and also to the large mass range covered by its isotopes (10 mass units), Cd might fractionate isotopically, for example during the outpouring of acidic volcanic magmas and/or the emplacement of granitoids. On another hand, isotopic fractionation could also occur during human activities like refuse incineration or industrial manufacturing, for instance. Finally, biologically-induced isotopic fractionation should not be ruled out, as it is clearly evidenced for other metals, like Fe. A high precision method has been developed for determining the isotopic composition of Cd by plasma source mass spectrometry (Neptune). This method holds on the standard-bracketing technique, owing to the availability of Cd solutions of known isotopic composition provided by the University of M\\H{u}nster. This allows to correct precisely for mass fractionation that occurs in the plasma source mass spectrometer. It is also critical for the analysis to be possible to work with Cd solutions of very high purity. Chemical isolation of Cd involves 3 steps, and may be also suitable for Cd isotopic measurements using solid source mass spectrometry. Preliminary results suggest that Cd is likely to fractionate during smelting activities, as indicated by measurements on mining waste. The calibration of a 110Cd-116Cd double spike is underway for absolute, true isotopic ratios to be derived. The double spike technique allows the isotopic analysis of Cd using a plasma source, but also a solid source mass spectrometer, as Cd ionizes efficiently in such mass spectrometers owing to the standard silicagel technique.

  14. Determination of serum levels of unesterified lathosterol by isotope dilution-mass spectrometry.

    PubMed

    Lund, E; Sisfontes, L; Reihner, E; Bjorkhem, I

    1989-04-01

    The synthesis of 2H3-labelled lathosterol is described. This compound was used together with 2H7-labelled cholesterol for simultaneous assay of unesterified lathosterol and cholesterol in serum by isotope dilution-mass spectrometry. After addition of a fixed amount of the two internal standards to a fixed amount of serum (in general 25 microliter), the steroids were extracted with chloroform and subjected to Lipidex 5000 chromatography. The fraction containing cholesterol and lathosterol was converted into trimethylsilyl ether and subjected to mass spectrometric analysis with selected monitoring of the ions at m/z 458 (molecular ion of the trimethylsilyl ether derivative of unlabelled cholesterol and lathosterol), m/z 461 (molecular ion of derivative of 2H3-labelled lathosterol) and m/z 465 (molecular ion of derivative of 2H7-labelled cholesterol). Individual standard curves were used for assay of each steroid. Under the conditions employed, the coefficient of variation of the two assays was less than 6%. In different recovery experiments the maximal difference between expected and found values was less than 7%. Using a less accurate method for analysis of lathosterol, we have shown previously that there is a high correlation between the hepatic HMG CoA reductase and the relative concentration of unesterified lathosterol in serum (concentration of lathosterol relative to cholesterol). This was confirmed with the present method and a correlation coefficient of about 0.94 was found between the two parameters. It is concluded that the present method may be suitable for detection of cases with accelerated rate of synthesis of cholesterol. PMID:2520369

  15. Non-selective photoionization for isotope ratio measurements by time of flight mass spectrometry with laser ablation

    NASA Astrophysics Data System (ADS)

    Vors, E.; Semerok, A.; Wagner, J.-F.; Fomichev, S. V.

    2000-12-01

    Isotope ratio measurements of metallic uranium samples were carried out by linear TOF mass spectrometry in combination with laser ablation. To eliminate the problems resulting from laser plasma ion energy and spatial dispersions, the uranium atoms were post-ionized by the third harmonic of a Nd-YAG laser. Experimental and theoretical results of the LA-TOF performance and non-selective photoionization of uranium atoms produced by laser ablation are presented.

  16. Experimental evaluation of the measurement of isotope ratios by time of flight mass spectrometry with laser ablation

    NASA Astrophysics Data System (ADS)

    Vors, E.; Semerok, A.; Wagner, J.-F.

    Time of flight mass spectrometry (TOF-MS) in combination with laser ablation (LA) applied for low isotope composition measurements is limited by energy and spatial dispersion of ions, spatial charge density, and some other factors. In order to reduce these factors that make the extraction of the plasma ions difficult, we used a second laser to create ions by non-isotope-selective photoionization of neutral particles. The photoionization was carried out in uranium vapor beam by the third harmonic of a pulsed Nd:YAG laser. This work presents the results of tentative experiments to estimate the characteristics of the LA-TOF-MS method with non-selective photoionization.

  17. In-Gel Stable-Isotope Labeling (ISIL): a strategy for mass spectrometry-based relative quantification.

    PubMed

    Asara, John M; Zhang, Xiang; Zheng, Bin; Christofk, Heather H; Wu, Ning; Cantley, Lewis C

    2006-01-01

    Most proteomics approaches for relative quantification of protein expression use a combination of stable-isotope labeling and mass spectrometry. Traditionally, researchers have used difference gel electrophoresis (DIGE) from stained 1D and 2D gels for relative quantification. While differences in protein staining intensity can often be visualized, abundant proteins can obscure less abundant proteins, and quantification of post-translational modifications is difficult. A method is presented for quantifying changes in the abundance of a specific protein or changes in specific modifications of a protein using In-gel Stable-Isotope Labeling (ISIL). Proteins extracted from any source (tissue, cell line, immunoprecipitate, etc.), treated under two experimental conditions, are resolved in separate lanes by gel electrophoresis. The regions of interest (visualized by staining) are reacted separately with light versus heavy isotope-labeled reagents, and the gel slices are then mixed and digested with proteases. The resulting peptides are then analyzed by LC-MS to determine relative abundance of light/heavy isotope pairs and analyzed by LC-MS/MS for identification of sequence and modifications. The strategy compares well with other relative quantification strategies, and in silico calculations reveal its effectiveness as a global relative quantification strategy. An advantage of ISIL is that visualization of gel differences can be used as a first quantification step followed by accurate and sensitive protein level stable-isotope labeling and mass spectrometry-based relative quantification. PMID:16396506

  18. Discovering Mercury Protein Modifications in Whole Proteomes Using Natural Isotope Distributions Observed in Liquid Chromatography-Tandem Mass Spectrometry

    SciTech Connect

    Polacco, Benjamin J.; Purvine, Samuel O.; Zink, Erika M.; LaVoie, Stephen P.; Lipton, Mary S.; Summers, Anne O.; Miller, Susan M.

    2011-08-01

    The identification of peptides that result from post-translational modifications is critical for understanding normal pathways of cellular regulation as well as identifying damage from, or exposures to xenobiotics, i.e. the exposome. However, because of their low abundance in proteomes, effective detection of modified peptides by mass spectrometry (MS) typically requires enrichment to eliminate false identifications. We present a new method for confidently identifying peptides with mercury (Hg)-containing adducts that is based on the influence of mercury’s seven stable isotopes on peptide isotope distributions detected by high-resolution MS. Using a pure protein and E. coli cultures exposed to phenyl mercuric acetate, we show the pattern of peak heights in isotope distributions from primary MS single scans efficiently identified Hg adducts in data from chromatographic separation coupled with tandem mass spectrometry with sensitivity and specificity greater than 90%. Isotope distributions are independent of peptide identifications based on peptide fragmentation (e.g. by SEQUEST), so both methods can be combined to eliminate false positives. Summing peptide isotope distributions across multiple scans improved specificity to 99.4% and sensitivity above 95%, affording identification of an unexpected Hg modification. We also illustrate the theoretical applicability of the method for detection of several less common elements including the essential element, selenium, as selenocysteine in peptides.

  19. Simultaneous Determination of Selected B Vitamins in the NIST SRM 3280 Multivitamin/Multielement Tablets by Liquid Chromatography Isotope Dilution Mass Spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is increased interest in accurately assessing the total dietary intake of vitamins from all sources, including foods and dietary supplements. Isotope dilution mass spectrometry (IDMS) can be a definitive analytical method for very accurate concentration determinations. A liquid chromatographic...

  20. Stable isotope liquid chromatography-tandem mass spectrometry assay for fatty acid amide hydrolase activity.

    PubMed

    Rakers, Christin; Zoerner, Alexander A; Engeli, Stefan; Batkai, Sandor; Jordan, Jens; Tsikas, Dimitrios

    2012-02-15

    Fatty acid amide hydrolase (FAAH) is the main enzyme responsible for the hydrolysis of the endocannabinoid anandamide (arachidonoyl ethanolamide, AEA) to arachidonic acid (AA) and ethanolamine (EA). Published FAAH activity assays mostly employ radiolabeled anandamide or synthetic fluorogenic substrates. We report a stable isotope liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for specific, sensitive, and high-throughput capable FAAH activity measurements. The assay uses AEA labeled with deuterium on the EA moiety (d₄-AEA) as substrate and measures the specific reaction product tetradeutero-EA (d₄-EA) and the internal standard ¹³C₂-EA. Selected reaction monitoring of m/z 66→m/z 48 (d₄-EA) and m/z 64→m/z 46 (¹³C₂-EA) in the positive electrospray ionization mode after liquid chromatographic separation on a HILIC (hydrophilic interaction liquid chromatography) column is performed. The assay was developed and thoroughly validated using recombinant human FAAH (rhFAAH) and then was applied to human blood and dog liver samples. rhFAAH-catalyzed d₄-AEA hydrolysis obeyed Michaelis-Menten kinetics (K(M)=12.3 μM, V(max)=27.6 nmol/min mg). Oleoyl oxazolopyridine (oloxa) was a potent, partial noncompetitive inhibitor of rhFAAH (IC₅₀=24.3 nM). Substrate specificity of other fatty acid ethanolamides decreased with decreasing length, number of double bonds, and lipophilicity of the fatty acid skeleton. In human whole blood, we detected FAAH activity that was inhibited by oloxa. PMID:22146559

  1. Carbon isotope ratio mass spectrometry for detection of endogenous steroid use: a testing strategy.

    PubMed

    Ahrens, Brian D; Butch, Anthony W

    2013-07-01

    Isotope ratio mass spectrometry (IRMS) testing is performed to determine if an atypical steroid profile is due to administration of an endogenous steroid. Androsterone (Andro) and etiocholanolone (Etio), and/or the androstanediols (5α- and 5β-androstane-3α,17β-diol) are typically analyzed by IRMS to determine the (13) C/(12) C ratio. The ratios of these target compounds are compared to the (13) C/(12) C ratio of an endogenous reference compound (ERC) such as 5β-pregnane-3α,20α-diol (Pdiol). Concentrations of Andro and Etio are high so (13) C/(12) C ratios can easily be measured in most urine samples. Despite the potentially improved sensitivity of the androstanediols for detecting the use of some testosterone formulations, additional processing steps are often required that increase labour costs and turnaround times. Since this can be problematic when performing large numbers of IRMS measurements, we established thresholds for Andro and Etio that can be used to determine the need for additional androstanediol testing. Using these criteria, 105 out of 2639 urine samples exceeded the Andro and/or Etio thresholds, with 52 of these samples being positive based on Andro and Etio IRMS testing alone. The remaining 53 urine samples had androstanediol IRMS testing performed and 3 samples were positive based on the androstanediol results. A similar strategy was used to establish a threshold for Pdiol to identify athletes with relatively (13) C-depleted values so that an alternative ERC can be used to confirm or establish a true endogenous reference value. Adoption of a similar strategy by other laboratories can significantly reduce IRMS sample processing and analysis times, thereby increasing testing capacity. PMID:23303562

  2. Quantitative analysis of prostate specific antigen isoforms using immunoprecipitation and stable isotope labeling mass spectrometry.

    PubMed

    Chen, Yi-Ting; Tuan, Li-Ping; Chen, Hsiao-Wei; Wei, I-An; Chou, Min-Yuan; Chen, Han-Min; Tyan, Yu-Chang; Chen, Sung-Fang

    2015-01-01

    Prostate specific antigen (PSA) is a widely used serum marker for prostate cancer (PCa), but has limited specificity for distinguishing early PCa from benign prostatic hyperplasia (BPH). Recently, proPSAs, comprised of native proPSA, as well as truncated proPSA forms, [-2] proPSA, [-5] proPSA, and [-7] proPSA, have been shown to be better diagnostic targets than PSA for PCa. Stable isotope labeling-multiple reaction monitoring mass spectrometry (SIL/MRM-MS) has been frequently used to measure low-abundance biomarkers in tissues and biofluids, owing to its high sensitivity and specificity, simplicity, and multiplexing capability. In this study, we have developed and optimized a strategy using immunoprecipitation in conjunction with SIL/MRM-MS assay which is capable of sensitive and accurate quantification of proPSA in serum. Since serum and plasma are by far the most complex biological fluids, the immunoprecipitation workflow was optimized to achieve sufficient sensitivity, efficiencies of protein purification with immunoaffinity depletion were determined. The developed strategy can detect proPSA and PSA with a limit of detection (LOD) and limit of quantitation (LOQ) at nanogram per milliliter levels, corresponding to a concentration 6 orders-of-magnitude lower than the most abundant serum proteins. Furthermore, the simultaneous measurement of multiple biomarkers, including the mature and precursor forms of PSA, can be achieved in a single multiplexed analysis using LC/MRM-MS. The strategy demonstrated here provides an attractive alternative to ELISAs or RIAs for the reliably measurement of proPSA to improve the specificity of PCa diagnosis. PMID:25427836

  3. Dansylation isotope labeling liquid chromatography mass spectrometry for parallel profiling of human urinary and fecal submetabolomes.

    PubMed

    Su, Xiaoling; Wang, Nan; Chen, Deying; Li, Yunong; Lu, Yingfeng; Huan, Tao; Xu, Wei; Li, Liang; Li, Lanjuan

    2016-01-15

    Human urine and feces can be non-invasively collected for metabolomics-based disease biomarker discovery research. Because urinary and fecal metabolomes are thought to be different, analysis of both biospecimens may generate a more comprehensive metabolomic profile that can be better related to the health state of an individual. Herein we describe a method of using differential chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS) for parallel metabolomic profiling of urine and feces. Dansylation labeling was used to quantify the amine/phenol submetabolome changes among different samples based on (12)C-labeling of individual samples and (13)C-labeling of a pooled urine or pooled feces and subsequent analysis of the (13)C-/(12)C-labeled mixture by LC-MS. The pooled urine and pooled feces are further differentially labeled, mixed and then analyzed by LC-MS in order to relate the metabolite concentrations of the common metabolites found in both biospecimens. This method offers a means of direct comparison of urinary and fecal submetabolomes. We evaluated the analytical performance and demonstrated the utility of this method in the analysis of urine and feces collected daily from three healthy individuals for 7 days. On average, 2534113 (n=126) peak pairs or metabolites could be detected from a urine sample, while 250777 (n=63) peak pairs were detected from a fecal sample. In total, 5372 unique peak pairs were detected from all the samples combined; 3089 and 3012 pairs were found in urine and feces, respectively. These results reveal that the urine and fecal metabolomes are very different, thereby justifying the consideration of using both biospecimens to increase the probability of finding specific biomarkers of diseases. Furthermore, the CIL LC-MS method described can be used to perform parallel quantitative analysis of urine and feces, resulting in more complete coverage of the human metabolome. PMID:26709303

  4. Cellular lipid extraction for targeted stable isotope dilution liquid chromatography-mass spectrometry analysis.

    PubMed

    Gelhaus, Stacy L; Mesaros, A Clementina; Blair, Ian A

    2011-01-01

    The metabolism of fatty acids, such as arachidonic acid (AA) and linoleic acid (LA), results in the formation of oxidized bioactive lipids, including numerous stereoisomers(1,2). These metabolites can be formed from free or esterified fatty acids. Many of these oxidized metabolites have biological activity and have been implicated in various diseases including cardiovascular and neurodegenerative diseases, asthma, and cancer(3-7). Oxidized bioactive lipids can be formed enzymatically or by reactive oxygen species (ROS). Enzymes that metabolize fatty acids include cyclooxygenase (COX), lipoxygenase (LO), and cytochromes P450 (CYPs)(1,8). Enzymatic metabolism results in enantioselective formation whereas ROS oxidation results in the racemic formation of products. While this protocol focuses primarily on the analysis of AA- and some LA-derived bioactive metabolites; it could be easily applied to metabolites of other fatty acids. Bioactive lipids are extracted from cell lysate or media using liquid-liquid (l-l) extraction. At the beginning of the l-l extraction process, stable isotope internal standards are added to account for errors during sample preparation. Stable isotope dilution (SID) also accounts for any differences, such as ion suppression, that metabolites may experience during the mass spectrometry (MS) analysis(9). After the extraction, derivatization with an electron capture (EC) reagent, pentafluorylbenzyl bromide (PFB) is employed to increase detection sensitivity(10,11). Multiple reaction monitoring (MRM) is used to increase the selectivity of the MS analysis. Before MS analysis, lipids are separated using chiral normal phase high performance liquid chromatography (HPLC). The HPLC conditions are optimized to separate the enantiomers and various stereoisomers of the monitored lipids(12). This specific LC-MS method monitors prostaglandins (PGs), isoprostanes (isoPs), hydroxyeicosatetraenoic acids (HETEs), hydroxyoctadecadienoic acids (HODEs), oxoeicosatetraenoic acids (oxoETEs) and oxooctadecadienoic acids (oxoODEs); however, the HPLC and MS parameters can be optimized to include any fatty acid metabolites(13). Most of the currently available bioanalytical methods do not take into account the separate quantification of enantiomers. This is extremely important when trying to deduce whether or not the metabolites were formed enzymatically or by ROS. Additionally, the ratios of the enantiomers may provide evidence for a specific enzymatic pathway of formation. The use of SID allows for accurate quantification of metabolites and accounts for any sample loss during preparation as well as the differences experienced during ionization. Using the PFB electron capture reagent increases the sensitivity of detection by two orders of magnitude over conventional APCI methods. Overall, this method, SID-LC-EC-atmospheric pressure chemical ionization APCI-MRM/MS, is one of the most sensitive, selective, and accurate methods of quantification for bioactive lipids. PMID:22127066

  5. Caution on the use of liquid nitrogen traps in stable hydrogen isotope-ratio mass spectrometry

    USGS Publications Warehouse

    Coplen, Tyler B.; Qi, Haiping

    2010-01-01

    An anomalous stable hydrogen isotopic fractionation of 4 ‰ in gaseous hydrogen has been correlated with the process of adding liquid nitrogen (LN2) to top off the dewar of a stainless-steel water trap on a gaseous hydrogen-water platinum equilibration system. Although the cause of this isotopic fractionation is unknown, its effect can be mitigated by (1) increasing the capacity of any dewars so that they do not need to be filled during a daily analytic run, (2) interspersing isotopic reference waters among unknowns, and (3) applying a linear drift correction and linear normalization to isotopic results with a program such as Laboratory Information Management System (LIMS) for Light Stable Isotopes. With adoption of the above guidelines, measurement uncertainty can be substantially improved. For example, the long-term (months to years) δ2H reproducibility (1& sigma; standard deviation) of nine local isotopic reference waters analyzed daily improved substantially from about 1‰ to 0.58 ‰. This isotopically fractionating mechanism might affect other isotope-ratio mass spectrometers in which LN2 is used as a moisture trap for gaseous hydrogen

  6. Caution on the use of liquid nitrogen traps in stable hydrogen isotope-ratio mass spectrometry

    USGS Publications Warehouse

    Coplen, T.B.; Qi, H.

    2010-01-01

    An anomalous stable hydrogen isotopic fractionation of 4 ??? in gaseous hydrogen has been correlated with the process of adding liquid nitrogen (LN2) to top off the dewar of a stainless-steel water trap on a gaseous hydrogen-water platinum equilibration system. Although the cause of this isotopic fractionation is unknown, its effect can be mitigated by (1) increasing the capacity of any dewars so that they do not need to be filled during a daily analytic run, (2) interspersing isotopic reference waters among unknowns, and (3) applying a linear drift correction and linear normalization to isotopic results with a program such as Laboratory Information Management System (LIMS) for Light Stable Isotopes. With adoption of the above guidelines, measurement uncertainty can be substantially improved. For example, the long-term (months to years) ??2H reproducibility (1?? standard deviation) of nine local isotopic reference waters analyzed daily improved substantially from about 1 ??? to 0.58 ???. This isotopically fractionating mechanism might affect other isotope-ratio mass spectrometers in which LN2 is used as a moisture trap for gaseous hydrogen. ?? This article not subject to U.S. Copyright. Published 2010 by the American Chemical Society.

  7. DETERMINATION OF 237NP AND PU ISOTOPES IN LARGE SOIL SAMPLES BY INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

    SciTech Connect

    Maxwell, S.

    2010-07-26

    A new method for the determination of {sup 237}Np and Pu isotopes in large soil samples has been developed that provides enhanced uranium removal to facilitate assay by inductively coupled plasma mass spectrometry (ICP-MS). This method allows rapid preconcentration and separation of plutonium and neptunium in large soil samples for the measurement of {sup 237}Np and Pu isotopes by ICP-MS. {sup 238}U can interfere with {sup 239}Pu measurement by ICP-MS as {sup 238}UH{sup +} mass overlap and {sup 237}Np via {sup 238}U peak tailing. The method provides enhanced removal of uranium by separating Pu and Np initially on TEVA Resin, then transferring Pu to DGA resin for additional purification. The decontamination factor for removal of uranium from plutonium for this method is greater than 1 x 10{sup 6}. Alpha spectrometry can also be applied so that the shorter-lived {sup 238}Pu isotope can be measured successfully. {sup 239}Pu, {sup 242}Pu and {sup 237}Np were measured by ICP-MS, while {sup 236}Pu and {sup 238}Pu were measured by alpha spectrometry.

  8. Determination of 237Np and Pu isotopes in large soil samples by inductively coupled plasma mass spectrometry.

    PubMed

    Maxwell, Sherrod L; Culligan, Brian K; Jones, Vernon D; Nichols, Sheldon T; Bernard, Maureen A; Noyes, Gary W

    2010-12-01

    A new method for the determination of (237)Np and Pu isotopes in large soil samples has been developed that provides enhanced uranium removal to facilitate assay by inductively coupled plasma mass spectrometry (ICP-MS). This method allows rapid preconcentration and separation of plutonium and neptunium in large soil samples for the measurement of (237)Np and Pu isotopes by ICP-MS. (238)U can interfere with (239)Pu measurement by ICP-MS as (238)UH(+) mass overlap and (237)Np via (238)U peak tailing. The method provides enhanced removal of uranium by separating Pu and Np initially on TEVA Resin, then transferring Pu to DGA resin for additional purification. The decontamination factor for removal of uranium from plutonium for this method is greater than 1×10(6). Alpha spectrometry can also be applied so that the shorter-lived (238)Pu isotope can be measured successfully. (239) Pu, (242)Pu and (237)Np were measured by ICP-MS, while (236)Pu and (238)Pu were measured by alpha spectrometry. PMID:21056724

  9. Natural variations of Se isotopic composition determined by hydride generation multiple collector inductively coupled plasma mass spectrometry

    NASA Astrophysics Data System (ADS)

    Rouxel, Olivier; Ludden, John; Carignan, Jean; Marin, Luc; Fouquet, Yves

    2002-09-01

    Multiple-collector inductively coupled plasma mass spectrometry has been used for the precise measurement of the isotopic composition of Se in geological samples. Se is chemically purified before analysis by using cotton impregnated with thioglycollic acid. This preconcentration step is required for the removal of matrix-interfering elements for hydride generation, such as transitional metals, and also for the quantitative separation of other hydride-forming elements, such as Ge, Sb, and As. The analyte is introduced in the plasma torch with a continuous-flow hydride generation system. Instrumental mass fractionation is corrected with a "standard-sample bracketing" approach. By use of this new technique, the minimum Se required per analysis is lowered to 10 ng, which is one order of magnitude less than the amount needed for the N-TIMS technique. The estimated external precision calculated for the 82Se/ 76Se isotope ratio is 0.25 (2?), and the data are reported as delta notation () relative to our internal standard (MERCK elemental standard solution). Measurements of Se isotopes are presented for samples of standard solutions and geological reference materials, such as silicate rocks, soils, and sediments. The Se isotopic composition of selected terrestrial and extraterrestrial materials are also presented. An overall Se isotope variation of 8 has been observed, suggesting that Se isotopes fractionate readily and are extremely useful tracers of natural processes.

  10. Determination of Polychlorinated Biphenyls in Solid Samples by Isotope Dilution Mass Spectrometry Using ?Cl-Labeled Analogues.

    PubMed

    Somoano-Blanco, Lourdes; Rodriguez-Gonzalez, Pablo; Garca Fonseca, Sergio; Alonso, J Ignacio Garcia

    2015-08-01

    This work describes the first application of (37)Cl-labeled compounds to isotope dilution mass spectrometry (IDMS). The synthesis of 12 (37)Cl-labeled polychlorinated biphenyls (PCBs) was carried out by the chlorination of biphenyl with isotopically enriched chlorine gas, generated by the direct oxidation of Na(37)Cl with potassium peroxymonosulfate. After an exhaustive purification due to the presence of other congeners, the concentration and the isotopic enrichment of all (37)Cl-labeled PCBs in the mixture was determined. The proposed procedure allows the simultaneous quantification of every isotope diluted PCB congener in a single gas chromatography-tandem mass spectrometry (GC-MS/MS) injection without resorting to a methodological calibration graph. The results obtained here demonstrate that the use of (37)Cl-labeled analogues provides results in agreement with the certified values of three different Certified Reference Materials (marine sediment SRM 1944, fish tissue 1947, and loamy soil CRM 962-50) and analytical figures of merit comparable to those obtained using regular IDMS procedures based on the use of commercially available (13)C-labeled analogues. PMID:26165349

  11. Production of highly-enriched 134Ba for a reference material for isotope dilution mass spectrometry measurements

    SciTech Connect

    Horkley, J. J.; Carney, K. P.; Gantz, E. M.; Davies, J. E.; Lewis, R. R.; Crow, J. P.; Poole, C. A.; Grimes, T. S.; Giglio, J. J.

    2015-03-17

    Isotope dilution mass spectrometry (IDMS) is an analytical technique capable of providing accurate and precise quantitation of trace isotope abundance and assay providing measurement uncertainties below 1 %. To achieve these low uncertainties, the IDMS method ideally utilizes chemically pure spike solutions that consist of a single highly enriched isotope that is well-characterized relating to the abundance of companion isotopes and concentration in solution. To address a current demand for accurate 137Cs/137Ba ratio measurements for age determination of radioactive 137Cs sources, Idaho National Laboratory (INL) is producing enriched 134Ba isotopes that are tobe used for IDMS spikes to accurately determine 137Ba accumulation from the decay of 137Cs. The final objective of this work it to provide a homogenous set of reference materials that the National Institute of Standards and Technology can certify as standard reference materials used for IDMS. The process that was developed at INL for the separation and isolation of Ba isotopes, chemical purification of the isotopes in solution, and the encapsulation of the materials will be described.

  12. Production of highly-enriched 134Ba for a reference material for isotope dilution mass spectrometry measurements

    DOE PAGESBeta

    Horkley, J. J.; Carney, K. P.; Gantz, E. M.; Davies, J. E.; Lewis, R. R.; Crow, J. P.; Poole, C. A.; Grimes, T. S.; Giglio, J. J.

    2015-03-17

    Isotope dilution mass spectrometry (IDMS) is an analytical technique capable of providing accurate and precise quantitation of trace isotope abundance and assay providing measurement uncertainties below 1 %. To achieve these low uncertainties, the IDMS method ideally utilizes chemically pure “spike” solutions that consist of a single highly enriched isotope that is well-characterized relating to the abundance of companion isotopes and concentration in solution. To address a current demand for accurate 137Cs/137Ba ratio measurements for “age” determination of radioactive 137Cs sources, Idaho National Laboratory (INL) is producing enriched 134Ba isotopes that are tobe used for IDMS spikes to accurately determinemore » 137Ba accumulation from the decay of 137Cs. The final objective of this work it to provide a homogenous set of reference materials that the National Institute of Standards and Technology can certify as standard reference materials used for IDMS. The process that was developed at INL for the separation and isolation of Ba isotopes, chemical purification of the isotopes in solution, and the encapsulation of the materials will be described.« less

  13. Production of highly-enriched 134Ba for a reference material for isotope dilution mass spectrometry measurements

    SciTech Connect

    Horkley, J. J.; Carney, K. P.; Gantz, E. M.; Davies, J. E.; Lewis, R. R.; Crow, J. P.; Poole, C. A.; Grimes, T. S.; Giglio, J. J.

    2015-03-17

    Isotope dilution mass spectrometry (IDMS) is an analytical technique capable of providing accurate and precise quantitation of trace isotope abundance and assay providing measurement uncertainties below 1 %. To achieve these low uncertainties, the IDMS method ideally utilizes chemically pure “spike” solutions that consist of a single highly enriched isotope that is well-characterized relating to the abundance of companion isotopes and concentration in solution. To address a current demand for accurate 137Cs/137Ba ratio measurements for “age” determination of radioactive 137Cs sources, Idaho National Laboratory (INL) is producing enriched 134Ba isotopes that are tobe used for IDMS spikes to accurately determine 137Ba accumulation from the decay of 137Cs. The final objective of this work it to provide a homogenous set of reference materials that the National Institute of Standards and Technology can certify as standard reference materials used for IDMS. The process that was developed at INL for the separation and isolation of Ba isotopes, chemical purification of the isotopes in solution, and the encapsulation of the materials will be described.

  14. Production of highly-enriched 134Ba for a reference material for isotope dilution mass spectrometry measurements

    SciTech Connect

    J.J. Horkley; K.P E.M. Gantz; J.E. Davis; R.R. Lewis; J.P. Crow; C.A. Poole; T.S. Grimes; J.J. Giglio

    2015-03-01

    t Isotope dilution mass spectrometry (IDMS) is an analytical technique capable of providing accurate and precise quantitation of trace isotope abundance and assay providing measurement uncertainties below 1 %. To achieve these low uncertainties, the IDMS method ideally utilizes chemically pure ‘‘spike’’ solutions that consist of a single highly enriched isotope that is well-characterized relating to the abundance of companion isotopes and concentration in solution. To address a current demand for accurate 137Cs/137Ba ratio measurements for ‘‘age’’ determination of radioactive 137Cs sources, Idaho National Laboratory (INL) is producing enriched 134Ba isotopes that are tobe used for IDMS spikes to accurately determine 137Ba accumulation from the decay of 137Cs. The final objective of this work it to provide a homogenous set of reference materials that the National Institute of Standards and Technology can certify as standard reference materials used for IDMS. The process that was developed at INL for the separation and isolation of Ba isotopes, chemical purification of the isotopes in solution,

  15. Discrepancies between isotope ratio infrared spectroscopy and isotope ratio mass spectrometry for the stable isotope analysis of plant and soil waters.

    PubMed

    West, Adam G; Goldsmith, Gregory R; Brooks, Paul D; Dawson, Todd E

    2010-07-30

    The use of isotope ratio infrared spectroscopy (IRIS) for the stable hydrogen and oxygen isotope analysis of water is increasing. While IRIS has many advantages over traditional isotope ratio mass spectrometry (IRMS), it may also be prone to errors that do not impact upon IRMS analyses. Of particular concern is the potential for contaminants in the water sample to interfere with the spectroscopy, thus leading to erroneous stable isotope data. Water extracted from plant and soil samples may often contain organic contaminants. The extent to which contaminants may interfere with IRIS and thus impact upon data quality is presently unknown. We tested the performance of IRIS relative to IRMS for water extracted from 11 plant species and one organic soil horizon. IRIS deviated considerably from IRMS for over half of the samples tested, with deviations as large as 46 per thousand (delta(2)H) and 15.4 per thousand (delta(18)O) being measured. This effect was reduced somewhat by using activated charcoal to remove organics from the water; however, deviations as large as 35 per thousand (delta(2)H) and 11.8 per thousand (delta(18)O) were still measured for these cleaned samples. Interestingly, the use of activated charcoal to clean water samples had less effect than previously thought for IRMS analyses. Our data show that extreme caution is required when using IRIS to analyse water samples that may contain organic contaminants. We suggest that the development of new cleaning techniques for removing organic contaminants together with instrument-based software to flag potentially problematic samples are necessary to ensure accurate plant and soil water analyses using IRIS. PMID:20552579

  16. Determination of lead, uranium, thorium, and thallium in silicate glass standard materials by isotope dilution mass spectrometry

    USGS Publications Warehouse

    Barnes, I.L.; Garner, E.L.; Gramlich, J.W.; Moore, L.J.; Murphy, T.J.; Machlan, L.A.; Shields, W.R.; Tatsumoto, M.; Knight, R.J.

    1973-01-01

    A set of four standard glasses has been prepared which have been doped with 61 different elements at the 500-, 50-, 1-, and 0.02-ppm level. The concentrations of lead, uranium, thorium, and thallium have been determined by isotope dilution mass spectrometry at a number of points in each of the glasses. The results obtained from independent determinations in two laboratories demonstrate the homogeneity of the samples and that precision of the order of 0.5% (95% L.E.) may be obtained by the method even at the 20-ppb level for these elements. The chemical and mass spectrometric procedures necessary are presented.

  17. Ion microscopy with resonant ionization mass spectrometry : time-of-flight depth profiling with improved isotopic precision.

    SciTech Connect

    Pellin, M. J.; Veryovkin, I. V.; Levine, J.; Zinovev, A.; Davis, A. M.; Stephan, T.; Tripa, C. E.; King, B. V.; Savina, M. R.

    2010-01-01

    There are four generally mutually exclusive requirements that plague many mass spectrometric measurements of trace constituents: (1) the small size (limited by the depth probed) of many interesting materials requires high useful yields to simply detect some trace elements, (2) the low concentrations of interesting elements require efficient discrimination from isobaric interferences, (3) it is often necessary to measure the depth distribution of elements with high surface and low bulk contributions, and (4) many applications require precise isotopic analysis. Resonant ionization mass spectrometry has made dramatic progress in addressing these difficulties over the past five years.

  18. Evaluation of the 34S/32S ratio of Soufre de Lacq elemental sulfur isotopic reference material by continuous flow isotope-ratio mass spectrometry

    USGS Publications Warehouse

    Qi, H.P.; Coplen, T.B.

    2003-01-01

    Soufre de Lacq elemental sulfur reference material (IAEA-S-4) isotopically is homogeneous in amounts as small as 41 ??g as determined by continuous flow isotope-ratio mass spectrometry. The ??34S value for this reference material is +16.90 ?? 0.12??? (1??) on a scale (Vienna Can??on Diablo troilite, VCDT) where IAEA-S-1 Ag2S is -0.3??? and IAEA-S-2 Ag2S is +22.67???. Published by Elsevier Science B.V.

  19. Metabolic flux in carbohydrate biosynthesis. New methods using stable isotopes, mass spectrometry, and NMR

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Structural analysis of carbohydrates involves three parameters: composition, linkage, and conformation, and tends to rely on the various forms of two techniques; mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. These techniques are enhanced and extended by the use of stable...

  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. Innovations in Mass Spectrometry for Precise and Accurate Isotope Ratio Determination from Very Small Analyte Quantities (Invited)

    NASA Astrophysics Data System (ADS)

    Lloyd, N. S.; Bouman, C.; Horstwood, M. S.; Parrish, R. R.; Schwieters, J. B.

    2010-12-01

    This presentation describes progress in mass spectrometry for analysing very small analyte quantities, illustrated by example applications from nuclear forensics. In this challenging application, precise and accurate () uranium isotope ratios are required from 1 - 2 m diameter uranium oxide particles, which comprise less than 40 pg of uranium. Traditionally these are analysed using thermal ionisation mass spectrometry (TIMS), and more recently using secondary ionisation mass spectrometry (SIMS). Multicollector inductively-coupled plasma mass spectrometry (MC-ICP-MS) can offer higher productivity compared to these techniques, but is traditionally limited by low efficiency of analyte utilisation (sample through to ion detection). Samples can either be introduced as a solution, or sampled directly from solid using laser ablation. Large multi-isotope ratio datasets can help identify provenance and intended use of anthropogenic uranium and other nuclear materials [1]. The Thermo Scientific NEPTUNE Plus (Bremen, Germany) with Jet Interface option offers unparalleled MC-ICP-MS sensitivity. An analyte utilisation of c. 4% has previously been reported for uranium [2]. This high-sensitivity configuration utilises a dry high-capacity (100 m3/h) interface pump, special skimmer and sampler cones and a desolvating nebuliser system. Coupled with new acquisition methodologies, this sensitivity enhancement makes possible the analysis of micro-particles and small sample volumes at higher precision levels than previously achieved. New, high-performance, full-size and compact discrete dynode secondary electron multipliers (SEM) exhibit excellent stability and linearity over a large dynamic range and can be configured to simultaneously measure all of the uranium isotopes. Options for high abundance-sensitivity filters on two ion beams are also available, e.g. for 236U and 234U. Additionally, amplifiers with high ohm (1012 - 1013) feedback resistors have been developed to optimise signal to noise ratios from low ion beam intensities on Faraday cups [2,3]. Data will be presented from the Thermo Scientific NEPTUNE Plus MC-ICP-MS, sampling sub-nanogram quantities of analyte from solution and by laser ablation. Faraday only measurements of sub-microgram analyte quantities will also be presented, using a 1012 ? amplifier for the minor isotope 234U. These data are compared to a dataset collected by a first generation MC-ICP-MS instrument, reported by Lloyd et al. [1]. [1] N. S. Lloyd, R. R. Parrish, M. S. A. Horstwood & S. R. N. Chenery, Journal of Analytical Atomic Spectrometry 24 (6), 752 (2009). [2] C. Bouman, J.B. Schwieters, M. Deerberg & D. Tuttas, Geochimica et Cosmochimica Acta 73 (13, Supplement 1) (2009). [3] D. Tuttas, J.B. Schwieters, & N.S. Lloyd, Geochimica et Cosmochimica Acta 74 (11, Supplement 1) (2010).

  2. High-precision measurement of variations in calcium isotope ratios in urine by multiple collector inductively coupled plasma mass spectrometry

    USGS Publications Warehouse

    Morgan, J.L.L.; Gordon, G.W.; Arrua, R.C.; Skulan, J.L.; Anbar, A.D.; Bullen, T.D.

    2011-01-01

    We describe a new chemical separation method to isolate Ca from other matrix elements in biological samples, developed with the long-term goal of making high-precision measurement of natural stable Ca isotope variations a clinically applicable tool to assess bone mineral balance. A new two-column procedure utilizing HBr achieves the purity required to accurately and precisely measure two Ca isotope ratios (44Ca/42Ca and 44Ca/43Ca) on a Neptune multiple collector inductively coupled plasma mass spectrometer (MC-ICPMS) in urine. Purification requirements for Sr, Ti, and K (Ca/Sr > 10000; Ca/Ti > 10000000; and Ca/K > 10) were determined by addition of these elements to Ca standards of known isotopic composition. Accuracy was determined by (1) comparing Ca isotope results for samples and standards to published data obtained using thermal ionization mass spectrometry (TIMS), (2) adding a Ca standard of known isotopic composition to a urine sample purified of Ca, and (3) analyzing mixtures of urine samples and standards in varying proportions. The accuracy and precision of δ44/42Ca measurements of purified samples containing 25 μg of Ca can be determined with typical errors less than ±0.2‰ (2σ).

  3. Quantifying Uranium Isotope Ratios Using Resonance Ionization Mass Spectrometry: The Influence of Laser Parameters on Relative Ionization Probability

    SciTech Connect

    Isselhardt, B H

    2011-09-06

    Resonance Ionization Mass Spectrometry (RIMS) has been developed as a method to measure relative uranium isotope abundances. In this approach, RIMS is used as an element-selective ionization process to provide a distinction between uranium atoms and potential isobars without the aid of chemical purification and separation. We explore the laser parameters critical to the ionization process and their effects on the measured isotope ratio. Specifically, the use of broad bandwidth lasers with automated feedback control of wavelength was applied to the measurement of {sup 235}U/{sup 238}U ratios to decrease laser-induced isotopic fractionation. By broadening the bandwidth of the first laser in a 3-color, 3-photon ionization process from a bandwidth of 1.8 GHz to about 10 GHz, the variation in sequential relative isotope abundance measurements decreased from >10% to less than 0.5%. This procedure was demonstrated for the direct interrogation of uranium oxide targets with essentially no sample preparation. A rate equation model for predicting the relative ionization probability has been developed to study the effect of variation in laser parameters on the measured isotope ratio. This work demonstrates that RIMS can be used for the robust measurement of uranium isotope ratios.

  4. Modified ion exchange separation for tungsten isotopic measurements from kimberlite samples using multi-collector inductively coupled plasma mass spectrometry.

    PubMed

    Sahoo, Yu Vin; Nakai, Shun'ichi; Ali, Arshad

    2006-03-01

    Tungsten isotope composition of a sample of deep-seated rock can record the influence of core-mantle interaction of the parent magma. Samples of kimberlite, which is known as a carrier of diamond, from the deep mantle might exhibit effects of core-mantle interaction. Although tungsten isotope anomaly was reported for kimberlites from South Africa, a subsequent investigation did not verify the anomaly. The magnesium-rich and calcium-rich chemical composition of kimberlite might engender difficulty during chemical separation of tungsten for isotope analyses. This paper presents a simple, one-step anion exchange technique for precise and accurate determination of tungsten isotopes in kimberlites using multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). Large quantities of Ca and Mg in kimberlite samples were precipitated and removed with aqueous H(2)SO(4). Highly pure fractions of tungsten for isotopic measurements were obtained following an anion exchange chromatographic procedure involving mixed acids. That procedure enabled efficient removal of high field strength elements (HFSE), such as Hf, Zr and Ti, which are small ions that carry strong charges and develop intense electrostatic fields. The tungsten yields were 85%-95%. Advantages of this system include less time and less use of reagents. Precise and accurate isotopic measurements are possible using fractions of tungsten that are obtained using this method. The accuracy and precision of these measurements were confirmed using various silicate standard rock samples, JB-2, JB-3 and AGV-1. PMID:16496054

  5. Determination of glycerol concentrations and glycerol isotopic enrichments in human plasma by gas chromatography/mass spectrometry.

    PubMed

    Ackermans, M T; Ruiter, A F; Endert, E

    1998-04-10

    An analytical method is presented to determine glycerol concentrations and stable isotope tracer enrichments in human plasma after intravenous tracer infusion in a single analytical run, using gas chromatography coupled to mass spectrometry. The method uses an internal standard, which is also a stable isotope labeled form of glycerol. Three substances were tested as model compounds viz. [2-13C]glycerol, and [1,2,3-13C3]glycerol, and [1,1,2,3, 3-2H5]glycerol. Any combination of two can be used (one as internal standard, one as tracer), even if overlapping of the mass spectra occurs. The method is precise (recovery of spiked glycerol and tracer are, respectively, 99.7 and 99.8%) and reproducible (intraassay variation <1.5%, interassay variation <6%) and needs only a small amount of plasma (100 microl). PMID:9527852

  6. Stable isotope labeling tandem mass spectrometry (SILT): Integration with peptide identification and extension to data-dependent scans

    PubMed Central

    Elbert, Donald L.; Mawuenyega, Kwasi G.; Scott, Evan A.; Wildsmith, Kristin R.; Bateman, Randall J.

    2009-01-01

    Quantitation of relative or absolute amounts of proteins by mass spectrometry can be prone to large errors. The use of MS/MS ion intensities and stable isotope labeling, which we term stable isotope labeling tandem mass spectrometry (SILT), decreases the effects of contamination from unrelated compounds. We present a software package (SILTmass) that automates protein identification and quantification by the SILT method. SILTmass has the ability to analyze the kinetics of protein turnover, in addition to relative and absolute protein quantitation. Instead of extracting chromatograms to find elution peaks, SILTmass uses only scans in which a peptide is identified and that meet an ion intensity threshold. Using only scans with identified peptides, the accuracy and precision of SILT is shown to be superior to precursor ion intensities, particularly at high or low dilutions of the isotope labeled compounds or with low amounts of protein. Using example scans, we demonstrate likely reasons for the improvements in quantitation by SILT. The appropriate use of variable modifications in peptide identification is described for measurement of protein turnover kinetics. The combination of identification with SILT facilitates quantitation without peak detection and helps to ensure the appropriate use of variable modifications for kinetics experiments. PMID:18774841

  7. 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.

  8. Determination of the sulfur isotope ratio in carbonyl sulfide using gas chromatography/isotope ratio mass spectrometry on fragment ions 32S+, 33S+, and 34S+.

    PubMed

    Hattori, Shohei; Toyoda, Akari; Toyoda, Sakae; Ishino, Sakiko; Ueno, Yuichiro; Yoshida, Naohiro

    2015-01-01

    Little is known about the sulfur isotopic composition of carbonyl sulfide (OCS), the most abundant atmospheric sulfur species. We present a promising new analytical method for measuring the stable sulfur isotopic compositions (?(33)S, ?(34)S, and ?(33)S) of OCS using nanomole level samples. The direct isotopic analytical technique consists of two parts: a concentration line and online gas chromatography-isotope ratio mass spectrometry (GC-IRMS) using fragmentation ions (32)S(+), (33)S(+), and (34)S(+). The current levels of measurement precision for OCS samples greater than 8 nmol are 0.42, 0.62, and 0.23 for ?(33)S, ?(34)S, and ?(33)S, respectively. These ? and ? values show a slight dependence on the amount of injected OCS for volumes smaller than 8 nmol. The isotope values obtained from the GC-IRMS method were calibrated against those measured by a conventional SF6 method. We report the first measurement of the sulfur isotopic composition of OCS in air collected at Kawasaki, Kanagawa, Japan. The ?(34)S value obtained for OCS (4.9 0.3) was lower than the previous estimate of 11. When the ?(34)S value for OCS from the atmospheric sample is postulated as the global signal, this finding, coupled with isotopic fractionation for OCS sink reactions in the stratosphere, explains the reported ?(34)S for background stratospheric sulfate. This suggests that OCS is a potentially important source for background (nonepisodic or nonvolcanic) stratospheric sulfate aerosols. PMID:25439590

  9. The use of stable isotopes and gas chromatography/mass spectrometry in the identification of steroid metabolites in the equine

    SciTech Connect

    Houghton, E.; Dumasia, M.C.; Teale, P.; Smith, S.J.; Cox, J.; Marshall, D.; Gower, D.B. )

    1990-10-01

    Stable isotope gas chromatography/mass spectrometry has been used successfully in the elucidation of structures of urinary steroid metabolites in the horse and in the identification of metabolites isolated from in vivo perfusion and in vitro incubation studies using equine tissue preparations. Deuterium-labeled steroids, testosterone, dehydroepiandrosterone, and 5-androstene-3 beta,17 beta-diol have been synthesized by base-catalyzed isotope exchange methods and the products characterized by gas chromatography/mass spectrometry. (16,16(-2)H2)Dehydroepiandrosterone (plus radiolabeled dehydroepiandrosterone) was perfused into a testicular artery of a pony stallion and was shown to be metabolized into 2H2-labeled testosterone, 4-androstenedione, isomers of 5-androstene-3,17-diol, 19-hydroxytestosterone, and 19-hydroxy-4-androstenedione. In further studies, equine testicular minces have been incubated with 2H2-labeled and radiolabeled dehydroepiandrosterone and 5-androstene-3 beta, 17 beta-diol. The metabolites, whose identity was confirmed by stable isotope gas chromatography/mass spectrometry, proved the interconversion of the two substrates, as well as formation of testosterone and 4-androstenedione. The aromatization of dehydroepiandrosterone was also confirmed, together with the formation of an isomer of 5(10)-estrene-3,17-diol from both substrates showing 19-demethylation without concomitant aromatization. In studies of the feto-placental unit, the allantochorion was shown to aromatize (2H5)testosterone to (2H4)estradiol, the loss of one 2H from the substrate being consistent with aromatization of the A ring. The formation of 6-hydroxyestradiol was also confirmed in this study. The same technique has been valuable in determining the structure of two metabolites of nandrolone isolated from horse urine.

  10. Stable Isotope Analyses of water and Aqueous Solutions by Conventional Dual-inlet Mass Spectrometry

    SciTech Connect

    Horita, Juske; Kendall, C.

    2004-01-01

    The foundation of various analytical methods for the stable isotope composition of water and other aqueous samples (natural abundance, {sup 1}H : {sup 2}H (D) = 99.985 : 0.015 atom%, and {sup 16}O : {sup 17}O : {sup 18}O = 99.762 : 0.038 : 0.200 atom%) was established during the Manhatten Project in the U.S.A., when large amounts of heavy water were produced for nuclear reactors (see Kirshenbaum, 1951, for a detailed account). From early on, there was great interest in the oxygen and hydrogen isotopic compositions of water, because they are the ideal tracers of water sources and reactions. The increased analytical precisions made possible by the subsequent development of modern gas-source isotope-ratio mass spectrometers with dual-inlets and multi-collectors, have caused the proliferation of new analytical methods and applications for the oxygen and hydrogen isotopic compositions of water. These stable isotopes have found wide applications in basic as well as applied sciences (chemistry, geology, hydrology, biology, medical sciences, and food sciences). This is because water is ubiquitous, is an essential and predominant ingredient of living organisms, and is perhaps the most reactive compound in the Earth.

  11. Precise Zn isotopic ratio measurements of human red blood cell and hair samples by multiple collector-ICP-mass spectrometry.

    PubMed

    Ohno, Takeshi; Shinohara, Atsuko; Chiba, Momoko; Hirata, Takafumi

    2005-04-01

    Precise 66Zn/64Zn and 68Zn/64Zn isotopic ratios of biochemical samples have been measured using multiple collector-ICP-mass spectrometry (MC-ICPMS). In order to eliminate the mass spectrometric interferences on Zn isotopes (e.g., 64Ni+ and 136Ba2+), we chemically purified the analyte using an ion chromatographic technique. The resulting precisions of the 66Zn/64Zn and 68Zn/64Zn ratio measurements were 0.05/1000 and 0.10/1000 (2SD), respectively, which were enough to detect the isotopic variation of Zn in nature. Red blood cell (RBC) samples were collected from five volunteers (four males and one female), including a series of 12 RBC samples from one person through monthly-based sampling over a year. These were analyzed to test possible seasonal changes and variations in 66Zn/64Zn and 68Zn/64Zn ratios among the individuals. The 66Zn/64Zn and 68Zn/64Zn ratios for a series of 12 RBC samples collected over a year were 0.43/1000 and 0.83/1000 higher than the values of highly purified Zn metal (JMC Zn), and no seasonal change could be found. The 66Zn/64Zn and 68Zn/64Zn ratios for RBC samples collected from five volunteers did not vary significantly. In order to investigate Zn isotopic heterogeneity in a human body, Zn isotopic ratios of a hair sample collected from one of the volunteers was also analyzed. The 66Zn/64Zn and 68Zn/64Zn ratios for the hair sample were 0.59/1000 and 1.14/1000 lower than the mean value of RBC samples. This result demonstrates that detectable isotopic fractionation occurs in the human body. The data obtained here suggest that the isotopic ratios of trace metals could provide new information about transportation of metal elements in vivo. PMID:15844339

  12. A comparison by stable isotope mass spectrometry of coal-oil coprocessing under thermal and severe-hydrotreatment conditions

    SciTech Connect

    Bartle, K.D.; Louie, P.K.K.; Taylor, N.; Kemp, W.; Steedman, W.

    1993-12-31

    The {sup 13}C/{sup 12}C ratios of saturated, aromatic, polar, and asphaltene fractions produced by co-processing of Point of Ayr coal with heavy petroleum residues under thermolytic and severe hydrotreatment conditions were measured by isotope ratio mass spectrometry. The incorporation of coal carbon into the aromatic, polar and asphaltene products was similar for both sets of conditions and was independent of the oil used. An increase in the saturated fraction during severe hydrotreatment is consistent with hydrothermolysis is of bound long alkyl chains.

  13. Comparing the precision of selenium isotope ratio measurements using collision cell and sector field inductively coupled plasma mass spectrometry.

    PubMed

    Elwaer, Nagmeddin; Hintelmann, Holger

    2008-03-15

    The performance of two different types of inductively coupled plasma mass spectrometry (ICP-MS) instruments for resolving spectral overlaps on Se isotopes was compared by means of selenium isotopic ratio measurements. Examined were a quadrupole-based, hexapole collisions cell CC-ICP-MS and a double-focusing sector field SF-ICP-MS. Due to the importance of precise and accurate isotope ratio determination in environmental, clinical and nutritional studies, a thorough investigation of the critical instrumental parameters of each technique was performed. A hydride generation system was coupled with SF-ICP-MS to maintain high signal-to-noise ratios (S/N) at high mass resolution. However, 80Se+ was not completely separated from the argon dimer (40)Ar2+ at m/z=80, even in high-resolution mode. The same hydride generation system was coupled to a collision cell instrument and it was found that argon dimers are significantly reduced using a mixture of H2 and He gas with the cell. A lower mass bias of 2.5% per amu was determined for measured Se isotopes using the SF-ICP-MS instrument compared 3.6% observed for the CC-ICP-MS instrument. Under optimized conditions, the precision for Se isotope ratio measurements of both instruments was evaluated and compared measuring NIST-3149 Se standard solution. On average, the uncertainty determined by repeated measurements over the span of three individual measuring sessions in a period of 3 weeks ranged from 0.06% to 0.15% and 0.09% to 0.30% R.S.D. for the various isotope ratios using the CC-ICP-MS and SF-ICP-MS instrument, respectively. The detection limits (3) for total Se were determined by measuring 82Se and found to be 1.7 and 4.0 ng L(-1) for the CC-ICP-MS and SF-ICP-MS, respectively. PMID:18371869

  14. 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 methods of isobar separation. These techniques are discussed in the latter part of the review. PMID:22031277

  15. Delta13C stable isotope analysis of atmospheric oxygenated volatile organic compounds by gas chromatography-isotope ratio mass spectrometry.

    PubMed

    Giebel, Brian M; Swart, Peter K; Riemer, Daniel D

    2010-08-15

    We present a new method for analyzing the delta(13)C isotopic composition of several oxygenated volatile organic compounds (OVOCs) from direct sources and ambient atmospheric samples. Guided by the requirements for analysis of trace components in air, a gas chromatograph isotope ratio mass spectrometer (GC-IRMS) system was developed with the goal of increasing sensitivity, reducing dead-volume and peak band broadening, optimizing combustion and water removal, and decreasing the split ratio to the isotope ratio mass spectrometer (IRMS). The technique relies on a two-stage preconcentration system, a low-volume capillary reactor and water trap, and a balanced reference gas delivery system. The instrument's measurement precision is 0.6 to 2.9 per thousand (1sigma), and results indicate that negligible sample fractionation occurs during gas sampling. Measured delta(13)C values have a minor dependence on sample size; linearity for acetone was 0.06 per thousand ng C(-1) and was best over 1-10 ng C. Sensitivity is approximately 10 times greater than similar instrumentation designs, incorporates the use of a diluted working reference gas (0.1% CO(2)), and requires collection of >0.7 ng C to produce accurate and precise results. With this detection limit, a 1.0 L sample of ambient air provides sufficient carbon for isotopic analysis. Emissions from vegetation and vehicle exhaust are compared and show clear differences in isotopic signatures. Ambient samples collected in metropolitan Miami and the Everglades National Park can be differentiated and reflect multiple sources and sinks affecting a single sampling location. Vehicle exhaust emissions of ethanol, and those collected in metropolitan Miami, have anomalously enriched delta(13)C values ranging from -5.0 to -17.2 per thousand; we attribute this result to ethanol's origin from corn and use as an additive in automotive fuels. PMID:20704369

  16. Stable isotope ratio mass spectrometry and physical comparison for the forensic examination of grip-seal plastic bags.

    PubMed

    Taylor, Erica; Carter, James F; Hill, Jenny C; Morton, Carolyn; Daeid, Niamh Nic; Sleeman, Richard

    2008-05-20

    Plastic bags are frequently used to package drugs, explosives and other contraband. There exists, therefore, a requirement in forensic casework to compare bags found at different locations. This is currently achieved almost exclusively by the use of physical comparisons such as birefringence patterns. This paper discusses some of the advantages and shortcomings of this approach, and presents stable isotope ratio mass spectrometry (IRMS) as a supplementary tool for effecting comparisons of this nature. Carbon and hydrogen isotopic data are presented for sixteen grip-seal plastic bags from a wide range of sources, in order to demonstrate the range of values which is likely to be encountered. Both isotopic and physical comparison (specifically birefringence) techniques are then applied to the analysis of rolls of bags from different manufacturing lots from a leading manufacturer. Both approaches are able to associate bags from a common production batch. IRMS can be applied to small fragments which are not amenable to physical comparisons, and is able to discriminate bags which could be confused using birefringence patterns alone. Similarly, in certain cases birefringence patterns discriminate bags with similar isotopic compositions. The two approaches are therefore complementary. When more than one isotopically distinct region exists within a bag (e.g. the grip-seal is distinct from the body) the ability to discriminate and associate bags is greatly increased. PMID:18308494

  17. Precise ruthenium fission product isotopic analysis using dynamic reaction cell inductively coupled plasma mass spectrometry (DRC-ICP-MS)

    SciTech Connect

    Brown, Christopher F.; Dresel, P. Evan; Geiszler, Keith N.; Farmer, Orville T.

    2006-05-09

    99Tc is a subsurface contaminant of interest at numerous federal, industrial, and international facilities. However, as a mono-isotopic fission product, 99Tc lacks the ability to be used as a signature to differentiate between the different waste disposal pathways that could have contributed to subsurface contamination at these facilities. Ruthenium fission-product isotopes are attractive analogues for the characterization of 99Tc sources because of their direct similarity to technetium with regard to subsurface mobility, and their large fission yields and low natural background concentrations. We developed an inductively coupled plasma mass spectrometry (ICP-MS) method capable of measuring ruthenium isotopes in groundwater samples and extracts of vadose zone sediments. Samples were analyzed directly on a Perkin Elmer ELAN DRC II ICP-MS after a single pass through a 1-ml bed volume of Dowex AG 50W-X8 100-200 mesh cation exchange resin. Precise ruthenium isotopic ratio measurements were achieved using a low-flow Meinhard-type nebulizer and long sample acquisition times (150,000 ms). Relative standard deviations of triplicate replicates were maintained at less than 0.5% when the total ruthenium solution concentration was 0.1 ng/ml or higher. Further work was performed to minimize the impact caused by mass interferences using the dynamic reaction cell (DRC) with O2 as the reaction gas. The aqueous concentrations of 96Mo and 96Zr were reduced by more than 99.7% in the reaction cell prior to injection of the sample into the mass analyzer quadrupole. The DRC was used in combination with stable-mass correction to quantitatively analyze samples containing up to 2-orders of magnitude more zirconium and molybdenum than ruthenium. The analytical approach documented herein provides an efficient and cost-effective way to precisely measure ruthenium isotopes and quantitate total ruthenium (natural vs. fission-product) in aqueous matrixes.

  18. On-line double isotope dilution laser ablation inductively coupled plasma mass spectrometry for the quantitative analysis of solid materials.

    PubMed

    Fernández, Beatriz; Rodríguez-González, Pablo; García Alonso, J Ignacio; Malherbe, Julien; García-Fonseca, Sergio; Pereiro, Rosario; Sanz-Medel, Alfredo

    2014-12-01

    We report on the determination of trace elements in solid samples by the combination of on-line double isotope dilution and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The proposed method requires the sequential analysis of the sample and a certified natural abundance standard by on-line IDMS using the same isotopically-enriched spike solution. In this way, the mass fraction of the analyte in the sample can be directly referred to the certified standard so the previous characterization of the spike solution is not required. To validate the procedure, Sr, Rb and Pb were determined in certified reference materials with different matrices, including silicate glasses (SRM 610, 612 and 614) and powdered samples (PACS-2, SRM 2710a, SRM 1944, SRM 2702 and SRM 2780). The analysis of powdered samples was carried out both by the preparation of pressed pellets and by lithium borate fusion. Experimental results for the analysis of powdered samples were in agreement with the certified values for all materials. Relative standard deviations in the range of 6-21% for pressed pellets and 3-21% for fused solids were obtained from n=3 independent measurements. Minimal sample preparation, data treatment and consumption of the isotopically-enriched isotopes are the main advantages of the method over previously reported approaches. PMID:25440666

  19. Mass spectrometry

    SciTech Connect

    Burlingame, A.L.; Maltby, D.; Russell, D.H.; Holland, P.T.

    1988-06-15

    This review series has served as a timely means to provide critical discussion of the advances and directions, strengths and weaknesses, and the state of maturity and promise of both new and established strategies and methods in a unifying single source. Widely disparate discoveries, inventions, and purposeful developments are required to enable mass spectrometric based strategies to take hold and make inroads into new types of issues at the molecular level of biological, medical, and chemical sciences. These are interdisciplinary endeavors. Of necessity, they have been selective both in the topics covered and in the contributions included but have endeavored to be sufficiently general so that both the new reader and the expert might readily find further literature and necessary detail. They have attempted to provide a thematic context for each topic. They note that this review series has a cumulative continuity about it, and the previous few Overview sections are still timely.

  20. Performance and optimization of a combustion interface for isotope ratio monitoring gas chromatography/mass spectrometry

    NASA Technical Reports Server (NTRS)

    Merritt, D. A.; Freeman, K. H.; Ricci, M. P.; Studley, S. A.; Hayes, J. M.

    1995-01-01

    Conditions and systems for on-line combustion of effluents from capillary gas chromatographic columns and for removal of water vapor from product streams were tested. Organic carbon in gas chromatographic peaks 15 s wide and containing up to 30 nanomoles of carbon was quantitatively converted to CO2 by tubular combustion reactors, 200 x 0.5 mm, packed with CuO or NiO. No auxiliary source of O2 was required because oxygen was supplied by metal oxides. Spontaneous degradation of CuO limited the life of CuO reactors at T > 850 degrees C. Since NiO does not spontaneously degrade, its use might be favored, but Ni-bound carbon phases form and lead to inaccurate isotopic results at T < 1050 degrees C if gas-phase O2 is not added. For all compounds tested except CH4, equivalent isotopic results are provided by CuO at 850 degrees C, NiO + O2 (gas-phase mole fraction, 10(-3)) at 1050 degrees C and NiO at 1150 degrees C. The combustion interface did not contribute additional analytical uncertainty, thus observed standard deviations of 13C/12C ratios were within a factor of 2 of shot-noise limits. For combustion and isotopic analyses of CH4, in which quantitative combustion required T approximately 950 degrees C, NiO-based systems are preferred, and precision is approximately 2 times lower than that observed for other analytes. Water must be removed from the gas stream transmitted to the mass spectrometer or else protonation of CO2 will lead to inaccuracy in isotopic analyses. Although thresholds for this effect vary between mass spectrometers, differential permeation of H2O through Nafion tubing was effective in both cases tested, but the required length of the Nafion membrane was 4 times greater for the more sensitive mass spectrometer.

  1. Determination of boron isotope ratios in geological materials by inductively coupled plasma mass spectrometry

    SciTech Connect

    Gregoire, D.C.

    1987-10-15

    A method for the determination of B isotopes ratios in a variety of geological materials is described. Boron isotope ratios are determined with a precision of 0.7% in materials containing as little as 0.5 ppm B. Sample material is leached with HCl in sealed pressure tubes or fused with sodium carbonate. Separation and/or preconcentration of B from matrix elements is accomplished by using Amberlite XE-243, Dowex 50W-X8, or Chelex-100 resins. The use of NASS-1 reference sea water is suggested as a reference material for calculating and comparing isotope shifts for different geological amterails. Nonspectroscopic interferences due to the presence of concomitant elements in solution are shown to cause /sup 11/B ion count rate suppression at concentrations of Na above 2000 ppm. The presence of excess amounts of concomitant elements causes a matrix-induced mass discrimination effect. Boron isotopes ratios (/sup 11/B//sup 10/B) for the materials studied ranged from 3.91 to 4.18 for basalt and sea water samples, respectively.

  2. High accuracy determination of malachite green and leucomalachite green in salmon tissue by exact matching isotope dilution mass spectrometry.

    PubMed

    Hall, Zoe; Hopley, Chris; O'Connor, Gavin

    2008-10-15

    A high accuracy method for the quantification of malachite green (MG) and leucomalachite green (LMG) in salmon is described. Analytical challenges including the effects of analyte instability and matrix suppression were minimised by the use of exact matching isotope dilution mass spectrometry. The developed method included overnight extraction in acidified acetonitrile/ammonium acetate buffer and analysis by LC-MS/MS utilising isotopic internal standards. This method was used to determine the level of MG and LMG in a sample of salmon used in an international inter-comparison organised by the Comité Consultatif pour la Quantité de Matière (CCQM). The sum of MG and LMG was found to be 9.32+/-0.98ngg(-1) at the 95% confidence interval (relative expanded uncertainty 10.5% (k=2)). This encompassed the mean and median of the CCQM inter-comparison. PMID:18818128

  3. Evidence for a possible dietary effect on the isotopic composition of Zn in blood via isotopic analysis of food products by multi-collector ICP-mass spectrometry.

    PubMed

    Costas-Rodrguez, Marta; Van Heghe, Lana; Vanhaecke, Frank

    2014-01-01

    In this work, the hypothesis of a possible dietary effect on the isotopic composition of Zn in blood from populations with different feeding habits, i.e. lacto-ovo vegetarians and omnivores, was investigated through isotopic analysis of Zn in common food products by multi-collector ICP - mass spectrometry (MC-ICP-MS). Several certified reference materials (CRMs) were also included in the sample set for comparison purposes. For these CRMs, the isotopic composition of Zn is expressed as ?-values, calculated with respect to both IRMM-3702 and JMC-ZnLyon, as isotopic standards. The range of ?(66)Zn values observed in food products was approximately 1.9. In general, vegetables, cereals and derived products showed an enrichment of the heavier Zn isotopes, whereas a depletion was observed in products of animal origin (meat, fish, egg and semi-skimmed milk), relative to human blood samples. Mussel, however, showed a significant enrichment of the heavier isotopes, which is hypothetically attributed to its accumulation behaviour. Thus, the lower ?(66)Zn values found in food products of animal origin appear to be reflected in the lower ?(66)Zn value observed in blood from an omnivorous population compared to that for a vegetarian population. PMID:24196216

  4. Adsorption in gas mass spectrometry. I. Effects on the measurement of individual isotopic species

    NASA Astrophysics Data System (ADS)

    Gonfiantini, Roberto; Valkiers, Staf; Taylor, Philip D. P.; de Bivre, Paul

    1997-05-01

    The adsorption-desorption process of gas molecules on the walls of the mass spectrometer inlet system was studied in order to assess quantitatively its influence on measurement results. The effects on individual isotopic species in SiF4 measurements required for the re-determination of the Avogadro constant are discussed in this paper, while the effects on isotope amount ratio determinations will be discussed in a companion paper. A model based on the Langmuir adsorption isotherm is developed, which fits well the experimental observations and provides the means to investigate adsorption and desorption kinetics in the inlet system. A parameter called the [`]apparent leak-rate coefficient' is introduced; this represents the relative variation with time of any isotopic species in the inlet system. All the adsorption parameters appearing in the balance equations are derived from the apparent leak-rate coefficient. Application of the model to long mass-spectrometric measurements of SiF4 yields a rate constant of 6.5 10-5 s-1 for SiF4 effusion through the molecular leak of the inlet system. Adsorption and desorption rate-constants are equal to 20-25% of the leak rate-constant, and the adsorption sites are about two orders of magnitude lower than the number of Ni and Cu atoms present on the inlet system walls.

  5. Simultaneous Measurement of Denitrification and Nitrogen Fixation Using Isotope Pairing with Membrane Inlet Mass Spectrometry Analysis†

    PubMed Central

    An, Soonmo; Gardner, Wayne S.; Kana, Todd

    2001-01-01

    A method for estimating denitrification and nitrogen fixation simultaneously in coastal sediments was developed. An isotope-pairing technique was applied to dissolved gas measurements with a membrane inlet mass spectrometer (MIMS). The relative fluxes of three N2 gas species (28N2, 29N2, and 30N2) were monitored during incubation experiments after the addition of 15NO3−. Formulas were developed to estimate the production (denitrification) and consumption (N2 fixation) of N2 gas from the fluxes of the different isotopic forms of N2. Proportions of the three isotopic forms produced from 15NO3− and 14NO3− agreed with expectations in a sediment slurry incubation experiment designed to optimize conditions for denitrification. Nitrogen fixation rates from an algal mat measured with intact sediment cores ranged from 32 to 390 μg-atoms of N m−2 h−1. They were enhanced by light and organic matter enrichment. In this environment of high nitrogen fixation, low N2 production rates due to denitrification could be separated from high N2 consumption rates due to nitrogen fixation. Denitrification and nitrogen fixation rates were estimated in April 2000 on sediments from a Texas sea grass bed (Laguna Madre). Denitrification rates (average, 20 μg-atoms of N m−2 h−1) were lower than nitrogen fixation rates (average, 60 μg-atoms of N m−2 h−1). The developed method benefits from simple and accurate dissolved-gas measurement by the MIMS system. By adding the N2 isotope capability, it was possible to do isotope-pairing experiments with the MIMS system. PMID:11229907

  6. Mass spectrometry in coupling with affinity capture-release and isotope-coded affinity tags for quantitative protein analysis.

    PubMed

    Turecek, Frantisek

    2002-01-01

    Affinity capture-release electrospray ionization mass spectrometry (ACESIMS) and isotope-coded affinity tags (ICAT) are two recently introduced techniques for the quantitation of protein activity and content with applications to clinical enzymology and functional proteomics, respectively. One common feature of these methods is that they use biotinylated tags that function as molecular handles for highly selective and reversible affinity capture of conjugates from complex biological mixtures such as cell homogenates and sub-cellular organelles. ACESIMS uses synthetic substrate conjugates specifically to target cellular enzymes that, when deficient, are the cause of genetic diseases. Multiplex determination of enzyme activities is used for the diagnosis of lysosomal storage diseases. The ICAT method relies on selective conjugation of cysteine thiol groups in proteins, followed by enzymatic digestion and quantitative analysis of peptide conjugates by mass spectrometry. Another common feature of the ACESIMS and ICAT approaches is that both use conjugates labeled with stable heavy isotopes as internal standards for quantitation. Selected applications of the ACESIMS and ICAT techniques are presented that include molecular-level diagnosis of genetic diseases in children and quantitative determination of protein expression in cells. PMID:11813306

  7. Ion Mobility Spectrometry-Hydrogen Deuterium Exchange Mass Spectrometry of Anions: Part 2. Assessing Charge Site Location and Isotope Scrambling.

    PubMed

    Khakinejad, Mahdiar; Ghassabi Kondalaji, Samaneh; Donohoe, Gregory C; Valentine, Stephen J

    2016-03-01

    Ion mobility spectrometry (IMS) coupled with gas-phase hydrogen deuterium exchange (HDX)-mass spectrometry (MS) and molecular dynamic simulations (MDS) has been used for structural investigation of anions produced by electrospraying a sample containing a synthetic peptide having the sequence KKDDDDDIIKIIK. In these experiments the potential of the analytical method for locating charge sites on ions as well as for utilizing collision-induced dissociation (CID) to reveal the degree of deuterium uptake within specific amino acid residues has been assessed. For diffuse (i.e., more elongated) [M - 2H](2-) ions, decreased deuterium content along with MDS data suggest that the D4 and D6 residues are charge sites, whereas for the more diffuse [M - 3H](3-) ions, the data suggest that the D4, D7, and the C-terminus are deprotonated. Fragmentation of mobility-selected, diffuse [M - 2H](2-) ions to determine deuterium uptake at individual amino acid residues reveals a degree of deuterium retention at incorporation sites. Although the diffuse [M - 3H](3-) ions may show more HD scrambling, it is not possible to clearly distinguish HD scrambling from the expected deuterium uptake based on a hydrogen accessibility model. The capability of the IMS-HDX-MS/MS approach to provide relevant details about ion structure is discussed. Additionally, the ability to extend the approach for locating protonation sites on positively-charged ions is presented. Graphical Abstract ᅟ. PMID:26802030

  8. Rapid determination of (237)Np and plutonium isotopes in urine by inductively-coupled plasma mass spectrometry and alpha spectrometry.

    PubMed

    Maxwell, Sherrod L; Culligan, Brian K; Jones, Vernon D; Nichols, Sheldon T; Noyes, Gary W; Bernard, Maureen A

    2011-08-01

    A new rapid separation method was developed for the measurement of plutonium and neptunium in urine samples by inductively-coupled plasma mass spectrometry (ICP-MS) and/or alpha spectrometry with enhanced uranium removal. This method allows separation and preconcentration of plutonium and neptunium in urine samples using stacked extraction chromatography cartridges and vacuum box flow rates to facilitate rapid separations. There is an increasing need to develop faster analytical methods for emergency response samples. There is also enormous benefit to having rapid bioassay methods in the event that a nuclear worker has an uptake (puncture wound, etc.) to assess the magnitude of the uptake and guide efforts to mitigate dose (e.g., tissue excision and chelation therapy). This new method focuses only on the rapid separation of plutonium and neptunium with enhanced removal of uranium. For ICP-MS, purified solutions must have low salt content and low concentration of uranium due to spectral interference of (238)U(1)H(+) on m/z 239. Uranium removal using this method is enhanced by loading plutonium and neptunium initially onto TEVA resin, then moving plutonium to DGA resin where additional purification from uranium is performed with a decontamination factor of almost 1×10(5). If UTEVA resin is added to the separation scheme, a decontamination factor of ~3 × 10(6) can be achieved. PMID:21709507

  9. Ion Mobility Spectrometry-Hydrogen Deuterium Exchange Mass Spectrometry of Anions: Part 2. Assessing Charge Site Location and Isotope Scrambling

    NASA Astrophysics Data System (ADS)

    Khakinejad, Mahdiar; Ghassabi Kondalaji, Samaneh; Donohoe, Gregory C.; Valentine, Stephen J.

    2016-01-01

    Ion mobility spectrometry (IMS) coupled with gas-phase hydrogen deuterium exchange (HDX)-mass spectrometry (MS) and molecular dynamic simulations (MDS) has been used for structural investigation of anions produced by electrospraying a sample containing a synthetic peptide having the sequence KKDDDDDIIKIIK. In these experiments the potential of the analytical method for locating charge sites on ions as well as for utilizing collision-induced dissociation (CID) to reveal the degree of deuterium uptake within specific amino acid residues has been assessed. For diffuse (i.e., more elongated) [M - 2H]2- ions, decreased deuterium content along with MDS data suggest that the D4 and D6 residues are charge sites, whereas for the more diffuse [M - 3H]3- ions, the data suggest that the D4, D7, and the C-terminus are deprotonated. Fragmentation of mobility-selected, diffuse [M - 2H]2- ions to determine deuterium uptake at individual amino acid residues reveals a degree of deuterium retention at incorporation sites. Although the diffuse [M - 3H]3- ions may show more HD scrambling, it is not possible to clearly distinguish HD scrambling from the expected deuterium uptake based on a hydrogen accessibility model. The capability of the IMS-HDX-MS/MS approach to provide relevant details about ion structure is discussed. Additionally, the ability to extend the approach for locating protonation sites on positively-charged ions is presented.

  10. Ion Mobility Spectrometry-Hydrogen Deuterium Exchange Mass Spectrometry of Anions: Part 2. Assessing Charge Site Location and Isotope Scrambling

    NASA Astrophysics Data System (ADS)

    Khakinejad, Mahdiar; Ghassabi Kondalaji, Samaneh; Donohoe, Gregory C.; Valentine, Stephen J.

    2016-03-01

    Ion mobility spectrometry (IMS) coupled with gas-phase hydrogen deuterium exchange (HDX)-mass spectrometry (MS) and molecular dynamic simulations (MDS) has been used for structural investigation of anions produced by electrospraying a sample containing a synthetic peptide having the sequence KKDDDDDIIKIIK. In these experiments the potential of the analytical method for locating charge sites on ions as well as for utilizing collision-induced dissociation (CID) to reveal the degree of deuterium uptake within specific amino acid residues has been assessed. For diffuse (i.e., more elongated) [M - 2H]2- ions, decreased deuterium content along with MDS data suggest that the D4 and D6 residues are charge sites, whereas for the more diffuse [M - 3H]3- ions, the data suggest that the D4, D7, and the C-terminus are deprotonated. Fragmentation of mobility-selected, diffuse [M - 2H]2- ions to determine deuterium uptake at individual amino acid residues reveals a degree of deuterium retention at incorporation sites. Although the diffuse [M - 3H]3- ions may show more HD scrambling, it is not possible to clearly distinguish HD scrambling from the expected deuterium uptake based on a hydrogen accessibility model. The capability of the IMS-HDX-MS/MS approach to provide relevant details about ion structure is discussed. Additionally, the ability to extend the approach for locating protonation sites on positively-charged ions is presented.

  11. Accuracy and Reproducibility in Quantification of Plasma Protein Concentrations by Mass Spectrometry without the Use of Isotopic Standards

    PubMed Central

    Kramer, Gertjan; Woolerton, Yvonne; van Straalen, Jan P.; Vissers, Johannes P. C.; Dekker, Nick; Langridge, James I.; Beynon, Robert J.; Speijer, Dave; Sturk, Auguste; Aerts, Johannes M. F. G.

    2015-01-01

    Background Quantitative proteomic analysis with mass spectrometry holds great promise for simultaneously quantifying proteins in various biosamples, such as human plasma. Thus far, studies addressing the reproducible measurement of endogenous protein concentrations in human plasma have focussed on targeted analyses employing isotopically labelled standards. Non-targeted proteomics, on the other hand, has been less employed to this end, even though it has been instrumental in discovery proteomics, generating large datasets in multiple fields of research. Results Using a non-targeted mass spectrometric assay (LCMSE), we quantified abundant plasma proteins (43 mg/mL—40 ug/mL range) in human blood plasma specimens from 30 healthy volunteers and one blood serum sample (ProteomeXchange: PXD000347). Quantitative results were obtained by label-free mass spectrometry using a single internal standard to estimate protein concentrations. This approach resulted in quantitative results for 59 proteins (cut off ≥11 samples quantified) of which 41 proteins were quantified in all 31 samples and 23 of these with an inter-assay variability of ≤ 20%. Results for 7 apolipoproteins were compared with those obtained using isotope-labelled standards, while 12 proteins were compared to routine immunoassays. Comparison of quantitative data obtained by LCMSE and immunoassays showed good to excellent correlations in relative protein abundance (r = 0.72–0.96) and comparable median concentrations for 8 out of 12 proteins tested. Plasma concentrations of 56 proteins determined by LCMSE were of similar accuracy as those reported by targeted studies and 7 apolipoproteins quantified by isotope-labelled standards, when compared to reference concentrations from literature. Conclusions This study shows that LCMSE offers good quantification of relative abundance as well as reasonable estimations of concentrations of abundant plasma proteins. PMID:26474480

  12. Alternative Methodology for Boron Isotopic Analysis of CaCO3 by Negative Thermal Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Dwyer, G. S.; Vengosh, A.

    2012-12-01

    Negative thermal ionization mass spectrometry (NTIMS) has been a common tool for investigating boron isotopes in CaCO3 and other environmental samples, the high sensitivity of BO2- ionization enabling measurements of ng levels of boron. However, B isotope measurement by this technique suffers from a number of problems, including: (1) fractionation induced by selective ionization of B isotopes in the mass spectrometer; (2) CNO- interference on mass 42 ([10BO2]-) that may be present in some filament load solutions (such as B-free seawater processed through ion-exchange resin), and (3) potential matrix effects due to widely differing chemistry of samples and standards. Here we examine a potentially improved NTIMS methodology that incudes removal of sample-related calcium (and other cations) by ion exchange and uses an alternative filament loading solution prepared from high-purity single-element solutions of Ca, Mg, Na, and K. Initial results suggest that this new method may offer significant improvement over the more traditional NTIMS approach in which digested CaCO3 samples are directly loaded onto filaments in B-free seawater. Replicate analyses of standards and samples yield a typical standard deviation of approximately 0.3 ?11B and boron isotopic compositions comparable to reported or consensus values. Fractionation during analysis has thus far typically been less than 0.5 ?11B. The method delivers boron ionization efficiency similar to directly-loaded seawater, and negligible signal at mass 26 (CN-), a proxy for the possible interfering molecular CNO- ion. Standards and samples behave similarly and predictably during filament heating and analysis, thus allowing for fully automated data acquisition, which in turn may increase sample throughput and reduce potential analytical inconsistencies associated with operator-controlled heating and analysis.

  13. Determination of Mineral-Specific Clumped Isotope Acid Digestion Fractionation Factors Using Heating Experiments and Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Henry, D.; Tang, J.; Mosenfelder, J. L.; Eagle, R.; Tripati, A.

    2014-12-01

    Clumped isotope thermometry involves the determination of formation temperatures of carbonates from the fraction of isotopologues containing multiple rare isotopes (oxygen-18 and carbon-13). At high temperatures, the abundance of these isotopologues should be stochastic. At lower temperatures, there is a tendency for heavy isotopes to form bonds with each other. However, spectroscopic determination of isotope ratios with high precision is difficult in solids, and so 13C-18O bond abundance is not measured in the solid phase. Instead, analysis of carbonates is performed using gas source mass spectrometry, by reacting the carbonate samples with phosphoric acid and measuring the evolved CO2 gas. As an oxygen atom is lost during the conversion of CO32- groups to CO2, this reaction is hypothesized to result in mineral and acid digestion temperature-dependent fractionation. In order to quantify this fractionation between CO32- and CO2, this experiment seeks to determine acid fractionation factors for carbonate samples of varying composition by randomizing samples through intense heating and comparing analyte CO2 measured composition to the expected composition for a stochastically distributed sample. From this analysis, future carbonate measurements can be calibrated to account for acid digestion fractionation.

  14. Determination of cadmium, mercury and lead in seawater by electrothermal vaporization isotope dilution inductively coupled plasma mass spectrometry

    NASA Astrophysics Data System (ADS)

    Liu, Hung-Wei; Jiang, Shiuh-Jen; Liu, Shin-Hung

    1999-09-01

    Electrothermal vaporization isotope dilution inductively coupled plasma mass spectrometry (ETV-ID-ICP-MS) has been applied to the determination of Cd, Hg and Pb in seawater samples. The isotope ratios of the elements studied in each analytical run were calculated from the peak areas of each isotope. Various modifiers were tested for the best signal of these elements. After preliminary studies, 0.15% m/v TAC and 4% v/v HCl were added to the sample solution to work as the modifier. The ETV-ID-ICP-MS method has been applied to the determination of Cd, Hg and Pb in NASS-4 and CASS-3 reference seawater samples and seawater samples collected from Kaohsiung area. The results for reference sample NASS-4 and CASS-3 agreed satisfactorily with the reference values. Results for other samples determined by isotope dilution and method of standard additions agreed satisfactorily. Detection limits were approximately 0.002, 0.005 and 0.001 ng ml -1 for Cd, Hg and Pb in seawater, respectively, with the ETV-ICP-MS method. Precision between sample replicates was better than 20% for most of the determinations.

  15. Discrimination of geographical origin of lentils (Lens culinaris Medik.) using isotope ratio mass spectrometry combined with chemometrics.

    PubMed

    Longobardi, F; Casiello, G; Cortese, M; Perini, M; Camin, F; Catucci, L; Agostiano, A

    2015-12-01

    The aim of this study was to predict the geographic origin of lentils by using isotope ratio mass spectrometry (IRMS) in combination with chemometrics. Lentil samples from two origins, i.e. Italy and Canada, were analysed obtaining the stable isotope ratios of δ(13)C, δ(15)N, δ(2)H, δ(18)O, and δ(34)S. A comparison between median values (U-test) highlighted statistically significant differences (p<0.05) for all isotopic parameters between the lentils produced in these two different geographic areas, except for δ(15)N. Applying principal component analysis, grouping of samples was observed on the basis of origin but with overlapping zones; consequently, two supervised discriminant techniques, i.e. partial least squares discriminant analysis and k-nearest neighbours algorithm were used. Both models showed good performances with external prediction abilities of about 93% demonstrating the suitability of the methods developed. Subsequently, isotopic determinations were also performed on the protein and starch fractions and the relevant results are reported. PMID:26041202

  16. Matrix effects of calcium on high-precision sulfur isotope measurement by multiple-collector inductively coupled plasma mass spectrometry.

    PubMed

    Liu, Chenhui; Bian, Xiao-Peng; Yang, Tao; Lin, An-Jun; Jiang, Shao-Yong

    2016-05-01

    Multiple-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) has been successfully applied in the rapid and high-precision measurement for sulfur isotope ratios in recent years. During the measurement, the presence of matrix elements would affect the instrumental mass bias for sulfur and these matrix-induced effects have aroused a lot of researchers' interest. However, these studies have placed more weight on highlighting the necessity for their proposed correction protocols (e.g., chemical purification and matrix-matching) while less attention on the key property of the matrix element gives rise to the matrix effects. In this study, four groups of sulfate solutions, which have different concentrations of sulfur (0.05-0.60mM) but a constant sequence of atomic calcium/sulfur ratios (0.1-50), are investigated under wet (solution) and dry (desolvation) plasma conditions to make a detailed evaluation on the matrix effects from calcium on sulfur isotope measurement. Based on a series of comparative analyses, we indicated that, the matrix effects of calcium on both measured sulfur isotope ratios and detected (32)S signal intensities are dependent mainly on the absolute calcium concentration rather than its relative concentration ratio to sulfur (i.e., atomic calcium/sulfur ratio). Also, for the same group of samples, the matrix effects of calcium under dry plasma condition are much more significant than that of wet plasma. This research affords the opportunity to realize direct and relatively precise sulfur isotope measurement for evaporite gypsum, and further provides some suggestions with regard to sulfur isotope analytical protocols for sedimentary pore water. PMID:26946020

  17. A comparison of lead-isotope measurements on exploration-type samples using inductively coupled plasma and thermal ionization mass spectrometry

    USGS Publications Warehouse

    Gulson, B.L.; Meier, A.L.; Church, S.E.; Mizon, K.J.

    1989-01-01

    Thermal ionization mass spectrometry (TI-MS) has long been the method of choice for Pb-isotope determinations. More recently, however, inductively coupled plasma mass spectrometry (ICP-MS) has been used to determine Pb-isotope ratios for mineral exploration. The ICP-MS technique, although not as precise as TI-MS, may promote a wider application of Ph-isotope ratio methods because it allows individual isotopes to be determined more rapidly, generally without need for chemical separation (e.g., Smith et al., 1984; Hinners et al., 1987). To demonstrate the utility of the ICP-MS method, we have conducted a series of Pb-isotope measurements on several suites of samples using both TI-MS and ICP-MS. ?? 1989.

  18. Simplified sample preparation procedure for measuring isotope-enriched methylmercury by gas chromatography and inductively coupled plasma mass spectrometry.

    PubMed

    Avramescu, Mary-Luyza; Zhu, Joy; Yumvihoze, Emmanuel; Hintelmann, Holger; Fortin, Danielle; Lean, David R S

    2010-06-01

    Many procedures have been developed to measure the concentration of monomethylmercury (MeHg) from different sample matrices, and the use of stable isotopes of mercury now provides opportunities to determine its formation and degradation rates. Here, a modified procedure for measuring mercury isotopes in sediment samples that uses acid leaching-ion exchange-thiosulfate extraction (TSE) to isolate and purify the methylated mercury from the matrix is proposed. The latter is followed by aqueous-phase ethylation, purge and trap on Tenax, gas chromatography separation of ethylated mercury compounds, and inductively coupled plasma mass spectrometry detection. The new TSE procedure bridges together two well-known methods, the acid-leaching and distillation-derivatization procedures, offering the advantages of artifact-free formation of the first, and low detection limits and the possibility of quantification of individual isotopes of mercury of the second. The modified procedure retains the derivatization, purge and trap, and gas chromatography and inductively coupled plasma mass spectrometry (GC-ICP-MS) detection steps from the distillation-derivatization procedure, and eliminates the distillation step, which is not only laborious but also expensive, due to the high cost of installation and time-consuming cleaning process. Major advantages of the TSE procedure proposed include the extraction and analysis of a large number of samples in a short time, excellent analyte recoveries, and the lack of artifact formation. Sediment certified reference materials (CRMs), BCR 580 and IAEA 405, were used to test the TSE procedure accuracy. Recoveries between 94 to 106% and 95 to 96% were obtained for CRMs and spiked samples (Milli-Q(R) water), respectively. Comparisons among thiosulfate extraction, distillation, and acid-leaching procedures have shown good agreement of methylmercury values. PMID:20821567

  19. On the interference of Kr during carbon isotope analysis of methane using continuous-flow combustion-isotope ratio mass spectrometry

    NASA Astrophysics Data System (ADS)

    Schmitt, Jochen; Seth, Barbara; Bock, Michael; van der Veen, Carina; Mller, Lars; Sapart, Celia; Prokopiou, Markella; Sowers, Todd; Rckmann, Thomas; Fischer, Hubertus

    2014-05-01

    Stable carbon isotope analysis of methane (?13C of CH4) on atmospheric samples is one key method to constrain the current and past atmospheric CH4 budget. A frequently applied measurement technique is gas chromatography isotope ratio mass spectrometry coupled to a combustion-preconcentration unit. This report shows that the atmospheric trace gas krypton can severely interfere during the mass spectrometric measurement leading to significant biases in ?13C of CH4 if krypton is not sufficiently separated during the analysis. According to our experiments, the krypton interference is likely composed of two individual effects with the lateral tailing of the doubly charged 86Kr peak affecting the neighbouring m/z 44 and partially the m/z 45 Faraday cups. Additionally, a broad signal affecting m/z 45 and especially m/z 46 is assumed to result from scattered ions of singly charged krypton. The introduced bias in the measured isotope ratios is dependent on the chromatographic separation, the Kr to CH4 mixing ratio in the sample, the mass spectrometer source tuning as well as the detector configuration and can amount to up to several permil in ?13C. Apart from technical solutions to avoid this interference we present correction routines to a posteriori remove the bias.

  20. On the interference of Kr during carbon isotope analysis of methane using continuous-flow combustion-isotope ratio mass spectrometry

    NASA Astrophysics Data System (ADS)

    Schmitt, J.; Seth, B.; Bock, M.; van der Veen, C.; Mller, L.; Sapart, C. J.; Prokopiou, M.; Sowers, T.; Rckmann, T.; Fischer, H.

    2013-05-01

    Stable carbon isotope analysis of methane (?13C of CH4) on atmospheric samples is one key method to constrain the current and past atmospheric CH4 budget. A frequently applied measurement technique is gas chromatography (GC) isotope ratio mass spectrometry (IRMS) coupled to a combustion-preconcentration unit. This report shows that the atmospheric trace gas krypton (Kr) can severely interfere during the mass spectrometric measurement, leading to significant biases in ?13C of CH4, if krypton is not sufficiently separated during the analysis. According to our experiments, the krypton interference is likely composed of two individual effects, with the lateral tailing of the doubly charged 86Kr peak affecting the neighbouring m/z 44 and partially the m/z 45 Faraday cups. Additionally, a broad signal affecting m/z 45 and especially m/z 46 is assumed to result from scattered ions of singly charged krypton. The introduced bias in the measured isotope ratios is dependent on the chromatographic separation, the krypton-to-CH4 mixing ratio in the sample, the focusing of the mass spectrometer as well as the detector configuration and can amount to up to several per mil in ?13C. Apart from technical solutions to avoid this interference, we present correction routines to a posteriori remove the bias.

  1. High-temperature pyrolysis/gas chromatography/isotope ratio mass spectrometry: simultaneous measurement of the stable isotopes of oxygen and carbon in cellulose.

    PubMed

    Woodley, Ewan J; Loader, Neil J; McCarroll, Danny; Young, Giles H F; Robertson, Iain; Heaton, Timothy H E; Gagen, Mary H; Warham, Joseph O

    2012-01-30

    Stable isotope analysis of cellulose is an increasingly important aspect of ecological and palaeoenvironmental research. Since these techniques are very costly, any methodological development which can provide simultaneous measurement of stable carbon and oxygen isotope ratios in cellulose deserves further exploration. A large number (3074) of tree-ring ?-cellulose samples are used to compare the stable carbon isotope ratios (?(13)C) produced by high-temperature (1400C) pyrolysis/gas chromatography (GC)/isotope ratio mass spectrometry (IRMS) with those produced by combustion GC/IRMS. Although the two data sets are very strongly correlated, the pyrolysis results display reduced variance and are strongly biased towards the mean. The low carbon isotope ratios of tree-ring cellulose during the last century, reflecting anthropogenic disturbance of atmospheric carbon dioxide, are thus overestimated. The likely explanation is that a proportion of the oxygen atoms are bonding with residual carbon in the reaction chamber to form carbon monoxide. The 'pyrolysis adjustment', proposed here, is based on combusting a stratified sub-sample of the pyrolysis results, across the full range of carbon isotope ratios, and using the paired results to define a regression equation that can be used to adjust all the pyrolysis measurements. In this study, subsamples of 30 combustion measurements produced adjusted chronologies statistically indistinguishable from those produced by combusting every sample. This methodology allows simultaneous measurement of the stable isotopes of carbon and oxygen using high-temperature pyrolysis, reducing the amount of sample required and the analytical costs of measuring them separately. PMID:22173798

  2. Authenticity of carbon dioxide bubbles in French ciders through multiflow-isotope ratio mass spectrometry measurements.

    PubMed

    Gaillard, Laetitia; Guyon, Francois; Salagoïty, Marie-Hélène; Médina, Bernard

    2013-12-01

    A procedure to detect whether carbon dioxide was added to French ciders has been developed. For this purpose, an optimised and simplified method is proposed to determine (13)C/(12)C isotope ratio of carbon dioxide (δ(13)C) in ciders. Three critical steps were checked: (1) influence of atmospheric CO2 remaining in the loaded vial, (2) impact of helium flush, (3) sampling speed. This study showed that atmospheric CO2 does not impact the measurement, that helium flush can lead to isotopic fractionation and finally, that a fractionation occurs only 5h after bottle opening. The method, without any other preparation, consists in sampling 0.2 mL of cold (4 °C) cider in a vial that is passed in an ultrasonic bath for 10 min at room temperature to enhance cider de-carbonation. The headspace CO2 is then analysed using the link Multiflow®-isotope ratio mass spectrometer. Each year, a data bank is developed by fermenting authentic apples juices in order to control cider authenticity. Over a four year span (2008-2011), the CO2 produced during the fermentation step was studied. This set of 61 authentic ciders, from various French production areas, was used to determine a δ(13)C value range of -22.59±0.92‰ for authentic ciders CO2 bubbles. 75 commercial ciders were analysed with this method. Most of the samples analysed present a gas δ(13)C value in the expected range. Nevertheless, some ciders have δ(13)C values outside the 3σ limit, revealing carbonation by technical CO2. This practice is not allowed for organic, "Controlled Appellation of Origin" ciders and ciders specifying natural carbonation on the label. PMID:23870934

  3. An analytical system for stable isotope analysis on carbon monoxide using continuous-flow isotope-ratio mass spectrometry

    NASA Astrophysics Data System (ADS)

    Pathirana, S. L.; van der Veen, C.; Popa, M. E.; Röckmann, T.

    2015-12-01

    A fully automated system for the determination of δ13C and δ18O in atmospheric CO has been developed. CO is extracted from an air sample and converted into carbon dioxide (CO2) using the Schütze reagent. The isotopic composition is determined with an isotope-ratio mass spectrometer (IRMS) technique. The entire system is continuously flushed with high-purity helium (He), the carrier gas. The blank signal of the Schütze reagent is ~ 4 nmol mol-1, or 1-3 % of the typical sample size. The repeatability is 0.1 ‰ for δ13C and 0.2 ‰ for δ18O. The peak area allows for simultaneous determination of the mole fraction with an analytical repeatability of ~ 0.7 nmol mol-1 for 100 mL of ambient air (185.4 nmol mol-1 of CO). An automated single measurement is performed in only 18 min, and the achieved time efficiency (and small volume of sample air) allows for repetitive measurements practically.

  4. Use of inductively coupled plasma-mass spectrometry in boron-10 stable isotope experiments with plants, rats, and humans.

    PubMed

    Vanderpool, R A; Hoff, D; Johnson, P E

    1994-11-01

    The commercial availability of inductively coupled plasma-mass spectrometry technology (ICP-MS) has presented the opportunity to measure the boron concentrations and isotope ratios in a large number of samples with minimal sample preparation. A typical analytical sequence for fecal samples consists of 25 acid blanks, 1 digestion blank, 5 calibration solutions, 4 standard reference material solutions, 10 samples, and 4 natural abundance bias standards. Boron detection limits (3 x 1 sigma) for acid blanks are 0.11 ppb for 10B, and 0.40 ppb for 11B. Isotope ratios were measured in fecal samples with 20 to 50 ppb boron with < 2% relative standard deviation. Rapid washout and minimal memory effects were observed for a 50 ppb beryllium internal standard, but a 200 ppb boron biological sample had a 1.0 ppb boron memory after a 6-min washout. Boron isotope ratios in geological materials are highly variable; apparently this variability is reflected in plants of a fixed natural abundance value for boron requires that a natural abundance ratio be determined for each sample or related data set. The natural abundance variability also prevents quantitation and calculation of isotope dilution by instrument-supplied software. To measure boron transport in animal systems, 20 micrograms of 10B were fed to a fasted rat. During the 3 days after a 10B oral dose, 95% of the 10B was recovered from the urine and 4% from the feces. Urinary isotope ratios, 11B/10B, changed from a natural abundance of 4.1140 to an enriched value of 0.95077, a 77% change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7889873

  5. Probing Protein 3D Structures and Conformational Changes Using Electrochemistry-Assisted Isotope Labeling Cross-Linking Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Zheng, Qiuling; Zhang, Hao; Wu, Shiyong; Chen, Hao

    2016-02-01

    This study presents a new chemical cross-linking mass spectrometry (MS) method in combination with electrochemistry and isotope labeling strategy for probing both protein three-dimensional (3D) structures and conformational changes. For the former purpose, the target protein/protein complex is cross-linked with equal mole of premixed light and heavy isotope labeled cross-linkers carrying electrochemically reducible disulfide bonds (i.e., DSP-d0 and DSP-d8 in this study, DSP = dithiobis[succinimidyl propionate]), digested and then electrochemically reduced followed with online MS analysis. Cross-links can be quickly identified because of their reduced intensities upon electrolysis and the presence of doublet isotopic peak characteristics. In addition, electroreduction converts cross-links into linear peptides, facilitating MS/MS analysis to gain increased information about their sequences and modification sites. For the latter purpose of probing protein conformational changes, an altered procedure is adopted, in which the protein in two different conformations is cross-linked using DSP-d0 and DSP-d8 separately, and then the two protein samples are mixed in 1:1 molar ratio. The merged sample is subjected to digestion and electrochemical mass spectrometric analysis. In such a comparative cross-linking experiment, cross-links could still be rapidly recognized based on their responses to electrolysis. More importantly, the ion intensity ratios of light and heavy isotope labeled cross-links reveal the conformational changes of the protein, as exemplified by examining the effect of Ca2+ on calmodulin conformation alternation. This new cross-linking MS method is fast and would have high value in structural biology.

  6. Emerging use of isotope ratio mass spectrometry as a tool for discrimination of 3,4-methylenedioxymethamphetamine by synthetic route.

    PubMed

    Buchanan, Hilary A S; Daéid, Niamh Nic; Meier-Augenstein, Wolfram; Kemp, Helen F; Kerr, William J; Middleditch, Michael

    2008-05-01

    Drug profiling, or the ability to link batches of illicit drugs to a common source or synthetic route, has long been a goal of law enforcement agencies. Research in the past decade has explored drug profiling with isotope ratio mass spectrometry (IRMS). This type of research can be limited by the use of substances seized by police, of which the provenance is unknown. Fortunately, however, some studies in recent years have been carried out on drugs synthesized in-house and therefore of known history. In this study, 18 MDMA samples were synthesized in-house from aliquots of the same precursor by three common reductive amination routes and analyzed for 13C, 15N, and 2H isotope abundance using IRMS. For these three preparative methods, results indicate that 2H isotope abundance data is necessary for discrimination by synthetic route. Furthermore, hierarchical cluster analysis using 2H data on its own or combined with 13C and/or 15N provides a statistical means for accurate discrimination by synthetic route. PMID:18355086

  7. Determination of the natural abundance ?15N of taurine by gas chromatography-isotope ratio measurement mass spectrometry.

    PubMed

    Tea, Illa; Antheaume, Ingrid; Besnard, Jorick; Robins, Richard J

    2010-12-15

    The measurement of the nitrogen isotope ratio of taurine (2-aminoethanesulphonic acid) in biological samples has a large number of potential applications. Taurine is a small water-soluble molecule which is notoriously difficult to analyze due to its polarity and functionality. A method is described which allows the determination of the natural abundance ?(15)N values of taurine and structural analogues, such as 3-amino-1-propanesulphonic acid (APSA), by isotope ratio mass spectrometry interfaced to gas chromatography (GC-irm-MS). The one-step protocol exploits the simultaneous derivatization of both functionalities of these aminosulphonic acids by reaction with triethylorthoacetate (TEOA). Conditions have been established which ensure quantitative reaction thus avoiding any nitrogen isotope fractionation during derivatization and workup. The differences in the ?(15)N values of derivatized and non-derivatized taurine and APSA all fall within the working range of 0.4 (-0.02 to 0.39). When applied to four sources of taurine with various ?(15)N values, the method achieved excellent reproducibility and accuracy. The optimized method enables the determination of the natural abundance ?(15)N values of taurine over the concentration range 1.5-7.84 mol.mL(-1) in samples of biological origin. PMID:21072793

  8. Determination of thiol metabolites in human urine by stable isotope labeling in combination with pseudo-targeted mass spectrometry analysis.

    PubMed

    Liu, Ping; Qi, Chu-Bo; Zhu, Quan-Fei; Yuan, Bi-Feng; Feng, Yu-Qi

    2016-01-01

    Precursor ion scan and multiple reaction monitoring scan (MRM) are two typical scan modes in mass spectrometry analysis. Here, we developed a strategy by combining stable isotope labeling (IL) with liquid chromatography-mass spectrometry (LC-MS) under double precursor ion scan (DPI) and MRM for analysis of thiols in 5 types of human cancer urine. Firstly, the IL-LC-DPI-MS method was applied for non-targeted profiling of thiols from cancer samples. Compared to traditional full scan mode, the DPI method significantly improved identification selectivity and accuracy. 103 thiol candidates were discovered in all cancers and 6 thiols were identified by their standards. It is worth noting that pantetheine, for the first time, was identified in human urine. Secondly, the IL-LC-MRM-MS method was developed for relative quantification of thiols in cancers compared to healthy controls. All the MRM transitions of light and heavy labeled thiols were acquired from urines by using DPI method. Compared to DPI method, the sensitivity of MRM improved by 2.1-11.3 folds. In addition, the concentration of homocysteine, ?-glutamylcysteine and pantetheine enhanced more than two folds in cancer patients compared to healthy controls. Taken together, the method demonstrated to be a promising strategy for identification and comprehensive quantification of thiols in human urines. PMID:26888486

  9. [Determination of polychlorinated naphthalenes in environmental samples by isotope dilution gas chromatography-triple quadrupole mass spectrometry].

    PubMed

    Liu, Zhitong; Zhang, Bing; Wang, Wenwen; Liu, Guorui; Gao, Lirong; Zheng, Minghui

    2013-09-01

    An isotope dilution gas chromatography combined with triple quadrupole mass spectrometry (GC-MS/MS) method was established for the analysis of twenty polychlorinated naphthalenes (PCNs) congeners in environmental samples. The linear correlation coefficients (R2) of calibration curves were greater than 0.99 in the concentration range of 0.5 - 200 microg/L for all the twenty PCN congeners. The average relative response factors (RRF) were calculated based on a seven-point calibration for the twenty PCN congeners. The relative standard deviations (RSDs) of all the congeners were below 15% (n = 7). The limits of detection (LOD) of the established method ranged from 0.04 to 0.48 microg/L for the twenty PCN congeners. The recoveries of matrix spiked samples ranged from 45.2% to 87.9%, and the RSDs ranged from 0.4% to 21.2%. The sediment samples and stack gas samples collected from secondary aluminum smelting were analyzed by the established method. The obtained results were also compared with the data analyzed by high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS) method. The comparison indicated that the data of the established method was in good agreement with those of HRGC/HRMS method with the RSDs of 0.5% - 41.4%. Consequently, the established GC-MS/MS method can be applied to the determination of PCNs in environmental samples. PMID:24392626

  10. Conformational changes of recombinant monoclonal antibodies by limited proteolytic digestion, stable isotope labeling, and liquid chromatography-mass spectrometry.

    PubMed

    Ponniah, Gomathinayagam; Nowak, Christine; Kita, Adriana; Cheng, Guilong; Kori, Yekaterina; Liu, Hongcheng

    2016-03-15

    Limited proteolytic digestion is a method with a long history that has been used to study protein domain structures and conformational changes. A method of combining limited proteolytic digestion, stable isotope labeling, and mass spectrometry was established in the current study to investigate protein conformational changes. Recombinant monoclonal antibodies with or without the conserved oligosaccharides, and with or without oxidation of the conserved methionine residues, were used to test the newly proposed method. All of the samples were digested in ammonium bicarbonate buffer prepared in normal water. The oxidized deglycosylated sample was also digested in ammonium bicarbonate buffer prepared in (18)O-labeled water. The sample from the digestion in (18)O-water was spiked into each sample digested in normal water. Each mixed sample was subsequently analyzed by liquid chromatography-mass spectrometry (LC-MS). The molecular weight differences between the peptides digested in normal water versus (18)O-water were used to differentiate peaks from the samples. The relative peak intensities of peptides with or without the C-terminal incorporation of (18)O atoms were used to determine susceptibility of different samples to trypsin and chymotrypsin. The results demonstrated that the method was capable of detecting local conformational changes of the recombinant monoclonal antibodies caused by deglycosylation and oxidation. PMID:26747642

  11. Determination of thiol metabolites in human urine by stable isotope labeling in combination with pseudo-targeted mass spectrometry analysis

    NASA Astrophysics Data System (ADS)

    Liu, Ping; Qi, Chu-Bo; Zhu, Quan-Fei; Yuan, Bi-Feng; Feng, Yu-Qi

    2016-02-01

    Precursor ion scan and multiple reaction monitoring scan (MRM) are two typical scan modes in mass spectrometry analysis. Here, we developed a strategy by combining stable isotope labeling (IL) with liquid chromatography-mass spectrometry (LC-MS) under double precursor ion scan (DPI) and MRM for analysis of thiols in 5 types of human cancer urine. Firstly, the IL-LC-DPI-MS method was applied for non-targeted profiling of thiols from cancer samples. Compared to traditional full scan mode, the DPI method significantly improved identification selectivity and accuracy. 103 thiol candidates were discovered in all cancers and 6 thiols were identified by their standards. It is worth noting that pantetheine, for the first time, was identified in human urine. Secondly, the IL-LC-MRM-MS method was developed for relative quantification of thiols in cancers compared to healthy controls. All the MRM transitions of light and heavy labeled thiols were acquired from urines by using DPI method. Compared to DPI method, the sensitivity of MRM improved by 2.1–11.3 folds. In addition, the concentration of homocysteine, γ-glutamylcysteine and pantetheine enhanced more than two folds in cancer patients compared to healthy controls. Taken together, the method demonstrated to be a promising strategy for identification and comprehensive quantification of thiols in human urines.

  12. Determination of thiol metabolites in human urine by stable isotope labeling in combination with pseudo-targeted mass spectrometry analysis

    PubMed Central

    Liu, Ping; Qi, Chu-Bo; Zhu, Quan-Fei; Yuan, Bi-Feng; Feng, Yu-Qi

    2016-01-01

    Precursor ion scan and multiple reaction monitoring scan (MRM) are two typical scan modes in mass spectrometry analysis. Here, we developed a strategy by combining stable isotope labeling (IL) with liquid chromatography-mass spectrometry (LC-MS) under double precursor ion scan (DPI) and MRM for analysis of thiols in 5 types of human cancer urine. Firstly, the IL-LC-DPI-MS method was applied for non-targeted profiling of thiols from cancer samples. Compared to traditional full scan mode, the DPI method significantly improved identification selectivity and accuracy. 103 thiol candidates were discovered in all cancers and 6 thiols were identified by their standards. It is worth noting that pantetheine, for the first time, was identified in human urine. Secondly, the IL-LC-MRM-MS method was developed for relative quantification of thiols in cancers compared to healthy controls. All the MRM transitions of light and heavy labeled thiols were acquired from urines by using DPI method. Compared to DPI method, the sensitivity of MRM improved by 2.1–11.3 folds. In addition, the concentration of homocysteine, γ-glutamylcysteine and pantetheine enhanced more than two folds in cancer patients compared to healthy controls. Taken together, the method demonstrated to be a promising strategy for identification and comprehensive quantification of thiols in human urines. PMID:26888486

  13. Quantitation of asparagine deamidation by isotope labeling and liquid chromatography coupled with mass spectrometry analysis.

    PubMed

    Liu, Hongcheng; Wang, Fengqiang; Xu, Wei; May, Kimberly; Richardson, Daisy

    2013-01-01

    Nonenzymatic asparagine (Asn) deamidation is one of the commonly observed posttranslational modifications of proteins. Recent development of several specific analytical methods has allowed for efficient identification and differentiation of the deamidation products (i.e., isoaspartate [isoAsp] and aspartate [Asp]). Isotope labeling of isoAsp and Asp that are generated during sample preparation by 18O has been developed and can differentiate isoAsp and Asp as analytical artifacts from those present in the samples prior to sample preparation for an accurate quantitation. However, the 18O labeling procedure has a limitation due to the additional incorporation of up to two 18O atoms into the peptide C-terminal carboxyl groups. Variability in the incorporation of 18O atoms into the peptide C-terminal carboxyl groups results in complicated mass spectra and hinders data interpretation. This limitation can be overcome by the dissection of the complicated mass spectra using a calculation method presented in the current study. The multiple-step calculation procedure has been successfully employed to determine the levels of isoAsp and Asp that are present in the sample prior to sample treatment. PMID:23017877

  14. Simultaneous determination of mass-dependent isotopic fractionation and radiogenic isotope variation of strontium in geochemical samples by multiple collector-ICP-mass spectrometry.

    PubMed

    Ohno, Takeshi; Hirata, Takafumi

    2007-11-01

    We present a method to determine (88)Sr/(86)Sr and (87)Sr/(86)Sr simultaneously. The former variation reflects the mass-dependent isotopic fractionation through the physico-chemical processes, and the latter originates from beta(-)-decay of the parent nuclide (87)Rb as well as the mass-dependent isotopic fractionation. In order to determine the mass-dependent isotopic fractionation, the mass-discrimination effect on (88)Sr/(86)Sr was externally corrected by an exponential law using Zr. For the radiogenic growth of (87)Sr/(86)Sr, the mass-dependent isotopic fractionation effect on (87)Sr/(86)Sr was corrected by a conventional correction technique using the (88)Sr/(86)Sr ratio. The reproducibility of the (88)Sr/(86)Sr and (87)Sr/(86)Sr measurements for a high-purity Sr chemical reagent was 0.06 per thousand (2SD, n = 20) and 0.07 per thousand (2SD, n = 20), respectively. Strontium isotopic ratios ((88)Sr/(86)Sr and (87)Sr/(86)Sr) were measured on six geochemical reference materials (igneous rock: JB-1a and JA-2; carbonate mineral: JLs-1, JDo-1, JCp-1 and JCt-1) and one seawater sample. The resulting (87)Sr/(86)Sr ratios obtained here were consistent with previously published data within the analytical uncertainties. The resulting (88)Sr/(86)Sr ratios for igneous rock samples did not vary significantly within the samples, whereas the carbonate samples showed enrichments of the lighter Sr isotopes over the seawater sample. The (88)Sr/(86)Sr ratio of geochemical samples could reflect the physico-chemical processes for the sample formation. Also, a combined discussion of (88)Sr/(86)Sr and (87)Sr/(86)Sr of samples will render multi-dimensional information on geochemical processes. PMID:17998744

  15. Application of Screening Experimental Designs to Assess Chromatographic Isotope Effect upon Isotope-Coded Derivatization for Quantitative Liquid ChromatographyMass Spectrometry

    PubMed Central

    2015-01-01

    Isotope effect may cause partial chromatographic separation of labeled (heavy) and unlabeled (light) isotopologue pairs. Together with a simultaneous matrix effect, this could lead to unacceptable accuracy in quantitative liquid chromatographymass spectrometry assays, especially when electrospray ionization is used. Four biologically relevant reactive aldehydes (acrolein, malondialdehyde, 4-hydroxy-2-nonenal, and 4-oxo-2-nonenal) were derivatized with light or heavy (d3-, 13C6-, 15N2-, or 15N4-labeled) 2,4-dinitrophenylhydrazine and used as model compounds to evaluate chromatographic isotope effects. For comprehensive assessment of retention time differences between light/heavy pairs under various gradient reversed-phase liquid chromatography conditions, major chromatographic parameters (stationary phase, mobile phase pH, temperature, organic solvent, and gradient slope) and different isotope labelings were addressed by multiple-factor screening using experimental designs that included both asymmetrical (Addelman) and PlackettBurman schemes followed by statistical evaluations. Results confirmed that the most effective approach to avoid chromatographic isotope effect is the use of 15N or 13C labeling instead of deuterium labeling, while chromatographic parameters had no general influence. Comparison of the alternate isotope-coded derivatization assay (AIDA) using deuterium versus 15N labeling gave unacceptable differences (>15%) upon quantifying some of the model aldehydes from biological matrixes. On the basis of our results, we recommend the modification of the AIDA protocol by replacing d3-2,4-dinitrophenylhydrazine with 15N- or 13C-labeled derivatizing reagent to avoid possible unfavorable consequences of chromatographic isotope effects. PMID:24922593

  16. Accuracy of some routine method used in clinical chemistry as judged by isotope dilution-mass spectrometry

    SciTech Connect

    Bjoerkhem, I.; Bergman, A.; Falk, O.; Kallner, A.; Lantto, O.; Svensson, L.; Akerloef, E.; Blomstrand, R.

    1981-05-01

    Serum from patients was pooled, filtered, dispensed, and frozen. This pooled specimen was used for accuracy control in 64 participating laboratories in Sweden. Mean values (state-of-the-art values) were obtained for creatinine, cholesterol, glucose, urea, uric acid, and cortisol. These values were compared with values obtained with highly accurate reference methods based on isotope dilution-mass spectrometry. Differences were marked in the case of determination of creatinine and cortisol. Concerning the other components, the differences between the state-of-the-art value and the values obtained with the reference methods were negligible. Moreover, the glucose oxidase and the oxime methods for determination of glucose and urea were found to give significantly lower values than the hexokinase and urease methods, respectively. Researchers conclude that methods with a higher degree of accuracy are required for routine determination of creatinine and cortisol.

  17. Ultra trace determination of fluorobenzoic acids in reservoir and ground water using isotope dilution gas chromatography mass spectrometry.

    PubMed

    Mller, Karsten; Seubert, Andreas

    2014-06-01

    The accurate ultra-trace analysis of six fluorobenzoic acids (FBAs) via isotope dilution gas chromatography mass spectrometry through their deuterated analogues is described. North Sea reservoir and ground water samples were spiked with six deuterated FBAs (dFBAs), enriched using solid-phase extraction (SPE) and analysed using GC/MS after derivatisation with BF 3 MeOH. All FBAs were enriched and determined simultaneously. SPE allowed a 250-fold enrichment of the acids if 100 mL of sample volume was used. The method enables the determination of FBAs down to the range of 8-37 ng L (-1) with recoveries between 66 % and 85 %. It uses low amounts of chemicals and is adaptable to larger and smaller sample volumes. PMID:24620719

  18. Determination of dicyandiamide in infant formula by stable isotope dilution hydrophilic interaction liquid chromatography with tandem mass spectrometry.

    PubMed

    Inoue, Koichi; Sakamoto, Tasuku; Min, Jun Zhe; Todoroki, Kenichiro; Toyo'oka, Toshimasa

    2014-08-01

    Dicyandiamide is a compound for reducing the negative effects of greenhouse gas emissions and nitrate leaching into waterways. In this study, the trace contamination of dicyandiamide in infant formula was analysed by stable isotope dilution hydrophilic interaction liquid chromatography with tandem mass spectrometry (HILIC-MS/MS). Dicyandiamide and a stable isotope internal standard were monitored by multiple reaction-monitoring with mass transitions: m/z 85?68/43 and m/z 89?71/45 in the electrospray positive ion mode. For sample preparation of the infant formula, a diluted/filtered procedure was developed for this assay. The calculated LOD and LOQ values were 0.01 or 0.05ng/mL for the standard solution, respectively. The averaged recovery and precision were 110.8% and 7.4%, respectively. This assay was applied to monitor 23 infant formulas, and the dicyandiamide contamination in one sample was detected and quantified at 79.11.2ng/g (ppb) powder. We suggest that it is necessary to cautiously monitor the DCD in common products from international countries. PMID:24629985

  19. Simultaneous Detection of Androgen and Estrogen Abuse in Breeding Animals by Gas Chromatography-Mass Spectrometry/Combustion/Isotope Ratio Mass Spectrometry (GC-MS/C/IRMS) Evaluated against Alternative Methods.

    PubMed

    Janssens, Geert; Mangelinckx, Sven; Courtheyn, Dirk; De Kimpe, Norbert; Matthijs, Bert; Le Bizec, Bruno

    2015-09-01

    The administration of synthetic homologues of naturally occurring steroids can be demonstrated by measuring (13)C/(12)C isotopic ratios of their urinary metabolites. Gas chromatography-mass spectrometry/combustion/isotope ratio mass spectrometry (GC-MS/C/IRMS) was used in this study to appraise in a global approach isotopic deviations of two 17β-testosterone metabolites (17α-testosterone and etiocholanolone) and one 17β-estradiol metabolite (17α-estradiol) together with those of 5-androstene-3β,17α-diol as endogenous reference compound (ERC). Intermediate precisions of 0.35‰, 1.05‰, 0.35‰, and 0.21‰, respectively, were observed (n = 8). To assess the performance of the analytical method, a bull and a heifer were treated with 17β-testosterone propionate and 17β-estradiol-3-benzoate. The sensitivity of the method permitted the demonstration of 17β-estradiol treatment up to 24 days. For 17β-testosterone treatment, the detection windows were 3 days and 24 days for the bull and the heifer, respectively. The capability of GC-MS/C/IRMS to demonstrate natural steroid abuse for urinary steroids was eventually compared to those of mass spectrometry (LC-MS/MS) when measuring intact steroid esters in blood and hair. PMID:26271751

  20. Metabolic Tracing Using Stable Isotope-Labeled Substrates and Mass Spectrometry in the Perfused Mouse Heart.

    PubMed

    Ruiz, Matthieu; Gélinas, Roselle; Vaillant, Fanny; Lauzier, Benjamin; Des Rosiers, Christine

    2015-01-01

    There has been a resurgence of interest for the field of cardiac metabolism catalyzed by evidence demonstrating a role of metabolic dysregulation in the pathogenesis of heart disease as well as the increased need for new therapeutic targets for patients with these diseases. In this regard, measuring substrate fluxes is critical in providing insight into the dynamics of cellular metabolism and in delineating the regulation of metabolite production and utilization. This chapter provides a comprehensive description of concepts, guidelines, and tips to assess metabolic fluxes relevant to energy substrate metabolism using (13)C-labeled substrates and (13)C-isotopomer analysis by gas chromatography-mass spectrometry (GC-MS), and the ex vivo working heart as study model. The focus will be on the mouse and on flux parameters, which are commonly assessed in the field, namely, those relevant to substrate selection for energy metabolism, specifically the relative contribution of carbohydrate (glucose, lactate, and pyruvate) and fatty acid oxidation to acetyl-CoA formation for citrate synthesis, glycolysis, as well as anaplerosis. We provide detailed procedures for the heart isolation and perfusion in the working mode as well as for sample processing for metabolite extraction and analysis by GC-MS and subsequent data processing for calculation of metabolic flux parameters. Finally, we address practical considerations and discuss additional applications and future challenges. PMID:26358903

  1. Potential of ion chromatography coupled to isotope ratio mass spectrometry via a liquid interface for beverages authentication.

    PubMed

    Guyon, Francois; Gaillard, Laetitia; Brault, Audrey; Gaultier, Nicolas; Salagoty, Marie-Hlne; Mdina, Bernard

    2013-12-27

    New tools for the determination of characteristic parameters for food authentication are requested to prevent food adulteration from which health concerns, unfair competition could follow. A new coupling in the area of compound-specific carbon 13 isotope ratio (?(13)C) analysis was developed to simultaneously quantify ?(13)C values of sugars and organic acids. The coupling of ion chromatography (IC) together with isotope ratio mass spectrometry (IRMS) can be achieved using a liquid interface allowing a chemical oxidation (co) of organic matter. Synthetic solutions containing 1 polyol (glycerol), 3 carbohydrates (sucrose, glucose and fructose) and 12 organic acids (gluconic, lactic, malic, tartaric, oxalic, fumaric, citric and isocitric) were used to optimize chromatographic conditions (concentration gradient and 3 types of column) and the studied isotopic range (-32.28 to -10.65) corresponds to the values found in food products. Optimum chromatographic conditions are found using an IonPac AS15, an elution flow rate of 0.3mLmin(-1) and a linear concentration gradient from 2 to 76mM (rate 21mMmin(-1)). Comparison between ?(13)C value individually obtained for each compound with the coupling IRMS and elemental analyzer, EA-IRMS, and the ones measured on the mixture of compounds by IC-co-IRMS does not reveal any isotope fractionation. Thus, under these experimental conditions, IC-co-IRMS results are accurate and reproducible. This new coupling was tested on two food matrices, an orange juice and a sweet wine. Some optimization is necessary as the concentration range between sugars and organic acids is too large: an increase in the filament intensity of the IRMS is necessary to simultaneously detect the two compound families. These first attempts confirm the good results obtained on synthetic solutions and the strong potential of the coupling IC-co-IRMS in food authentication area. PMID:24267317

  2. Accurate determination of selected pesticides in soya beans by liquid chromatography coupled to isotope dilution mass spectrometry.

    PubMed

    Huertas Prez, J F; Sejere-Olsen, B; Fernndez Alba, A R; Schimmel, H; Dabrio, M

    2015-05-01

    A sensitive, accurate and simple liquid chromatography coupled with mass spectrometry method for the determination of 10 selected pesticides in soya beans has been developed and validated. The method is intended for use during the characterization of selected pesticides in a reference material. In this process, high accuracy and appropriate uncertainty levels associated to the analytical measurements are of utmost importance. The analytical procedure is based on sample extraction by the use of a modified QuEChERS (quick, easy, cheap, effective, rugged, safe) extraction and subsequent clean-up of the extract with C18, PSA and Florisil. Analytes were separated on a C18 column using gradient elution with water-methanol/2.5 mM ammonium acetate mobile phase, and finally identified and quantified by triple quadrupole mass spectrometry in the multiple reaction monitoring mode (MRM). Reliable and accurate quantification of the analytes was achieved by means of stable isotope-labelled analogues employed as internal standards (IS) and calibration with pure substance solutions containing both, the isotopically labelled and native compounds. Exceptions were made for thiodicarb and malaoxon where the isotopically labelled congeners were not commercially available at the time of analysis. For the quantification of those compounds methomyl-(13)C2(15)N and malathion-D10 were used respectively. The method was validated according to the general principles covered by DG SANCO guidelines. However, validation criteria were set more stringently. Mean recoveries were in the range of 86-103% with RSDs lower than 8.1%. Repeatability and intermediate precision were in the range of 3.9-7.6% and 1.9-8.7% respectively. LODs were theoretically estimated and experimentally confirmed to be in the range 0.001-0.005 mg kg(-1) in the matrix, while LOQs established as the lowest spiking mass fractionation level were in the range 0.01-0.05 mg kg(-1). The method reliably identifies and quantifies the selected pesticides in soya beans at appropriate uncertainty levels, making it suitable for the characterization of candidate reference materials. PMID:25770614

  3. On the interference of 86Kr2+ during carbon isotope analysis of atmospheric methane using continuous flow combustion - isotope ratio mass spectrometry

    NASA Astrophysics Data System (ADS)

    Schmitt, J.; Seth, B.; Bock, M.; van der Veen, C.; Mller, L.; Sapart, C. J.; Prokopiou, M.; Sowers, T.; Rckmann, T.; Fischer, H.

    2013-02-01

    Stable carbon isotope analysis of methane (?13C of CH4) on atmospheric samples is one key method to constrain the current and past atmospheric CH4 budget. A frequently applied measurement technique is gas chromatography isotope ratio mass spectrometry coupled to a combustion-preconcentration unit. This report shows that the atmospheric trace gas krypton can severely interfere during the mass spectrometric measurement leading to significant biases in ?13C of CH4 if krypton is not sufficiently separated during the analysis. The effect comes about by the lateral tailing of the peak of doubly charged 86Kr in the neighbouring m/z, 44, 45, and 46 Faraday cups. Accordingly, the introduced bias is dependent on the chromatographic separation, the Kr to CH4 mixing ratio in the sample, the mass spectrometer source tuning as well as the detector configuration and can amount to up to several permil in ?13C. Apart from technical solutions to avoid this interference we present correction routines to a posteriori remove the bias.

  4. Determination of technetium-99 in aqueous samples by isotope dilution inductively coupled plasma-mass spectrometry

    SciTech Connect

    Beals, D.M.

    1992-09-01

    An isotope dilution/inductively coupled plasma mass spectrometric method (ID/ICP-MS) for measuring the concentration of technetium-99 in aqueous samples was developed at the Savannah River Technology Center (SRTC). The procedure is faster than radiometric techniques, is also less subject to interferences, and has equal or better detection limits. It is currently being used to measure the concentration of {sup 99}Tc in samples of Savannah River water collected in the vicinity of the Savannah River Site. In this method, one liter samples of water are spiked with {sup 97}Tc. After equilibration, the technetium is extracted from the sample with a chromatographic resin. Interfering elements, molybdenum and ruthenium, are either not retained by the resin or are washed off with dilute nitric acid. The technetium is then eluted with more concentrated nitric acid, and the {sup 99}Tc/{sup 97}Tc ratio in the eluant is measured with an ICP-MS. The {sup 99}Tc concentration in the original sample is calculated from the {sup 99}Tc/{sup 97}Tc ratio. The chemical recovery of the extraction procedure is greater than 90%. The detection limit of the instrument, taken as three times the background counts at m/z = 99, is 0.6 part per trillion (ppt). The detection limit of the procedure, taken as three times the standard deviation of several reagent blank analyses, is 0.33 pCi/L.

  5. Determination of technetium-99 in aqueous samples by isotope dilution inductively coupled plasma-mass spectrometry

    SciTech Connect

    Beals, D.M.

    1992-01-01

    An isotope dilution/inductively coupled plasma mass spectrometric method (ID/ICP-MS) for measuring the concentration of technetium-99 in aqueous samples was developed at the Savannah River Technology Center (SRTC). The procedure is faster than radiometric techniques, is also less subject to interferences, and has equal or better detection limits. It is currently being used to measure the concentration of {sup 99}Tc in samples of Savannah River water collected in the vicinity of the Savannah River Site. In this method, one liter samples of water are spiked with {sup 97}Tc. After equilibration, the technetium is extracted from the sample with a chromatographic resin. Interfering elements, molybdenum and ruthenium, are either not retained by the resin or are washed off with dilute nitric acid. The technetium is then eluted with more concentrated nitric acid, and the {sup 99}Tc/{sup 97}Tc ratio in the eluant is measured with an ICP-MS. The {sup 99}Tc concentration in the original sample is calculated from the {sup 99}Tc/{sup 97}Tc ratio. The chemical recovery of the extraction procedure is greater than 90%. The detection limit of the instrument, taken as three times the background counts at m/z = 99, is 0.6 part per trillion (ppt). The detection limit of the procedure, taken as three times the standard deviation of several reagent blank analyses, is 0.33 pCi/L.

  6. Measurement of Niacin in a Variety of Food Samples by High Performance Liquid Chromatography-Stable Isotope Dilution Mass Spectrometry (Experimental Biology, April, 2007, Washington, D.C.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The availability of deuterium-labeled nicotinic acid makes stable isotope dilution mass spectrometry (SIDMS) coupled with liquid chromatography (LC) an attractive option for the determination of the water-soluble B-vitamin, niacin, in food samples. We have developed a method based on AOAC Peer-Verif...

  7. Measurement of Niacin in a Variety of Food Samples by High Performance Liquid Chromatography-Stable Isotope Dilution Mass Spectrometry (AOAC Annual Meeting, Minneapolis, MN, Sept. 2006)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The availability of deuterium-labeled nicotinic acid makes stable isotope dilution mass spectrometry (SIDMS) coupled with liquid chromatography (LC) an attractive option for the determination of the water-soluble B-vitamin, niacin, in food samples. We have developed a method based on AOAC Peer-Verif...

  8. DETERMINATION OF 5-METHYLTETRAHYDROFOLIC ACID IN HUMAN SERUM BY STABLE-ISOTOPE DILUTION HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This report describes a stable isotope liquid chromatography-mass spectrometry (LC-MS) method that was developed for the quantitative determination of 5-methyltetrahydrofolic acid (5-MTHFA) and folic acid in a variety of citrus juices. Folates were extracted from juices and the polyglutamyl side ch...

  9. Evaluation of matrix effect in isotope dilution mass spectrometry based on quantitative analysis of chloramphenicol residues in milk powder.

    PubMed

    Li, Xiu Qin; Yang, Zong; Zhang, Qing He; Li, Hong Mei

    2014-01-01

    In the present study, we developed a comprehensive strategy to evaluate matrix effect (ME) and its impact on the results of isotope dilution mass spectrometry (IDMS) in analysis of chloramphenicol (CAP) residues in milk powder. Stable isotope-labeled internal standards do not always compensate ME, which brings the variation of the ratio (the peak area of analyte/the peak area of isotope). In our investigation, impact factors of this variation were studied in the extraction solution of milk powder using three mass spectrometers coupled with different ion source designs, and deuterium-labeled chloramphenicol (D5-CAP) was used as the internal standard. ME from mobile phases, sample solvents, pre-treatment methods, sample origins and instruments was evaluated, and its impact on the results of IDMS was assessed using the IDMS correction factor (?). Our data showed that the impact of ME of mobile phase on the correction factor was significantly greater than that of sample solvent. Significant ion suppression and enhancement effects were observed in different pre-treated sample solutions. The IDMS correction factor in liquid-liquid extraction (LLE) and molecular imprinted polymer (MIP) extract with different instruments was greater or less 1.0, and the IDMS correction factor in hydrophilic lipophilic balance (HLB) and mix-mode cation exchange (MCX) extract with different instruments was all close to 1.0. To the instrument coupled with different ion source design, the impact of ME on IDMS quantitative results was significantly different, exhibiting a large deviation of 11.5%. Taken together, appropriate chromatographic conditions, pre-treatment methods and instruments were crucial to overcome ME and obtain reliable results, when IDMS methods were used in the quantitative analysis of trace target in complex sample matrix. PMID:24356223

  10. Isotope label-aided mass spectrometry reveals the influence of environmental factors on metabolism in single eggs of fruit fly.

    PubMed

    Tseng, Te-Wei; Wu, June-Tai; Chen, Yu-Chie; Urban, Pawel L

    2012-01-01

    In order to investigate the influence of light/dark cycle on the biosynthesis of metabolites during oogenesis, here we demonstrate a simple experimental protocol which combines in-vivo isotopic labeling of primary metabolites with mass spectrometric analysis of single eggs of fruit fly (Drosophila melanogaster). First, fruit flies were adapted to light/dark cycle using artificial white light. Second, female flies were incubated with an isotopically labeled sugar ((13)C(6)-glucose) for 12 h--either during the circadian day or the circadian night, at light or at dark. Third, eggs were obtained from the incubated female flies, and analyzed individually by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS): this yielded information about the extent of labeling with carbon-13. Since the incorporation of carbon-13 to uridine diphosphate glucose (UDP-glucose) in fruit fly eggs is very fast, the labeling of this metabolite was used as an indicator of the biosynthesis of metabolites flies/eggs during 12-h periods, which correspond to circadian day or circadian night. The results reveal that once the flies adapted to the 12-h-light/12-h-dark cycle, the incorporation of carbon-13 to UDP-glucose present in fruit fly eggs was not markedly altered by an acute perturbation to this cycle. This effect may be due to a relationship between biosynthesis of primary metabolites in developing eggs and an alteration to the intake of the labeled substrate - possibly related to the change of the feeding habit. Overall, the study shows the possibility of using MALDI-MS in conjunction with isotopic labeling of small metazoans to unravel the influence of environmental cues on primary metabolism. PMID:23185587

  11. Compound-specific hydrogen isotope analysis of heteroatom-bearing compounds via gas chromatography-chromium-based high-temperature conversion (Cr/HTC)-isotope ratio mass spectrometry.

    PubMed

    Renpenning, Julian; Kümmel, Steffen; Hitzfeld, Kristina L; Schimmelmann, Arndt; Gehre, Matthias

    2015-09-15

    The traditional high-temperature conversion (HTC) approach toward compound-specific stable isotope analysis (CSIA) of hydrogen for heteroatom-bearing (i.e., N, Cl, S) compounds has been afflicted by fractionation bias due to formation of byproducts HCN, HCl, and H2S. This study presents a chromium-based high-temperature conversion (Cr/HTC) approach for organic compounds containing nitrogen, chlorine, and sulfur. Following peak separation along a gas chromatographic (GC) column, the use of thermally stable ceramic Cr/HTC reactors at 1100-1500 °C and chemical sequestration of N, Cl, and S by chromium result in quantitative conversion of compound-specific organic hydrogen to H2 analyte gas. The overall hydrogen isotope analysis via GC-Cr/HTC-isotope ratio mass spectrometry (IRMS) achieved a precision of better than ± 5 mUr along the VSMOW-SLAP scale. The accuracy of GC-Cr/HTC-IRMS was validated with organic reference materials (RM) in comparison with online EA-Cr/HTC-IRMS and offline dual-inlet IRMS. The utility and reliability of the GC-Cr/HTC-IRMS system were documented during the routine measurement of more than 500 heteroatom-bearing organic samples spanning a δ(2)H range of -181 mUr to 629 mUr. PMID:26291200

  12. 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 holds conferences on mass spectrometry. For ten years, a special journal Mass-spektrometria has published papers on all disciplines of mass spectrometry. PMID:24378462

  13. Analysis of organophosphate flame retardants and plasticisers in water by isotope dilution gas chromatography-electron ionisation tandem mass spectrometry.

    PubMed

    Teo, Tiffany L L; McDonald, James A; Coleman, Heather M; Khan, Stuart J

    2015-10-01

    The widespread use of organophosphate flame retardants (PFRs) in commercial products have led to their increased presence in the environment. In this study, a rapid and reliable analytical method was developed for the analysis of five PFRs in water using gas chromatography tandem mass spectrometry (GC-MS/MS) with electron ionisation (EI) and a run time of 13 min. The PFRs investigated were tributyl phosphate (TBP), tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCPP), tris(1,3-dichloro-2-propyl) phosphate (TDCP) and triphenyl phosphate (TPP). Solid phase extraction (SPE) was undertaken to extract and concentrate target analytes from aqueous matrices. All water samples were extracted from a volume of 500 mL. Isotopically labelled compounds were used to account for analytical variability and for accurate quantification by isotope dilution. Method recoveries for all compounds were above 80% in all tested water samples. Method detection limits for all target analytes ranged from 0.3 to 24 ng/L in ultrapure water, tap water, seawater, surface water, secondary effluent and swimming pool water. Validation of this method confirmed satisfactory method stability with less than 1% coefficients of variation, verifying that this approach produced good reproducibility. PMID:26078137

  14. Geographical origin of cereal grains based on element analyser-stable isotope ratio mass spectrometry (EA-SIRMS).

    PubMed

    Wu, Yuluan; Luo, Donghui; Dong, Hao; Wan, Juan; Luo, Haiying; Xian, Yanping; Guo, Xindong; Qin, Fangfang; Han, Wanqing; Wang, Li; Wang, Bin

    2015-05-01

    The stable carbon and nitrogen isotopic compositions (?(13)C and ?(13)N) of different cereal grains from different regions were determined, using element analyser-stable isotope ratio mass spectrometry (EA-SIRMS) as the key method. Systematically, ?(13)C and ?(13)N of 5 kinds of cereal grains of different origins, 30 wheat samples from different cultivation areas and 160 rice samples of different cultivars from Guangdong province of China were examined. The results indicated that the ?(13)C values of rice, soybean, millet, wheat and corn were significantly (P < 0.05) different within different origins (Heilongjiang, Shandong and Jiangsu province of China), respectively, while ?(13)N values were not. Interestingly, there exists discrimination between these 5 kinds of cereals grains, no matter C-3 or C-4 plants. Further study showed that the ?(13)C values of wheat from Australia, the USA, Canada, and Jiangsu and Shandong province of China were also significantly (P < 0.01) different. Furthermore, the P-value test for 160 rice samples of 5 cultivars was not significant (P > 0.05), which indicated that the cultivar of cereal grains was not significant based on ?(13)C value. Thus, the comparison of ?(13)C would be potentially useful for rapid and routine discrimination of geographical origin of cereal grains. PMID:25529718

  15. Simultaneous determination of ?-, ?- and ?-hexabromocyclododecane diastereoisomers in water samples by isotope dilution mass spectrometry using (81)Br-labeled analogs.

    PubMed

    Somoano-Blanco, Lourdes; Rodriguez-Gonzalez, Pablo; Centineo, Giusepe; Fonseca, Sergio Garca; Garcia Alonso, J Ignacio

    2016-01-15

    This work describes the synthesis, characterization and application of three (81)Br-labeled diastereosiomers of hexabromocyclododecane (HBCD) for the accurate and precise determination of ?-, ?- and ?-HBCD in water samples by isotope dilution mass spectrometry. The synthesis of the labeled analogs was carried out by bromination of cis, trans, trans-1,5,9-cyclododecatriene with (81)Br-enriched bromine. After isolation and purification by semipreparative HPLC, each diastereoisomer was characterized in terms of concentration and isotopic enrichment. Then, they were added to the samples to simultaneously quantify the three HBCD diastereoisomers in a single LC-MS/MS injection without resorting to a methodological calibration graph. The results obtained here demonstrate that the use of (81)Br-labeled analogs provides accurate and precise determinations of ?-, ?- and ?-HBCD in real water samples. The limits of quantification obtained in real samples for ?-, ?- and ?-HBCD were 0.022, 0.073 and 0.015ngL(-1), respectively, significantly lower than those required by the European Directive 2013/39/EC. PMID:26739916

  16. Quantification of Cr(VI) in soil samples from a contaminated area in northern Italy by isotope dilution mass spectrometry.

    PubMed

    Guidotti, Laura; Queipo Abad, Silvia; Rodríguez-González, Pablo; García Alonso, J Ignacio; Beone, Gian Maria

    2015-11-01

    The aims of the work were to detect and quantify hexavalent chromium in 14 soil samples from an area in Lombardia (northern Italy) contaminated by two polluted water plumes. Cr(VI) was extracted from the solid samples by applying focused microwaves in an alkaline medium after Cr(III) complexation with EDTA. Cr(VI) was reduced to Cr(III) when previously reported extraction conditions for the analysis of certified reference materials were used, and Cr(VI) could not be reliably quantified in the soil samples. The influence of organic matter and iron contents in the samples on the reduction of Cr(VI) was subsequently studied using a new set of soil samples with different iron and organic matter concentrations. Isotope dilution mass spectrometry (IDMS) measured two different enriched stable isotopes of Cr (54 and 53) to evaluate the reduction extent of hexavalent chromium during the analytical procedure. The extraction conditions were optimized to obtain the lowest amount of Cr(VI) reduction and quantify Cr(VI) in the polluted soil samples from Lombardia. PMID:26141979

  17. Monitoring protein conformational changes and dynamics using stable-isotope labeling and mass spectrometry (CDSiL-MS)

    PubMed Central

    Kahsai, Alem W.; Rajagopal, Sudarshan; Sun, Jinpeng; Xiao, Kunhong

    2015-01-01

    Understanding the mechanism accompanying functional conformational changes associated with protein activation has important implications for drug design. Here, we describe a powerful method, CDSiL-MS (conformational changes and dynamics using stable-isotope labeling and mass-spectrometry), which involves chemical-labeling by isotope-coded forms of N-ethylmaleimide or succinic anhydride to site-specifically label the side-chains of cysteines or lysines, respectively, in native proteins. Subsequent MS-analysis allows the quantitative monitoring of reactivity of residues as a function of time, providing a measurement of the labeling kinetics, thereby enabling elucidation of conformational changes of proteins. We demonstrate the utility of this method using a model G-protein coupled receptor, the ?2-adrenergic receptor including experiments that characterize the functional conformational-changes associated with activation of distinct signaling pathways induced by different ?-adrenoceptor ligands. The procedure requires five days and can easily be adapted to systems where soluble and detergent-solubilized membrane protein targets, which undergo function-dependent conformational-changes, can be interrogated structurally to allow drug screening. PMID:24810039

  18. Quantitative Gingival Crevicular Fluid Proteome in Health and Periodontal Disease Using Stable-Isotope Chemistries and Mass Spectrometry

    PubMed Central

    Carneiro, Leandro G.; Nouh, Hesham; Salih, Erdjan

    2014-01-01

    Aim Application of quantitative stable-isotope-labeling chemistries and mass spectrometry (MS) to determine alterations in gingival crevicular fluid (GCF) proteome in periodontal disease. Materials and Methods Quantitative proteome of GCF from 40 healthy individuals versus 40 patients with periodontal disease was established using 320 GCF samples and stable-isotope-labeling reagents, ICAT and mTRAQ, with MS technology and validated by enzyme-linked immunosorbent methods. Results We have identified 238 distinct proteins of which 180 were quantified in GCF of both healthy and periodontal patients with additional 26 and 32 distinct proteins that were found only in GCF of healthy or periodontal patients. In addition, 42 pathogenic bacterial proteins and 11 yeast proteins were quantified. The data highlighted a series of proteins not quantified previously by large-scale MS approaches in GCF with relevance to periodontal disease, such as host derived Ig alpha-2 chain C, Kallikrein-4, S100-A9, transmembrane proteinase 13, peptidase S1 domain, several collagen types and pathogenic bacterial proteins e.g., formamidase, leucine amidopeptidase and virulence factor OMP85. Conclusions The innovative analytical approaches provided detailed novel changes in both host and microbial derived GCF proteomes of periodontal patients. The study defined 50 host and 16 pathogenic bacterial proteins significantly elevated in periodontal disease most of which were novel with significant potential for application in the clinical arena of periodontal disease. PMID:24738839

  19. Isotopic Ratio Outlier Analysis of the S. cerevisiae Metabolome Using Accurate Mass Gas Chromatography/Time-of-Flight Mass Spectrometry: A New Method for Discovery.

    PubMed

    Qiu, Yunping; Moir, Robyn; Willis, Ian; Beecher, Chris; Tsai, Yu-Hsuan; Garrett, Timothy J; Yost, Richard A; Kurland, Irwin J

    2016-03-01

    Isotopic ratio outlier analysis (IROA) is a (13)C metabolomics profiling method that eliminates sample to sample variance, discriminates against noise and artifacts, and improves identification of compounds, previously done with accurate mass liquid chromatography/mass spectrometry (LC/MS). This is the first report using IROA technology in combination with accurate mass gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS), here used to examine the S. cerevisiae metabolome. S. cerevisiae was grown in YNB media, containing randomized 95% (13)C, or 5%(13)C glucose as the single carbon source, in order that the isotopomer pattern of all metabolites would mirror the labeled glucose. When these IROA experiments are combined, the abundance of the heavy isotopologues in the 5%(13)C extracts, or light isotopologues in the 95%(13)C extracts, follows the binomial distribution, showing mirrored peak pairs for the molecular ion. The mass difference between the (12)C monoisotopic and the (13)C monoisotopic equals the number of carbons in the molecules. The IROA-GC/MS protocol developed, using both chemical and electron ionization, extends the information acquired from the isotopic peak patterns for formulas generation. The process that can be formulated as an algorithm, in which the number of carbons, as well as the number of methoximations and silylations are used as search constraints. In electron impact (EI/IROA) spectra, the artifactual peaks are identified and easily removed, which has the potential to generate "clean" EI libraries. The combination of chemical ionization (CI) IROA and EI/IROA affords a metabolite identification procedure that enables the identification of coeluting metabolites, and allowed us to characterize 126 metabolites in the current study. PMID:26820234

  20. Investigation of the origin of ephedrine and methamphetamine by stable isotope ratio mass spectrometry: a Japanese experience.

    PubMed

    Makino, Y; Urano, Y; Nagano, T

    2005-01-01

    Illicit drug abuse is a serious global problem that can only be solved through international cooperation. In Asian countries, the abuse of methamphetamine is one of the most pressing problems. To assist in the control of methamphetamine, the authors investigated in detail the character of ephedrine, which is a key precursor for the illicit manufacture of methamphetamine. Commercial ephedrine is produced by one of three methods: (a) extraction from Ephedra plants, (b) full chemical synthesis or (c) via a semi-synthetic process involving the fermentation of sugar, followed by amination. Although chemically there is no difference between ephedrine samples from different origins (natural, synthetic or semi-synthetic), scientific and analytical tools such as drug-characterization and impurity-profiling programmes may provide valuable information for law enforcement and regulatory activities as part of precursor control strategies. During the research under discussion in the present article, in addition to classical impurity profiling of manufacturing by-products, the use of stable isotope ratio mass spectrometry was investigated for determining the origin of the ephedrine that had been used as a precursor in seized methamphetamine samples. The results of carbon and nitrogen stable isotope ratio (delta13C and delta15N) analysis of samples of crystalline methamphetamine seized in Japan suggested that the drug had been synthesized from either natural or semi-synthetic ephedrine and not from synthetic ephedrine. Stable isotope ratio analysis is expected to be a useful tool for tracing the origins of seized methamphetamine. It has attracted much interest from precursor control authorities in Japan and the East Asian region and may prove useful in the international control of precursors. PMID:21338016

  1. Determination of mercury in coal by isotope dilution cold-vapor generation inductively coupled plasma mass spectrometry.

    PubMed

    Long, Stephen E; Kelly, W Robert

    2002-04-01

    A method based on isotope dilution cold-vapor inductively coupled plasma mass spectrometry (ID-CV-ICPMS) has been developed for high-accuracy determinations of mercury in bituminous and sub-bituminous coals. A closed-system digestion process employing a Carius tube is used to completely oxidize the coal matrix and chemically equilibrate the mercury in the sample with a 201Hg isotopic spike. The digestates are diluted with high-purity quartz-distilled water, and the mercury is released as a vapor by reduction with tin(II) chloride. Measurements of 201Hg/202Hg isotope ratios are made using a quadrupole ICPMS system in time-resolved analysis mode. The new method has some significant advantages over existing methods. The instrument detection limit is less than 1 pg/mL. The average blank (n = 17) is 30 pg, which is roughly 1 order of magnitude lower than the equivalent microwave digestion procedure. The detection limit in coal is blank limited and is approximately 40 pg/g. Memory effects are very low. The relative reproducibility of the analytical measurements is approximately 0.5% for mercury concentrations in the range 10-150 ng/g. The method has been used to measure mercury concentrations in six coal reference materials, SRM 1632b (77.4 ng/g), SRM 1632c (94.3 ng/g), BCR 40 (433.2 ng/g), BCR 180 (125.0 ng/g), BCR 181 (135.8 ng/g), and SARM 20 (252.6 ng/g), as well as a coal fly ash, SRM 1633b (143.1 ng/g). The method is equally applicable to other types of fossil fuels including both crude and refined oils. PMID:12033233

  2. Differential isotopic enrichment to facilitate characterization of asymmetric multimeric proteins using hydrogen/deuterium exchange mass spectrometry

    PubMed Central

    Pascal, Bruce D.; Bauman, Joseph D.; Patel, Disha; Arnold, Eddy; Griffin, Patrick R.

    2015-01-01

    Hydrogen/deuterium exchange (HDX) coupled to mass spectrometry has emerged as a powerful tool for analyzing the conformational dynamics of protein-ligand and protein-protein interactions. Recent advances in instrumentation and methodology have expanded the utility of HDX for the analysis of large and complex proteins; however, asymmetric dimers with shared amino acid sequence present a unique challenge for HDX because assignment of peptides with identical sequence to their subunit of origin remains ambiguous. Here we report the use of differential isotopic labeling to facilitate HDX analysis of multimers using HIV-1 reverse transcriptase (RT) as a model. RT is an asymmetric heterodimer of 51 kDa (p51) and 66 kDa (p66) subunits. The first 440 residues of p51 and p66 are identical. In this study differentially labeled RT was reconstituted from isotopically enriched (15N-labeled) p51 and unlabeled p66. In order to enable detection of 15N-deuterated RT peptides, the software HDX Workbench was modified to follow a 100% 15N model. Our results demonstrated that 15N enrichment of p51 did not affect its conformational dynamics compared to unlabeled p51, but 15N-labeled p51 did show different conformational dynamics than p66 in the RT heterodimer. Differential HDX-MS of isotopically labeled RT in the presence of the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) showed subunit-specific perturbation in the rate of HDX consistent with previously published results and the RT-EFV co-crystal structure. PMID:25763479

  3. The use of ?13C isotope ratio mass spectrometry for methamphetamine profiling: comparison of ephedrine and pseudoephedrine-based samples to P2P-based samples.

    PubMed

    Toske, Steven G; Morello, David R; Berger, Jennifer M; Vazquez, Etienne R

    2014-01-01

    Differentiating methamphetamine samples produced from ephedrine and pseudoephedrine from phenyl-2-propanone precursors is critical for assigning synthetic route information for methamphetamine profiling. The use of isotope ratio mass spectrometry data is now a key component for tracking precursor information. Recent carbon (?(13)C) isotope results from the analysis of numerous methamphetamine samples show clear differentiation for ephedrine and pseudoephedrine-produced samples compared to P2P-produced samples. The carbon isotope differences were confirmed from synthetic route precursor studies. PMID:24378294

  4. The Absolute Isotopic Composition of Zn in Terrestrial Materials Determined Using Double Spike Thermal Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Ghidan, O. Y.; Loss, R. D.

    2008-12-01

    Although long suspected to be widespread in nature, until recently, little was known about the extent of the variation of the isotopic composition, or isotopic fractionation, of Zn in natural materials. During the last decade an increasing number of high precision Zn isotopic fractionation data have been reported using MC- ICP-MS (MARECHAL et al., 1999; PETIT et al., 2008; PICHAT et al., 2003), but none have been reported on an absolute scale which is essential for interlaboratory comparison of results. In this work we report sub- permil Zn fractionation in a range of natural materials relative to the internationally proposed absolute Zn isotopic reference material (? zero) (PONZEVERA et al., 2006)using the Thermal Ionization Mass Spectrometry double spike technique. Repeated double spike analysis of the laboratory standard relative to itself demonstrated a long term reproducibility of +0.006 0.039 permil amu-1. The measured isotopic composition of Zn in minerals and igneous rocks SRMs was found to be the same as the proposed absolute (? zero) which makes it possible to consider the proposed absolute Zn isotopic standard as being representative of "bulk earth" Zn. A significant and consistent fractionation of ~+0.3 permil amu-1 was found in 5 sediments from a range of localities. The results obtained for metamorphic SRMs indicate that the fractionation of Zn in these rocks is the same as found in igneous rocks but are different from the Zn found in sedimentary rocks. A clay SRM sample TILL-3 appears to exhibit a consistently Zn fractionation of +0.12 0.10 permil amu-1. The isotopic composition of Zn was also measured in two plant SRMs and one animal SRM sample. The fractionation of (-0.088 0.070 permil amu-1) of Zn in the Rice (a C3 type plant material) sample suggested that Zn may be used to study Zn systematics in plants. The result obtained for MURST-ISS-A2 (Antarctic Krill) was +0.21 0.11 permil amu-1 relative to the laboratory standard which is similar to the average Zn fractionation results of +0.281 0.083 permil amu-1 obtained for marine sediments. The fractionation of Zn in seven ultra pure Zn standard materials was also measured relative to the laboratory standard and found to range from -5.11 0.36 permil amu-1 for AE 10760 to +0.12 0.16 permil amu-1 for Zn IRMM 10440 confirming that that significant care must be exercised in the selection of Zn isotope laboratory standards (TANIMIZU et al., 2002). A pilot study to determine the concentration and the isotopic composition of Zn in river and tap water, and a number of processed materials was also performed. The implications and applications of these results, such as on the atomic weight of Zn will be presented.

  5. Simultaneous detection of multiple hydroxylated polychlorinated biphenyls from a complex tissue matrix using gas chromatography/isotope dilution mass spectrometry.

    PubMed

    Eguchi, Akifumi; Nomiyama, Kei; Ochiai, Mari; Mizukawa, Hazuki; Nagano, Yasuko; Nakagawa, Katsuhiro; Tanaka, Kouki; Miyagawa, Haruhiko; Tanabe, Shinsuke

    2014-01-01

    In this study, we developed a comprehensive, highly sensitive, and robust method for determining 53 congeners of three to eight chlorinated OH-PCBs in liver and brain samples by using isotope dilution gas chromatography (GC) coupled with electron capture negative ionization mass spectrometry (ECNI-MS). These results were compared with those from GC coupled with electron ionization high-resolution mass spectrometry (EI-HRMS). Clean-up procedures for analysis of OH-PCBs homologs in liver and brain samples involve a pretreatment step consisting of acetonitrile partition and 5% hydrated silica-gel chromatography before derivatization. Recovery rates of tri- and tetra-chlorinated OH-PCBs in the acetonitrile partition method followed by the 5% hydrated silica-gel column (82% and 91%) were higher than conventional sulfuric acid treatment (2.0% and 3.5%). The method detection limits of OH-PCBs for each matrix obtained by GC/ECNI-MS and GC/EI-HRMS were 0.58-2.6 pg g(-1) and 0.36-1.6 pg g(-1) wet wt, respectively. Recovery rates of OH-PCB congeners in spike tests using sample matrices (10 and 50 pg) were 64.7-117% (CV: 4.7-14%) and 70.4-120% (CV: 2.3-12%), respectively. This analytical method may enable the simultaneous detection of various OH-PCBs from complex tissue matrices. Furthermore, this method allows more comprehensive assessment of the biological effects of OH-PCB exposure on critical organs. PMID:24274296

  6. Overcoming matrix effects in electrospray: quantitation of ?-agonists in complex matrices by isotope dilution liquid chromatography-mass spectrometry using singly (13)C-labeled analogues.

    PubMed

    Gonzlez-Antua, Ana; Domnguez-Romero, Juan C; Garca-Reyes, Juan F; Rodrguez-Gonzlez, Pablo; Centineo, Giuseppe; Garca Alonso, J Ignacio; Molina-Daz, Antonio

    2013-05-01

    In this work, the implementation of isotope dilution mass spectrometry (IDMS) using minimal labeling and isotope pattern deconvolution (IPD) is evaluated as a strategy for the minimization of matrix effects during trace determination of ?2-agonists in complex matrices by liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). First, the parameters affecting the measurement of isotopic composition of organic compounds by liquid chromatography electrospray ionization high resolution mass spectrometry with a time-of-flight analyzer were evaluated using as a case of study three different ?2-agonists: clenbuterol, clenproperol and brombuterol. Then, a calibration graph-free IDMS methodology was evaluated in order to overcome matrix effects in LC-ESI-MS in complex samples. In this procedure singly (13)C-labeled analogues of clenbuterol, clenproperol and brombuterol were employed in combination with IPD. Using this approach accurate and precise results were obtained in the simultaneous quantification of ?2-agonists in human urine and bovine liver, even at the sub ngg(-1) and particularly in spite of the previously reported matrix effects. Recovery rates in the range of 97-114% in fortified human urine and from 95% to 111% in fortified bovine liver were obtained with RSD (%) of independent recovery experiments always lower than 6%. These results demonstrate that the proposed methodology based on the use of (13)C1-labeled standards and IPD is a reliable approach for accurate LC-MS quantitation of small molecules and compatible with full-scan high-resolution mass spectrometry. PMID:23523066

  7. Carbon Isotope Measurements of Experimentally-Derived Hydrothermal Mineral-Catalyzed Organic Products by Pyrolysis-Isotope Ratio Mass Spectrometry

    NASA Technical Reports Server (NTRS)

    Socki, Richard A.; Fu, Qi; Niles, Paul B.

    2011-01-01

    We report results of experiments to measure the C isotope composition of mineral catalyzed organic compounds derived from high temperature and high pressure synthesis. These experiments make use of an innovative pyrolysis technique designed to extract and measure C isotopes. To date, our experiments have focused on the pyrolysis and C isotope ratio measurements of low-molecular weight intermediary hydrocarbons (organic acids and alcohols) and serve as a proof of concept for making C and H isotope measurements on more complicated mixtures of solid-phase hydrocarbons and intermediary products produced during high temperature and high pressure synthesis on mineral-catalyzed surfaces. The impetus for this work stems from recently reported observations of methane detected within the Martian atmosphere [1-4], coupled with evidence showing extensive water-rock interaction during Martian history [5-7]. Methane production on Mars could be the result of synthesis by mineral surface-catalyzed reduction of CO2 and/or CO by Fischer-Tropsch Type (FTT) reactions during serpentization reactions [8,9]. Others have conducted experimental studies to show that FTT reactions are plausible mechanisms for low-molecular weight hydrocarbon formation in hydrothermal systems at mid-ocean ridges [10-12]. Further, recent experiments by Fu et al. [13] focus on examining detailed C isotope measurements of hydrocarbons produced by surface-catalyzed mineral reactions. Work described in this paper details the experimental techniques used to measure intermediary organic reaction products (alcohols and organic acids).

  8. An online method combining a thermal conversion elemental analyzer with isotope ratio mass spectrometry for the determination of hydrogen isotope composition and water concentration in geological samples.

    PubMed

    Gong, Bing; Zheng, Yong-Fei; Chen, Ren-Xu

    2007-01-01

    An online continuous-flow method, combining a thermal conversion elemental analyzer (TC/EA) with isotope ratio mass spectrometry (MS), is evaluated for the determination of both the hydrogen isotope composition and the water concentration of hydrous and nominally anhydrous minerals. The technique involves reduction of hydrous minerals or nominally anhydrous minerals by reaction with glassy carbon at 1450 degrees C in a helium stream. The product gases, H2 and CO, are separated on a gas chromatographic column prior to analysis in the mass spectrometer. Calibration curves for the H concentration analysis were generated from a standard of benzoic acid (C7H6O2) that has an H concentration of 5.0 wt%; the analytical uncertainties were better than +/-0.05% in our runs. Two standards of material with given D values, polyethylene IAEA-CH-7 and biotite NBS-30, were tested for the purpose of calibrating a natural garnet 04BXL02 representing nominally anhydrous minerals. Preheating at 90 degrees C for 12 h was found to be suitable for removing adsorption water on the sample surface. This results in constant D values and total H2O contents for the garnet, with weighted means of -94 +/- 1 and 522 +/- 11 ppm (wt), respectively. The TC/EA-MS technique allows routine analysis of sample sizes as small as 0.01 microL H2O. For natural minerals, absolute reproducibilities for D values are +/-0.5 to +/-2 (1) and relative uncertainties for total H2O concentrations are at levels of +/-1% to +/-3% (1). Therefore, this online method can be used for the quantitative determination of H isotope composition and H2O concentration of either hydrous or anhydrous minerals. PMID:17370247

  9. Isotope-Encoded Carboxyl Group Footprinting for Mass Spectrometry-Based Protein Conformational Studies

    NASA Astrophysics Data System (ADS)

    Zhang, Hao; Liu, Haijun; Blankenship, Robert E.; Gross, Michael L.

    2016-01-01

    We report an isotope-encoding method coupled with carboxyl-group footprinting to monitor protein conformational changes. The carboxyl groups of aspartic/glutamic acids and of the C-terminus of proteins can serve as reporters for protein conformational changes when labeled with glycine ethyl ester (GEE) mediated by carbodiimide. In the new development, isotope-encoded "heavy" and "light" GEE are used to label separately the two states of the orange carotenoid protein (OCP) from cyanobacteria. Two samples are mixed (1:1 ratio) and analyzed by a single LC-MS/MS experiment. The differences in labeling extent between the two states are represented by the ratio of the "heavy" and "light" peptides, providing information about protein conformational changes. Combining isotope-encoded MS quantitative analysis and carboxyl-group footprinting reduces the time of MS analysis and improves the sensitivity of GEE and other footprinting.

  10. Isotope-Encoded Carboxyl Group Footprinting for Mass Spectrometry-Based Protein Conformational Studies

    NASA Astrophysics Data System (ADS)

    Zhang, Hao; Liu, Haijun; Blankenship, Robert E.; Gross, Michael L.

    2015-09-01

    We report an isotope-encoding method coupled with carboxyl-group footprinting to monitor protein conformational changes. The carboxyl groups of aspartic/glutamic acids and of the C-terminus of proteins can serve as reporters for protein conformational changes when labeled with glycine ethyl ester (GEE) mediated by carbodiimide. In the new development, isotope-encoded "heavy" and "light" GEE are used to label separately the two states of the orange carotenoid protein (OCP) from cyanobacteria. Two samples are mixed (1:1 ratio) and analyzed by a single LC-MS/MS experiment. The differences in labeling extent between the two states are represented by the ratio of the "heavy" and "light" peptides, providing information about protein conformational changes. Combining isotope-encoded MS quantitative analysis and carboxyl-group footprinting reduces the time of MS analysis and improves the sensitivity of GEE and other footprinting.

  11. Isotope-Encoded Carboxyl Group Footprinting for Mass Spectrometry-Based Protein Conformational Studies.

    PubMed

    Zhang, Hao; Liu, Haijun; Blankenship, Robert E; Gross, Michael L

    2016-01-01

    We report an isotope-encoding method coupled with carboxyl-group footprinting to monitor protein conformational changes. The carboxyl groups of aspartic/glutamic acids and of the C-terminus of proteins can serve as reporters for protein conformational changes when labeled with glycine ethyl ester (GEE) mediated by carbodiimide. In the new development, isotope-encoded "heavy" and "light" GEE are used to label separately the two states of the orange carotenoid protein (OCP) from cyanobacteria. Two samples are mixed (1:1 ratio) and analyzed by a single LC-MS/MS experiment. The differences in labeling extent between the two states are represented by the ratio of the "heavy" and "light" peptides, providing information about protein conformational changes. Combining isotope-encoded MS quantitative analysis and carboxyl-group footprinting reduces the time of MS analysis and improves the sensitivity of GEE and other footprinting. Graphical Abstract ?. PMID:26384685

  12. Stable Chlorine Isotopes and Elemental Chlorine by Thermal Ionization Mass Spectrometry and Ion Chromatography; Martian Meteorites, Carbonaceous Chondrites and Standard Rocks

    NASA Technical Reports Server (NTRS)

    Nakamura, N.; Nyquist, L. E.; Reese, Y.; Shih, C.-Y.; Fujitani, T.; Okano, O.

    2011-01-01

    Recently significantly large mass fractionation of stable chlorine isotopes has been reported for terrestrial and lunar samples [1,2]. In addition, in view of possible early solar system processes [3] and also potential perchlorate-related fluid/microbial activities on the Martian surface [4,5], a large chlorine isotopic fractionation might be expected for some types of planetary materials. Due to analytical difficulties of isotopic and elemental analyses, however, current chlorine analyses for planetary materials are controversial among different laboratories, particularly between IRMS (gas source mass spectrometry) and TIMS (Thermal Ionization Mass Spectrometry) groups [i.e. 1,6,7] for isotopic analyses, as well as between those doing pyrohydrolysis and other groups [i.e. 6,8]. Additional careful investigations of Cl isotope and elemental abundances are required to confirm real chlorine isotope and elemental variations for planetary materials. We have developed a TIMS technique combined with HF-leaching/ion chromatography at NASA JSC that is applicable to analysis of small amounts of meteoritic and planetary materials. We present here results for several standard rocks and meteorites, including Martian meteorites.

  13. Quantifying precision and accuracy of measurements of dissolved inorganic carbon stable isotopic composition using continuous-flow isotope-ratio mass spectrometry

    PubMed Central

    Waldron, Susan; Marian Scott, E; Vihermaa, Leena E; Newton, Jason

    2014-01-01

    RATIONALE We describe an analytical procedure that allows sample collection and measurement of carbon isotopic composition (δ13CV-PDB value) and dissolved inorganic carbon concentration, [DIC], in aqueous samples without further manipulation post field collection. By comparing outputs from two different mass spectrometers, we quantify with the statistical rigour uncertainty associated with the estimation of an unknown measurement. This is rarely undertaken, but it is needed to understand the significance of field data and to interpret quality assurance exercises. METHODS Immediate acidification of field samples during collection in evacuated, pre-acidified vials removed the need for toxic chemicals to inhibit continued bacterial activity that might compromise isotopic and concentration measurements. Aqueous standards mimicked the sample matrix and avoided headspace fractionation corrections. Samples were analysed using continuous-flow isotope-ratio mass spectrometry, but for low DIC concentration the mass spectrometer response could be non-linear. This had to be corrected for. RESULTS Mass spectrometer non-linearity exists. Rather than estimating precision as the repeat analysis of an internal standard, we have adopted inverse linear calibrations to quantify the precision and 95% confidence intervals (CI) of the δ13CDIC values. The response for [DIC] estimation was always linear. For 0.05–0.5 mM DIC internal standards, however, changes in mass spectrometer linearity resulted in estimations of the precision in the δ13CVPDB value of an unknown ranging from ± 0.44‰ to ± 1.33‰ (mean values) and a mean 95% CI half-width of ±1.1–3.1‰. CONCLUSIONS Mass spectrometer non-linearity should be considered in estimating uncertainty in measurement. Similarly, statistically robust estimates of precision and accuracy should also be adopted. Such estimations do not inhibit research advances: our consideration of small-scale spatial variability at two points on a small order river system demonstrates field data ranges larger than the precision and uncertainties. However, without such statistical quantification, exercises such as inter-lab calibrations are less meaningful. PMID:24711275

  14. Determination of a correction to improve mass measurement accuracy of isotopically unresolved polymerase chain reaction amplicons by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Null, Allison P; Muddiman, David C

    2003-01-01

    The experimental determination of average mass by mass spectrometry is limited for large molecules due to the negative bias introduced by the natural distribution of isotopic abundances. This results in the measurement of the top-of-centroid (ToC) as opposed to the true centroid. We have developed a practical correction factor that is applied to the ToC measurement to largely remove the systematic bias introduced by nature. The correction factor is calculated easily using the average molecular mass (<100 kDa) of the analyte molecule and the full-width half maximum resolving power (<3,500) of the measurement. In addition, an approach to calculating resolving power is described that accurately predicts resolving power achievable for Fourier transform ion cyclotron resonance (FT-ICR) mass analysis of large molecules. A combination of internal calibration with a dual-electrospray source and application of the correction factor to average mass measurements improved the mass error from 192.5 to -35.0 ppm for a 44 kDa PCR amplicon. PMID:12872276

  15. Nicotine, acetanilide and urea multi-level 2H-, 13C- and 15N-abundance reference materials for continuous-flow isotope ratio mass spectrometry.

    PubMed

    Schimmelmann, Arndt; Albertino, Andrea; Sauer, Peter E; Qi, Haiping; Molinie, Roland; Mesnard, François

    2009-11-01

    Accurate determinations of stable isotope ratios require a calibration using at least two reference materials with different isotopic compositions to anchor the isotopic scale and compensate for differences in machine slope. Ideally, the delta values of these reference materials should bracket the isotopic range of samples with unknown delta values. While the practice of analyzing two isotopically distinct reference materials is common for water (VSMOW-SLAP) and carbonates (NBS 19 and L-SVEC), the lack of widely available organic reference materials with distinct isotopic composition has hindered the practice when analyzing organic materials by elemental analysis/isotope ratio mass spectrometry (EA-IRMS). At present only L-glutamic acids USGS40 and USGS41 satisfy these requirements for delta13C and delta15N, with the limitation that L-glutamic acid is not suitable for analysis by gas chromatography (GC). We describe the development and quality testing of (i) four nicotine laboratory reference materials for on-line (i.e. continuous flow) hydrogen reductive gas chromatography-isotope ratio mass-spectrometry (GC-IRMS), (ii) five nicotines for oxidative C, N gas chromatography-combustion-isotope ratio mass-spectrometry (GC-C-IRMS, or GC-IRMS), and (iii) also three acetanilide and three urea reference materials for on-line oxidative EA-IRMS for C and N. Isotopic off-line calibration against international stable isotope measurement standards at Indiana University adhered to the 'principle of identical treatment'. The new reference materials cover the following isotopic ranges: delta2H(nicotine) -162 to -45 per thousand, delta13C(nicotine) -30.05 to +7.72 per thousand, delta15N(nicotine) -6.03 to +33.62 per thousand; delta15N(acetanilide) +1.18 to +40.57 per thousand; delta13C(urea) -34.13 to +11.71 per thousand, delta15N(urea) +0.26 to +40.61 per thousand (recommended delta values refer to calibration with NBS 19, L-SVEC, IAEA-N-1, and IAEA-N-2). Nicotines fill a gap as the first organic nitrogen stable isotope reference materials for GC-IRMS that are available with different delta15N values. Comparative delta13C and delta15N on-line EA-IRMS data from 14 volunteering laboratories document the usefulness and reliability of acetanilides and ureas as EA-IRMS reference materials. PMID:19844968

  16. Nicotine, acetanilide and urea multi-level2H-,13C- and15N-abundance reference materials for continuous-flow isotope ratio mass spectrometry

    USGS Publications Warehouse

    Schimmelmann, A.; Albertino, A.; Sauer, P.E.; Qi, H.; Molinie, R.; Mesnard, F.

    2009-01-01

    Accurate determinations of stable isotope ratios require a calibration using at least two reference materials with different isotopic compositions to anchor the isotopic scale and compensate for differences in machine slope. Ideally, the S values of these reference materials should bracket the isotopic range of samples with unknown S values. While the practice of analyzing two isotopically distinct reference materials is common for water (VSMOW-SLAP) and carbonates (NBS 19 and L-SVEC), the lack of widely available organic reference materials with distinct isotopic composition has hindered the practice when analyzing organic materials by elemental analysis/isotope ratio mass spectrometry (EA-IRMS). At present only L-glutamic acids USGS40 and USGS41 satisfy these requirements for ??13C and ??13N, with the limitation that L-glutamic acid is not suitable for analysis by gas chromatography (GC). We describe the development and quality testing of (i) four nicotine laboratory reference materials for on-line (i.e. continuous flow) hydrogen reductive gas chromatography-isotope ratio mass-spectrometry (GC-IRMS), (ii) five nicotines for oxidative C, N gas chromatography-combustion-isotope ratio mass-spectrometry (GC-C-IRMS, or GC-IRMS), and (iii) also three acetanilide and three urea reference materials for on-line oxidative EA-IRMS for C and N. Isotopic off-line calibration against international stable isotope measurement standards at Indiana University adhered to the 'principle of identical treatment'. The new reference materials cover the following isotopic ranges: ??2Hnicotine -162 to -45%o, ??13Cnicotine -30.05 to +7.72%, ?? 15Nnicotine -6.03 to +33.62%; ??15N acetanilide +1-18 to +40.57%; ??13Curea -34.13 to +11.71%, ??15Nurea +0.26 to +40.61% (recommended ?? values refer to calibration with NBS 19, L-SVEC, IAEA-N-1, and IAEA-N-2). Nicotines fill a gap as the first organic nitrogen stable isotope reference materials for GC-IRMS that are available with different ??13N values. Comparative ??13C and ??15N on-line EA-IRMS data from 14 volunteering laboratories document the usefulness and reliability of acetanilides and ureas as EA-IRMS reference materials.

  17. Fourier Transform Mass Spectrometry

    PubMed Central

    Scigelova, Michaela; Hornshaw, Martin; Giannakopulos, Anastassios; Makarov, Alexander

    2011-01-01

    This article provides an introduction to Fourier transform-based mass spectrometry. The key performance characteristics of Fourier transform-based mass spectrometry, mass accuracy and resolution, are presented in the view of how they impact the interpretation of measurements in proteomic applications. The theory and principles of operation of two types of mass analyzer, Fourier transform ion cyclotron resonance and Orbitrap, are described. Major benefits as well as limitations of Fourier transform-based mass spectrometry technology are discussed in the context of practical sample analysis, and illustrated with examples included as figures in this text and in the accompanying slide set. Comparisons highlighting the performance differences between the two mass analyzers are made where deemed useful in assisting the user with choosing the most appropriate technology for an application. Recent developments of these high-performing mass spectrometers are mentioned to provide a future outlook. PMID:21742802

  18. Stable isotope imaging of biological samples with high resolution secondary ion mass spectrometry and complementary techniques

    PubMed Central

    Jiang, H.; Favaro, E.; Goulbourne, C. N.; Rakowska, P. D.; Hughes, G. M.; Ryadnov, M. G.; Fong, L.G.; Young, S. G.; Ferguson, D. J. P.; Harris, A. L.; Grovenor, C. R. M.

    2014-01-01

    Stable isotopes are ideal labels for studying biological processes because they have little or no effect on the biochemical properties of target molecules. The NanoSIMS is a tool that can image the distribution of stable isotope labels with up to 50 nm spatial resolution and with good quantitation. This combination of features has enabled several groups to undertake significant experiments on biological problems in the last decade. Combining the NanoSIMS with other imaging techniques also enables us to obtain not only chemical information but also the structural information needed to understand biological processes. This article describes the methodologies that we have developed to correlate atomic force microscopy and backscattered electron imaging with NanoSIMS experiments to illustrate the imaging of stable isotopes at molecular, cellular, and tissue scales. Our studies make it possible to address 3 biological problems: (1) the interaction of antimicrobial peptides with membranes; (2) glutamine metabolism in cancer cells; and (3) lipoprotein interactions in different tissues. PMID:24556558

  19. Spatially resolved ?13C analysis using laser ablation isotope ratio mass spectrometry

    NASA Astrophysics Data System (ADS)

    Moran, J.; Riha, K. M.; Nims, M. K.; Linley, T. J.; Hess, N. J.; Nico, P. S.

    2014-12-01

    Inherent geochemical, organic matter, and microbial heterogeneity over small spatial scales can complicate studies of carbon dynamics through soils. Stable isotope analysis has a strong history of helping track substrate turnover, delineate rhizosphere activity zones, and identifying transitions in vegetation cover, but most traditional isotope approaches are limited in spatial resolution by a combination of physical separation techniques (manual dissection) and IRMS instrument sensitivity. We coupled laser ablation sampling with isotope measurement via IRMS to enable spatially resolved analysis over solid surfaces. Once a targeted sample region is ablated the resulting particulates are entrained in a helium carrier gas and passed through a combustion reactor where carbon is converted to CO2. Cyrotrapping of the resulting CO2 enables a reduction in carrier gas flow which improves overall measurement sensitivity versus traditional, high flow sample introduction. Currently we are performing sample analysis at 50 ?m resolution, require 65 ng C per analysis, and achieve measurement precision consistent with other continuous flow techniques. We will discuss applications of the laser ablation IRMS (LA-IRMS) system to microbial communities and fish ecology studies to demonstrate the merits of this technique and how similar analytical approaches can be transitioned to soil systems. Preliminary efforts at analyzing soil samples will be used to highlight strengths and limitations of the LA-IRMS approach, paying particular attention to sample preparation requirements, spatial resolution, sample analysis time, and the types of questions most conducive to analysis via LA-IRMS.

  20. A 10-fold improvement in the precision of boron isotopic analysis by negative thermal ionization mass spectrometry.

    PubMed

    Shen, Jason Jiun-San; You, Chen-Feng

    2003-05-01

    Boron isotopes are potentially very important to cosmochemistry, geochemistry, and paleoceanography. However, the application has been hampered by the large sample required for positive thermal ionization mass spectrometry (PTIMS), and high mass fractionation for negative-TIMS (NTIMS). Running as BO(2)(-), NTIMS is very sensitive and requires only nanogram sized samples, but it has rather poor precision (approximately 0.7-2.0 per thousand) as a result of the larger mass fractionation associated with the relatively light ion. In contrast, running as the much heavier molecule of Cs(2)BO(2)(+), PTIMS usually achieves better precision around 0.1-0.4 per thousand. Moreover, there is a consistent 10 per thousand offset in the (11)B/(10)B ratio for NIST SRM 951 standard boric acid between the NTIMS and the certified value, but the cause of this offset is unclear. In this paper, we have adapted a technique we developed earlier to measure the (138)La/(139)La using LaO(+) (1) to improve the NTIMS technique for BO(2). We were able to correct for instrumental fractionation by measuring BO(2)(-) species not only at masses of 42 and 43, but also at 45, which enabled us to normalize (45)BO(2)/(43)BO(2) to an empirical (18)O/(16)O value. We found that both I(45)/I(42) = ((11)B(16)O(18)O/(10)B(16)O(16)O) and (I(43)/I(42))(C) = ((11)B(16)O(16)O/(10)B(16)O(16)O) vary linearly with (I(45)/I(43))(C) x 0.5 = ((11)B(16)O(18)O/(11)B(16)O(16)O) x 0.5 = (18)O/(16)O. In addition, different activators and different chemical forms of B yield different slopes for the fractionation lines. After normalizing (11)B(16)O(18)O/(11)B(16)O(16)O x 0.5 to a fixed (18)O/(16)O value, we obtained a mean (11)B/(10)B value of NIST SRM 951 that matches the NIST certified value at 4.0430 +/- 0.0015 (+/-0.36 per thousand, n = 11). As a result, our technique can achieve precision and accuracy comparable to that of PTIMS with only 1 per thousand of the sample required. This new NTIMS technique for B isotopes is critical to the studies of early solids in the solar system and individual foraminifera in sediments that require both high sensitivity and precision. PMID:12720329

  1. 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 ?g 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

  2. A novel methodological approach for ?(18)O analysis of sugars using gas chromatography-pyrolysis-isotope ratio mass spectrometry.

    PubMed

    Zech, Michael; Saurer, Matthias; Tuthorn, Mario; Rinne, Katja; Werner, Roland A; Siegwolf, Rolf; Glaser, Bruno; Juchelka, Dieter

    2013-01-01

    Although the instrumental coupling of gas chromatography-pyrolysis-isotope ratio mass spectrometry (GC-Py-IRMS) for compound-specific ?(18)O analysis has been commercially available for more than a decade, this method has been hardly applied so far. Here we present the first GC-Py-IRMS ?(18)O results for trimethylsilyl-derivatives of plant sap-relevant sugars and a polyalcohol (glucose, fructose, sucrose, raffinose and pinitol). Particularly, we focus on sucrose, which is assimilated in leaves and which is the most important transport sugar in plants and hence of utmost relevance in plant physiology and paleoclimate studies. Replication measurements of sucrose standards and concentration series indicate that the GC-Py-IRMS ?(18)O measurements are not stable over time and that they are amount (area) dependent. We, therefore, suggest running sample batch replication measurements in alternation with standard concentration series of reference material. This allows for carrying out (i) a drift correction, (ii) a calibration against reference material and (iii) an amount (area) correction. Tests with (18)O-enriched water do not provide any evidence for oxygen isotope exchange reactions affecting sucrose and raffinose. We present the first application of GC-Py-IRMS ?(18)O analysis for sucrose from needle extract (soluble carbohydrate) samples. The obtained ?(18)Osucrose/ Vienna Standard Mean Ocean Water (VSMOW) values are more positive and vary in a wider range (32.1-40.1 ) than the ?(18)Obulk/ VSMOW values (24.6-27.2 ). Furthermore, they are shown to depend on the climate parameters maximum day temperature, relative air humidity and cloud cover. These findings suggest that ?(18)Osucrose of the investigated needles very sensitively reflects the climatically controlled evaporative (18)O enrichment of leaf water and thus highlights the great potential of GC-Py-IRMS ?(18)Osucrose analysis for plant physiology and paleoclimate studies. PMID:24313371

  3. Determination of ultratrace levels of tributyltin in waters by isotope dilution and gas chromatography coupled to tandem mass spectrometry.

    PubMed

    Rodrguez-Cea, Andrs; Rodrguez-Gonzlez, Pablo; Font Cardona, Nuria; Aranda Mares, Jos Lus; Ballester Nebot, Salom; Garca Alonso, J Ignacio

    2015-12-18

    The current EU legislation lays down the Environmental Quality Standards (EQS) of 45 priority substances in surface water bodies. In particular, the concentration of tributyltin (TBT) must not exceed 0.2ngL(-1) and analytical methodologies with a Limit of Quantification (LOQ) equal or below 0.06ngL(-1) are urged to be developed. This work presents a procedure for the determination of ultratrace levels of TBT in water samples by Isotope Dilution and GC-MS/MS operating in Selected Reaction Monitoring (SRM) mode which meets current EU requirements. The method requires the monitorization of five consecutive transitions (287>175 to 291>179) for the sensitive and selective detection of TBT. The measured isotopic distribution of TBT fragment ions was in agreement with the theoretical values computed by a polynomial expansion algorithm. The combined use of Tandem Mass Spectrometry, a sample volume of 250mL, the preconcentration of 1mL of organic phase to 30?L and an injection volume of 25?L by Programmed Temperature Vaporization provided a LOQ of 0.0426ngL(-1) for TBT (calculated as ten times the standard deviation of nine independent blanks). The recovery for TBT calculated in Milli-Q water at the EQS level was 106.34%. A similar procedure was also developed for the quantification of dibutyltin (DBT) and monobutyltin (MBT) in water samples showing satisfactory results. The method was finally implemented in a routine testing laboratory to demonstrate its applicability to real samples obtaining quantitative recoveries for TBT at the EQS level in mineral water, river water and seawater. PMID:26614170

  4. Differential Isotope Labeling of 38 Dietary Polyphenols and Their Quantification in Urine by Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry.

    PubMed

    Achaintre, David; Buleté, Audrey; Cren-Olivé, Cécile; Li, Liang; Rinaldi, Sabina; Scalbert, Augustin

    2016-03-01

    A large number of polyphenols are consumed with the diet and may contribute to the prevention of chronic diseases such as cardiovascular diseases, diabetes, cancers, and neurodegenerative diseases. More comprehensive methods are needed to measure exposure to this complex family of bioactive plant compounds in epidemiological studies. We report here a novel method enabling the simultaneous measurement in urine of 38 polyphenols representative of the main classes and subclasses found in the diet. This method is based on differential (12)C-/(13)C-isotope labeling of polyphenols through derivatization with isotopic dansyl chloride reagents and on the analysis of the labeled polyphenols by tandem mass spectrometry. This derivatization approach overcomes the need for costly labeled standards. Different conditions for enzyme hydrolysis of polyphenol glucuronides and sulfate esters, extraction, and dansylation of unconjugated aglycones were tested and optimized. Limits of quantification varied from 0.01 to 1.1 μM depending on polyphenols. Intrabatch coefficients of variation varied between 3.9% and 9.6%. Interbatch variations were lower than 15% for 31 compounds and lower than 29% for 6 additional polyphenols out of the 38 tested. Thirty seven polyphenols were validated and then analyzed in 475, 24 h urine samples from the European Prospective Investigation on Cancer and Nutrition (EPIC) study. Thirty four polyphenols could be detected and successfully estimated and showed large interindividual variations of concentrations (2-3 orders of magnitude depending on the compound), with median concentrations spanning from 0.01 to over 1000 μM for all 34 compounds. PMID:26814424

  5. Determination of Mercury Content in a Shallow Firn Core from Summit, Greenland by Isotope Dilution Inductively Coupled Plasma Mass Spectrometry

    NASA Technical Reports Server (NTRS)

    Mann, Jacqueline L.; Long, Stephen E.; Shuman, Christopher A.; Kelly, W. Robert

    2003-01-01

    The total mercury Hg content was determined in 6 cm sections of a near-surface 7 m firn core and in surrounding surface snow from Summit, Greenland (elevation: 3238 m, 72.58 N, 38.53 W) in May 2001 by isotope dilution cold-vapor inductively coupled plasma mass spectrometry (ID-CV-ICP-MS). The focus of this research was to evaluate the capability of the ID-CV-ICPMS technique for measuring trace levels of Hg typical of polar snow and firn. Highly enriched Hg-201 isotopic spike is added to approximately 10 ml melted core and thoroughly mixed. The Hg(+2) in the sample is reduced on line with tin (II) chloride (SnCl2) and the elemental Hg (Hg(0)) vapor pre-concentrated on to gold gauze using a commercial amalgam system. The Hg is then thermally desorbed and introduced into a quadrupole ICP-MS. The blank corrected Hg concentrations determined for all samples ranged from 0.25 ng/L to 1.74 ng/L (ppt) (average 0.59 ng/L plus or minus 0.28 ng/L) and fall within the range of those previously determined by Boutron et al., 1998 (less than or equal to 0.05 ng/L to 2.0 ng/L) for the Summit site. The average blank value was 0.19 ng/L plus or minus 0.045 ng/L (n=6). The Hg values specifically for the firn core range from 0.25 ng/L to 0.87 ng/L (average 0.51 ng/L plus or minus 0.13 ng/L) and show both values declining with time and larger variability in concentration in the top 1.8 m.

  6. Two-dimensional gas chromatography with heart-cutting for isotope ratio mass spectrometry analysis of steroids in doping control.

    PubMed

    Brailsford, A D; Gavrilovi?, I; Ansell, R J; Cowan, D A; Kicman, A T

    2012-12-01

    The accuracy and precision of gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) measurements are highly dependent on analyte purity. Reliable analysis of urinary steroids for doping control therefore requires extensive and time-consuming sample preparation (i.e. liquid chromatography fraction collection) prior to GC-C-IRMS analysis. The use of two-dimensional GC (GC-GC) with heart-cutting (Deans Switch) as a possible approach to reduce the sample purification required for IRMS analysis is described herein. The system uses a low thermal mass oven (LTM) incorporated into an existing GC-C-IRMS system. GC-GC allowed the use of a cyanopropyl/phenyl column in the first dimension to optimize the separation of underivatized steroids, while a phenyl-methylpolysiloxane column in the second dimension focuses the selectively cut analytes into narrower peaks for more sensitive and reliable MS analysis. In addition, to confirm analyte identity, eluent from the second GC was split, with 20 % entering a scanning MS, and 80 % flowing to the IRMS. As a proof concept, the developed method was then used to analyze a single spot urine (5 ml) from an individual receiving T therapy (2 50 mg sachets of Testogel()). The T delta value (-27.8 , [T]?= 38 ng/ml) was clearly distinct from 11-ketoetiocholanolone (-22.5 ) (used as an endogenous reference compound (ERC)), indicating T as being of exogenous origin. The simultaneous analysis by the scanning MS yielded a full scan mass spectrum of the same chromatographic peak, thus confirming the peak to be T. PMID:22761127

  7. 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)

  8. Determining mycotoxins in baby foods and animal feeds using stable isotope dilution and liquid chromatography tandem mass spectrometry.

    PubMed

    Zhang, Kai; Wong, Jon W; Krynitsky, Alexander J; Trucksess, Mary W

    2014-09-10

    We developed a stable isotope dilution assay with liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine multiple mycotoxins in baby foods and animal feeds. Samples were fortified with [(13)C]-uniformly labeled mycotoxins as internal standards ([(13)C]-IS) and prepared by solvent extraction (50% acetonitrile in water) and filtration, followed by LC-MS/MS analysis. Mycotoxins in each sample were quantitated with the corresponding [(13)C]-IS. In general, recoveries of aflatoxins (2-100 ng/g), deoxynivalenol, fumonisins (50-2000 ng/g), ochratoxin A (20-1000 ng/kg), T-2 toxin, and zearalenone (40-2000 ng/g) in tested matrices (grain/rice/oatmeal-based formula, animal feed, dry cat/dog food) ranged from 70 to 120% with relative standard deviations (RSDs) <20%. The method provides sufficient selectivity, sensitivity, accuracy, and reproducibility to screen for aflatoxins at ng/g concentrations and deoxynivalenol and fumonisins at low ?g/g concentrations in baby foods and animal feeds, without using conventional standard addition or matrix-matched calibration standards to correct for matrix effects. PMID:25153173

  9. Spatially tracking (13) C-labelled substrate (bicarbonate) accumulation in microbial communities using laser ablation isotope ratio mass spectrometry.

    PubMed

    Moran, James J; Doll, Charles G; Bernstein, Hans C; Renslow, Ryan S; Cory, Alexandra B; Hutchison, Janine R; Lindemann, Stephen R; Fredrickson, James K

    2014-12-01

    Microbial mats are characterized by extensive metabolic interactions, rapidly changing internal geochemical gradients, and prevalent microenvironments within tightly constrained physical structures. We present laser ablation isotope ratio mass spectrometry (LA-IRMS) as a culture-independent, spatially specific technology for tracking the accumulation of (13) C-labelled substrate into heterogeneous microbial mat communities. This study demonstrates the novel LA-IRMS approach by tracking labeled bicarbonate incorporation into a cyanobacteria-dominated microbial mat system. The spatial resolution of 50??m was sufficient for distinguishing different mat strata and the approach effectively identified regions of greatest label incorporation. Sample preparation for LA-IRMS is straightforward and the spatial selectivity of LA-IRMS minimizes the volume of mat consumed, leaving material for complimentary analyses. We present analysis of DNA extracted from a sample post-ablation and suggest pigments, lipids or other biomarkers could similarly be extracted following ablation. LA-IRMS is well positioned to spatially resolve the accumulation of any (13) C-labelled substrate provided to a mat, making this a versatile tool for studying carbon transfer and interspecies exchanges within the limited spatial confines of such systems. PMID:25155264

  10. Development of an SI-Traceable HPLC-Isotope Dilution Mass Spectrometry Method To Quantify ?-Lactoglobulin in Milk Powders.

    PubMed

    Yang, Wang; Liqing, Wu; Fei, Duan; Bin, Yang; Yi, Yang; Jing, Wang

    2014-03-31

    ?-Lactoglobulin (?-LG) is one of the major allergenic proteins in milk. There is an urgent demand for an accurate and traceable method to develop ?-LG certified reference material (CRM). In this work, ?-LG was enzymatically digested and a specific peptide was chosen for quantitation by isotope-dilution mass spectrometry (IDMS). With amino acid CRMs as standards, the results could be traced to SI unit. By the proposed method, the recovery ranged from 86.0% to 118.3% with CVs <9.0%. The LOD and LOQ were 4.8 10(-5) g/g and 1.6 10(-4) g/g of ?-LG in milk powder, respectively. Ten samples from domestic market were analyzed with CVs <5.6%, and the relative expanded uncertainties ranged from 4.2% to 5.9% (k = 2). With the CRMs, it is expected that the comparability of ?-LG quantitation results will be improved among different laboratories. PMID:24628306

  11. Sensitive isotope dilution liquid chromatography/electrospray ionization tandem mass spectrometry method for the determination of acrylamide in chocolate.

    PubMed

    Ren, Yiping; Zhang, Yu; Jiao, Jingjing; Cai, Zengxuan; Zhang, Ying

    2006-03-01

    Isotope dilution liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS) was applied to the quantification of acrylamide in chocolate matrixes (dark chocolate, milk chocolate, chocolate with nuts, chocolate with almonds, and chocolate with wheat best element). The method included defatting with petroleum ether, extracting with aqueous solution of 2 mol l(-1) sodium chloride and clean-up by solid-phase (SPE) with OASIS HLB 6 cm3 cartridges. Acrylamide was detected with an Atlantis dC18 5 microm 210 x 1.5 mm column using 10% methanol/0.1% formic acid in water as the mobile phase. The analytical method was in-house validated and good results were obtained with respect to repeatability (RSD < 3.5%) and recovery (86-93%), which fulfilled the requirements defined by European Union legislation. The acrylamide levels in chocolate were 23-537 microg kg(-1). Therefore, the method was successfully used for the quantitative analysis of acrlyamide in various chocolate products. PMID:16517524

  12. Analysis of nitromethane from samples exposed in vitro to chloropicrin by stable isotope dilution headspace gas chromatography with mass spectrometry.

    PubMed

    Halme, Mia; Pesonen, Maija; Grandell, Toni; Kuula, Matti; Pasanen, Markku; Vhkangas, Kirsi; Vanninen, Paula

    2015-10-01

    Chloropicrin (trichloronitromethane) is a widely used soil fumigant and an old chemical warfare agent. The metabolism of chloropicrin is not well known in mammals but nitromethane has been shown to be one of its main metabolites. Here, a fast and simple headspace gas chromatography with mass spectrometry method was applied for the measurement of nitromethane from aqueous samples. The analytical method was validated using stable isotope labeled internal standard and a small sample volume of 260 ?L. No conventional sample preparation steps were needed. The method was accurate (relative standard deviations ?1.5%) and linear (R(2) = 0.9996) within the concentration range of 0.1-6.0 ?g/mL. This method was used to measure nitromethane in in vitro incubations with human and pig liver cell fractions containing enzymes for xenobiotic metabolism, exposed to chloropicrin. The results indicate that the presence of glutathione is necessary for the formation of nitromethane from chloropicrin. Also, nitromethane was formed mostly in liver cytosol fractions, but not in microsomal fractions after the incubation with chloropicrin. Our results suggest that although nitromethane is not the unequivocal biomarker of chloropicrin exposure, this method could be applied for screening the elevated levels in humans after chloropicrin exposure. PMID:26255649

  13. Accurate determination of ochratoxin A in Korean fermented soybean paste by isotope dilution-liquid chromatography tandem mass spectrometry.

    PubMed

    Ahn, Seonghee; Lee, Suyoung; Lee, Joonhee; Kim, Byungjoo

    2016-01-01

    Ochratoxin A (OTA), a naturally occurring mycotoxin, has been frequently detected in doenjang, a traditional fermented soybean paste, when it is fermented under improper conditions. Reliable screening of OTA in traditional fermented soybean paste (doenjang) is a special food-safety issue in Korea. Our laboratory, the National Metrology Institute of Korea, established an isotope dilution-liquid chromatography tandem mass spectrometry (ID-LC/MS/MS) method as a higher-order reference method to be used for SI-traceable value-assignment of OTA in certified reference materials (CRMs). (13)C20-OTA was used as an internal standard. Sample preparation conditions and LC/MS measurement parameters were optimised for this purpose. The analytical method was validated by measuring samples fortified with OTA at various levels. Repeatability and reproducibility studies showed that the ID-LC/MS/MS method is reliable and reproducible within 2% relative standard deviation. The analytical method was applied to determine OTA in various commercial doenjang products and home-made doenjang products. PMID:26212984

  14. Protein Stable Isotope Fingerprinting (P-SIF): Multidimensional Protein Chromatography Coupled to Stable Isotope-Ratio Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Pearson, A.; Bovee, R. J.; Mohr, W.; Tang, T.

    2012-12-01

    As metagenomics increases our insight into microbial community diversity and metabolic potential, new approaches are required to determine the biogeochemical expression of this potential within ecosystems. Because stable isotopic analysis of the major bioactive elements (C, N) has been used historically to map flows of substrates and energy among macroscopic food webs, similar principles may apply to microbes. To address this challenge, we have developed a new analytical approach called Protein Stable Isotope Fingerprinting (P-SIF). P-SIF generates natural stable isotopic fingerprints of microbial individual or community proteomes. The main advantage of P-SIF is the potential to bridge the gap between diversity and function, thereby providing a window into the "black box" of environmental microbiology and helping to decipher the roles of uncultivated species. Our method implements a three-way, orthogonal scheme to separate mixtures of whole proteins into subfractions dominated by single or closely-related proteins. Protein extracts first are isoelectrically focused in a gel-free technique that yields 12 fractions separated over a gradient of pH 3-10. Each fraction then is separated by size-exclusion chromatography into 20 pools, ranging from >100kD to ~10kD. Finally, each of these pools is subjected to HPLC and collected in 40 time-slices based on protein hydrophobicity. Theoretical calculation reveals that the true chromatographic resolution of the total scheme is 5000, somewhat less than the 9600 resulting fractions. High-yielding fractions are subjected to ?13C analysis by spooling-wire microcombustion irMS (SWiM-irMS) optimized for samples containing 1-5 nmol carbon. Here we will present the method, results for a variety of pure cultures, and preliminary data for a sample of mixed environmental proteins. The data show the promise of this method for unraveling the metabolic complexity hidden within microbial communities.

  15. Metabolomics relative quantitation with mass spectrometry using chemical derivatization and isotope labeling

    DOE PAGESBeta

    O'Maille, Grace; Go, Eden P.; Hoang, Linh; Want, Elizabeth J.; Smith, Colin; O'Maille, Paul; NordstrÖm, Anders; Morita, Hirotoshi; Qin, Chuan; Uritboonthai, Wilasinee; et al

    2008-01-01

    Comprehensive detection and quantitation of metabolites from a biological source constitute the major challenges of current metabolomics research. Two chemical derivatization methodologies, butylation and amination, were applied to human serum for ionization enhancement of a broad spectrum of metabolite classes, including steroids and amino acids. LC-ESI-MS analysis of the derivatized serum samples provided a significant signal elevation across the total ion chromatogram to over a 100-fold increase in ionization efficiency. It was also demonstrated that derivatization combined with isotopically labeled reagents facilitated the relative quantitation of derivatized metabolites from individual as well as pooled samples.

  16. Measurement of the isotopic composition of uranium micrometer-size particles by femtosecond laser ablation-inductively coupled plasma mass spectrometry

    NASA Astrophysics Data System (ADS)

    Hubert, Amlie; Claverie, Fanny; Pcheyran, Christophe; Pointurier, Fabien

    In this paper, we will describe and indicate the performance of a new method based on the use of femtosecond laser ablation (fs-LA) coupled to a quadrupole-based inductively coupled plasma mass spectrometer (ICP-QMS) for analyzing the isotopic composition of micrometer-size uranium particles. The fs-LA device was equipped with a high frequency source (till 10 kHz). We applied this method to 1-2 ?m diameter-uranium particles of known isotopic composition and we compared this technique with the two techniques currently used for uranium particle analysis: Secondary Ionization Mass Spectrometry (SIMS) and Fission Track Thermal Ionization Mass Spectrometry (FT-TIMS). By optimizing the experimental conditions, we achieved typical accuracy and reproducibility below 4% on 235U/238U for short transient signals of only 15 s related to 10 to 200 pg of uranium. The detection limit (at the 3 sigma level) was ~ 350 ag for the 235U isotope, meaning that 235U/238U isotope ratios in natural uranium particles of ~ 220 nm diameter can be measured. We also showed that the local contamination resulting from the side deposition of ablation debris at ~ 100 ?m from the ablation crater represented only a small percentage of the initial uranium signal of the ablated particle. Despite the use of single collector ICP-MS, we were able to demonstrate that fs-LA-ICP-MS is a promising alternative technique for determining uranium isotopic composition in particle analysis.

  17. Assay of tyrosol and hydroxytyrosol in olive oil by tandem mass spectrometry and isotope dilution method.

    PubMed

    Mazzotti, Fabio; Benabdelkamel, Hicham; Di Donna, Leonardo; Maiuolo, Loredana; Napoli, Anna; Sindona, Giovanni

    2012-12-01

    Hydroxytyrosol and tyrosol, the strong antioxidant present in large amount in virgin olive oil have been assayed by LC-MS/MS under MRM condition and isotope dilution method, using d(2)-labelled internal standards obtained by simple synthetic procedures. The assay has been performed under MRM condition monitoring two transitions for each analyte to improve the specificity. This paper deals with a modern approach for assaying the content of this polyphenols in virgin olive oil down to a limit of a few hundreds of parts per billion. Tyrosol and hydroxytyrosol ranged from 10 to 47ppm and from 5 to 25ppm in commercial olive oil, respectively. The accuracy (98-107%) and analytical parameters values confirm the reliability of the proposed approach. The method can be extended to any natural matrices, including mill wastes, after a simple step of sample preparation. PMID:22953817

  18. An in-depth evaluation of accuracy and precision in Hg isotopic analysis via pneumatic nebulization and cold vapor generation multi-collector ICP-mass spectrometry.

    PubMed

    Rua-Ibarz, Ana; Bolea-Fernandez, Eduardo; Vanhaecke, Frank

    2016-01-01

    Mercury (Hg) isotopic analysis via multi-collector inductively coupled plasma (ICP)-mass spectrometry (MC-ICP-MS) can provide relevant biogeochemical information by revealing sources, pathways, and sinks of this highly toxic metal. In this work, the capabilities and limitations of two different sample introduction systems, based on pneumatic nebulization (PN) and cold vapor generation (CVG), respectively, were evaluated in the context of Hg isotopic analysis via MC-ICP-MS. The effect of (i) instrument settings and acquisition parameters, (ii) concentration of analyte element (Hg), and internal standard (Tl)-used for mass discrimination correction purposes-and (iii) different mass bias correction approaches on the accuracy and precision of Hg isotope ratio results was evaluated. The extent and stability of mass bias were assessed in a long-term study (18months, n?=?250), demonstrating a precision ?0.006% relative standard deviation (RSD). CVG-MC-ICP-MS showed an approximately 20-fold enhancement in Hg signal intensity compared with PN-MC-ICP-MS. For CVG-MC-ICP-MS, the mass bias induced by instrumental mass discrimination was accurately corrected for by using either external correction in a sample-standard bracketing approach (SSB) or double correction, consisting of the use of Tl as internal standard in a revised version of the Russell law (Baxter approach), followed by SSB. Concomitant matrix elements did not affect CVG-ICP-MS results. Neither with PN, nor with CVG, any evidence for mass-independent discrimination effects in the instrument was observed within the experimental precision obtained. CVG-MC-ICP-MS was finally used for Hg isotopic analysis of reference materials (RMs) of relevant environmental origin. The isotopic composition of Hg in RMs of marine biological origin testified of mass-independent fractionation that affected the odd-numbered Hg isotopes. While older RMs were used for validation purposes, novel Hg isotopic data are provided for the latest generations of some biological RMs. PMID:26549115

  19. Stable isotope gas chromatography-tandem mass spectrometry determination of aminoethylcysteine ketimine decarboxylated dimer in biological samples.

    PubMed

    Tsikas, Dimitrios; Evans, Christopher E; Denton, Travis T; Mitschke, Anja; Gutzki, Frank-Mathias; Pinto, John T; Khomenko, Tetyana; Szabo, Sandor; Cooper, Arthur J L

    2012-11-01

    Aminoethylcysteine ketimine decarboxylated dimer (AECK-DD; systematic name: 1,2-3,4-5,6-7,8-octahydro-1,8a-diaza-4,6-dithiafluoren-9(8aH)-one) is a previously described metabolite of cysteamine that has been reported to be present in mammalian brain, urine, plasma, and cells in culture and vegetables and to possess potent antioxidative properties. Here, we describe a stable isotope gas chromatography-tandem mass spectrometry (GC-MS/MS) method for specific and sensitive determination of AECK-DD in biological samples. (13)C(2)-labeled AECK-DD was synthesized and used as the internal standard. Derivatization was carried out by N-pentafluorobenzylation with pentafluorobenzyl bromide in acetonitrile. Quantification was performed by selected reaction monitoring of the mass transitions m/z 328 to 268 for AECK-DD and m/z 330 to 270 for [(13)C(2)]AECK-DD in the electron capture negative ion chemical ionization mode. The procedure was systematically validated for human plasma and urine samples. AECK-DD was not detectable in human plasma above approximately 4nM but was present in urine samples of healthy humans at a maximal concentration of 46nM. AECK-DD was detectable in rat brain at very low levels of approximately 8pmol/g wet weight. Higher levels of AECK-DD were detected in mouse brain (∼1nmol/g wet weight). Among nine dietary vegetables evaluated, only shallots were found to contain trace amounts of AECK-DD (∼6.8pmol/g fresh tissue). PMID:22858756

  20. 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…

  1. Using Punnett Squares To Facilitate Students' Understanding of Isotopic Distributions in Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Sein, Lawrence T., Jr.

    2006-02-01

    Punnett squares, widely used in the teaching of biology, are shown to be useful in teaching chemistry. A novel re-interpretation of the Punnett square is demonstratedusing Punnett squares to interpret and predict low-resolution mass spectra. This application will be particularly helpful to instructors and students of analytical chemistry and environmental science.

  2. Quantitative Analysis of rRNA Modifications Using Stable Isotope Labeling and Mass Spectrometry

    PubMed Central

    2015-01-01

    Post-transcriptional RNA modifications that are introduced during the multistep ribosome biogenesis process are essential for protein synthesis. The current lack of a comprehensive method for a fast quantitative analysis of rRNA modifications significantly limits our understanding of how individual modification steps are coordinated during biogenesis inside the cell. Here, an LC-MS approach has been developed and successfully applied for quantitative monitoring of 29 out of 36 modified residues in the 16S and 23S rRNA from Escherichia coli. An isotope labeling strategy is described for efficient identification of ribose and base methylations, and a novel metabolic labeling approach is presented to allow identification of MS-silent pseudouridine modifications. The method was used to measure relative abundances of modified residues in incomplete ribosomal subunits compared to a mature 15N-labeled rRNA standard, and a number of modifications in both 16S and 23S rRNA were present in substoichiometric amounts in the preribosomal particles. The RNA modification levels correlate well with previously obtained profiles for the ribosomal proteins, suggesting that RNA is modified in a schedule comparable to the association of the ribosomal proteins. Importantly, this study establishes an efficient workflow for a global monitoring of ribosomal modifications that will contribute to a better understanding of mechanisms of RNA modifications and their impact on intracellular processes in the future. PMID:24422502

  3. Investigation of the feeding effect on the 13C/12C isotope ratio of the hormones in bovine urine using gas chromatography/combustion isotope ratio mass spectrometry.

    PubMed

    Balizs, Gabor; Jainz, Annett; Horvatovich, Peter

    2005-03-01

    The effect of the feeding on the 13C/12C isotope ratio of four endogenous steroid hormones testosterone (T), epi-testosterone (epi-T), dehydroepiandrosterone (DHEA) and etiocholanolone (ETIO) in bovine urine was investigated. An analytical method to determine the accurate isotope ratio was developed including an extensive clean up followed by enrichment of the analytes in two steps of HPLC fractionation. Feeding experiments with four young animals were performed using C3 and C4 plants (grass, maize silage, hay, etc.) over a time period of about 280 days. One cattle was used as a control animal with no change of its diet over the full period. The detection of the 13C/12C isotope ratio of the acetylated extracts was performed by gas chromatography/combustion isotope ratio mass spectrometry. After the first change of the feeding from C4 to C3 plants significant changes of the delta 13C % values were observed from the -19 to -23% level to the -24 to -32% level for etiocholanolone and epi-testosterone in urine of three animals, whereas the DHEA values remained under the level of the two metabolites. Testosterone could not be detected with GC-C-IRMS due to its low concentration in young animals. After the second change of the diet from C3 to C4 plants (after 222 days), the measured delta 13C % values have been stabilised at the original level. The results show that in case of the feeding with only C3 plants the endogenous delta values of -32% can be reached. In this case the contribution of exogenous material with a delta value of -32% could not be detected independently of the concentration. If the diet contains C4 plants the difference or the ratio of the delta 13C % values becomes the determinant in the discriminatory power. For validation of the method a human and a cattle were treated with testosterone and the delta 13C % values were measured in incurred human and cattle urine. PMID:15844538

  4. Comparison of secondary ion mass spectrometry and micromilling/continuous flow isotope ratio mass spectrometry techniques used to acquire intra-otolith delta18O values of wild Atlantic salmon (Salmo salar).

    PubMed

    Hanson, N N; Wurster, C M; Todd, C D

    2010-09-15

    The chemical signals in the sequential layers of fish otoliths have the potential to provide fisheries biologists with temporal and spatial details of migration which are difficult to obtain without expensive tracking methods. Signal resolution depends, however, on the extraction technique used. We compared the use of mechanical micromilling and continuous flow isotope ratio mass spectrometry (CF-IRMS) methods with secondary ion mass spectrometry (SIMS) to obtain delta(18)O profiles from otoliths of wild Atlantic salmon (Salmo salar) and used these to corroborate the time of freshwater emigration of the juvenile with macroscopic patterns within the otolith. Both techniques showed the transition occurring at the same visible feature on the otolith, allowing future analyses to easily identify the juvenile (freshwater) versus adult (marine) life-stages. However, SIMS showed a rapid and abrupt transition whereas micromilling provided a less distinct signal. The number of samples that could be obtained per unit area sampled using SIMS was 2 to 3 times greater than that when using micromilling/CF-IRMS although the delta(18)O values and analytical precisions (approximately 0.2 per thousand) of the two methods were comparable. In addition, SIMS delta(18)O results were used to compare otolith aragonite values with predicted values calculated using various isotope fractionation equations. PMID:20740522

  5. Synthesis of deuterium-labeled 17-hydroxyprogesterone suitable as an internal standard for isotope dilution mass spectrometry

    SciTech Connect

    Shimizu, K.; Yamaga, N.; Kohara, H.

    1988-03-01

    A synthesis is reported of 17-hydroxyprogesterone, labeled with four atoms of deuterium at ring C and suitable for use as an internal standard for isotope dilution mass spectrometry. Base-catalyzed equilibration of methyl 3 alpha-acetoxy-12-oxo-cholanate (III) with /sup 2/H/sub 2/O, followed by reduction of the 12-oxo group by the modified Wolff-Kisher method using (/sup 2/H)diethylene glycol and (/sup 2/H)hydrazine hydrate afforded (11,11,12,12,23,23(-2)H)lithocholic acid (V). The Meystre-Miescher degradation of the side chain of V yielded 3 alpha-hydroxy-5 beta-(11,11,12,12(-2)H)pregnan-20-one (X). Oxidation of the 3,20-enol-diacetate of X with perbenzoic acid followed by saponification afforded 3 alpha,17-dihydroxy-5 beta-(11,11,12,12(-2)H)pregnan-20-one (XI). Oxidation of XI with N-bromoacetamide yielded 17-hydroxy-5 beta-(11,11,12,12(-2)H)pregnane-3,20-dione (XII). Bromination of XII followed by dehydrobromination yielded 17-hydroxy-(11,11,12,12(-2)H) progesterone (XIV), consisting of 0.3% /sup 2/H0-, 1.1% /sup 2/H/sub 1/-, 8.6% /sup 2/H/sub 2/-, 37.1% /sup 2/H/sub 3/-, 52.1% /sup 2/H/sub 4/-, and 0.8% /sup 2/H/sub 5/-species.

  6. Comprehensive and highly sensitive urinary steroid hormone profiling method based on stable isotope-labeling liquid chromatography-mass spectrometry.

    PubMed

    Dai, Weidong; Huang, Qiang; Yin, Peiyuan; Li, Jia; Zhou, Jia; Kong, Hongwei; Zhao, Chunxia; Lu, Xin; Xu, Guowang

    2012-12-01

    Steroid hormones are crucial substances that mediate a wide range of vital physiological functions of the body. Determination of the levels of steroid hormones plays an important role in understanding the mechanism of the steroid hormone-related diseases. In this study, we present a novel targeted metabolic profiling method based on the introduction of an easily protonated stable isotope tag to a hydroxyl-containing steroid hormone with a synthesized derivatization reagent, deuterium 4-(dimethylamino)-benzoic acid (d(4)-DMBA), and liquid chromatography-mass spectrometry (LC-MS). Different from other reported derivatization reagents that have been used to enhance the sensitivities for estrogens or androgens, our method is comprehensive with the capability of covering hydroxyl-containing androgens, estrogens, corticoids, and progestogens. Furthermore, the nonderivatized steroid hormones (e.g., 17α-hydroxyprogesterone, progesterone, and androstenedione) were not destroyed during the derivatization process, and their levels could still be obtained in one LC-MS run. We were able to detect 24 steroid hormones at subng/mL levels (the lower limit of detection could reach 5 pg/mL for estrone and 16α-hydroxy estrone, which is equivalent to 0.1 pg on column) with maximum sensitivity enhancement factors of more than 10(3)- to 10(4)-fold after derivatization. The method was successfully applied to the measurement of free (unconjugated) steroid hormones in urine samples of males, females, and pregnant women. Because the significant role the steroid hormone pathway plays in humans, a comprehensive, sensitive, specific, and accurate method for profiling the steroid hormone metabolome shall offer new insights into hormone-related diseases. PMID:23110480

  7. Simultaneous detection of five one-carbon metabolites in plasma using stable isotope dilution liquid chromatography tandem mass spectrometry.

    PubMed

    Adaikalakoteswari, Antonysunil; Webster, Craig; Goljan, Ilona; Saravanan, Ponnusamy

    2016-02-15

    Disturbance in one-carbon (1-C) cycle occurs due to nutritional deficiencies (vitamin B12/folate) or specific genetic polymorphisms. This leads to altered levels of key 1-C metabolites such as SAM (s-adenosyl methionine), SAH (s-adenosyl homocysteine), methionine, homocysteine and MMA (methyl malonic acid). These 1-C metabolites are determinants of cellular methylation potential and epigenetic modifications of DNA which impairs metabolic pathways in several pathological diseases and developmental programming. Though methods were able to measure these analytes only independently, none of the methods detect simultaneously. Therefore we developed a method to measure these five 1-C metabolites in a single run using liquid chromatography tandem mass spectrometry (LC-MS/MS). We used stable isotopes dilution LC-MS/MS to measure the 1-C metabolites in human plasma. Blood samples were collected from pregnant women (n=30) at early gestation in the ongoing, multicentre, prospective PRiDE study. Linearity exhibited across the calibration range for all the analytes with the limit of detection (LOD) of 1.005nmol/l for SAM, 0.081nmol/l for SAH, 0.002?mol/l for methionine, 0.046?mol/l for homocysteine and 3.920nmol/l for MMA. The average recovery for SAM was 108%, SAH-110%, methionine-97%, homocysteine-91% and MMA-102%. The inter-assay CV for SAM was 7.3, SAH-5.6%, methionine-3.5%, homocysteine-7.0% and MMA-4.0%. The intra-assay CV for SAM was 8.7%, SAH-4.7%, methionine-5.4%, homocysteine-8.1% and MMA-6.1%. Pregnant women at early gestation with low B12 levels had significantly higher homocysteine, MMA, lower levels of methionine, SAM and SAM:SAH ratio and higher triglycerides. We developed a simple and rapid method to simultaneously quantify 1-C metabolites such as SAM, SAH, methionine, homocysteine and MMA in plasma by stable isotope dilution LC-MS/MS which would be useful to elucidate the epigenetic mechanisms related in the gene-nutrient interactions. PMID:26851522

  8. 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.

  9. Conceptual Study on New Isotope Analysis Technique with Resonance Ionization Mass Spectrometry Using Inductively Coupled Plasma as an Atomic Source (ICP-RIMS)

    NASA Astrophysics Data System (ADS)

    Watanabe, K.; Higuchi, Y.; Tomita, H.; Kawarabayashi, J.; Uritani, A.; Iguchi, T.

    2009-03-01

    We have proposed the novel isotope analysis technique with Resonance Ionization Mass Spectrometry using Inductively Coupled Plasma as an atomic source (ICP-RIMS). Each component of ICP-RIMS is conceptually designed. We conclude that the orthogonal acceleration time-of-flight mass spectrometer (oa-TOF-MS) driven by a high-repetition-rate pulsed laser would be suitable system for ICP-RIMS. We, additionally, suggest that the first vacuum stage of the vacuum interface, which is between the sampling and skimmer cones, is desired to maintain as low pressure as possible in order to suppress the Doppler broadening and to skim the supersonic jet effectively.

  10. Comparison of 265 nm Femtosecond and 213 nm Nanosecond Laser Ablation Inductively Coupled Plasma Mass Spectrometry for Pb Isotope Ratio Measurements.

    PubMed

    Ohata, Masaki; Nonose, Naoko; Dorta, Ladina; Gnther, Detlef

    2015-01-01

    The analytical performance of 265 nm femtosecond laser ablation (fs-LA) and 213 nm nanosecond laser ablation (ns-LA) systems coupled with multi-collector inductively coupled plasma mass spectrometry (MC-ICPMS) for Pb isotope ratio measurements of solder were compared. Although the time-resolved signals of Pb measured by fs-LA-MC-ICPMS showed smoother signals compared to those obtained by ns-LA-MC-ICPMS, similar precisions on Pb isotope ratio measurements were obtained between them, even though their operating conditions were slightly different. The mass bias correction of the Pb isotope ratio measurement was carried out by a comparison method using a Pb standard solution prepared from NIST SRM 981 Pb metal isotopic standard, which was introduced into the ICP by a desolvation nebulizer (DSN) via a dual-sample introduction system, and it was successfully demonstrated for Pb isotope ratio measurements for either NIST 981 metal isotopic standard or solder by fs-LA-MC-ICPMS since the analytical results agreed well with the certified value as well as the determined value within their standard deviations obtained and the expanded uncertainty of the certified or determined value. The Pb isotope ratios of solder obtained by ns-LA-MC-ICPMS also showed agreement with respect to the determined value within their standard deviations and expanded uncertainty. From these results, it was evaluated that the mass bias correction applied in the present study was useful and both LA-MC-ICPMS could show similar analytical performance for the Pb isotope ratio microanalysis of metallic samples such as solder. PMID:26656823

  11. Bromine isotope ratio measurements in seawater by multi-collector inductively coupled plasma-mass spectrometry with a conventional sample introduction system.

    PubMed

    de Gois, Jefferson S; Vallelonga, Paul; Spolaor, Andrea; Devulder, Veerle; Borges, Daniel L G; Vanhaecke, Frank

    2016-01-01

    A simple and accurate methodology for Br isotope ratio measurements in seawater by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) with pneumatic nebulization for sample introduction was developed. The Br(+) signals could be measured interference-free at high mass resolution. Memory effects for Br were counteracted using 5 mmol L(-1) of NH4OH in sample, standard, and wash solutions. The major cation load of seawater was removed via cation exchange chromatography using Dowex 50WX8 resin. Subsequent Br preconcentration was accomplished via evaporation of the sample solution at 90 °C, which did not induce Br losses or isotope fractionation. Mass discrimination was corrected for by external correction using a Cl-matched standard measured in a sample-standard bracketing approach, although Sr, Ge, and Se were also tested as potential internal standards for internal correction for mass discrimination. The δ(81)Br (versus standard mean ocean bromide (SMOB)) values thus obtained for the NaBr isotopic reference material NIST SRM 977 and for IRMM BCR-403 seawater certified reference material are in agreement with literature values. For NIST SRM 977, the (81)Br/(79)Br ratio (0.97291) was determined with a precision ≤0.08‰ relative standard deviation (RSD). Graphical Abstract A simple and accurate methodology for Br isotope ratio measurement in seawater by multi-collector inductively coupled plasma-mass spectrometry was developed. The cation load of seawater was removed using cation exchange chromatography. Spectral interference was avoided using high mass resolution. PMID:26123436

  12. 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)

  13. 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)

  14. Demonstration of femtosecond laser ablation inductively coupled plasma mass spectrometry for uranium isotopic measurements in U-10Mo nuclear fuel foils

    SciTech Connect

    Havrilla, George Joseph; Gonzalez, Jhanis

    2015-06-10

    The use of femtosecond laser ablation inductively coupled plasma mass spectrometry was used to demonstrate the feasibility of measuring the isotopic ratio of uranium directly in U-10Mo fuel foils. The measurements were done on both the flat surface and cross sections of bare and Zr clad U-10Mo fuel foil samples. The results for the depleted uranium content measurements were less than 10% of the accepted U235/238 ratio of 0.0020. Sampling was demonstrated for line scans and elemental mapping over large areas. In addition to the U isotopic ratio measurement, the Zr thickness could be measured as well as trace elemental composition if required. A number of interesting features were observed during the feasibility measurements which could provide the basis for further investigation using this methodology. The results demonstrate the feasibility of using fs-LA-ICP-MS for measuring the U isotopic ratio in U-10Mo fuel foils.

  15. Improvement in Thermal-Ionization Mass Spectrometry (TIMS) using Total Flash Evaporation (TFE) method for lanthanides isotope ratio measurements in transmutation targets

    SciTech Connect

    Mialle, S.; Gourgiotis, A.; Aubert, M.; Stadelmann, G.; Gautier, C.; Isnard, H.

    2011-07-01

    The experiments involved in the PHENIX french nuclear reactor to obtain precise and accurate data on the total capture cross sections of the heavy isotopes and fission products require isotopic ratios measurements with uncertainty of a few per mil. These accurate isotopic ratio measurements are performed with mass spectrometer equipped with multi-collector system. The major difficulty for the analyses of these actinides and fission products is the low quantity of the initial powder enclosed in steel container (3 to 5 mg) and the very low quantities of products formed (several {mu}g) after irradiation. Specific analytical developments are performed by Thermal Ionization Mass Spectrometry (TIMS) to be able to analyse several nanograms of elements with this technique. A specific method of acquisition named Total Flash Evaporation was adapted in this study in the case of lanthanide measurements for quantity deposited on the filament in the order of 2 ng and applied on irradiated fuel. To validate the analytical approach and discuss about the accuracy of the data, the isotopic ratios obtained by TIMS are compared with other mass spectrometric techniques such as Multiple-Collector Inductively Coupled Plasma Mass Spectrometer (MC-ICPMS). (authors)

  16. High-sensitivity mass spectrometry with a tandem accelerator

    SciTech Connect

    Henning, W.

    1983-01-01

    The characteristic features of accelerator mass spectrometry are discussed. A short overview is given of the current status of mass spectrometry with high-energy (MeV/nucleon) heavy-ion accelerators. Emphasis is placed on studies with tandem accelerators and on future mass spectrometry of heavier isotopes with the new generation of higher-voltage tandems.

  17. Determination of Atto- to Femtogram Levels of Americium and Curium Isotopes in Large-Volume Urine Samples by Compact Accelerator Mass Spectrometry.

    PubMed

    Dai, Xiongxin; Christl, Marcus; Kramer-Tremblay, Sheila; Synal, Hans-Arno

    2016-03-01

    Ultralow level analysis of actinides in urine samples may be required for dose assessment in the event of internal exposures to these radionuclides at nuclear facilities and nuclear power plants. A new bioassay method for analysis of sub-femtogram levels of Am and Cm in large-volume urine samples was developed. Americium and curium were co-precipitated with hydrous titanium oxide from the urine matrix and purified by column chromatography separation. After target preparation using mixed titanium/iron oxides, the final sample was measured by compact accelerator mass spectrometry. Urine samples spiked with known quantities of Am and Cm isotopes in the range of attogram to femtogram levels were measured for method evaluation. The results are in good agreement with the expected values, demonstrating the feasibility of compact accelerator mass spectrometry (AMS) for the determination of minor actinides at the levels of attogram/liter in urine samples to meet stringent sensitivity requirements for internal dosimetry assessment. PMID:26822907

  18. A novel quantification strategy of transferrin and albumin in human serum by species-unspecific isotope dilution laser ablation inductively coupled plasma mass spectrometry (ICP-MS).

    PubMed

    Feng, Liuxing; Zhang, Dan; Wang, Jun; Shen, Dairui; Li, Hongmei

    2015-07-16

    Species-specific (SS) isotope dilution analysis with gel electrophoresis (GE)-laser ablation (LA)-ICP-MS is a promising technique for the quantification of particular metal-binding proteins in biological samples. However, unavailable isotopically enriched spike and metal losses in GE separation are main limitations for SS-isotope dilution PAGE-LA-ICP-MS. In this study, we report for the first time the absolute quantification of transferrin (Tf) and albumin (Alb) in human serum by non-denaturing (native) GE combined with species-unspecific isotope dilution mass spectrometry (IDMS). In order to achieve a homogeneous distribution of both protein and isotope-enriched spike (simulated isotope equilibration), immersing the protein strips with (34)S spike solution after gel electrophoresis was demonstrated to be an effective way of spike addition. Furthermore, effects of immersion time and (34)S spike concentration were investigated to obtain optimal conditions of the post-electrophoresis isotope dilution method. The relative mass of spike and ablated sample (m(sp)/m(sam)) in IDMS equation was calculated by standard Tf and Alb proteins, which could be applied to the quantification of Tf and Alb in ERM-DA470k/IFCC for method confirmation. The results were in agreement with the certified value with good precision and small uncertainty (1.5-3%). In this method, species-specific spike protein is not necessary and the integrity of the heteroatom-protein could be maintained in sample preparation process. Moreover, the application of species-unspecific isotope dilution GE-LA-ICP-MS has the potential to offer reliable, direct and simultaneous quantification of proteins after conventional 1D and 2D gel electrophoretic separations. PMID:26073803

  19. Mass Spectrometry and Glycomics

    PubMed Central

    2010-01-01

    Abstract Glycosylation defines the adhesive properties of animal cell surfaces and the surrounding extracellular environments. Because cells respond to stimuli by altering glycan expression, glycan structures vary according to spatial location in tissue and temporal factors. These dynamic structural expression patterns, combined with the essential roles glycans play in physiology, drive the need for analytical methods for glycoconjugates. In addition, recombinant glycoprotein drug products represent a multibillion dollar market. Effective analytical methods are needed to speed the identification of new targets and the development of industrial glycoprotein products, both new and biosimilar. Mass spectrometry is an enabling technology in glycomics. This review summarizes mass spectrometry of glycoconjugate glycans. The intent is to summarize appropriate methods for glycans given their chemical properties as distinct from those of proteins, lipids, and small molecule metabolites. Special attention is given to the uses of mass spectral profiling for glycomics with respect to the N-linked, O-linked, ganglioside, and glycosaminoglycan compound classes. Next, the uses of tandem mass spectrometry of glycans are summarized. The review finishes with an update on mass spectral glycoproteomics. PMID:20443730

  20. MASS SPECTROMETRY OF RNA

    PubMed Central

    Meng, Zhaojing; Limbach, Patrick A.

    2008-01-01

    Ribonucleic acids (RNAs) are continuing to attract increased attention as they are found to play pivotal roles in biological system. Just as genomics and proteomics have been enabled by the development of effective analytical techniques and instrumentation, the large-scale analysis of non-protein coding (nc)RNAs will benefit as new analytical methodologies are developed which are appropriate to RNA analysis. Mass spectrometry offers a number of advantageous for RNA analysis arising from its ability to provide mass and sequence information starting with limited amounts of sample. This Briefings will highlight recent developments in the field that enable the characterization of RNA modification status, RNA tertiary structures, and ncRNA expression levels. These developments will also be placed in perspective of how mass spectrometry of RNAs can help elucidate the link between the genome and proteome. PMID:16769684

  1. Development of a stable isotope approach for the inductively coupled plasma-mass spectrometry determination of oxidized metallothionein in biological materials.

    PubMed

    Valles Mota, J P; Linde Arias, A R; Fernández de la Campa, M R; García Alonso, J I; Sanz-Medel, A

    2000-07-01

    The use of isotope dilution analysis (IDA) with inductively coupled plasma-mass spectrometry (ICP-MS) for the determination of oxidized metallothionein (MT) by a Cd-saturation method is investigated. The method developed here is a modification of an earlier methodology which used a radioactive Cd isotope ((109)Cd). While retaining the many advantages of this previous approach, the procedure presented here uses stable isotope ratio measurements ((114)Cd/(111)Cd) for the determination of MT. Experimental parameters governing the instrumental precision and accuracy for isotope ratio measurements of Cd by ICP-MS were characterized. Systematic errors, including mass bias, detector dead time, and spectroscopic interferences, could be easily corrected. The isotope dilution ICP-MS method was validated by the determination of very low levels of cadmium in biological certified reference materials (NIST SRM 2670 freeze-dried urine, IAEA H-8 horse kidney, and BCR TP-25 lichens). Finally, the IDA procedure was evaluated for the determination of oxidized MT by a Cd-saturation method previously developed using radioactive (109)Cd. The final procedure was applied to the quantification of MT in Long-Evans Cinnamon rat liver cytosol samples and the results were compared with data obtained for the same samples using the reference (109)Cd methodology. A good agreement between the analytical values obtained by both methods was observed. PMID:10873273

  2. Xanthine oxidoreductase activity assay in tissues using stable isotope-labeled substrate and liquid chromatography high-resolution mass spectrometry.

    PubMed

    Murase, Takayo; Nampei, Mai; Oka, Mitsuru; Ashizawa, Naoki; Matsumoto, Koji; Miyachi, Atsushi; Nakamura, Takashi

    2016-01-01

    Studies of pathological mechanisms and XOR inhibitor characterization, such as allopurinol, febuxostat, and topiroxostat, require accurate and sensitive measurements of XOR activity. However, the established assays have some disadvantages such as susceptibility to endogenous substances such as uric acid (UA), xanthine, or hypoxanthine. Here, we aimed to develop a novel XOR activity assay utilizing a combination of high-performance liquid chromatography (LC) and high-resolution mass spectrometry (HRMS) for tissues such as the liver, kidney, and plasma. Stable isotope-labeled [(15)N2]-xanthine was utilized as substrate and the production of [(15)N2]-uric acid was determined. [(15)N2]-UA production by XOR was dependent on the amounts of [(15)N2]-xanthine and enzyme and the time of reaction. Because high concentrations of endogenous xanthine and hypoxanthine affect XOR activities, we employed a multi-component analysis using LC/HRMS to improve the accuracy of XOR activity assay. Quantification of [(15)N2]-UA was validated and showed good linearity, accuracy, and precision. We measured the XOR activities of retired ICR mice using [(15)N2]-xanthine and LC/MS. The XOR activities in plasma, kidney, and liver samples were 38.10.7, 1585, 92825pmol/min/mg of protein, respectively (meanSD, n=5). Furthermore, we measured the XOR activities in the same samples using the LC/ultraviolet and LC/fluorescence (FL) methods. The level of [(15)N2]-xanthine oxidation by XOR was equal to that of xanthine oxidation and approximately 7.9-8.9 times higher than that of pterin oxidation. We found a good correlation between XOR activities examined using LC/MS assay with [(15)N2]-xanthine and those examined using LC/FL assay with pterin. This result suggested that although both the LC/MS assay with [(15)N2]-xanthine and the LC/FL assay with pterin were useful, the former provided information regarding XOR activities that more directly reflected the physiological condition than the latter. PMID:26673227

  3. Determination of the 87Sr/86Sr isotope ratio in USGS silicate reference materials by multi-collector ICP-mass spectrometry

    NASA Astrophysics Data System (ADS)

    Balcaen, Lieve; Schrijver, Isabel De; Moens, Luc; Vanhaecke, Frank

    2005-04-01

    Multi-collector ICP-mass spectrometry (MC-ICP-MS) was used for 87Sr/86Sr isotope ratio determination in newly introduced silicate reference materials from the US Geological Survey (USGS): granite G-3, andesite AGV-2, and basalt BCR-2. Next to the SrCO3 isotopic standard NIST SRM 987, also analogous USGS reference materials from the previous generation, and for which reference 87Sr/86Sr data obtained by TIMS are available, were analysed for validation purposes. Sample preparation consisted of acid digestion and subsequent isolation of Sr by means of a dedicated and commercially available crown ether-based resin. The Sr fractions thus obtained were analysed via MC-ICP-MS whereby mass discrimination was corrected for internally, while the isobaric interference at a mass-to-charge ratio of 86 caused by Kr impurities in the Ar gas was mathematically corrected for by using the signal for a Kr isotope free from spectral overlap. Finally, also the effect of the small amount of Rb that may still be present in the Sr fraction was corrected for mathematically on the basis of the signal intensity for 85Rb. The MC-ICP-MS results for G-2, AGV-1 and BCR-1 showed an excellent agreement with the corresponding TIMS values (<0.003% bias in all cases), such that it can be assumed that also the 87Sr/86Sr isotope ratio results obtained for the new reference materials are reliable.

  4. Multi-Isotope Secondary Ion Mass Spectrometry Combining Heavy Water 2H with 15N Labeling As Complementary Tracers for Metabolic Heterogeneity at the Single-Cell Level

    NASA Astrophysics Data System (ADS)

    Kopf, S.; McGlynn, S.; Cowley, E.; Green, A.; Newman, D. K.; Orphan, V. J.

    2014-12-01

    Metabolic rates of microbial communities constitute a key physiological parameter for understanding the in situ growth constraints for life in any environment. Isotope labeling techniques provide a powerful approach for measuring such biological activity, due to the use of isotopically enriched substrate tracers whose incorporation into biological materials can be detected with high sensitivity by isotope-ratio mass spectrometry. Nano-meter scale secondary ion mass spectrometry (NanoSIMS) combined with stable isotope labeling provides a unique tool for studying the spatiometabolic activity of microbial populations at the single cell level in order to assess both community structure and population diversity. However, assessing the distribution and range of microbial activity in complex environmental systems with slow-growing organisms, diverse carbon and nitrogen sources, or heterotrophic subpopulations poses a tremendous technical challenge because the introduction of isotopically labeled substrates frequently changes the nutrient availability and can inflate or bias measures of activity. Here, we present the use of hydrogen isotope labeling with deuterated water as an important new addition to the isotopic toolkit and apply it for the determination of single cell microbial activities by NanoSIMS imaging. This tool provides a labeling technique that minimally alters any aquatic chemical environment, can be administered with strong labels even in minimal addition (natural background is very low), is an equally universal substrate for all forms of life even in complex, carbon and nitrogen saturated systems, and can be combined with other isotopic tracers. The combination of heavy water labeling with the most commonly used NanoSIMS tracer, 15N, is technically challenging but opens up a powerful new set of multi-tracer experiments for the study of microbial activity in complex communities. We present the first truly simultaneous single cell triple isotope system measurements of 2H/1H, 13C/12C and 15N/14N and apply it to study of microbial metabolic heterogeneity and nitrogen metabolism in a continuous culture case study. Our data provide insight into both the diversity of microbial activity rates, as well as patterns of ammonium utilization at the single cell level.

  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. New commercial method for the enzymatic determination of creatinine in serum and urine evaluated: Comparison with a kinetic Jaffe method and isotope dilution-mass spectrometry

    SciTech Connect

    Lindbaeck, B.B.; Bergman, A.

    1989-05-01

    We evaluated a new, simple, enzymatic kinetic method from Wako Chemicals GmbH in comparison with a kinetic Jaffe method by using isotope dilution-mass spectrometry (ID-MS) as a reference method. An ID-MS-calibrated serum standard was used. Both the enzymatic and the Jaffe method correlated well with ID-MS, except for sera with high concentrations of bilirubin. Ethyl acetoacetate, acetone, and glucose in serum interfered somewhat with the Jaffe method but not with the enzymatic method. We conclude that the present enzymatic method has merit as compared with a Jaffe method for routine work, but is more expensive.

  8. Sensitive, Efficient Quantitation of 13C-Enriched Nucleic Acids via Ultrahigh-Performance Liquid Chromatography–Tandem Mass Spectrometry for Applications in Stable Isotope Probing

    PubMed Central

    Wilhelm, Roland; Szeitz, András; Klassen, Tara L.

    2014-01-01

    Stable isotope probing (SIP) of nucleic acids is a powerful tool for studying the functional traits of microbial populations within complex communities, but SIP involves a number of technical challenges. Many of the difficulties in DNA-SIP and RNA-SIP experiments can be effectively overcome with an efficient, sensitive method for quantitating the isotopic enrichment of nucleic acids. Here, we present a sensitive method for quantitating 13C enrichment of nucleic acids, requiring a few nanograms of sample, and we demonstrate its utility in typical DNA-SIP and RNA-SIP experiments. All five nucleobases (adenine, guanine, cytosine, thymine, and uracil) were separated and detected by using ultrahigh-performance liquid chromatography–tandem mass spectrometry. We detected all isotopic species in samples with as low as 1.5 atom% 13C above natural abundance, using 1-ng loadings. Quantitation was used to characterize the isotopic enrichment kinetics of cellulose- and lignin-based microcosm experiments and to optimize the recovery of enriched nucleic acids. Application of our method will minimize the quantity of expensive isotopically labeled substrates required and reduce the risk of failed experiments due to insufficient recovery of labeled nucleic acids for sequencing library preparation. PMID:25217022

  9. Sensitive, Efficient Quantitation of 13C-Enriched Nucleic Acids via Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry for Applications in Stable Isotope Probing.

    PubMed

    Wilhelm, Roland; Szeitz, András; Klassen, Tara L; Mohn, William W

    2014-12-01

    Stable isotope probing (SIP) of nucleic acids is a powerful tool for studying the functional traits of microbial populations within complex communities, but SIP involves a number of technical challenges. Many of the difficulties in DNA-SIP and RNA-SIP experiments can be effectively overcome with an efficient, sensitive method for quantitating the isotopic enrichment of nucleic acids. Here, we present a sensitive method for quantitating (13)C enrichment of nucleic acids, requiring a few nanograms of sample, and we demonstrate its utility in typical DNA-SIP and RNA-SIP experiments. All five nucleobases (adenine, guanine, cytosine, thymine, and uracil) were separated and detected by using ultrahigh-performance liquid chromatography-tandem mass spectrometry. We detected all isotopic species in samples with as low as 1.5 atom% (13)C above natural abundance, using 1-ng loadings. Quantitation was used to characterize the isotopic enrichment kinetics of cellulose- and lignin-based microcosm experiments and to optimize the recovery of enriched nucleic acids. Application of our method will minimize the quantity of expensive isotopically labeled substrates required and reduce the risk of failed experiments due to insufficient recovery of labeled nucleic acids for sequencing library preparation. PMID:25217022

  10. The use of static mass spectrometry to determine the combined stable isotopic composition of small samples of atmospheric methane.

    PubMed

    Jackson; Morgan; Morse; Butterworth; Pillinger

    1999-07-01

    Global budgets of atmospheric trace gases are increasingly being constrained by means of stable isotope measurements. Published analytical techniques for studying the parallel stable isotopic composition of methane (delta(13)C and deltaD) require prohibitively large quantities of methane for analysis, making them unsuitable for studies where sample size is small, e.g. soil methane fluxes. A highly sensitive static mass spectrometer has been developed which uniquely uses CH(4) as the analyte. The method requires only 8 ng of CH(4) for analysis (<10 mL ambient air), making replicated measurements of the isotopic composition of CH(4) in small samples feasible for the first time. This paper provides the first detailed description of the instrumentation and the analytical technique. The technique has been used to analyse small samples of air collected in Snowdonia over 21 months. The combined stable isotopic composition (delta(17)M) ranged from 29.5 to 35.5 per thousand, with an average value of 32.2 per thousand, and was strongly correlated with wind direction (p <0.01, r(2) = 0.71). Copyright 1999 John Wiley & Sons, Ltd. PMID:10407320

  11. Using Gas Chromatography/Isotope Ratio Mass Spectrometry to Determine the Fractionation Factor for H2 Production by Hydrogenases

    SciTech Connect

    Yang, Hui; Ghandi, H.; Shi, Liang; Kreuzer, Helen W.; Ostrom, Nathaniel; Hegg, Eric L.

    2012-01-15

    Hydrogenases catalyze the reversible formation of H2, and they are key enzymes in the biological cycling of H2. H isotopes should be a very useful tool in quantifying proton trafficking in biological H2 production processes, but there are several obstacles that have thus far limited the use of this tool. In this manuscript, we describe a new method that overcomes some of these barriers and is specifically designed to measure isotopic fractionation during enzyme-catalyzed H2 evolution. A key feature of this technique is that purified hydrogenases are employed, allowing precise control over the reaction conditions and therefore a high level of precision. A custom-designed high-throughput gas chromatography-isotope ratio mass spectrometer is employed to measure the isotope ratio of the H2. Using this method, we determined that the fractionation factor of H2 production by the [NiFe]-hydrogenase from Desulfivibrio fructosovran is 0.27. This result indicates that, as expected, protons are highly favored over deuterons during H2 evolution. Potential applications of this new method are discussed.

  12. Easy Extraction Method To Evaluate ?13C Vanillin by Liquid Chromatography-Isotopic Ratio Mass Spectrometry in Chocolate Bars and Chocolate Snack Foods.

    PubMed

    Bononi, Monica; Quaglia, Giancarlo; Tateo, Fernando

    2015-05-20

    An easy extraction method that permits the use of a liquid chromatography-isotopic ratio mass spectrometry (LC-IRMS) system to evaluate ?(13)C of vanillin in chocolate products and industrial flavorings is presented. The method applies the determination of stable isotopes of carbon to discriminate between natural vanillin from vanilla beans and vanillin from other sources (mixtures from beans, synthesis, or biotechnology). A series of 13 chocolate bars and chocolate snack foods available on the Italian market and 8 vanilla flavorings derived from industrial quality control processes were analyzed. Only 30% of products considered in this work that declared "vanilla" on the label showed data that permitted the declaration "vanilla" according to European Union (EU) Regulation 1334/2008. All samples not citing "vanilla" or "natural flavoring" on the label gave the correct declaration. The extraction method is presented with data useful for statistical evaluation. PMID:25965784

  13. Direct isotope ratio analysis of individual uranium-plutonium mixed particles with various U/Pu ratios by thermal ionization mass spectrometry.

    PubMed

    Suzuki, Daisuke; Esaka, Fumitaka; Miyamoto, Yutaka; Magara, Masaaki

    2015-02-01

    Uranium and plutonium isotope ratios in individual uranium-plutonium (U-Pu) mixed particles with various U/Pu atomic ratios were analyzed without prior chemical separation by thermal ionization mass spectrometry (TIMS). Prior to measurement, micron-sized particles with U/Pu ratios of 1, 5, 10, 18, and 70 were produced from uranium and plutonium certified reference materials. In the TIMS analysis, the peaks of americium, plutonium, and uranium ion signals were successfully separated by continuously increasing the evaporation filament current. Consequently, the uranium and plutonium isotope ratios, except the (238)Pu/(239)Pu ratio, were successfully determined for the particles at all U/Pu ratios. This indicates that TIMS direct analysis allows for the measurement of individual U-Pu mixed particles without prior chemical separation. PMID:25479434

  14. Determination of stable isotopic enrichment and concentration of glycerol in plasma via gas chromatography-mass spectrometry for the estimation of lipolysis in vivo.

    PubMed

    Flakoll, P J; Zheng, M; Vaughan, S; Borel, M J

    2000-07-01

    Measuring glycerol's rate of appearance into the plasma compartment provides an excellent estimation of whole-body lipolysis. The glycerol rate of appearance can be calculated by estimating the plasma dilution of continuously infused stable or radioactive isotopes of glycerol. Previously, determination of glycerol stable isotopic enrichment has required either chemical ionization gas chromatography-mass spectrometry (GC-MS) or electron impact ionization GC-MS in which a fragment containing only a portion of the glycerol molecule was measured. The present method uses tert.-butyldimethylsilyl (tBDMS) derivatization and electron impact ionization to measure a fragment including the entire glycerol molecule. The method determines concentration and enrichment of plasma glycerol in a simple, precise, and cost-efficient manner, providing a basis from which lipid homeostasis can be assessed. PMID:10985565

  15. "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.

  16. "Magic" Ionization Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Trimpin, Sarah

    2015-10-01

    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.

  17. Multidimensional enantio gas chromtography/mass spectrometry and gas chromatography-combustion-isotopic ratio mass spectrometry for the authenticity assessment of lime essential oils (C. aurantifolia Swingle and C. latifolia Tanaka).

    PubMed

    Bonaccorsi, Ivana; Sciarrone, Danilo; Schipilliti, Luisa; Dugo, Paola; Mondello, Luigi; Dugo, Giovanni

    2012-02-24

    This article focuses on the genuineness assessment of Lime oils (Citrus aurantifolia Swingle and C. latifolia Tanaka), by Multi Dimensional Gas Chromatography (MDGC) to determine the enantiomeric distribution of ?-thujene, camphene, ?-pinene, sabinene, ?-phellandrene, ?-phellandrene, limonene, linalool, terpinen-4-ol, ?-terpineol and by gas chromatography-combustion isotope ratio mass spectrometry (GC-C-IRMS) to determine the isotopic ratios of ?-pinene, ?-pinene, limonene, ?-terpineol, neral, geranial, ?-caryophyllene, trans-?-bergamotene, germacrene B. To the author's knowledge this is the first attempt to assess the authenticity and differentiate Persian Lime from Key lime oils by GC-C-IRMS. The results of the two analytical approaches were compared. The simultaneous use of the two techniques provides more reliable capability to detect adulteration in Citrus essential oils. In fact, in some circumstance only one of the two techniques allows to discriminate adulterated or contaminated oils. In cases where only small anomalies are detected by the two techniques due to subtle adulterations, their synergic use allows to express judgments. The advantage of both techniques is the low number of components the analyst must evaluate, reducing the complexity of the data necessary to deal with. Moreover, the conventional analytical approach based on the evaluation of the whole volatile fraction can fail to reveal the quality of the oils, if the adulteration is extremely subtle. PMID:22088669

  18. High-Precision Tungsten Isotopic Analysis by Multicollection Negative Thermal Ionization Mass Spectrometry Based on Simultaneous Measurement of W and (18)O/(16)O Isotope Ratios for Accurate Fractionation Correction.

    PubMed

    Trinquier, Anne; Touboul, Mathieu; Walker, Richard J

    2016-02-01

    Determination of the (182)W/(184)W ratio to a precision of 5 ppm (2?) is desirable for constraining the timing of core formation and other early planetary differentiation processes. However, WO3(-) analysis by negative thermal ionization mass spectrometry normally results in a residual correlation between the instrumental-mass-fractionation-corrected (182)W/(184)W and (183)W/(184)W ratios that is attributed to mass-dependent variability of O isotopes over the course of an analysis and between different analyses. A second-order correction using the (183)W/(184)W ratio relies on the assumption that this ratio is constant in nature. This may prove invalid, as has already been realized for other isotope systems. The present study utilizes simultaneous monitoring of the (18)O/(16)O and W isotope ratios to correct oxide interferences on a per-integration basis and thus avoid the need for a double normalization of W isotopes. After normalization of W isotope ratios to a pair of W isotopes, following the exponential law, no residual W-O isotope correlation is observed. However, there is a nonideal mass bias residual correlation between (182)W/(i)W and (183)W/(i)W with time. Without double normalization of W isotopes and on the basis of three or four duplicate analyses, the external reproducibility per session of (182)W/(184)W and (183)W/(184)W normalized to (186)W/(183)W is 5-6 ppm (2?, 1-3 ?g loads). The combined uncertainty per session is less than 4 ppm for (183)W/(184)W and less than 6 ppm for (182)W/(184)W (2?m) for loads between 3000 and 50 ng. PMID:26751903

  19. 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.

  20. Determination of 2H/1H and 13C/12C isotope ratios of (E)-methyl cinnamate from different sources using isotope ratio mass spectrometry.

    PubMed

    Fink, Kathrin; Richling, Elke; Heckel, Frank; Schreier, Peter

    2004-05-19

    For the authenticity assessment of (E)-methyl cinnamate from different origins, combustion/pyrolysis-isotope ratio mass spectrometry (C/P-IRMS) was used by an elemental analyzer (EA) and on-line capillary gas chromatography coupling (HRGC-C/P-IRMS). For that reason, (E)-methyl cinnamate self-prepared from synthetic, natural, and semisynthetic educts was analyzed in comparison to the commercial synthetic and natural ester. In addition, (E)-methyl cinnamate from basil extract and a number of commercial natural aromas was investigated. The data of self-synthesized synthetic (E)-methyl cinnamate, i.e., delta(13)C(V)(-)(PDB) = -33.8 per thousand and delta(2)H(V)(-)(SMOW) = +349 per thousand, corresponded with that found for the commercial synthetic samples (-29.5 to -31.4 per thousand and +328 to +360 per thousand for delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW), respectively). The ester produced from natural educts by acid as well as Candida antarctica catalysis revealed delta(13)C(V)(-)(PDB) = -25.6 and -30.1 per thousand as well as delta(2)H(V)(-)(SMOW) = -162 and -169 per thousand, respectively. Acid-catalyzed semisynthetic products differed in their delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW) values depending on the origin of their educts. For the ester from synthetic methanol and natural cinnamic acid, -27.3 and -126 per thousand were determined for delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW), respectively, whereas for the ester produced from natural methanol and synthetic acid delta(13)C(V)(-)(PDB) = -30.6 per thousand and delta(2)H(V)(-)(SMOW) = +287 per thousand were found. Basil extract showed -28.9 and -133 per thousand for delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW), respectively. Commercial aromas declared to be natural revealed delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW) data ranging from -25.7 to -28.5 per thousand as well as -85 to -191 per thousand, respectively, indicating, in part, incorrect declaration. PMID:15137854

  1. A novel approach to measure isotope ratios via multi-collector-inductively coupled plasma-mass spectrometry based on sample mixing with a non-enriched standard.

    PubMed

    Costas-Rodríguez, Marta; Lobo, Lara; Vanhaecke, Frank

    2014-07-01

    In this work, a novel approach to measure isotope ratios via multi-collector-inductively coupled plasma-mass spectrometry (MC-ICP-MS) for low amounts of target element is proposed. The methodology is based on mixing of the sample (target element isolate) with a non-enriched in-house standard, previously characterized for its isotopic composition. This methodology has been applied to isotopic analysis of Cu and of Fe in whole blood samples. For this purpose, different mixtures of sample + in-house standard were prepared and adjusted to a final concentration of 500 μg/L of the target elements for isotopic analysis. δ(65)Cu, δ(56)Fe, and δ(57)Fe varied linearly as a function of the amount of in-house standard (or of sample) present in the mixture. The isotopic composition of the sample was calculated considering the isotope ratios measured for (i) the mixture and (ii) the in-house standard and (iii) the relative concentrations of target element contributed by the sample and the standard to the mixture, respectively. For validation purposes, the isotopic analysis of whole blood Cu was carried out using both the conventional (using 2 mL of whole blood) and the newly developed approach (using 500 μL of whole blood). The δ(65)Cu values obtained using mixtures containing 40 % (200 μg/L) of Cu from the blood samples and 60 % (300 μg/L) of Cu from the in-house standard were in good agreement with the δ(65)Cu value obtained using the conventional approach (bias ≤0.15 ‰). PMID:24828978

  2. Application of laser ablation multicollector inductively coupled plasma mass spectrometry for the measurement of calcium and lead isotope ratios in packaging for discriminatory purposes.

    PubMed

    Santamaria-Fernandez, Rebeca; Wolff, Jean-Claude

    2010-07-30

    The potential of high-precision calcium and lead isotope ratio measurements using laser ablation coupled to multicollector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) to aid distinction between four genuine and five counterfeit pharmaceutical packaging samples and further classification of counterfeit packaging samples has been evaluated. We highlight the lack of reference materials for LA-MC-ICP-MS isotope ratio measurements in solids. In this case the problem is minimised by using National Institute of Standards and Technology Standard Reference Material (NIST SRM) 915a calcium carbonate (as solid pellets) and NIST SRM610 glass disc for sample bracketing external standardisation. In addition, a new reference material, NIST SRM915b calcium carbonate, has been characterised in-house for Ca isotope ratios and is used as a reference sample. Significant differences have been found between genuine and counterfeit samples; the method allows detection of counterfeits and aids further classification of packaging samples. Typical expanded uncertainties for measured-corrected Ca isotope ratio values ((43)Ca/(44)Ca and (42)Ca/(44)Ca) were found to be below 0.06% (k = 2, 95% confidence) and below 0.2% for measured-corrected Pb isotope ratios ((207)Pb/(206)Pb and (208)Pb/(206)Pb). This is the first time that Ca isotope ratios have been measured in packaging materials using LA coupled to a multicollector (MC)-ICP-MS instrument. The use of LA-MC-ICP-MS for direct measurement of Ca and Pb isotopic variations in cardboard/ink in packaging has definitive potential to aid counterfeit detection and classification. PMID:20552700

  3. Correction for the 17O interference in δ(13C) measurements when analyzing CO2 with stable isotope mass spectrometry

    USGS Publications Warehouse

    Coplen, Tyler B.; Brand, Willi A.; Assonov, Sergey S.

    2010-01-01

    Measurements of δ(13C) determined on CO2 with an isotope-ratio mass spectrometer (IRMS) must be corrected for the amount of 17O in the CO2. For data consistency, this must be done using identical methods by different laboratories. This report aims at unifying data treatment for CO2 IRMS by proposing (i) a unified set of numerical values, and (ii) a unified correction algorithm, based on a simple, linear approximation formula. Because the oxygen of natural CO2 is derived mostly from the global water pool, it is recommended that a value of 0.528 be employed for the factor λ, which relates differences in 17O and 18O abundances. With the currently accepted N(13C)/N(12C) of 0.011 180(28) in VPDB (Vienna Peedee belemnite) reevaluation of data yields a value of 0.000 393(1) for the oxygen isotope ratio N(17O)/N(16O) of the evolved CO2. The ratio of these quantities, a ratio of isotope ratios, is essential for the 17O abundance correction: [N(17O)/N(16O)]/[N(13C)/N(12C)] = 0.035 16(8). The equation [δ(13C) ≈ 45δVPDB-CO2 + 2 17R/13R (45δVPDB-CO2 – λ46δVPDB-CO2)] closely approximates δ(13C) values with less than 0.010 ‰ deviation for normal oxygen-bearing materials and no more than 0.026 ‰ in extreme cases. Other materials containing oxygen of non-mass-dependent isotope composition require a more specific data treatment. A similar linear approximation is also suggested for δ(18O). The linear approximations are easy to implement in a data spreadsheet, and also help in generating a simplified uncertainty budget.

  4. Comparative analysis of S-fatty acylation of gel-separated proteins by stable isotope-coded fatty acid transmethylation and mass spectrometry.

    PubMed

    Dong, Linjie; Li, Jianjian; Li, Lun; Li, Tingting; Zhong, Hongying

    2011-09-01

    Covalent attachment of palmitic acid or other fatty acids to the thiol groups of cysteine residues of proteins through reversible thioester bonds has an important role in the regulation of diverse biological processes. We describe here the development of a mass spectrometry protocol based on stable isotope-coded fatty acid transmethylation (iFAT) for qualitative and comparative analysis of protein S-fatty acylation under different experimental conditions. In this approach, cellular proteins extracted from different cell states are separated by SDS-PAGE and then the gel is stained with either Coomassie blue or Nile red for improved sensitivity. Protein bands are excised and then an in-gel stable iFAT procedure is performed. The fatty acid methyl esters resulting from derivatization with d0- and d3-methanol are identified by mass spectrometry. By measuring the intensities of labeled and unlabeled fragment ion pairs of fatty acid methyl esters, the levels of S-fatty acylation in different cells or tissues can be compared. This approach has been applied to monitor the changes of S-fatty acylation of zebrafish liver proteome in response to environmental dichlorodiphenyltrichloroethane exposure. Compared with the approach using metabolic incorporation of radioactive fatty acid analogs, it is not only simple and effective but also eliminates the hazards of handling radioactive isotopes. PMID:21886103

  5. Determination of steroid hormones in a human-serum reference material by isotope dilution--mass spectrometry: A candidate definitive method for cortisol

    SciTech Connect

    Patterson, D.G.; Patterson, M.B.; Culbreth, P.H.; Fast, D.M.; Holler, J.S.; Sampson, E.J.; Bayse, D.D.

    1984-05-01

    We report a method, based on isotope dilution--mass spectrometry, for determining cortisol in a pooled specimen of human serum. Isotopically labeled cortisol is added to 5.0 mL of serum so that the molar concentrations of labeled cortisol and unlabeled cortisol are approximately equal. The specimen and two calibration standards are extracted with dichloromethane, and the extracted cortisol is converted to the methoxime-trimethylsilyl ether derivative. Samples and standards are analyzed by gas chromatography--mass spectrometry by monitoring the peak areas for m/z 605 and 608. The cortisol concentration is calculated by linear interpolation between the two bracketing standards. Variances of data collected during six weeks showed that the overall coefficient of variation (CV) was 0.69% (n . 32); the within-vial CV, 0.63%; the among-vial CV, 0.22%; and the among-day CV, 0.15% (means . 3.973 nmol/vial). Method specificity was demonstrated by liquid chromatographic as well as C/sub 8/ mini-column cleanup of samples before derivation, by alternative ion monitoring at m/z 636 and 639, and by negative-ion chemical ionization at m/z 459 and 462. Derivatives of all observed degradation products of cortisol under basic, neutral, and acidic conditions did not interfere.

  6. Determination of steroid hormones in a human-serum reference material by isotope dilution--mass spectrometry: a candidate definitive method for cortisol.

    PubMed

    Patterson, D G; Patterson, M B; Culbreth, P H; Fast, D M; Holler, J S; Sampson, E J; Bayse, D D

    1984-05-01

    We report a method, based on isotope dilution--mass spectrometry, for determining cortisol in a pooled specimen of human serum. Isotopically labeled cortisol is added to 5.0 mL of serum so that the molar concentrations of labeled cortisol and unlabeled cortisol are approximately equal. The specimen and two calibration standards are extracted with dichloromethane, and the extracted cortisol is converted to the methoxime-trimethylsilyl ether derivative. Samples and standards are analyzed by gas chromatography--mass spectrometry by monitoring the peak areas for m/z 605 and 608. The cortisol concentration is calculated by linear interpolation between the two bracketing standards. Variances of data collected during six weeks showed that the overall coefficient of variation (CV) was 0.69% (n = 32); the within-vial CV, 0.63%; the among-vial CV, 0.22%; and the among-day CV, 0.15% (means = 3.973 nmol/vial). Method specificity was demonstrated by liquid chromatographic as well as C8 mini-column cleanup of samples before derivation, by alternative ion monitoring at m/z 636 and 639, and by negative-ion chemical ionization at m/z 459 and 462. Derivatives of all observed degradation products of cortisol under basic, neutral, and acidic conditions did not interfere. PMID:6370495

  7. [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.

  8. 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.

  9. 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 valuable tool in the determination of neutron capture cross-section measurements and the application of such determinations in Planetary Science. PMID:19877268

  10. Bioaffinity Mass Spectrometry Screening.

    PubMed

    Yang, Ben; Feng, Yun Jiang; Vu, Hoan; McCormick, Brendan; Rowley, Jessica; Pedro, Liliana; Crowther, Gregory J; Van Voorhis, Wesley C; Forster, Paul I; Quinn, Ronald J

    2016-02-01

    Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS or ESI-FTMS) was used to screen 192 natural product extracts and a 659-member natural product-based fragment library for bindings to a potential malaria drug target, Plasmodium falciparum Rab11a (PfRab11a, PF13_0119). One natural product extract and 11 fragments showed binding activity. A new natural product, arborside E, was identified from the active extract of Psydrax montigena as a weak binder. Its binding activity and inhibitory activity against PfRab11a were confirmed by ESI-FTMS titration experiments and an orthogonal enzyme assay. PMID:26773071

  11. Glow discharge mass spectrometry.

    PubMed

    Hoffmann, Volker; Kasik, Martin; Robinson, Peter K; Venzago, Cornel

    2005-01-01

    Over the past twenty years or so, glow discharge mass spectrometry (GDMS) has become the industry standard for the analysis of trace elements in metals and semiconductors. A review of its history is followed by a picture of the present situation and a look to where the future may lie. Applications are summarised, including the ability of GDMS to offer depth-resolved data and non-conductor analysis, and the well-documented quantitative nature of the results is reviewed. The effects resulting from the physical properties of the analyte material are discussed at length. Finally, recent work such as "fast flow" sources and pulsed glow discharges is reviewed. PMID:15624101

  12. Multiple spiking species-specific isotope dilution analysis by molecular mass spectrometry: simultaneous determination of inorganic mercury and methylmercury in fish tissues.

    PubMed

    Castillo, Angel; Rodrguez-Gonzlez, Pablo; Centineo, Giuseppe; Roig-Navarro, Antoni Francesc; Garca Alonso, J Ignacio

    2010-04-01

    This work demonstrates, for the first time, the applicability of multiple spiking isotope dilution analysis to molecular mass spectrometry exemplified by the speciation analysis of mercury using GC(EI)MS instrumentation. A double spike isotope dilution approach using isotopically enriched mercury isotopes has been applied for the determination of inorganic mercury Hg(II) and methylmercury (MeHg) in fish reference materials. The method is based on the application of isotope pattern deconvolution for the simultaneous determination of degradation-corrected concentrations of methylmercury and inorganic mercury. Mass isotopomer distributions are employed instead of isotope ratios to calculate the corrected concentrations of the Hg species as well as the extent of species degradation reactions. The isotope pattern deconvolution equations developed here allow the calculation of the different molar fractions directly from the GC(EI)MS mass isotopomer distribution pattern and take into account possible impurities present in the spike solutions employed. The procedure has been successfully validated with the analysis of two different certified reference materials (BCR-464 and DOLT-4) and with the comparison of the results obtained by GC(ICP)MS. For the tuna fish matrix (BCR-464), no interconversion reactions were observed at the optimized conditions of open focused microwave extraction at 70 degrees C during 8 min. However, significant demethylation was found under the same conditions in the case of the certified dogfish liver DOLT-4. Methylation and demethylation factors were confirmed by GC(ICP)MS. Transformation reactions have been found to depend on the sample matrix and on the derivatization reagent employed. Thus, it is not possible to recommend optimum extraction conditions suitable for all types of matrices demonstrating the need to apply multiple spiking methodologies for the determination of MeHg and Hg(II) in biological samples. Double spike isotope dilution analysis methodologies using widespread GC(EI)MS instrumentation are proposed here for the routine analysis of inorganic mercury and methylmercury in fish samples. The estimated method detection limits were below 10 ng g(-1) for both mercury species. Precision was evaluated for the concentrations present in the certified reference materials (CRMs) which vary from 0.1 to 5 microg g(-1), achieving values of coefficients of variation ranging from 7% to 2%. The concentrations obtained in both CRMs analyzed were in excellent agreement with the certified values, demonstrating the accuracy of the method at these concentration levels. PMID:20192179

  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. Exploring the limits of robust detection of incorporation of 13C by mass spectrometry in protein-based stable isotope probing (protein-SIP).

    PubMed

    Taubert, Martin; Baumann, Sven; von Bergen, Martin; Seifert, Jana

    2011-10-01

    One of the features of protein-based stable isotope probing is the parallel identification of differentially labeled peptide forms and the accurate calculation of their relative isotope abundances. The level of incorporation is informative of the metabolic activity of the species that synthesized the said protein and peptide. To model the carbon flux in a microbial community, an accurate assessment is crucial. Since the initial processes in carbon consumption are one of the most interesting objectives in microbial ecology, the methodology to detect low amounts of incorporation was tuned, and the limits of robust detection were analyzed. For this, Pseudomonas fluorescens DSM 50090T was grown on galactose using different ratios of (12)C/(13)C galactose from 10% down to 0.1% labeled galactose. After prolonged cultivation to ensure complete labeling, protein samples were separated by one-dimensional gel electrophoresis, subsequently tryptically digested and analyzed by ultra-performance liquid chromatography (UPLC) Orbitrap tandem mass spectrometry (MS/MS) measurements. The isotopic patterns from identified peptides in the mass spectra were used to calculate the (13)C relative isotope abundance (RIA) in the respective peptides. The statistic distribution of the RIA values in dependence of the number of analyzed peptides was compared between the different ratios of unlabeled/labeled substrate. The acquired data showed that the applied method is capable of detecting a difference in (13)C incorporation of 0.1% RIA based on at least 20 peptides. This sensitivity makes protein-stable isotope probing a valuable method for quantitative assessment of species specific metabolic activity in metaproteomics. PMID:21822970

  15. Deletion of Genes Encoding Arginase Improves Use of “Heavy” Isotope-Labeled Arginine for Mass Spectrometry in Fission Yeast

    PubMed Central

    Borek, Weronika E.; Zou, Juan; Rappsilber, Juri; Sawin, Kenneth E.

    2015-01-01

    The use of “heavy” isotope-labeled arginine for stable isotope labeling by amino acids in cell culture (SILAC) mass spectrometry in the fission yeast Schizosaccharomyces pombe is hindered by the fact that under normal conditions, arginine is extensively catabolized in vivo, resulting in the appearance of “heavy”-isotope label in several other amino acids, most notably proline, but also glutamate, glutamine and lysine. This “arginine conversion problem” significantly impairs quantification of mass spectra. Previously, we developed a method to prevent arginine conversion in fission yeast SILAC, based on deletion of genes involved in arginine catabolism. Here we show that although this method is indeed successful when 13C6-arginine (Arg-6) is used for labeling, it is less successful when 13C615N4-arginine (Arg-10), a theoretically preferable label, is used. In particular, we find that with this method, “heavy”-isotope label derived from Arg-10 is observed in amino acids other than arginine, indicating metabolic conversion of Arg-10. Arg-10 conversion, which severely complicates both MS and MS/MS analysis, is further confirmed by the presence of 13C515N2-arginine (Arg-7) in arginine-containing peptides from Arg-10-labeled cells. We describe how all of the problems associated with the use of Arg-10 can be overcome by a simple modification of our original method. We show that simultaneous deletion of the fission yeast arginase genes car1+ and aru1+ prevents virtually all of the arginine conversion that would otherwise result from the use of Arg-10. This solution should enable a wider use of heavy isotope-labeled amino acids in fission yeast SILAC. PMID:26075619

  16. Isotopic analysis of Cu in blood serum by multi-collector ICP-mass spectrometry: a new approach for the diagnosis and prognosis of liver cirrhosis?

    PubMed

    Costas-Rodríguez, Marta; Anoshkina, Yulia; Lauwens, Sara; Van Vlierberghe, Hans; Delanghe, Joris; Vanhaecke, Frank

    2015-03-01

    The isotopic composition of blood serum Cu has been investigated as a potential parameter for the diagnosis and prognosis of liver cirrhosis. Serum samples from supposedly healthy women (reference population) and from a group of female patients suffering from liver cirrhosis of different etiologies were analysed. The procedure for isolation of serum Cu and the measurement protocol for its isotopic analysis by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) were evaluated. Significant differences in the isotopic composition of Cu were observed between the reference population and the patients. A wide spread in δ(65)Cu was observed within the cirrhosis population and δ(65)Cu seems to be linked to the severity of the disease. Patients with end-stage liver disease showed a significantly lighter serum Cu isotopic composition. Many clinical parameters used for the diagnosis and monitoring of liver diseases, i.e. the levels of aspartate aminotransferase, De Ritis ratio, prothrombin and international normalized ratio, albumin, bilirubin, Na and C-reactive protein, correlate well with the δ(65)Cu values, as did the ceruloplasmin level and the ceruloplasmin/Cu concentration ratio. The isotopic composition of serum Cu appears to reveal the synthetic and hepatocellular function of the liver synergistically with inflammation and fluid retention in the cohort studied. A relevant relationship was also observed between δ(65)Cu and scores of mortality risk, such as the Model for End-stage Liver Disease (MELD) and MELD-Na. Thus, the isotopic composition of serum Cu shows potential as a new approach for the prognosis of liver disease, and although further investigation is required, for evaluation of the mortality risk in end-stage liver disease and prioritization of liver transplants. PMID:25644127

  17. 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 high-purity materials and environmental samples) is used in order to improve the detection limits of trace elements. Furthermore, the determination of chemical elements in the trace and ultratrace concentration range is often difficult and can be disturbed through mass interferences of analyte ions by molecular ions at the same nominal mass. By applying double-focusing sector field mass spectrometry at the required mass resolutionby the mass spectrometric separation of molecular ions from the analyte ionsit is often possible to overcome these interference problems. Commercial instrumental equipment, the capability (detection limits, accuracy, precision) and the analytical application fields of mass spectrometric methods for the determination of trace and ultratrace elements and for surface analysis are discussed.

  18. Method for ultra-trace cesium isotope ratio measurements from environmental samples using thermal ionization mass spectrometry

    SciTech Connect

    Snow, Mathew S.; Snyder, Darin C.; Mann, Nick R.; White, Byron M.

    2015-05-01

    135Cs/137Cs isotope ratios can provide the age, origin and history of environmental Cs contamination. Relatively high precision 135Cs/137Cs isotope ratio measurements from samples containing femtogram quantities of 137Cs are needed to accurately track contamination resuspension and redistribution following environmental 137Cs releases; however, mass spectrometric analyses of environmental samples are limited by the large quantities of ionization inhibitors and isobaric interferences which are present at relatively high concentrations in the environment. We report a new approach for Cs purification from environmental samples. An initial ammonium molybdophosphate-polyacrylonitrile (AMP-PAN) column provides a robust method for extracting Cs under a wide variety of sample matrices and mass loads. Cation exchange separations using a second AMP-PAN column result in more than two orders of magnitude greater Cs/Rb separation factors than commercially available strong cation exchangers. Coupling an AMP-PAN cation exchanging step to a microcation column (AG50W resin) enables consistent 2-4% (2σ) measurement errors for samples containing 3-6,000 fg 137Cs, representing the highest precision 135Cs/137Cs ratio measurements currently reported for soil samples at the femtogram level.

  19. New even-parity high-lying levels of Sm I and measurement of isotope shifts by two-color resonance ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Seema, A. U.; Mandal, P. K.; Rath, Asawari D.; Dev, Vas

    2014-09-01

    In this work, we investigate the even-parity high-lying levels of Sm I in the energy region 33136-33960 cm-1 by performing two-color three-photon resonance ionization spectroscopy in an atomic beam coupled to a time-of-flight mass spectrometer using two tunable pulsed dye lasers. We observe twenty-one new and confirm eight previously reported even-parity energy levels of Sm I in this spectral region. Absolute energies of these levels are determined with an accuracy of 0.3 cm-1. Using electric dipole selection rule, total angular momentum (J-value) of the most newly observed levels is assigned uniquely. Further, employing two-color three-step resonance ionization mass spectrometry, we measure the isotope shift between 154Sm and 144Sm of sixteen high-lying levels with a moderate accuracy of 30 mK.

  20. A novel sample decomposition technique at atmospheric pressure for the determination of Os abundances in iron meteorites using isotope dilution inductively coupled plasma-mass spectrometry.

    PubMed

    Hattori, M; Hirata, T

    2001-06-01

    A safe and reliable analytical technique for the determination of Os abundances in ten iron meteorites of various chemical groups was developed using isotope dilution inductively coupled plasma-mass spectrometry coupled with a sample decomposition technique. A major advantage of the sample decomposition technique developed here is that the pressure inside the reaction flask is not increased through the decomposition reaction because the flask is a fully opened system, obviating the risk of explosion of the glass apparatus. Another advantage is that there is no restriction in the sample size being decomposed. In this study, about 2 g of metallic sample were decomposed safely, and this sample size, > 10 times larger than that typically used for the Carius tube technique, allows one to obtain more reliable Os data for heterogeneous samples. The metallic samples were decomposed in a glass flask purged with Ar. Since the O2 was purged from the reaction flask, Os was not oxidised to volatile OsO4, thereby preventing significant evaporation loss of Os. The typical recovery of Os throughout the sample decomposition and separation processes was > 80%, and the total Os blank through the decomposition of a 1 g amount of sample was less than 20 pg. Os abundances were determined by means of stable isotope dilution mass spectrometry using a 190Os-enriched isotopic tracer. Except for Sikhote-Alin, the measured Os abundances in almost all the iron meteorites exhibited a good agreement with the previously published Os abundance data, within the analytical uncertainty achieved in this study (2-5%). For the Sikhote-Alin meteorite, on the basis of a better correlation between Os and Ir abundances, we believe that our Os abundance data should be more reliable. The Os abundance data obtained in this work clearly demonstrated the suitability of the newly developed sample decomposition procedure for low level Os determinations. PMID:11445949

  1. An inter-laboratory comparative study into sample preparation for both reproducible and repeatable forensic 2H isotope analysis of human hair by continuous flow isotope ratio mass spectrometry.

    PubMed

    Meier-Augenstein, Wolfram; Chartrand, Michelle M G; Kemp, Helen F; St-Jean, Gilles

    2011-11-15

    Stable isotope analysis of organic materials for their hydrogen ((2)H), carbon ((13)C), nitrogen ((15)N) or oxygen ((18)O) isotopic composition using continuous flow isotope ratio mass spectrometry (CF-IRMS) is an increasingly used tool in forensic chemical analysis. (2)H isotopic analysis can present a huge challenge, especially when dealing with exhibits comprising exchangeable hydrogen such as human scalp hair. However, to yield forensic data that are fit for purpose, analysis of the (2)H isotopic composition of the same homogeneous human hair sample by any laboratory worldwide must yield the same isotopic composition within analytical uncertainty. This paper presents longitudinal (2)H isotope data for four human hair samples of different provenance, measured by three different laboratories whose sample preparation was based on a two-stage H exchange equilibration method. Although each laboratory employed varying means to comply with the generic features of the sample preparation protocol such as the (2)H isotopic composition of exchange waters or drying down of samples prior to analysis, within each laboratory the Principle of Identical Treatment (P.I.T.) was applied for each individual experiment. Despite the variation in materials and procedures employed by the three laboratories, repeatable and reproducible 'true' (2)H isotope values (?(2)H(hair,true)) were determined by each laboratory for each of the four stock samples of human scalp hair. The between-laboratory differences for obtained ?(2)H(hair,true) values ranged from 0.1 to 2.5 . With an overall 95% confidence interval of 2.8 , these differences were not significantly different, which suggests that the general method of two-stage exchange equilibration carried out at ambient temperature is suitable for accurately and reproducibly determining 'true' ?(2)H-values for hair and other proteins provided that certain key conditions are met. PMID:22006397

  2. Determination of cadmium in oyster tissue using isotope dilution inductively coupled plasma mass spectrometry: comparison of results obtained in the standard and He/H2 cell modes.

    PubMed

    Yip, Yiu-chung; Chu, Hei-shing; Chan, Kwok-chu; Chan, Kam-kit; Cheung, Ping-yuk; Sham, Wing-cheong

    2006-11-01

    An inductively coupled plasma quadrupole mass spectrometer equipped with an octopole collision/reaction cell was used for the determination of cadmium in oyster tissue samples using isotope dilution inductively coupled plasma mass spectrometry. The oyster samples in question were found to contain Mo and Zr. In our feasibility study on a Cd standard solution (10 microg L(-1)) containing a matrix of Mo (1000 microg L(-1)) or Zr (250 microg L(-1)), the potentially interfering species (MoO(+) or ZrO(+)) present at the analytical mass of cadmium concerned (m/z 111, 112 or 114) was reduced effectively through the use of a mixture of He and H(2) as cell gases. The accuracy of the method was validated by the analysis of a matrix-matched certified reference material (CRM) of NIST SRM 1566b. The CRM was analyzed under the standard and He/H(2) cell modes. Two isotopic pairs of (114)Cd/(111)Cd and (112)Cd/(111)Cd were selected for quantification purposes. The recoveries of cadmium obtained in the two cell modes were compared with each other. The validated method was applied successfully to the APMP.QM-P5 pilot study for international comparability purposes. PMID:16953319

  3. Molecular formula analysis of fragment ions by isotope-selective collision-induced dissociation tandem mass spectrometry of pharmacologically active compounds.

    PubMed

    Bianco, Giuliana; Buchicchio, Alessandro; Lelario, Filomena; Cataldi, Tommaso R I

    2014-12-01

    The purpose of this work is to explore the mass fragment characterization of commonly used drugs through a novel approach, which involves isotope-selective tandem mass spectrometry (MS/MS). Collision-induced dissociation (CID) was performed with a low-resolution linear ion trap mass spectrometer in positive electrospray ionization. Three pharmacologically active ingredients, i.e. omeprazole, meloxicam and brinzolamide, selected as model compounds in their own formulation, were investigated as a sodiated adduct [C17 H19 N3 O3 S + Na](+) (omeprazole) and as protonated adducts, [C14 H13 N3 O4 S2  + H](+) and [C12 H21 N3 O5 S3  + H](+) , meloxicam and brinzolamide, respectively. Selecting a narrow window of ±0.5 m/z units, precursor ion fragmentation by CID-MS/MS of isotopologues A + 0, A + 1 and A + 2 was found very useful to confirm the chemical formula of product ions, thus aiding the establishment of characteristic fragmentation pathways of all three examined compounds. The correctness of putative molecular formula of product ions was easily demonstrated by exploiting the isotope peak abundance ratios (i.e. IF+0 /IF+1 and IF+0 /IF+2 ) as simple constraints in low-resolution MS instrumentations. PMID:25476951

  4. Trace analysis of acidic pharmaceutical residues in waters with isotope dilution gas chromatography-mass spectrometry via methylation derivatization.

    PubMed

    Hu, Ruikang; Yang, Zhaoguang; Zhang, Lifeng

    2011-09-30

    Acidic pharmaceutical residues are pollutants of emerging concern and are generally monitored by HPLC-MS/MS. However, due to the limited separation efficiency of HPLC column and lack of suitable mass transition for confirmation analysis, some interference may not be separated completely and differentiated from ibuprofen, which may cause the results with interference, especially in sample with complex matrix. The objective of this study is to develop a sensitive and reliable method for the determination of acidic pharmaceutical residues in water samples by GC-MS with better resolution by using methylation derivatization and isotope dilution techniques. TMSDM, a mild reagent, was used as the derivatization reagent coupling with the isotope dilution technique, for the first time, to improve the precision and accuracy of the analytical method to determine the pharmaceutical residues in water. The MDLs for the five acidic organic compounds: ibuprofen, gemfibrozil, naproxen, ketoprofen and diclofenac were from 0.7 to 1.1 ng/L, with recoveries ranging from 93 to 110%. Alternative to the HPLC-MS/MS method, the developed GC-MS protocols provides an additional option for the analysis of acidic pharmaceutical residues in water, with better separation efficiency in reducing interferences from complicated sample matrix, for determination of ibuprofen residues. PMID:21872014

  5. Isotope ratio analysis of actinides, fission products, and geolocators by high-efficiency multi-collector thermal ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Bürger, S.; Riciputi, L. R.; Bostick, D. A.; Turgeon, S.; McBay, E. H.; Lavelle, M.

    2009-09-01

    A ThermoFisher "Triton" multi-collector thermal ionization mass spectrometer (MC-TIMS) was evaluated for trace and ultra-trace level isotope ratio analysis of actinides (uranium, plutonium, and americium), fission products and geolocators (strontium, cesium, and neodymium). Total efficiencies (atoms loaded to ions detected) of up to 0.5-2% for U, Pu, and Am, and 1-30% for Sr, Cs, and Nd can be reported employing resin bead load techniques onto flat ribbon Re filaments or resin beads loaded into a millimeter-sized cavity drilled into a Re rod. This results in detection limits of <0.1 fg (104 atoms to 105 atoms) for 239-242+244Pu, 233+236U, 241-243Am, 89,90Sr, and 134,135,137Cs, and <=1 pg for natural Nd isotopes (limited by the chemical processing blank) using a secondary electron multiplier (SEM) or multiple-ion counters (MICs). Relative standard deviations (RSD) as small as 0.1% and abundance sensitivities of 1 × 106 or better using a SEM are reported here. Precisions of RSD [approximate]0.01-0.001% using a multi-collector Faraday cup array can be achieved at sub-nanogram concentrations for strontium and neodymium and are suitable to gain crucial geolocation information. The analytical protocols reported herein are of particular value for nuclear forensic and nuclear safeguard applications.

  6. Reduced mass range ion trap mass spectrometry for atomic ions

    SciTech Connect

    Barinaga, C.J.; Eiden, G.C.; Koppenaal, D.W.

    1995-12-31

    In an attempt to apply some of the real and perceived advantages of quadrupole ion trap mass spectrometry to elemental/isotopic mass analysis a prototype Inductively Coupled Plasma-Ion Trap Mass Spectrometer (ICP-ITMS) has been built with a linear quadrupole between the vacuum interface and the ion trap. Initial results show some promise for ICP-ITMS to be a useful technique. However two limitations are the charge capacity and dynamic range of the standard Finnigan ITMS.

  7. Airborne measurements of sulfur dioxide, dimethyl sulfide, carbon disulfide, and carbonyl sulfide by isotope dilution gas chromatography/mass spectrometry

    NASA Technical Reports Server (NTRS)

    Bandy, Alan R.; Thornton, Donald C.; Driedger, Arthur R., III

    1993-01-01

    A gas chromatograph/mass spectrometer is described for determining atmospheric sulfur dioxide, carbon disulfide, dimethyl sulfide, and carbonyl sulfide from aircraft and ship platforms. Isotopically labelled variants of each analyte were used as internal standards to achieve high precision. The lower limit of detection for each species for an integration time of 3 min was 1 pptv for sulfur dioxide and dimethyl sulfide and 0.2 pptv for carbon disulfide and carbonyl sulfide. All four species were simultaneously determined with a sample frequency of one sample per 6 min or greater. When only one or two species were determined, a frequency of one sample per 4 min was achieved. Because a calibration is included in each sample, no separate calibration sequence was needed. Instrument warmup was only a few minutes. The instrument was very robust in field deployments, requiring little maintenance.

  8. The assay of pterostilbene in spiked matrices by liquid chromatography tandem mass spectrometry and isotope dilution method.

    PubMed

    Mazzotti, Fabio; Di Donna, Leonardo; Benabdelkamel, Hicham; Gabriele, Bartolo; Napoli, Anna; Sindona, Giovanni

    2010-04-01

    Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is an active component found in several plant species, exhibiting important pharmacological properties. A new and reliable method of assaying this phyto compound in various matrices is presented; the assay is based on (1) the selectivity of liquid chromatography (LC) hyphenated with electrospray ionisation (ESI), (2) the specificity of a two-step mass spectrometric analysis (MS/MS) and (3) the accuracy of the isotope dilution method. The labelled analogue may be conveniently synthesised in a few steps. The sensitivity of the method is confirmed by the very low limit of detection (LOD) and limit of quantitation (LOQ) values achieved in the assay of pterostilbene in two distinct fortified matrices, and is further supported by the observed accuracy values. PMID:20198601

  9. Laser ablation molecular isotopic spectrometry of carbon isotopes

    SciTech Connect

    Bol'shakov, Alexander A.; Jain, Jinesh; Russo, Richard E.; McIntyre, Dustin; Mao, Xianglei

    2015-08-28

    Quantitative determination of carbon isotopes using Laser Ablation Molecular Isotopic Spectrometry (LAMIS) is described. Optical emission of diatomic molecules CN and C2 is used in these measurements. Two quantification approaches are presented:empirical calibration of spectra using a set of reference standards and numerical fitting of a simulated spectrum to the experimental one. Formation mechanisms of C2 and CN in laser ablation plasma are briefly reviewed to provide insights for implementation of LAMIS measurements. A simulated spectrum of the 12C2 Swan system was synthesized using four constituents within 473.5–476.5 nm. Simulation included three branches of 12C2 (1-0), branches R(0-0) and R(1-1), and branch P(9-8) of 12C2. Spectral positions of the tail lines in R(0-0) and R(1-1) were experimentally measured, since they were not accurately known before. The Swan band (1-0) of the isotopologue 13C12C was also simulated. Fitting to the experimental spectrumyielded the ratio 13C/12C = 1.08% in a good agreement with measurements by isotope ratio mass spectrometry. LAMIS promises to be useful in coal, oil and shale exploration, carbon sequestration monitoring, and agronomy studies

  10. Laser ablation molecular isotopic spectrometry of carbon isotopes

    NASA Astrophysics Data System (ADS)

    Bol?shakov, Alexander A.; Mao, Xianglei; Jain, Jinesh; McIntyre, Dustin L.; Russo, Richard E.

    2015-11-01

    Quantitative determination of carbon isotopes using Laser Ablation Molecular Isotopic Spectrometry (LAMIS) is described. Optical emission of diatomic molecules CN and C2 is used in these measurements. Two quantification approaches are presented: empirical calibration of spectra using a set of reference standards and numerical fitting of a simulated spectrum to the experimental one. Formation mechanisms of C2 and CN in laser ablation plasma are briefly reviewed to provide insights for implementation of LAMIS measurements. A simulated spectrum of the 12C2 Swan system was synthesized using four constituents within 473.5-476.5 nm. Simulation included three branches of 12C2 (1-0), branches R(0-0) and R(1-1), and branch P(9-8) of 12C2. Spectral positions of the tail lines in R(0-0) and R(1-1) were experimentally measured, since they were not accurately known before. The Swan band (1-0) of the isotopologue 13C12C was also simulated. Fitting to the experimental spectrum yielded the ratio 13C/12C = 1.08% in a good agreement with measurements by isotope ratio mass spectrometry. LAMIS promises to be useful in coal, oil and shale exploration, carbon sequestration monitoring, and agronomy studies.

  11. ?D and ?13C analyses of atmospheric volatile organic compounds by thermal desorption gas chromatography isotope ratio mass spectrometry.

    PubMed

    von Eckstaedt, Christiane Vitzthum; Grice, Kliti; Ioppolo-Armanios, Marisa; Chidlow, Geoff; Jones, Mark

    2011-09-16

    This paper describes the establishment of a robust method to determine compound specific ?D and ?(13)C values of volatile organic compounds (VOCs) in a standard mixture ranging between C(6) and C(10) and was applied to various complex emission samples, e.g. from biomass combustion and car exhaust. A thermal desorption (TD) unit was linked to a gas chromatography isotope ratio mass spectrometer (GC-irMS) to enable compound specific isotope analysis (CSIA) of gaseous samples. TenaxTA was used as an adsorbent material in stainless steel TD tubes. We determined instrument settings to achieve a minimal water background level for reliable ?D analysis and investigated the impact of storage time on ?D and ?(13)C values of collected VOCs (176 days and 40 days of storage, respectively). Most of the standard compounds investigated showed standard deviations (SD)<6 (?D) when stored for 148 days at 4 C. However, benzene revealed occasionally D depleted values (21 SD) for unknown reasons. ?(13)C analysis demonstrated that storage of 40 days had no effect on VOCs investigated. We also showed that breakthrough (benzene and toluene, 37% and 7%, respectively) had only a negligible effect (0.7 and 0.4, respectively) on ?(13)C values of VOCs on the sample tube. We established that the sample portion collected at the split flow effluent of the TD unit can be used as a replicate sample for isotope analysis saving valuable sampling time and resources. We also applied TD-GC-irMS to different emission samples (biomass combustion, petrol and diesel car engines exhaust) and for the first time ?D values of atmospheric VOCs in the above range are reported. Significant differences in ?D of up to 130 were observed between VOCs in emissions from petrol car engine exhaust and biomass combustion (Karri tree). However, diesel car emissions showed a high content of highly complex unresolved mixtures thus a baseline separation of VOCs was not achieved for stable hydrogen isotope analysis. The ability to analyse ?D by TD-GC-irMS complements the characterisation of atmospheric VOCs and is maybe used for establishing further source(s). PMID:21807368

  12. Dual element ((15)N/(14)N, (13)C/(12)C) isotope analysis of glyphosate and AMPA by derivatization-gas chromatography isotope ratio mass spectrometry (GC/IRMS) combined with LC/IRMS.

    PubMed

    Mogusu, Emmanuel O; Wolbert, J Benjamin; Kujawinski, Dorothea M; Jochmann, Maik A; Elsner, Martin

    2015-07-01

    To assess sources and degradation of the herbicide glyphosate [N-(phosphonomethyl) glycine] and its metabolite AMPA (aminomethylphosphonic acid), concentration measurements are often inconclusive and even (13)C/(12)C analysis alone may give limited information. To advance isotope ratio analysis of an additional element, we present compound-specific (15)N/(14)N analysis of glyphosate and AMPA by a two step derivatization in combination with gas chromatography/isotope ratio mass spectrometry (GC/IRMS). The N-H group was derivatized with isopropyl chloroformate (iso-PCF), and remaining acidic groups were subsequently methylated with trimethylsilyldiazomethane (TMSD). Iso-PCF treatment at pH <10 gave too low (15)N/(14)N ratios indicating an incomplete derivatization; in contrast, too high (15)N/(14)N ratios at pH >10 indicated decomposition of the derivative. At pH 10, and with an excess of iso-PCF by 10-24, greatest yields and accurate (15)N/(14)N ratios were obtained (deviation from elemental analyzer-IRMS: -0.2??0.9% for glyphosate; -0.4??0.7% for AMPA). Limits for accurate ?(15)N analysis of glyphosate and AMPA were 150 and 250 ng injected, respectively. A combination of ?(15)N and ?(13)C analysis by liquid chromatography/isotope ratio mass spectrometry (LC/IRMS) (1) enabled an improved distinction of commercial glyphosate products and (2) showed that glyphosate isotope values during degradation by MnO2 clearly fell outside the commercial product range. This highlights the potential of combined carbon and nitrogen isotopes analysis to trace sources and degradation of glyphosate. PMID:25967147

  13. Iron absorption in man calculated from erythrocyte incorporation of the stable isotope iron-54 determined by fast atom bombardment mass spectrometry

    SciTech Connect

    Lehmann, W.D.; Fischer, R.; Heinrich, H.C.

    1988-07-01

    The methodology of precise isotope abundance determinations of erythrocyte iron by fast atom bombardment mass spectrometry and signal averaging is established. For the determination of the 54Fe/56Fe ratio a relative precision of 0.5% and an absolute precision of 0.03% is achieved. After oral loading with 54Fe-enriched samples in the range between 5 and 25 mg per subject, the 14-day erythrocyte incorporation of 54Fe has been determined in five individuals, namely, two adults, two children, and one infant. In the two adults, the oral dose of 54Fe was simultaneously labeled with a trace amount of carrier-free 59Fe. In these double-isotope loading tests, a good agreement was observed between the absorption data determined on the basis of whole body retention of 59Fe and on the basis of the 54Fe erythrocyte incorporation. The stable isotope methodology applied allows measurement of the iron absorption using highly enriched 54Fe at a dose of 25 mg for an adult or at a dose of 5 mg for infants of about 1 year of age.

  14. Determination of lead, cadmium, indium, thallium and silver in ancient ices from Antarctica by isotope dilution-thermal ionization mass spectrometry

    USGS Publications Warehouse

    Matsumoto, A.; Hinkley, T.K.

    1997-01-01

    The concentrations of five chalcophile elements (Pb, Cd, In, Tl and Ag) and the lead isotope rarios in ancient ices from the Taylor Dome near coastal Antarctica, have been determined by the isotope dilutionthermal ionization mass spectrometry (ID-TIMS), with ultra-clean laboratory techniques. The samples were selected from segments of cores, one of which included a visible ash layer. Electric conductivity measurement (ECM) or dielectric properties (DEP) gave distinctive sharp peaks for some of the samples c hosen. Exterior portions of the sample segments were trimmed away by methods described here. Samples w ere evaporated to dryness and later separated into fractions for the five elements using an HBr-HNO3 a nion exchange column method. The concentrations are in the range 2.62-36.7 pg Pb/g of ice, 0.413-2.83 pg Cd/g, 0.081-0.34 pg In/g, 0.096-2.8 pg Tl/g and 0.15-0.84 pg Ag/g. respectively. The dispersions in duplicate analyses are about ??1% for lead and cadmium, ??2% for indium. ??4% for thallium and ??6% for silver, respectively. The concentrations of lead obtained are commonly higher than those in the present-day Antarctic surface snows, but the isotope ratios are distinctively higher than those of the present-day snows and close to those of the other ancient ice collected from a different Antarctic area.

  15. Use of Isotope Ratio Mass Spectrometry (IRMS) Determination ((18)O/(16)O) to Assess the Local Origin of Fish and Asparagus in Western Switzerland.

    PubMed

    Rossier, Jol S; Maury, Valrie; de Voogd, Blaise; Pfammatter, Elmar

    2014-10-01

    Here we present the use of isotope ratio mass spectrometry (IRMS) for the detection of mislabelling of food produced in Switzerland. The system is based on the analysis of the oxygen isotope distribution in water (?(18)O). Depending on the location on the earth, lake or groundwater has a specific isotopic distribution, which can serve as a fingerprint in order to verify whether a product has grown by means of the corresponding water. This report presents specifically the IRMS technique and the results obtained in the origin detection of fish grown in selected Swiss lakes as well as asparagus grown in Valais ground. Strengths and limitations of the method are presented for both cited products; on one hand, the technique is relatively universal for any product which contains significant water but on the other hand, it necessitates a rather heavy workload to build up a database of water ?(18)O values of products of different origins. This analytical tool is part of the concept of combating fraud currently in use in Switzerland. PMID:25437160

  16. Rapid analysis of biogenic amines from rice wine with isotope-coded derivatization followed by high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Cai, Yiping; Sun, Zhiwei; Chen, Guang; Liu, Xiaomei; You, Jinmao; Zhang, Caiqing

    2016-02-01

    A pair of isotope-coded derivatization reagents, d0-10-methyl-acridone-2-sulfonyl chloride (d0-MASC, light form) and d3-10-methyl-acridone-2-sulfonyl chloride (d3-MASC, heavy form), were used for labeling biogenic amines (BAs). On basis of the isotope-coded derivatization, a global isotope internal standard quantitative method for determining seven BAs by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed. The d0-MASC and d3-MASC can easily label BAs under mild conditions within 15 min at 50 C. The obtained light and heavy labeled BAs were monitored by the transitions of [M+H](+) ? 208 and [M+H](+) ? 211, respectively. Relative quantification of BAs was achieved by calculation of the peak area ratios of d0-MASC/d3-MASC labeled derivatives. Excellent linear responses for relative quantification were observed in the range of 1/10-10/1. The developed method has been successfully applied to the quantification of BAs in Chinese rice wine with recoveries ranging from 94.9% to 104.5%. PMID:26304364

  17. An analytical system for studying the stable isotopes of carbon monoxide using continuous flow-isotope ratio mass spectrometry (CF-IRMS)

    NASA Astrophysics Data System (ADS)

    Pathirana, S. L.; van der Veen, C.; Popa, M. E.; Rckmann, T.

    2015-02-01

    In the atmosphere, carbon monoxide (CO) is the major sink for the hydroxyl radical (OH •), has multiple anthropogenic and natural sources and considerable spatial and seasonal variability. Measurements of CO isotopic composition are useful in constraining the strengths of its individual source and sink processes and thus its global cycle. A fully automated system for ?13C and ?18O analysis has been developed to extract CO from an air sample, convert CO into carbon dioxide (CO2) using the Schtze reagent, and then determine the isotopic composition in an isotope ratio mass spectrometer (IRMS). The entire system is continuously flushed with high-purity helium (He), the carrier gas. The blank signal of the Schtze reagent is only 1-3% of the typical sample size. The repeatability is 0.1 for ?13C and 0.2 for ?18O. The peak area allows simultaneous determination of the mole fraction with an analytical repeatability of ~0.7 nmol mol-1 for 100 mL of typical ambient air (185.4 nmol mol-1 of CO). A single, automated, measurement is performed in 18 min, so multiple measurements can be combined conveniently to improve precision.

  18. Determination of Glyphosate, its Degradation Product Aminomethylphosphonic Acid, and Glufosinate, in Water by Isotope Dilution and Online Solid-Phase Extraction and Liquid Chromatography/Tandem Mass Spectrometry

    USGS Publications Warehouse

    Meyer, Michael T.; Loftin, Keith A.; Lee, Edward A.; Hinshaw, Gary H.; Dietze, Julie E.; Scribner, Elisabeth A.

    2009-01-01

    The U.S. Geological Survey method (0-2141-09) presented is approved for the determination of glyphosate, its degradation product aminomethylphosphonic acid (AMPA), and glufosinate in water. It was was validated to demonstrate the method detection levels (MDL), compare isotope dilution to standard addition, and evaluate method and compound stability. The original method USGS analytical method 0-2136-01 was developed using liquid chromatography/mass spectrometry and quantitation by standard addition. Lower method detection levels and increased specificity were achieved in the modified method, 0-2141-09, by using liquid chromatography/tandem mass spectrometry (LC/MS/MS). The use of isotope dilution for glyphosate and AMPA and pseudo isotope dilution of glufosinate in place of standard addition was evaluated. Stable-isotope labeled AMPA and glyphosate were used as the isotope dilution standards. In addition, the stability of glyphosate and AMPA was studied in raw filtered and derivatized water samples. The stable-isotope labeled glyphosate and AMPA standards were added to each water sample and the samples then derivatized with 9-fluorenylmethylchloroformate. After derivatization, samples were concentrated using automated online solid-phase extraction (SPE) followed by elution in-line with the LC mobile phase; the compounds separated and then were analyzed by LC/MS/MS using electrospray ionization in negative-ion mode with multiple-reaction monitoring. The deprotonated derivatized parent molecule and two daughter-ion transition pairs were identified and optimized for glyphosate, AMPA, glufosinate, and the glyphosate and AMPA stable-isotope labeled internal standards. Quantitative comparison between standard addition and isotope dilution was conducted using 473 samples analyzed between April 2004 and June 2006. The mean percent difference and relative standard deviation between the two quantitation methods was 7.6 plus or minus 6.30 (n = 179), AMPA 9.6 plus or minus 8.35 (n = 206), and glufosinate 9.3 plus or minus 9.16 (n = 16). The analytical variation of the method, comparison of quantitation by isotope dilution and multipoint linear regressed standard curves, and method detection levels were evaluated by analyzing six sets of distilled-water, groundwater, and surface-water samples spiked in duplicate at 0.0, 0.05, 0.10 and 0.50 microgram per liter and analyzed on 6 different days during 1 month. The grand means of the normalized concentration percentage recovery for glyphosate, AMPA, and glufosinate among all three matrices and spiked concentrations ranged from 99 to 114 plus or minus 2 to 7 percent of the expected spiked concentration. The grand mean of the percentage difference between concentrations calculated by standard addition and linear regressed multipoint standard curves ranged from 8 to 15 plus or minus 2 to 9 percent for the three compounds. The method reporting levels calculated from all the 0.05- microgram per liter spiked samples were 0.02 microgram per liter for all three compounds. Compound stability experiments were conducted on 10 samples derivatized four times for periods between 136 to 269 days. The glyphosate and AMPA concentrations remained relatively constant in samples held up to 136 days before derivatization. The half life of glyphosate varied from 169 to 223 days in the underivatized samples. Derivatized samples were analyzed the day after derivitization, and again 54 and 64 days after derivatization. The derivatized samples analyzed at days 52 and 64 were within 20 percent of the concentrations of the derivatized samples analyzed the day after derivatization.

  19. Strontium isotope ratios (87Sr/86Sr) of tooth enamel: a comparison of solution and laser ablation multicollector inductively coupled plasma mass spectrometry methods.

    PubMed

    Copeland, Sandi R; Sponheimer, Matt; le Roux, Petrus J; Grimes, Vaughan; Lee-Thorp, Julia A; de Ruiter, Darryl J; Richards, Michael P

    2008-10-01

    Strontium isotope ratios (87Sr/86Sr) in tooth enamel provide a means to investigate migration and landscape use in humans and other animals. Established methods for measuring (87)Sr/(86)Sr in teeth use bulk sampling (5-20 mg) and labor-intensive elemental purification procedures before analysis by either thermal ionization mass spectrometry (TIMS) or multicollector inductively coupled plasma mass spectrometry (MC-ICP-MS). Another method for measuring 87Sr/86Sr is laser ablation MC-ICP-MS, but concerns have been expressed about its accuracy for measuring tooth enamel. In this study we test the precision and accuracy of the technique by analyzing 30 modern rodent teeth from the Sterkfontein Valley, South Africa by laser ablation MC-ICP-MS and solution MC-ICP-MS. The results show a mean difference in 87Sr/86Sr measured by laser ablation and by solution of 0.0003 +/- 0.0002. This degree of precision is well within the margin necessary for investigating the potential geographic origins of humans or animals in many areas of the world. Because laser ablation is faster, less expensive, and less destructive than bulk sampling solution methods, it opens the possibility for conducting 87Sr/86Sr analyses of intra-tooth samples and small and/or rare specimens such as micromammal and fossil teeth. PMID:18803330

  20. Direct determination of fatty acid esters of 3-chloro-1, 2-propanediol in edible vegetable oils by isotope dilution - ultra high performance liquid chromatography - triple quadrupole mass spectrometry.

    PubMed

    Li, Heli; Chen, Dawei; Miao, Hong; Zhao, Yunfeng; Shen, Jianzhong; Wu, Yongning

    2015-09-01

    A selective and sensitive ultra-high performance liquid chromatography - triple quadrupole mass spectrometry (UHPLC-MS/MS) method coupled with matrix solid phase dispersion (MSPD) extraction was developed for the direct determination of fatty acid esters of 3-chloro-1,2-propanediol (3-MCPD esters) in edible vegetable oils. The method integrated the isotope dilution technique, MSPD extraction and UHPLC - MS/MS analysis with multi-reaction monitoring mode (MRM). Matrix-matched calibration curves showed good linearity within the range of 0.01-10mgL(-1) with the correlation coefficient not less than 0.999. Limits of detection (LODs) and limit of quantification (LOQs) of the 3-MCPD esters fell into the range of 0.0001-0.02mgkg(-1) and 0.0004-0.05mgkg(-1), respectively. The recoveries for the spiked extra virgin olive oils ranged from 94.4% to 108.3%, with the relative standard deviations (RSD) ranging from 0.6% to 10.5%. The method was applied for the oil sample (T2642) of the official Food Analysis Performance Assessment Scheme (FAPAS) in 2014 and other real samples from supermarket, and the results showed that the present method was comparative to the gas chromatography-mass spectrometry (GC-MS) method based on the improved German Society for Fat Science (DGF) standard method C-III 18 (09) except for palm oil. PMID:26239698

  1. Analytical approach for the determination of steroid profile of humans by gas chromatography isotope ratio mass spectrometry aimed at distinguishing between endogenous and exogenous steroids.

    PubMed

    Bulska, Ewa; Gorczyca, Damian; Zalewska, Izabela; Pokrywka, Andrzej; Kwiatkowska, Dorota

    2015-03-15

    The contamination of commonly used supplements by unknown steroids as well as their metabolites (parent compounds) become a challenge for the analytical laboratories. Although the determination of steroids profile is not trivial because of the complex matrix and low concentration of single compound, one of the most difficult current problem is to distinguish, during analytical procedure, endogenous androgens such as testosterone, dehydrotestosterone or dehydroepiandrosterone from their synthetic equivalents. The aim of this work was to develop and validate an analytical procedure for determination of the steroid profile in human urine by gas chromatography-combustion-isotope ratio mass spectrometry (GC/C/IRMS) toward distinguishing between endogenous and exogenous steroids. Beside the optimization of the experimental parameters for gas chromatography separation and mass spectrometry, attention was focused on urine sample preparation. Using an optimized sample preparation protocol it was possible to achieve better chromatographic resolutions and better sensitivity enabling the determination of 5 steroids, androsterone, etiocholanolone, testosterone, 5-androstandiol, 11-hydroxyandrdostane, pregnandiol, with the expanded uncertainty (k=2) below 1. This enable to evaluate the significant shift of the ?(13)C/(12)C [] values for each of examined steroids (excluding ERC). The analytical protocol described in this work was successfully used for the confirmation of positive founding urine by evaluation T/E ratio after GC/C/IRMS analysis. PMID:25498150

  2. Amino acid precursors from a simulated lower atmosphere of titan: experiments of cosmic ray energy source with C- and ?O-stable isotope probing mass spectrometry.

    PubMed

    Taniuchi, Toshinori; Takano, Yoshinori; Kobayashi, Kensei

    2013-01-01

    The organic haze of aerosols that shrouds the Saturnian moon Titan has previously been studied by both observations and laboratory simulation experiments. Here we report the abiotic formation of amino acid precursors in complex organic molecules during experimental simulation of the environment near Titan's surface with proton irradiation. Pyrolysis of the organic molecules formed in the simulated Titan atmosphere by proton irradiation at 600C yielded compounds that contained HCN and NH? (m/z = 27 and 17). These experimental results are consistent with the molecular information obtained by pyrolysis gas chromatography/mass spectrometry (pyrolysis GC/MS) of samples collected by the Huygens probe to Titan. Scanning electron microscopy (SEM) and three-dimensional atomic force microscopy (AFM) images of the irradiation products reveal nanometer-scale filaments and globules in complex amorphous structures (approximately 1000 Da). Isotope probing experiments by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) show that oxygen atoms were incorporated into the racemic amino acids by hydrolysis of ?O-labeled water. We suggest that the amino acid precursors possibly formed after water hydrolysis, as suggested in a previous observational study (C. A. Griffith, T. Owen, T. R. Geballe, J. Rayner, and P. Rannou, Science, 2003, 300, 628). We propose that cosmic rays are a significant and effective energy source for producing complex organics and amino acid precursors in Titan's atmospheric haze. PMID:23934557

  3. Biomedical accelerator mass spectrometry

    NASA Astrophysics Data System (ADS)

    Freeman, Stewart P. H. T.; Vogel, John S.

    1995-05-01

    Ultrasensitive SIMS with accelerator based spectrometers has recently begun to be applied to biomedical problems. Certain very long-lived radioisotopes of very low natural abundances can be used to trace metabolism at environmental dose levels ( [greater-or-equal, slanted] z mol in mg samples). 14C in particular can be employed to label a myriad of compounds. Competing technologies typically require super environmental doses that can perturb the system under investigation, followed by uncertain extrapolation to the low dose regime. 41Ca and 26Al are also used as elemental tracers. Given the sensitivity of the accelerator method, care must be taken to avoid contamination of the mass spectrometer and the apparatus employed in prior sample handling including chemical separation. This infant field comprises the efforts of a dozen accelerator laboratories. The Center for Accelerator Mass Spectrometry has been particularly active. In addition to collaborating with groups further afield, we are researching the kinematics and binding of genotoxins in-house, and we support innovative uses of our capability in the disciplines of chemistry, pharmacology, nutrition and physiology within the University of California. The field can be expected to grow further given the numerous potential applications and the efforts of several groups and companies to integrate more the accelerator technology into biomedical research programs; the development of miniaturized accelerator systems and ion sources capable of interfacing to conventional HPLC and GMC, etc. apparatus for complementary chemical analysis is anticipated for biomedical laboratories.

  4. Extreme Expression of DNA Repair Protein Apurinic/Apyrimidinic Endonuclease 1 (APE1) in Human Breast Cancer As Measured by Liquid Chromatography and Isotope Dilution Tandem Mass Spectrometry.

    PubMed

    Coskun, Erdem; Jaruga, Pawel; Reddy, Prasad T; Dizdaroglu, Miral

    2015-09-29

    Apurinic/apyrimidinic endonuclease 1 (APE1) is a DNA repair protein and plays other important roles. Increased levels of APE1 in cancer have been reported. However, available methods for measuring APE1 levels are indirect and not quantitative. We previously developed an approach using liquid chromatography and tandem mass spectrometry with isotope dilution to accurately measure APE1 levels. Here, we applied this methodology to measure APE1 levels in normal and cancerous human breast tissues. Extreme expression of APE1 in malignant tumors was observed, suggesting that breast cancer cells may require APE1 for survival. Accurate measurement of APE1 may be essential for the development of novel treatment strategies and APE1 inhibitors as anticancer drugs. PMID:26359670

  5. Sectional power-law correction for the accurate determination of lutetium by isotope dilution multiple collector-inductively coupled plasma-mass spectrometry

    NASA Astrophysics Data System (ADS)

    Yuan, Hong-Lin; Gao, Shan; Zong, Chun-Lei; Dai, Meng-Ning

    2009-11-01

    In this study, we employ a sectional power-law (SPL) correction that provides accurate and precise measurements of 176Lu/ 175Lu ratios in geological samples using multiple collector-inductively coupled plasma-mass spectrometry (MC-ICP-MS). Three independent power laws were adopted based on the 176Lu/ 176Yb ratios of samples measured after chemical chromatography. Using isotope dilution (ID) techniques and the SPL correction method, the measured lutetium contents of United States Geological Survey rock standards (BHVO-1, BHVO-2, BCR-2, AGV-1, and G-2) agree well with the recommended values. Results obtained by conventional ICP-MS and INAA are generally higher than those obtained by ID-TIMS and ID-MC-ICP-MS; this discrepancy probably reflects oxide interference and inaccurate corrections.

  6. A rapid, sensitive method for the quantitation of specific metabolites of sulfur mustard in human urine using isotope-dilution gas chromatography-tandem mass spectrometry.

    PubMed

    Young, Carrie L; Ash, Doris; Driskell, W J; Boyer, Anne E; Martinez, Rodolfo A; Silks, L A; Barr, John R

    2004-01-01

    Sulfur mustard agent (HD) (2,2'-dichloroethyl sulfide), a Schedule I compound on the Chemical Weapons Convention Schedule of Chemicals, remains a public health concern because it is simple to synthesize and it is in the chemical weapon stockpiles of several countries. A sensitive, rapid, accurate, and precise method was developed to quantitate trace levels of 1,1'-sulfonylbis [2-(methylthio) ethane] (SBMTE) in human urine as a means of assessing exposure to HD. The method used immobilized liquid-liquid extraction with diatomaceous earth, followed by the analysis of the urine extract using isotope-dilution gas chromatography-tandem mass spectrometry. Relative standard deviations were less than 8.6% at 1 ng/mL and 3.6% at 20 ng/mL. The limit of detection for SBMTE was 0.038 ng/mL in 0.5 mL of urine. PMID:15239853

  7. Capture of the volatile carbonyl metabolite of flecainide on 2,4-dinitrophenylhydrazine cartridge for quantitation by stable-isotope dilution mass spectrometry coupled with chromatography

    PubMed Central

    Prokai, Laszlo; Szarka, Szabolcs; Wang, Xiaoli; Prokai-Tatrai, Katalin

    2012-01-01

    Carbonyl compounds are common byproducts of many metabolic processes. These volatile chemical entities are usually derivatized before mass spectrometric analysis to enhance the sensitivity of their detections. The classically used reagent for this purpose is 2,4-dinitrophenylhydrazine (DNPH) that forms the corresponding hydrazones. When DNPH is immobilized on specific cartridges it permits solvent-free collection and simultaneous derivatization of aldehydes and ketones from gaseous samples. The utility of this approach was tested by assembling a simple apparatus for the in vitro generation of trifluoroacetaldehyde (TFAA) and its subsequent capture on the attached DNPH cartridge. TFAA was generated via cytochrome P450-catalyzed dealkylation of flecainide, an antiarrhythmic agent, in pooled human liver microsomes. Stable-isotope dilution mass spectrometry coupled with GC and LC using negative chemical ionization (NCI) and electrospray ionization (ESI) was evaluated for quantitative analyses. To eliminate isotope effects observed with the use of deuterium-labeled DNPH, we selected its 15N4-labeled analog to synthesize the appropriate TFAA adduct, as internal standard. Quantitation by GCNCI-MS using selected-ion monitoring outperformed LCESI-MS methods considering limits of detection and linearity of the assays. The microsomal metabolism of 1.5 ?mol of flecainide for 1.5 h resulted in 2.6 0.5 ?g TFAA-DNPH, corresponding to 9.3 1.7 nmol TFAA, captured by the cartridge. PMID:22342210

  8. A Method Revealing Bacterial Cell-wall Architecture by Time-dependent Isotope Labeling and Quantitative Liquid Chromatography/Mass Spectrometry

    PubMed Central

    Patti, Gary J.; Chen, Jiawei; Gross, Michael L.

    2009-01-01

    The molecular details of the biosynthesis and resulting architecture of the bacterial cell wall remain unclear but are essential to understanding the activity of glycopeptide antibiotics, the recognition of pathogens by hosts, and the processes of bacterial growth and division. Here we report a new strategy to elucidate bacterial cell-wall architecture based on time-dependent isotope labeling of bacterial cells quantified by liquid chromatography/accurate mass measurement mass spectrometry. The results allow us to track the fate of cell-wall precursors (which contain the vancomycin-binding site) in Enterococcus faecium, a leading antibiotic-resistant pathogen. By comparing isotopic enrichments of post-insertionally modified cell-wall precursors, we find that tripeptides and species without Asx bridges are specific to mature cell wall. Additionally, we find that the sequence of cell-wall maturation varies throughout a cell cycle. We suggest that actively dividing E. faecium cells have three zones of unique peptidoglycan processing. Our results reveal new organizational characteristics of the bacterial cell wall that are important to understanding tertiary structure and designing novel drugs for antibiotic-resistant pathogens. PMID:19281243

  9. Accurate Determination of Amino Acids in Serum Samples by Liquid Chromatography-Tandem Mass Spectrometry Using a Stable Isotope Labeling Strategy.

    PubMed

    Song, Cuihua; Zhang, Shijuan; Ji, Zhongyin; Li, Yipeng; You, Jinmao

    2015-10-01

    An accurate and sensitive liquid chromatography-tandem mass spectrometry method was developed for the analysis of amino acids (isoleucine, leucine, valine, tyrosine, phenylalanine and tryptophan) in serum samples using a stable isotope labeling strategy. Amino acid samples and standards were, respectively, derivatized by 10-methyl-acridone-2-sulfonyl chloride (d0-MASC) and its deuterated counterpart d3-MASC to form isotopic pairs which co-eluted and were detected by an MS detector at the same time. Accurate internal standard-based quantification was thereby achieved without the use of any internal standard analogy. The labeling reaction of MASC with amino acids is fast, simple and robust. Besides, derivatization increased the molecular weight of amino acids, and therefore they were shifted out of the background noise which was often observed in low mass region. The instrument LODs were in the range of 1.0-2.5 nmol/L. Linearities calculated by comparing theoretical peak area ratios of d0-/d3-MASC derivatives with the experimental peak area ratios were excellent with correlation coefficients of >0.995. The proposed method was successfully applied to the analysis of amino acids in serum samples with high sensitivity and accuracy. PMID:25940231

  10. Accelerator Mass Spectrometry of Actinides in Ground- and Seawater: An Innovative Method Allowing for the Simultaneous Analysis of U, Np, Pu, Am, and Cm Isotopes below ppq Levels.

    PubMed

    Quinto, Francesca; Golser, Robin; Lagos, Markus; Plaschke, Markus; Schfer, Thorsten; Steier, Peter; Geckeis, Horst

    2015-06-01

    (236)U, (237)Np, and Pu isotopes and (243)Am were determined in ground- and seawater samples at levels below ppq (fg/g) with a maximum sample size of 250 g. Such high sensitivity was possible by using accelerator mass spectrometry (AMS) at the Vienna Environmental Research Accelerator (VERA) with extreme selectivity and recently improved efficiency and a significantly simplified separation chemistry. The use of nonisotopic tracers was investigated in order to allow for the determination of (237)Np and (243)Am, for which isotopic tracers either are rarely available or suffer from various isobaric mass interferences. In the present study, actinides were concentrated from the sample matrix via iron hydroxide coprecipitation and measured sequentially without previous chemical separation from each other. The analytical method was validated by the analysis of the Reference Material IAEA 443 and was applied to groundwater samples from the Colloid Formation and Migration (CFM) project at the deep underground rock laboratory of the Grimsel Test Site (GTS) and to natural water samples affected solely by global fallout. While the precision of the presented analytical method is somewhat limited by the use of nonisotopic spikes, the sensitivity allows for the determination of ?10(5) atoms in a sample. This provides, e.g., the capability to study the long-term release and retention of actinide tracers in field experiments as well as the transport of actinides in a variety of environmental systems by tracing contamination from global fallout. PMID:25938849

  11. Mass spectrometry in ionospheric research.

    PubMed

    Ferguson, Eldon E

    2007-01-01

    Mass spectrometry played a key role in the development of the understanding of the earth's ionosphere. Of primary importance was its use for in situ atmospheric measurements of the ion and neutral composition of the atmosphere. Mass spectrometry has also played an essential role in the laboratory measurement of critical ionospheric molecular processes. Examples of both are given. PMID:17099890

  12. Separating Autotrophic and Heterotrophic Contributions to Soil Respiration in Maize-Based Agroecosystems Using Stable Carbon Isotope Ratio Mass Spectrometry.

    NASA Astrophysics Data System (ADS)

    Amos, B.; Walters, D. T.; Madhavan, S.; Arkebauer, T. J.; Scoby, D. L.

    2005-12-01

    Any effort to establish a carbon budget for a growing crop by means of a thorough accounting of all C sources and sinks will require the ability to discriminate between autotrophic and heterotrophic contributions to soil surface CO2 flux. Autotrophic soil respiration (Ra) is defined as combined root respiration and the respiration of soil microorganisms residing in the rhizosphere and using root-derived carbohydrates as an energy source, while heterotrophic respiration (Rh) is defined as the respiration of soil microorganisms and macroorganisms not directly under the influence of the live root system and using SOM as an energy source. We partition soil surface CO2 flux into its autotrophic and heterotrophic components by combining root exclusion with stable carbon isotope techniques in production scale (~65 ha) maize-based agroecosystems. After flux measurements, small chambers are placed on collars in both root excluded shields and in non-root excluded soil, ambient headspace CO2 is removed using a soda lime trap, and soil-respired C is allowed to collect in the chambers. Soil respiration samples are then collected in 12mL evacuated exetainers and analyzed for ?13C by means of a Finnigan Delta-S isotope ratio mass spectrometer interfaced with a Thermo Finnigan GasBench II and a cryogenic trap to increase CO2 concentration. These ?13C measurements were made throughout the 2005 growing season in maize fields representing three agroecosystems: irrigated continuous maize, irrigated maize-soybean rotation, and rainfed maize soybean rotation. Estimates of autotrophic and heterotrophic soil respiration along with other results of this study will be presented.

  13. Oxygen isotopic distribution along the otolith growth axis by secondary ion mass spectrometry: Applications for studying ontogenetic change in the depth inhabited by deep-sea fishes

    NASA Astrophysics Data System (ADS)

    Shiao, Jen-Chieh; Itoh, Shoichi; Yurimoto, Hisayoshi; Iizuka, Yoshiyuki; Liao, Yun-Chih

    2014-02-01

    This study using tuna otoliths as working standards established a high lateral resolution and precision analysis to measure ?18Ootolith by secondary ion mass spectrometry. This analytical approach of the ion probe was applied to deep-sea fishes to reconstruct the likely depths inhabited by the fishes at different life history stages based on the measured ?18Ootolith values as a proxy of water temperature. Dramatic increases up to 5-6 in ?18Ootolith, representing a temperature decrease of approximately 20 C, were detected in a blind cusk eel (Barathronus maculatus) otolith and in the otoliths of Synaphobranchus kaupii during leptocephalus metamorphosis to glass eel, inferred from the drop of otolith Sr/Ca ratios and increase of otolith growth increment width. ?18Ootolith profiles clearly divided the fish's life history into a planktonic stage in the mixed layer of the ocean and a benthic stage on the deep-sea ocean bottom. The habitat shift signal was recorded within a 150 ?m width of otolith growth zone, which was too narrow to be clearly detected by mechanical drilling and conventional isotopic ratio mass spectrometry. However, variations down to -7 were found in ?18Ootolith profiles as the result of Cs2+ beam sputter in the core and larval portions of the otoliths. Carbon mapping by electron probe microanalyzer and staining by toluidine blue suggested abundant proteins existed in the areas with anomaly negative ?18Ootolith values, which cannot be interpreted as a habitat change but due to the isotopic fractionation by O emission from the proteins. These results implied that careful design and understanding of the chemical composition of the analytical areas or tracks on the heterogeneous otolith was essential for highly accurate and precise analysis.

  14. Analysis of cytochrome P450 metabolites of arachidonic acid by stable isotope probe labeling coupled with ultra high-performance liquid chromatography/mass spectrometry.

    PubMed

    Zhu, Quan-Fei; Hao, Yan-Hong; Liu, Ming-Zhou; Yue, Jiang; Ni, Jian; Yuan, Bi-Feng; Feng, Yu-Qi

    2015-09-01

    Cytochrome P450 metabolites of arachidonic acid (AA) belong to eicosanoids and are potent lipid mediators of inflammation. It is well-known that eicosanoids play an important role in numerous pathophysiological processes. Therefore, quantitative analysis of cytochrome P450 metabolites of AA, including hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatreinoic acids (EETs), and dihydroxyeicosatrienoic acids (DHETs) can provide crucial information to uncover underlying mechanisms of cytochrome P450 metabolites of AA related diseases. Herein, we developed a highly sensitive method to identify and quantify HETEs, EETs, and DHETs in lipid extracts of biological samples based on stable isotope probe labeling coupled with ultra high-performance liquid chromatography/mass spectrometry. To this end, a pair of stable isotope probes, 2-dimethylaminoethylamine (DMED) and d4-2-dimethylaminoethylamine (d4-DMED), were utilized to facilely label eicosanoids. The heavy labeled eicosanoid standards were prepared and used as internal standards for quantification to minimize the matrix and ion suppression effects in mass spectrometry analysis. In addition, the detection sensitivities of DMED labeled eicosanoids improved by 3-104 folds in standard solution and 5-138 folds in serum matrix compared with unlabeled analytes. Moreover, a good separation of eicosanoids isomers was achieved upon DMED labeling. The established method provided substantial sensitivity (limit of quantification at sub-picogram), high specificity, and broad linear dynamics range (3 orders of magnitude). We further quantified cytochrome P450 metabolites of AA in rat liver, heart, brain tissues and human serum using the developed method. The results showed that 19 eicosanoids could be distinctly detected and the contents of 11-, 15-, 16-, 20-HETE, 5,6-EET, and 14,15-EET in type 2 diabetes mellitus patients and 5-, 11-, 12-, 15-, 16-, 20-HETE, 8,9-EET, and 5,6-DHET in myeloid leukemia patients had significant changes, demonstrating that these eicosanoids may have important roles on the pathogenesis of type 2 diabetes mellitus and myeloid leukemia. PMID:26253834

  15. Altered Retinoic Acid Metabolism in Diabetic Mouse Kidney Identified by 18O Isotopic Labeling and 2D Mass Spectrometry

    PubMed Central

    Starkey, Jonathan M.; Zhao, Yingxin; Sadygov, Rovshan G.; Haidacher, Sigmund J.; LeJeune, Wanda S.; Dey, Nilay; Luxon, Bruce A.; Kane, Maureen A.; Napoli, Joseph L.; Denner, Larry; Tilton, Ronald G.

    2010-01-01

    Background Numerous metabolic pathways have been implicated in diabetes-induced renal injury, yet few studies have utilized unbiased systems biology approaches for mapping the interconnectivity of diabetes-dysregulated proteins that are involved. We utilized a global, quantitative, differential proteomic approach to identify a novel retinoic acid hub in renal cortical protein networks dysregulated by type 2 diabetes. Methodology/Principal Findings Total proteins were extracted from renal cortex of control and db/db mice at 20 weeks of age (after 12 weeks of hyperglycemia in the diabetic mice). Following trypsinization, 18O- and 16O-labeled control and diabetic peptides, respectively, were pooled and separated by two dimensional liquid chromatography (strong cation exchange creating 60 fractions further separated by nano-HPLC), followed by peptide identification and quantification using mass spectrometry. Proteomic analysis identified 53 proteins with fold change ?1.5 and p?0.05 after Benjamini-Hochberg adjustment (out of 1,806 proteins identified), including alcohol dehydrogenase (ADH) and retinaldehyde dehydrogenase (RALDH1/ALDH1A1). Ingenuity Pathway Analysis identified altered retinoic acid as a key signaling hub that was altered in the diabetic renal cortical proteome. Western blotting and real-time PCR confirmed diabetes-induced upregulation of RALDH1, which was localized by immunofluorescence predominantly to the proximal tubule in the diabetic renal cortex, while PCR confirmed the downregulation of ADH identified with mass spectrometry. Despite increased renal cortical tissue levels of retinol and RALDH1 in db/db versus control mice, all-trans-retinoic acid was significantly decreased in association with a significant decrease in PPAR?/? mRNA. Conclusions/Significance Our results indicate that retinoic acid metabolism is significantly dysregulated in diabetic kidneys, and suggest that a shift in all-trans-retinoic acid metabolism is a novel feature in type 2 diabetic renal disease. Our observations provide novel insights into potential links between altered lipid metabolism and other gene networks controlled by retinoic acid in the diabetic kidney, and demonstrate the utility of using systems biology to gain new insights into diabetic nephropathy. PMID:20559430

  16. Establishing Ion Ratio Thresholds Based on Absolute Peak Area for Absolute Protein Quantification using Protein Cleavage Isotope Dilution Mass Spectrometry

    PubMed Central

    Loziuk, Philip L.; Sederoff, Ronald R.; Chiang, Vincent L.; Muddiman, David C.

    2014-01-01

    Quantitative mass spectrometry has become central to the field of proteomics and metabolomics. Selected reaction monitoring is a widely used method for the absolute quantification of proteins and metabolites. This method renders high specificity using several product ions measured simultaneously. With growing interest in quantification of molecular species in complex biological samples, confident identification and quantitation has been of particular concern. A method to confirm purity or contamination of product ion spectra has become necessary for achieving accurate and precise quantification. Ion abundance ratio assessments were introduced to alleviate some of these issues. Ion abundance ratios are based on the consistent relative abundance (RA) of specific product ions with respect to the total abundance of all product ions. To date, no standardized method of implementing ion abundance ratios has been established. Thresholds by which product ion contamination is confirmed vary widely and are often arbitrary. This study sought to establish criteria by which the relative abundance of product ions can be evaluated in an absolute quantification experiment. These findings suggest that evaluation of the absolute ion abundance for any given transition is necessary in order to effectively implement RA thresholds. Overall, the variation of the RA value was observed to be relatively constant beyond an absolute threshold ion abundance. Finally, these RA values were observed to fluctuate significantly over a 3 year period, suggesting that these values should be assessed as close as possible to the time at which data is collected for quantification. PMID:25154770

  17. Determination of melamine and its analogues in egg by gas chromatography-tandem mass spectrometry using an isotope dilution technique.

    PubMed

    Miao, H; Fan, S; Zhou, P P; Zhang, L; Zhao, Y F; Wu, Y N

    2010-11-01

    A method was developed for the simultaneous determination of melamine, ammeline, ammelide, and cyanuric acid in egg using gas chromatography-tandem mass spectrometry (GC-MS/MS). The samples were first extracted by the solution of diethylamine-water-acetonitrile (10:40:50, v/v/v). Clean-up employed an 'On Guard II' RP cartridge, and the dried elute was derivatised using bis-(trimethylsilyl)trifluoroacetamide (BSTFA) with 1% trimethylchlorosilane (TMCS). Derivatised samples were analysed by GC-MS/MS using multiple-reaction monitoring (MRM) with (13)C(3)-(15)N(3)-labelled melamine and cyanuric acid as internal standards. Blank samples of egg were spiked with the four analytes at concentration level of 0.1, 0.5, 1.0 mg kg(-1), and the intra-day and inter-day recoveries were in the range 75.7-122.5% with the relative standard deviation (RSD) from 2.6% to 22.8%. Decision limits (CC?, ? = 0.01) for melamine, ammeline, ammelide, and cyanuric acid in egg samples and milk powder were 3.5-5.9 and 2.5 to 3.8 g kg(-1), and the detection capabilities (CC?, ? = 0.05) were 4.9-8.4 and 3.6-9.5 g kg(-1), respectively. The method was successfully applied to egg samples and milk products as well. Satisfactory results were obtained as part of the 2009 European Union melamine proficiency test. PMID:20700844

  18. Quantification of ricin, RCA and comparison of enzymatic activity in 18 Ricinus communis cultivars by isotope dilution mass spectrometry.

    PubMed

    Schieltz, David M; McWilliams, Lisa G; Kuklenyik, Zsuzsanna; Prezioso, Samantha M; Carter, Andrew J; Williamson, Yulanda M; McGrath, Sara C; Morse, Stephen A; Barr, John R

    2015-03-01

    The seeds of the Ricinus communis (Castor bean) plant are the source of the economically important commodity castor oil. Castor seeds also contain the proteins ricin and R. communis agglutinin (RCA), two toxic lectins that are hazardous to human health. Radial immunodiffusion (RID) and the enzyme linked immunosorbent assay (ELISA) are two antibody-based methods commonly used to quantify ricin and RCA; however, antibodies currently used in these methods cannot distinguish between ricin and RCA due to the high sequence homology of the respective proteins. In this study, a technique combining antibody-based affinity capture with liquid chromatography and multiple reaction monitoring (MRM) mass spectrometry (MS) was used to quantify the amounts of ricin and RCA independently in extracts prepared from the seeds of eighteen representative cultivars of R. communis which were propagated under identical conditions. Additionally, liquid chromatography and MRM-MS was used to determine rRNA N-glycosidase activity for each cultivar and the overall activity in these cultivars was compared to a purified ricin standard. Of the cultivars studied, the average ricin content was 9.3 mg/g seed, the average RCA content was 9.9 mg/g seed, and the enzymatic activity agreed with the activity of a purified ricin reference within 35% relative activity. PMID:25576235

  19. Proteomic Analysis of Protein Turnover by Metabolic Whole Rodent Pulse-Chase Isotopic Labeling and Shotgun Mass Spectrometry Analysis.

    PubMed

    Savas, Jeffrey N; Park, Sung Kyu; Yates, John R

    2016-01-01

    The analysis of protein half-life and degradation dynamics has proven critically important to our understanding of a broad and diverse set of biological conditions ranging from cancer to neurodegeneration. Historically these protein turnover measures have been performed in cells by monitoring protein levels after "pulse" labeling of newly synthesized proteins and subsequent chase periods. Comparing the level of labeled protein remaining as a function of time to the initial level reveals the protein's half-life. In this method we provide a detailed description of the workflow required for the determination of protein turnover rates on a whole proteome scale in vivo.Our approach starts with the metabolic labeling of whole rodents by restricting all the nitrogen in their diet to exclusively nitrogen-15 in the form of spirulina algae. After near complete organismal labeling with nitrogen-15, the rodents are then switched to a normal nitrogen-14 rich diet for time periods of days to years. Tissues are harvested, the extracts are fractionated, and the proteins are digested to peptides. Peptides are separated by multidimensional liquid chromatography and analyzed by high resolution orbitrap mass spectrometry (MS). The nitrogen-15 containing proteins are then identified and measured by the bioinformatic proteome analysis tools Sequest, DTASelect2, and Census. In this way, our metabolic pulse-chase approach reveals in vivo protein decay rates proteome-wide. PMID:26867752

  20. Measurement of ?18O, ?17O, and 17O-excess in Water by Off-Axis Integrated Cavity Output Spectroscopy and Isotope Ratio Mass Spectrometry

    PubMed Central

    Berman, Elena S.F.; Levin, Naomi E.; Landais, Amaelle; Li, Shuning; Owano, Thomas

    2013-01-01

    Stable isotopes of water have long been used to improve understanding of the hydrological cycle, catchment hydrology, and polar climate. Recently, there has been increasing interest in measurement and use of the less-abundant 17O isotope in addition to 2H and 18O. Off-axis integrated cavity output spectroscopy (OA-ICOS) is demonstrated for accurate and precise measurements ?18O, ?17O, and 17O-excess in liquid water. OA-ICOS involves no sample conversion and has a small footprint, allowing measurements to be made by researchers collecting the samples. Repeated (514) high-throughput measurements of the international isotopic reference water standard GISP demonstrate the precision and accuracy of OA-ICOS: ?18OVSMOW-SLAP =?24.74 0.07 (1?) and ?17OVSMOW-SLAP = ?13.12 0.05 (1?). For comparison, the IAEA value for ?18OVSMOW-SLAP is ?24.76 0.09 (1?) and an average of previously reported values for ?17OVSMOW-SLAP is ?13.12 0.06 (1?). Multiple (26) high-precision measurements of GISP provide a 17O-excessVSMOW-SLAP of 23 10 per meg (1?); an average of previously reported values for 17O-excessVSMOW-SLAP is 22 11 per meg (1?). For all these OA-ICOS measurements, precision can be further enhanced by additional averaging. OA-ICOS measurements were compared with two independent isotope ratio mass spectrometry (IRMS) laboratories and shown to have comparable accuracy and precision as the current fluorination-IRMS techniques in ?18O, ?17O, and 17O-excess. The ability to measure accurately ?18O, ?17O, and 17O-excess in liquid water inexpensively and without sample conversion is expected to increase vastly the application of ?17O and 17O-excess measurements for scientific understanding of the water cycle, atmospheric convection, and climate modeling among others. PMID:24032448

  1. [International comparison APMP. QM-S6: determination of clenbuterol in porcine meat by isotopic dilution mass spectrometry].

    PubMed

    Xu, Sen; Li, Xiuqin; Luo, Ximing; Zhang, Qinghe

    2014-10-01

    A method was developed for the determination of clenbuterol in porcine meat by iso- topic dilution mass spectrometry (IDMS). National Institute of Metrology of China (NIM) par- ticipated in the international comparison activity organized by Asia Pacific Metrology (APMP) and got an international mutual recognition result using this method. The important factors of the method, such as the spray voltage, mobile phase, chromatographic column, extraction, purification and filtration conditions were investigated to acquire optimum conditions. The opti- mization results showed that the composition and pH value of the mobile phase had effects on the response of the mass spectrum of clenbuterol and the optimal value of the spray voltage. The solvent of sample had influences on the chromatographic retention behavior of clenbuterol. It was found that methanol caused a serious solvent effect, even made chromatographic peak split. Since clenbuterol was easily adsorbed on hydrophilic filter membranes and solid phase extraction columns, there were interference suppressions for the quantification of clenbuterol because of the eluate of the solid phase extraction columns. The homogenate method with extraction solvent of 0.1% (v/v) formic acid in acetonitrile had the highest extraction efficiency. The limit of the detection (LOD, S/N > 3) of the method was 0.2 ?g/kg. The determination results of clenbuterol in the porcine meat by this method were 5.18 ?g/kg 0.50 ?g/kg (k = 2). This method is accurate, reliable, reproducible, and suitable for the determination of clenbuterol with trace quantity in porcine meat. PMID:25739271

  2. Secondary ion mass spectrometry combined with alpha track detection for isotope abundance ratio analysis of individual uranium-bearing particles.

    PubMed

    Esaka, Fumitaka; Magara, Masaaki

    2014-03-01

    Secondary ion mass spectrometry (SIMS) was used in combination with alpha track detection for the efficient analysis of uranium-bearing particles with higher (235)U abundances in environmental samples. A polycarbonate film containing particles was prepared and placed in contact with a CR-39 plastic detector. After exposure for 28 days, the detector was etched in a NaOH solution and each uranium-bearing particle was identified through observation of the alpha tracks recorded in the detector. A portion of the film containing each uranium-bearing particle was cut out and put onto a glassy carbon planchet. The films on the planchet were decomposed through plasma ashing for subsequent uranium abundance ratio analysis with SIMS. The alpha track-SIMS analysis of 10 uranium-bearing particles in a sample taken from a nuclear facility enabled n((235)U)/n((238)U) abundance ratios in the range 0.0072-0.25 to be detected, which were significantly higher than those obtained by SIMS without alpha track detection. The duration of the whole analytical process for analysis of 10 particles was about 32 days. The detection efficiency was calculated to be 27.1±6.5%, based on the analysis of the particles in uranium reference materials. The detection limits, defined as the diameter of the particle which produces alpha tracks more than one for a 28-days exposure, were estimated to be 0.8, 0.9, 1.1, 2.1 and 3.0 μm for the particles having the same uranium abundance ratios with NBL CRM U850, U500, U350, U050 and U010 reference materials, respectively. The use of alpha track detection for subsequent SIMS analysis is an inexpensive and an efficient way to measure uranium-bearing particles with higher (235)U abundances. PMID:24468381

  3. Analysis of LDEF experiment AO187-2: Chemically and isotopic measurements of micrometeoroids by secondary ion mass spectrometry

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Numerous 'extended impacts' found in both leading and trailing edge capture cells have been successfully analyzed for the chemical composition of projectile residues by secondary ion mass spectrometry (SIMS). Most data have been obtained from the trailing edge cells where 45 of 58 impacts have been classified as 'probably natural' and the remainder as 'possibly man-made debris.' This is in striking contrast to leading edge cells where 9 of 11 impacts so far measured are definitely classified as orbital debris. Although all the leading edge cells had lost their plastic entrance foils during flight, the rate of foil failure was similar to that of the trailing edge cells, 10 percent of which were recovered intact. Ultra-violet embrittlement is suspected as the major cause of failure on both leading and trailing edges. The major impediment to the accurate determination of projectile chemistry is the fractionation of volatile and refractory elements in the hypervelocity impact and redeposition processes. This effect had been noticed in simulation experiment but is more pronounced in the Long Duration Exposure Facility (LDEF) capture cells, probably due to the higher average velocities of the space impacts. Surface contamination of the pure Ge surfaces with a substance rich in Si but also containing Mg and Al provides an additional problem for the accurate determination of impactor chemistry. The effect is variable, being much larger on surfaces that were exposed to space than in those cells that remained intact. Future work will concentrate on the analyses of more leading edge impacts and the development of new SIMS techniques for the measurement of elemental abundances in extended impacts.

  4. Measurement of CO{sub 2} and N{sub 2}O at nanomolar amounts using continuous-flow isotope-ratio mass spectrometry (CF-IRMS)

    SciTech Connect

    Patel, A; Downie, S.; Webster, E.; Hopkins, D.W.; Rennie, M.J.

    1994-12-01

    We are currently developing methods using Continuous Flow Isotope Ratio Mass Spectrometry (CF-IRMS) in conjunction with a thermal desorption purification unit to measure nanomolar levels of C0{sub 2} and N{sub 2}0. Samples of the pure gases diluted in He/air and transferred to septum capped Exetainers (Labco) provided a simple means to investigate the technique. We analyzed C0{sub 2} at natural abundance in the concentration range 50 to 5 nmoles and N{sub 2}0 at two concentrations between 25 and 5 nmoles. The technique was then used to measure C0{sub 2} (natural abundance and {sup 13}C-labeled) generated from the ninhydrin reaction. The results are summarized in a table; values are expressed in delta {sup 13}C notation relative to Pee Dee Belemnite. The data show that, provided care is taken to minimize or eliminate sources of contamination (air leaks, etc.), CF-IRMS coupled with a thermal desorption unit permits measurement of {sup 13}C enrichment in much smaller amounts of isolated amino acids than has been possible until now. The new methodology, including thermal desorption, should allow stable-isotope investigations on much smaller samples than are possible with other currently available techniques-while maintaining high precision.

  5. Rapid and Precise Measurement of Serum Branched-Chain and Aromatic Amino Acids by Isotope Dilution Liquid Chromatography Tandem Mass Spectrometry

    PubMed Central

    Yang, Ruiyue; Dong, Jun; Guo, Hanbang; Li, Hongxia; Wang, Shu; Zhao, Haijian; Zhou, Weiyan; Yu, Songlin; Wang, Mo; Chen, Wenxiang

    2013-01-01

    Background Serum branched-chain and aromatic amino acids (BCAAs and AAAs) have emerged as predictors for the future development of diabetes and may aid in diabetes risk assessment. However, the current methods for the analysis of such amino acids in biological samples are time consuming. Methods An isotope dilution liquid chromatography tandem mass spectrometry (ID-LC/MS/MS) method for serum BCAAs and AAAs was developed. The serum was mixed with isotope-labeled BCAA and AAA internal standards and the amino acids were extracted with acetonitrile, followed by analysis using LC/MS/MS. The LC separation was performed on a reversed-phase C18 column, and the MS/MS detection was performed via the positive electronic spray ionization in multiple reaction monitoring mode. Results Specific analysis of the amino acids was achieved within 2 min. Intra-run and total CVs for the amino acids were less than 2% and 4%, respectively, and the analytical recoveries ranged from 99.6 to 103.6%. Conclusion A rapid and precise method for the measurement of serum BCAAs and AAAs was developed and may serve as a quick tool for screening serum BCAAs and AAAs in studies assessing diabetes risk. PMID:24339906

  6. Development of isotope labeling liquid chromatography-mass spectrometry for metabolic profiling of bacterial cells and its application for bacterial differentiation.

    PubMed

    Wu, Yiman; Li, Liang

    2013-06-18

    Quantitative and comprehensive profiling of cellular metabolites is currently a challenging task in bacterial metabolomics. In this work, a simple and robust method for profiling the amine- and phenol-containing metabolome of bacterial cells is described. The overall workflow consists of methanol-based cell lysis and metabolite extraction with ultrasonication, differential isotope dansylation labeling of cellular metabolites, and analysis of the labeled metabolites by liquid chromatography-mass spectrometry (LC-MS). Over a thousand peak pairs or putative metabolites can be detected from bacterial cells in a 25 min LC-MS run and near 2500 putative metabolites can be found in one bacterium from combined results of multiple analyses. After careful examination and optimization of the sample preparation process, this method is shown to be effective for both Gram-positive and Gram-negative bacteria. An idea of applying LC-ultraviolet (UV) detection to quantify the total amount of labeled metabolites is shown to be effective for normalizing the amounts of metabolites present in different samples for metabolome comparison. The use of differential isotopic labeling allows relative quantification of each individual metabolite, which facilitates comparative metabolomics studies and the generation of a metabolic fingerprint of a bacterium. Finally, this method is demonstrated to be useful for the differentiation of three bacterial species in cultured media and spiked human urine samples. PMID:23495969

  7. Determination of the alkylpyrazine composition of coffee using stable isotope dilution-gas chromatography-mass spectrometry (SIDA-GC-MS).

    PubMed

    Pickard, Stephanie; Becker, Irina; Merz, Karl-Heinz; Richling, Elke

    2013-07-01

    A stable isotope dilution analysis based on gas chromatography-mass spectrometry analysis (SIDA-GC-MS) was developed for the quantitative analysis of 12 alkylpyrazines found in commercially available coffee samples. These compounds contribute to coffee flavor. The accuracy of this method was tested by analyzing model mixtures of alkylpyrazines. Comparisons of alkylpyrazine-concentrations suggested that water as extraction solvent was superior to dichloromethane. The distribution patterns of alkylpyrazines in different roasted coffees were quite similar. The most abundant alkylpyrazine in each coffee sample was 2-methylpyrazine, followed by 2,6-dimethylpyrazine, 2,5-dimethylpyrazine, 2-ethylpyrazine, 2-ethyl-6-methylpyrazine, 2-ethyl-5-methylpyrazine, and 2,3,5-trimethylpyrazine, respectively. Among the alkylpyrazines tested, 2,3-dimethylpyrazine, 2-ethyl-3-methylpyrazine, 2-ethyl-3,6-dimethylpyrazine, and 2-ethyl-3,5-dimethylpyrazine revealed the lowest concentrations in roasted coffee. By the use of isotope dilution analysis, the total concentrations of alkylpyrazines in commercially available ground coffee ranged between 82.1 and 211.6 mg/kg, respectively. Decaffeinated coffee samples were found to contain lower amounts of alkylpyrazines than regular coffee samples by a factor of 0.3-0.7, which might be a result of the decaffeination procedure. PMID:23745606

  8. Simultaneous analysis of phthalates, adipate and polycyclic aromatic hydrocarbons in edible oils using isotope dilution-gas chromatography-mass spectrometry.

    PubMed

    Oh, Min-Seok; Lee, Seon-Hwa; Moon, Myeong Hee; Lee, Dong Soo; Park, Hyun-Mee

    2014-01-01

    A method for simultaneous determination of 12 priority phthalates, adipate and polycyclic aromatic hydrocarbons (PAHs) in edible oils by isotope dilution-gas chromatography-mass spectrometry (ID-GC-MS) was developed for fast, accurate and trace analysis. The extraction and clean-up procedures were optimised, and using stable isotope-labelled internal standards for each analyte, relative standard deviations (RSDs) of 0.92-10.6% and spiked sample recoveries of 80.6-97.8% were obtained. Limits of detection for PAHs were in the range of 0.15-0.77 g/kg and those for phthalates were in the range of 4.6-10.0 g/kg. The calibration curves exhibited good linearities with regression coefficients of R(2) ? 0.99. Twelve edible oils were examined to evaluate the efficiency of this method. Among the 12 analytes, dibutyl phthalates (DBP), diethylhexyl phthalates (DEHP), diethylhexyl adipate (DEHA), benzo[a]anthracene (B[a]A), chrysene (Chry) and benzo[b]fluoranthene (B[b]F) were detected in the range of 1.17-806 g/kg. PMID:25029399

  9. Quantitative isomer-specific N-glycan fingerprinting using isotope coded labeling and high performance liquid chromatography-electrospray ionization-mass spectrometry with graphitic carbon stationary phase.

    PubMed

    Michael, Claudia; Rizzi, Andreas M

    2015-02-27

    Glycan reductive isotope labeling (GRIL) using (12)C6-/(13)C6-aniline as labeling reagent is reported with the aim of quantitative N-glycan fingerprinting. Porous graphitized carbon (PGC) as stationary phase in capillary scale HPLC coupled to electrospray mass spectrometry with time of flight analyzer was applied for the determination of labeled N-glycans released from glycoproteins. The main benefit of using stable isotope-coding in the context of comparative glycomics lies in the improved accuracy and precision of the quantitative analysis in combined samples and in the potential of correcting for structure-dependent incomplete enzymatic release of oligosaccharides when comparing identical target proteins. The method was validated with respect to mobile phase parameters, reproducibility, accuracy, linearity and limit of detection/quantification (LOD/LOQ) using test glycoproteins. It is shown that the developed method is capable of determining relative amounts of N-glycans (including isomers) comparing two samples in one single HPLC-MS run. The analytical potential and usefulness of GRIL in combination with PGC-ESI-TOF-MS is demonstrated comparing glycosylation in human monoclonal antibodies produced in Chinese hamster ovary cells (CHO) and hybridoma cell lines. PMID:25638265

  10. 13C-Isotope ratio mass spectrometry as a potential tool for the forensic analysis of white architectural paint: a preliminary study.

    PubMed

    Reidy, L J; Meier-Augenstein, W; Kalin, R M

    2005-01-01

    Paints have a dual role in society, to protect materials from environmental agents such as ultraviolet light, moisture and oxygen, and to make painted materials look more attractive. Variability in paint samples is often due to binder and pigment type within the sample. The most common resin used in decorative paints is drying oil alkyd resin, which incorporates soybean oil and vinyl acrylic based latexes. Traditional analytical methods used by forensic scientists may be able to say whether two paint samples are indistinguishable but cannot conclusively say that they both originate from the same source. To find out if isotopic composition can provide an added dimension of information, 28 different white architectural paints were analysed for (13)C abundance using isotope ratio mass spectrometry. In addition, variations in application, drying time and thickness were also investigated to assess the discriminatory power of (13)C data from white paints with an unknown history. Preliminary results indicate that this method could aid screening of paint samples. PMID:15945023

  11. Simultaneous determination of platinum group elements and rhenium in rock samples using isotope dilution inductively coupled plasma mass spectrometry after cation exchange separation followed by solvent extraction.

    PubMed

    Shinotsuka, Kazunori; Suzuki, Katsuhiko

    2007-11-12

    A simple and precise determination method for platinum group elements (PGEs) and Re in rock samples was developed using isotope dilution coupled with inductively coupled plasma mass spectrometry (ID-ICP-MS). Cation exchange separation was employed for simplicity, because it is applicable to group separation and simultaneous isotopic measurement in contrast with the widely used anion exchange separation which entails separate elution. However, its application to ID-ICP-MS has been limited due to spectral interferences from impurities retained in the PGE fraction even after ion chromatography. To overcome this limitation, solvent extraction using N-benzoyl-N-phenylhydroxylamine (BPHA) in chloroform was successfully applied for further purification. After the examination of optimum experimental parameters in cation exchange separation and solvent extraction using synthetic PGE solution, the established procedure was applied to the determination of PGEs and Re in some geochemical reference materials. The obtained results agreed well with the literature data determined using the different digestion methods (NiS fire assay and the use of a high-pressure asher) within the analytical uncertainties of each other. Significant difference in reproducibility between Ru, Ir, Pt and Os group, and Pd and Re group was observed in the results for BHVO-2 and JA-2. By considering the error factors affecting analytical reproducibility, we concluded that the difference is ascribed to the sample heterogeneity of minor minerals enriched in Ru, Ir, Pt and Os. PMID:17963832

  12. Use of stable isotopically enriched proteins and directly coupled high-performance liquid chromatography inductively coupled plasma mass spectrometry for quantitatively monitoring the transfer of metals between proteins.

    PubMed

    Mason, Andrew Z; Moeller, Rhonda; Thrippleton, Kelly A; Lloyd, Douglas

    2007-10-01

    Studies have shown that metallothionein (MT) may play an important role in modulating the activity of certain Zn-regulated enzymes under various oxidoreductive conditions by either donating or removing Zn. To better determine the role of MT in interprotein metal transfer, we describe a procedure that uses stable isotopically enriched (67)Zn(7) metallothionein 2 ((67)Zn(7)-MT-2) to quantitatively determine the stoichiometry of transfer of Zn from the protein to a recipient apo-metalloenzyme, apo-carbonic anhydrase (apo-CA) by directly coupled ion exchange high-performance liquid chromatography inductively coupled plasma mass spectrometry. Quantitatively, the transfer of (67)Zn was consistent with the enzymatic activation of the apo-enzyme as judged by its esterase activity and ability to cleave p-nitrophenyl acetate. Maximum enzyme activation occurred at an MT-2:apo-CA molar ratio of 1, implying the release of a single atom of Zn from MT-2. Preincubation of (67)Zn(7)-MT-2 with an excess of oxidized glutathione (GSSG) increased metal donation fourfold, whereas reduced glutathione (GSH) inhibited donation by approximately 50%. By using multiple recipient and donor proteins having different stable isotopic signatures, the technique has the potential for quantitatively studying the kinetic and thermodynamic aspects of Zn transfer between numerous competing ligands in vitro, an important first step toward understanding the regulatory role of this metal in protein functioning and cellular metabolism in vivo. PMID:17673155

  13. Quantitative analysis using gas chromatography/combustion/isotope ratio mass spectrometry and standard addition of intrinsically labelled standards (SAIL)--application to isoflavones in foods.

    PubMed

    Bluck, Leslie J C; Jones, Kerry S; Thomas, Jane; Liggins, Jason; Harding, Marilyn; Bingham, Sheila A; Coward, W Andrew

    2002-01-01

    We have investigated a novel application of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) for the quantitative analysis of the isoflavones in food matrices. Previous methods have been hampered by the lack of analytical standards to introduce early enough in the extraction procedure to allow compensations for losses at all stages of the procedure. In this work we have produced standard materials that can be added at the initial extraction, by intrinsically labelling soya plants by growing them in an atmosphere enriched in the stable isotope of carbon in CO(2). On analysis these plants were shown to contain phytoestrogens at a high (up to 20%) level of enrichment. The dried plant material has been used to estimate the isoflavone concentrations of a set of spiked flours. For daidzein the methodology was shown to produce results comparable to those achieved by GC/MS techniques. The method was less successful for genistein, possibly due to the greater fragility of this compound under the conditions required for the analysis. PMID:12478567

  14. Re-evaluation of interferences of doubly charged ions of heavy rare earth elements on Sr isotopic analysis using multi-collector inductively coupled plasma mass spectrometry

    NASA Astrophysics Data System (ADS)

    Yang, Yue-Heng; Wu, Fu-Yuan; Xie, Lie-Wen; Chu, Zhu-Yin; Yang, Jin-Hui

    2014-07-01

    We re-evaluate the interference of doubly charged heavy rare earth elements during Sr isotopic analysis using multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). A series of mixed solutions of standard reference material SRM 987, rare earth elements, and Sr separated from rock reference materials are measured to assess the influence of isobaric interferences on the MC-ICP-MS analysis of Sr isotopes. After sample dissolution, conventional cation-exchange chromatography is employed for Sr purification of rock reference materials prior to MC-ICP-MS measurement. It has been demonstrated that if the natural abundances of Er and Yb are used to correct for doubly charged ion interferences on Sr, an overcorrection results. In contrast, the use of measured doubly charged ion ratios results in an accurate and precise correction of isobaric interference. This finding is confirmed by analytical results for several certified reference materials from mafic (basaltic) to felsic (granitic) silicate rocks. It is noteworthy that, because Er is more prone to doubly charged ion formation, it dominates over Yb doubly charged ions as an interference source.

  15. Quantitative detection of trichloroacetic acid in human urine using isotope dilution high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.

    PubMed

    Kuklenyik, Zsuzsanna; Ashley, David L; Calafat, Antonia M

    2002-05-01

    The chemical disinfection of drinking water to control microbial contaminants results in the formation of disinfection byproducts (DBPs). The volatile trihalomethanes and the nonvolatile haloacetic acids (HAAs) are the most prevalent DBPs. It is important to monitor human exposure to HAAs because of their potential adversehealth effects, such as cancer. Among the HAAs, urinary trichloroacetic acid (TCAA) is a potential valid biomarker for assessing chronic ingestion exposure to HAAs from drinking water. We have developed a rugged, high-throughput, sensitive, accurate, and precise assay for the measurement of trace levels of TCAA in human urine using a simple solid-phase extraction (SPE) cleanup followed by isotope dilution high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). TCAA is extracted from the urine using SPE, separated from other extract components by reversed-phase HPLC, and analyzed by negative ion electrospray ionization-isotope dilution-MS/MS using a multiple reaction monitoring experiment. The method is simple and fast and is not labor intensive (sample preparation and analysis can be performed in approximately 15 min) with a limit of detection of 0.5 ng/mL in 1 mL of urine. PMID:12033307

  16. Multiplexed Immunoaffinity Enrichment of Peptides with Anti-peptide Antibodies and Quantification by Stable Isotope Dilution Multiple Reaction Monitoring Mass Spectrometry.

    PubMed

    Kuhn, Eric; Carr, Steven A

    2016-01-01

    Immunoaffinity enrichment of peptides using anti-peptide antibodies and their subsequent analysis by targeted mass spectrometry using stable isotope-labeled peptide standards is a sensitive and relatively high-throughput assay technology for unmodified and modified peptides in cells, tissues, and biofluids. Suppliers of antibodies and peptides are increasingly aware of this technique and have started incorporating customized quality measures and production protocols to increase the success rate, performance, and supply of the necessary reagents. Over the past decade, analytical biochemists, clinical diagnosticians, antibody experts, and mass spectrometry specialists have shared ideas, instrumentation, reagents, and protocols, to demonstrate that immuno-MRM-MS is reproducible across laboratories. Assay performance is now suitable for verification of candidate biomarkers from large scale discovery "omics" studies, measuring diagnostic proteins in plasma in the clinical laboratory, and for developing a companion assay for preclinical drug studies. Here we illustrate the process for developing these assays with a step-by-step guide for a 20-plex immuno-MRM-MS assay. We emphasize the need for analytical validation of the assay to insure that antibodies, peptides, and mass spectrometer are working as intended, in a multiplexed manner, with suitable assay performance (median values for 20 peptides: CV?=?12.4 % at 740 amol/?L, LOD?=?310 amol/?L) for applications in quantitative biology and candidate biomarker verification. The assays described conform to Tier 2 (of 3) level of analytical assay validation (1), meaning that the assays are capable of repeatedly measuring sets of analytes of interest within and across samples/experiments and employ internal standards for each analyte for confident detection and precise quantification. PMID:26867743

  17. Characterization of TATP gas phase product ion chemistry via isotope labeling experiments using ion mobility spectrometry interfaced with a triple quadrupole mass spectrometer.

    PubMed

    Tomlinson-Phillips, Jill; Wooten, Alfred; Kozole, Joseph; Deline, James; Beresford, Pamela; Stairs, Jason

    2014-09-01

    Identification of the fragment ion species associated with the ion reaction mechanism of triacetone triperoxide (TATP), a homemade peroxide-based explosive, is presented. Ion mobility spectrometry (IMS) has proven to be a key analytical technique in the detection of trace explosive material. Unfortunately, IMS alone does not provide chemical identification of the ions detected; therefore, it is unknown what ion species are actually formed and separated by the IMS. In IMS, ions are primarily characterized by their drift time, which is dependent on the ion׳s mass and molecular cross-section; thus, IMS as a standalone technique does not provide structural signatures, which is in sharp contrast to the chemical and molecular information that is generally obtained from other customary analytical techniques, such as NMR, Raman and IR spectroscopy and mass spectrometry. To help study the ion chemistry that gives rise to the peaks observed in IMS, the hardware of two different commercial IMS instruments has been directly coupled to triple quadrupole (QQQ) mass spectrometers, in order to ascertain each ion׳s corresponding mass/charge (m/z) ratios with different dopants at two temperatures. Isotope labeling was then used to help identify and confirm the molecular identity of the explosive fragment and adduct ions of TATP. The m/z values and isotope labeling experiments were used to help propose probable molecular formulas for the ion fragments. In this report, the fragment and adduct ions m/z 58 and 240 of TATP have been confirmed to be [C3H6NH·H](+) and [TATP·NH4](+), respectively; while the fragment ions m/z 73 and 89 of TATP are identified as having the molecular formulas [C4H9NH2](+) and [C4H9O2](+), respectively. It is anticipated that the work in this area will not only help to facilitate improvements in mobility-based detection (IMS and MS), but also aid in the development and optimization of MS-based detection algorithms for TATP. PMID:24913870

  18. Automated high-speed analysis of selected organic compounds in urban air by on-line isotopic dilution cryofocusing gas chromatography/mass spectrometry.

    PubMed

    Davoli, E; Cappellini, L; Maggi, M; Fanelli, R

    1994-11-01

    An automated environmental air monitor has been developed to measure selected organic compounds in urban air. The instrument is based on a cryofocusing-thermal desorption gas chromatographic mass spectrometry technique where the mass spectrometer is a slightly modified residual gas analyzer (RGA). The RGA was chosen as a detector because the whole system must be robust for long periods, with 24-h continuous air monitoring. RCA are extremely simple and seemed the most reliable mass spectrometers for this purpose. Moreover, because they have no physically limited ion source, contamination is considerably reduced, so maintenance intervals are longer.The gas chromatograph is equipped with a computer-controlled six-way sampling valve, with a 100-mL sampling loop and thermal desorption cold trap injector. Environmental air is enriched with an isotopically labeled internal standard in the sampling line. This internal standard is added with a validated, custom-made, permeation tube device. The "on-line" internal standard provides for high quality quantitative data because all variations in instrument sensitivity in cryofocusing or in thermal desorption efficiency are taken into account. High repetition rates (down to 5 min for a full analytical cycle) are obtained with the use of an isothermal gas chromatography program, microbore capillary column, and environmental air sampling during the gas chromatography run. PMID:24226389

  19. A World without Sample Preparation: Developing Rapid Uranium Isotope Measurement Capabilities by Resonance Ionization Mass Spectrometry (RIMS)

    SciTech Connect

    Knight, K B; Hutcheon, I D; Isselhardt, B H; Savina, M R; Prussin, S G

    2009-06-08

    We are developing highly sensitive, highly discriminating laser-based techniques for rapid determination of isotopic compositions. Rapid command of such information is critical to assessment of the origin and history of nuclear materials, particularly in post-detonation scenarios.

  20. Methods to reduce interference effects in thermal conversion elemental analyzer/continuous flow isotope ratio mass spectrometry delta18O measurements of nitrogen-containing compounds.

    PubMed

    Accoe, Frederik; Berglund, Michael; Geypens, Benny; Taylor, Philip

    2008-07-01

    On-line determination of the oxygen isotopic composition (delta(18)O value) in organic and inorganic samples is commonly performed using a thermal conversion elemental analyzer (TC-EA) linked to a continuous flow isotope ratio mass spectrometry (IRMS) system. Accurate delta(18)O analysis of N-containing compounds (like nitrates) by TC-EA-IRMS may be complicated because of interference of the N(2) peak on the m/z 30 signal of the CO peak. In this study we evaluated the effectiveness of two methods to overcome this interference which do not require any hardware modifications of standard TC-EA-IRMS systems. These methods were (1) reducing the amount of N(2) introduced into the ion source through He dilution of the N(2) peak and (2) an improved background correction on the CO m/z 30 sample peak integration. Our results show that He dilution is as effective as diverting the N(2) peak in order to eliminate this interference. We conclude that the He-dilution technique is a viable method for the delta(18)O analysis of nitrates and other N-containing samples (which are not routinely measured using He dilution) using TC-EA-IRMS, since it can easily be programmed in the standard software of IRMS systems. With the He-dilution technique delta(18)O values of the nitrate isotope standards USGS34, IAEA-N3 and USGS35 were measured using the shortest possible traceability chain to the VSMOW-SLAP scale, and the results were -28.1 +/- 0.1 per thousand, +25.5 +/- 0.1 per thousand and +57.5 +/- 0.2 per thousand, respectively. An improved background correction was also an effective method, but required manual correction of the raw data. PMID:18561208

  1. Thermal ionization cavity source for mass spectrometry

    SciTech Connect

    Olivares, J.A.; Chamberlin, E.P.; Duan, Yixiang

    1995-12-31

    Thermal ionization mass spectrometry (TIMS) is widely used for isotopic determination, and elemental concentration measurements by isotope dilution. TIMS is applicable to over 70 elements in the periodic table, often, with very high sensitivity, low detection limits, high precision, and high accuracy. Probably due to its success and simplicity, the traditional resistively heated filament type ion source, used in TIMS, has remained relatively unchanged in the past 50 years. Only minor changes in the number of filaments used for vaporization and ionization, and the shape of the filament have been employed. Much of the science of thermal ionization has focused on sample preparation, and chemical ionization enhancers. Beyer et al., in the USSR, and Johnson et al., later in the US, introduced a new high temperature cavity-type thermal ionization source for isotope separation on-line (ISOL) projects. Delmore et al. introduced a similar cavity-type source for the study of thermal emission of primary ions for secondary ionization mass spectrometry (SIMS). A new thermal ionization cavity-type source for mass spectrometry has been developed in this laboratory.

  2. Stable isotope dilution liquid chromatography-mass spectrometry analysis of cellular and tissue medium- and long-chain acyl-coenzyme A thioesters

    PubMed Central

    Snyder, Nathaniel W.; Basu, Sankha S.; Zhou, Zinan; Worth, Andrew J.; Blair, Ian A.

    2014-01-01

    RATIONALE Acyl-Coenzyme A (CoA) thioesters are the principal form of activated carboxylates in cells and tissues. They are employed as acyl carriers that facilitate the transfer of acyl groups to lipids and proteins. Quantification of medium-chain and long-chain acyl-CoAs represents a significant bioanalytical challenge because of their instability. METHODS Stable isotope dilution-liquid chromatography-selected reaction monitoring-mass spectrometry (LC-SRM/MS) provides the most specific and sensitive method for the analysis of CoA species. However, relevant heavy isotope standards are not available and they are challenging to prepare by chemical synthesis. Stable isotope labeling by essential nutrients in cell culture (SILEC) developed originally for the preparation of stable isotope labeled short-chain acyl-CoA thioester standards has now been extended to medium-chain and long-chain acyl-CoAs and used for LC-SRM/MS analyses. RESULTS Customized SILEC standards with > 98 % isotopic purity were prepared using mouse Hepa 1c1c7 cells cultured in pantothenic-free media fortified with [13C315N1]-pantothenic acid and selected fatty acids. A SILEC standard in combination with LC-SRM/MS was employed to quantify cellular concentrations of arachidonoyl-CoA (a representative long-chain acyl-CoA) in two human colon cancer cell lines. A panel of SILEC standards was also employed in combination LC-SRM/MS to quantify medium- and long-chain acyl-CoAs in mouse liver. CONCLUSION This new SILEC-based method in combination with LC-SRM/MS will make it possible to rigorously quantify medium- and long-chain acyl-CoAs in cells and tissues. The method will facilitate studies of medium- and long-chain acyl-CoA dehydrogenase deficiencies as well as studies on the role of medium- and long-chain acyl-CoAs in cellular metabolism. PMID:25559454

  3. Investigation of amino acid δ 13C signatures in bone collagen to reconstruct human palaeodiets using liquid chromatography-isotope ratio mass spectrometry

    NASA Astrophysics Data System (ADS)

    Choy, Kyungcheol; Smith, Colin I.; Fuller, Benjamin T.; Richards, Michael P.

    2010-11-01

    This research presents the individual amino acid δ 13C values in bone collagen of humans ( n = 9) and animals ( n = 27) from two prehistoric shell midden sites in Korea. We obtained complete baseline separation of 16 of the 18 amino acids found in bone collagen by using liquid chromatography-isotope ratio mass spectrometry (LC-IRMS). The isotopic results reveal that the humans and animals in the two sites had similar patterns in essential amino acids (EAAs) and non-essential amino acids (NEAAs). The EAA and NEAA δ 13C values in humans are intermediate between those in marine and terrestrial animals. However, the threonine δ 13C values in humans and animals measured in this study are more highly enriched than those of other amino acids. At both sites, all amino acids in marine animals are 13C-enriched relative to those of the terrestrial animals. The isotopic evidence suggests that the Tongsamdong human had EAAs and NEAAs from marine food resources, while the Nukdo humans mainly had EAAs from terrestrial food resources but obtained NEAAs from both terrestrial and marine resources. The δ 13C isotopic differences in amino acids between marine and terrestrial animals were the largest for glycine (NEAA) and histidine (EAA) and the smallest for tyrosine (NEAA) and phenylalanine (EAA). In addition, threonine among the EAAs also had a large difference (˜8‰) in δ 13C values between marine and terrestrial animals, and has the potential to be used as an isotopic marker in palaeodietary studies. Threonine δ 13C values were used in conjunction with the established Δ 13C Glycine-phenylalanine values and produced three distinct dietary groups (terrestrial, omnivorous, and marine). In addition, threonine δ 13C values and Δ 13C Serine-phenylalanine values were discovered to separate between two dietary groups (terrestrial vs. marine), and these δ 13C values may provide a potential new indicator for investigating the distinction between marine and terrestrial protein sources in human diets.

  4. Linear electric field mass spectrometry

    DOEpatents

    McComas, David J. (Los Alamos, NM); Nordholt, Jane E. (Los Alamos, NM)

    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.

  5. 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.

  6. Ultratrace Uranium Fingerprinting with Isotope Selective Laser Ionization Spectrometry

    SciTech Connect

    Ziegler, Summer L.; Bushaw, Bruce A.

    2008-08-01

    Uranium isotope ratios can provide source information for tracking uranium contamination in a variety of fields, ranging from occupational bioassay to monitoring aftereffects of nuclear accidents. We describe the development of Isotope Selective Laser Ionization Spectrometry (ISLIS) for ultratrace measurement of the minor isotopes 234U, 235U, and 236U with respect to 238U. Optical isotopic selectivity in three-step excitation with single-mode continuous wave lasers is capable of measuring the minor isotopes at relative abundances below 1 ppm, and is not limited by isobaric interferences such as 235UH+ during measurement of 236U. This relative abundance limit approaches the threshold for measurement of uranium minor isotopes with conventional mass spectrometry, typically 10-7, but without mass spectrometric analysis of the laser-created ions. Uranyl nitrate standards from an international blind comparison were used to test analytical performance for different isotopic compositions and with quantities ranging from 11 ng to 10 g total uranium. Isotopic ratio determination was demonstrated over a linear dynamic range of 7 orders of magnitude with a few percent relative precision and detection limits below 500 fg for the minor isotopes.

  7. [Determination of 18 pesticide residues in red wine by ultra high performance liquid chromatography-high resolution mass spectrometry with isotope dilution technique].

    PubMed

    Chen, Dawei; L, Bing; Ding, Hao; Zou, Jianhong; Yang, Xin; Zhao, Yunfeng; Miao, Hong

    2014-05-01

    A method for the simultaneous determination of 18 pesticide residues in red wine was developed using ultra high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) with isotope dilution technique. The red wine samples were extracted with acetonitrile, and the extracts were cleaned up with dispersive solid phase extraction (dSPE) using the mixture of N-propyl ethylene diamine (PSA) and C18 powder as sorbent. The extracted components were separated on a BEH C18 column by gradient elution. The qualitative and quantitative analyses were operated under full scan/data dependent MS/MS (ddms2) and targeted selective ion monitoring (tSIM) by high resolution mass spectrometry, respectively. Carbendazim-D4, chlorpyrifos-D10, imidacloprid-D4, methoxyfenozide-D9, pyrimethanil-D5 and tebuconazole-D6 were used as the internal standards to reduce the matrix effects. The response of each pesticide showed a good linearity in the range of 0.5-50 microg/kg with the correlation coefficient more than 0.999. The limits of detection and quantification for the 18 pesticides in the spiked blank red wine were 0.5 microg/kg and 1.0 microg/kg, respectively. The recovery results with spiked blank red wine samples at the levels of 1 to 40 microg/kg were satisfactory with average recoveries of 85.4% - 117.9% and the RSDs of 0.5%-6.1%. The method was applied for the determination of the red wine real samples from the market. Carbendazim, imidacloprid, pyrimethanil, tebuconazole and triadimenol were detected in the samples. The results show that the method is suitable for the rapid screening and quantitative analysis of pesticide residues in red wine. PMID:25185308

  8. Stable isotope dilution ultra-high performance liquid chromatography-tandem mass spectrometry quantitative profiling of tryptophan-related neuroactive substances in human serum and cerebrospinal fluid.

    PubMed

    Hnykov, Eva; Vrnov, Hana P?ikrylov; Amakorov, Petra; Pospil, Tom; ukauskait?, Asta; Vl?kov, Magdalna; Urbnek, Lubor; Novk, Ond?ej; Mare, Jan; Ka?ovsk, Petr; Strnad, Miroslav

    2016-03-11

    Many compounds related to L-tryptophan (L-TRP) have interesting biological or pharmacological activity, and their abnormal neurotransmission seems to be linked to a wide range of neurodegenerative and psychiatric diseases. A high-throughput method based on ultra-high performance liquid chromatography connected to electrospray tandem mass spectrometry (UHPLC-ESI-MS/MS) was developed for the quantitative analysis of L-TRP and 16 of its metabolites in human serum and cerebrospinal fluid (CSF), representing both major and minor routes of L-TRP catabolism. The combination of a fast LC gradient with selective tandem mass spectrometry enabled accurate analysis of almost 100 samples in 24h. The standard isotope dilution method was used for quantitative determination. The method's lower limits of quantification for serum and cerebrospinal fluid ranged from 0.05 to 15nmol/L and 0.3 to 45nmol/L, respectively. Analytical recoveries ranged from 10.4 to 218.1% for serum and 22.1 to 370.0% for CSF. The method's accuracy ranged from 82.4 to 128.5% for serum matrix and 90.7 to 127.7% for CSF matrix. All intra- and inter-day coefficients of variation were below 15%. These results demonstrate that the new method is capable of quantifying endogenous serum and CSF levels of a heterogeneous group of compounds spanning a wide range of concentrations. The method was used to determine the physiological levels of target analytes in serum and CSF samples from 18 individuals, demonstrating its reliability and potential usefulness in large-scale epidemiological studies. PMID:26879452

  9. Multiplexed Analysis of Cage and Cage Free Chicken Egg Fatty Acids Using Stable Isotope Labeling and Mass Spectrometry

    PubMed Central

    Torde, Richard G.; Therrien, Andrew J.; Shortreed, Michael R.; Smith, Lloyd M.; Lamos, Shane M.

    2014-01-01

    Binary stable isotope labeling couple with LC-ESI-MS has been used as a powerful non-targeted approach for the relative quantification of lipids, amino acids, and many other important metabolite classes. A multiplexed approach using three or more isotopic labeling reagents greatly reduces analytical run-time while maintaining excellent sensitivity and reproducibility. Three isotopic cholamine labeling reagents have been developed to take advantage of the pre-ionized character of cholamine, for ESI, and the ease by which stable isotopes can be incorporated into the cholamine structure. These three cholamine labeling reagents have been used to relatively quantify three fatty acid samples simultaneously. The quantification resulted in the observation of 12 fatty acids that had an average absolute error of 0.9% and an average coefficient of variation of 6.1%. Caged versus cage-free isotope labeling experiments showed that cage-free eggs have an increased level of omega-3 fatty acids as compared to caged eggs. This multiplexed fatty acid analysis provides an inexpensive and expedited tool for broad-based lipid profiling that will further aid discoveries in the mechanisms of fatty acid action in cells. PMID:24317525

  10. Quantification of cellular poly(ADP-ribosyl)ation by stable isotope dilution mass spectrometry reveals tissue- and drug-dependent stress response dynamics.

    PubMed

    Martello, Rita; Mangerich, Aswin; Sass, Sabine; Dedon, Peter C; Bürkle, Alexander

    2013-07-19

    Poly(ADP-ribosyl)ation is an essential post-translational modification with the biopolymer poly(ADP-ribose) (PAR). The reaction is catalyzed by poly(ADP-ribose) polymerases (PARPs) and plays key roles in cellular physiology and stress response. PARP inhibitors are currently being tested in clinical cancer treatment, in combination therapy, or as monotherapeutic agents by inducing synthetic lethality. We have developed an accurate and sensitive bioanalytical platform based on isotope dilution mass spectrometry in order to quantify steady-state and stress-induced PAR levels in cells and tissues and to characterize pharmacological properties of PARP inhibitors. In contrast to existing PAR-detection techniques, the LC-MS/MS method uses authentic isotope-labeled standards, which provide unequivocal chemical specificity to quantify cellular PAR in absolute terms with femtomol sensitivity. Using this platform we analyzed steady-state levels as well as stress-induced dynamics of poly(ADP-ribosyl)ation in a series of biological systems including cancer cell lines, mouse tissues, and primary human lymphocytes. Our results demonstrate a rapid and transient stress-induced increase in PAR levels by >100-fold in a dose- and time-dependent manner with significant differences between cell types and individual human lymphocyte donors. Furthermore, ex vivo pharmacodynamic studies in human lymphocytes provide new insight into pharmacological properties of clinically relevant PARP inhibitors. Finally, we adapted the LC-MS/MS method to quantify poly(ADP-ribosyl)ation in solid tissues and identified tissue-dependent associations between PARP1 expression and PAR levels in a series of different mouse organs. In conclusion, this study demonstrates that mass spectrometric quantification of cellular poly(ADP-ribosyl)ation has a wide range of applications in basic research as well as in drug development. PMID:23631432

  11. Characterization and quantification of histidine degradation in therapeutic protein formulations by size exclusion-hydrophilic interaction two dimensional-liquid chromatography with stable-isotope labeling mass spectrometry.

    PubMed

    Wang, Chunlei; Chen, Sike; Brailsford, John A; Yamniuk, Aaron P; Tymiak, Adrienne A; Zhang, Yingru

    2015-12-24

    Two dimensional liquid chromatography (2D-LC) coupling size exclusion (SEC) and hydrophilic interaction chromatography (HILIC) is demonstrated as a useful tool to study polar excipients, such as histidine and its degradant, in protein formulation samples. The SEC-HILIC setup successfully removed interferences from complex sample matrices and enabled accurate mass measurement of the histidine degradation product, which was then determined to be trans-urocanic acid. Because the SEC effluent is a strong solvent for the second dimension HILIC, experimental parameters needed to be carefully chosen, i.e., small transferring loop, fast gradient at high flow rates for the second dimension gradient, in order to mitigate the solvent mismatch and to ensure good peak shapes for HILIC separations. In addition, the generation of trans-urocanic acid was quantified by single heart-cutting SEC-HILIC 2D-LC combined with stable-isotope labeling mass spectrometry. Compared with existing 2D quantification methods, the proposed approach is fast, insensitive to solvent mismatch between dimensions, and tolerant of small retention time shifts in the first dimension. Finally, the first dimension diode array detector was found to be a potential degradation source for photolabile analytes such as trans-urocanic acid. PMID:26674608

  12. Validation of the determination of the B isotopic composition in Roman glasses with laser ablation multi-collector inductively coupled plasma-mass spectrometry

    NASA Astrophysics Data System (ADS)

    Devulder, Veerle; Gerdes, Axel; Vanhaecke, Frank; Degryse, Patrick

    2015-03-01

    The applicability of laser ablation multi-collector inductively coupled plasma-mass spectrometry (LA-MC-ICP-MS) for the determination of the B isotopic composition in Roman glasses was investigated. The δ11B values thus obtained provide information on the natron flux used during the glass-making process. The glass samples used for this purpose were previously characterized using pneumatic nebulization (PN) MC-ICP-MS. Unfortunately, this method is time-consuming and labor-intensive and consumes some 100 mg of sample, which is a rather high amount for ancient materials. Therefore, the use of the less invasive and faster LA-MC-ICP-MS approach was explored. In this work, the results for 29 Roman glasses and 4 home-made glasses obtained using both techniques were compared to assess the suitability of LA-MC-ICP-MS in this context. The results are in excellent agreement within experimental uncertainty. No difference in overall mass discrimination was observed between the Roman glasses, NIST SRM 610 reference glass and B6 obsidian. The expanded uncertainty of the LA-MC-ICP-MS approach was estimated to be < 2‰, which is similar to that obtained upon sample digestion and PN-MC-ICP-MS measurement.

  13. The determination of carbon dioxide concentration using atmospheric pressure ionization mass spectrometry/isotopic dilution and errors in concentration measurements caused by dryers.

    PubMed

    DeLacy, Brendan G; Bandy, Alan R

    2008-01-01

    An atmospheric pressure ionization mass spectrometry/isotopically labeled standard (APIMS/ILS) method has been developed for the determination of carbon dioxide (CO(2)) concentration. Descriptions of the instrumental components, the ionization chemistry, and the statistics associated with the analytical method are provided. This method represents an alternative to the nondispersive infrared (NDIR) technique, which is currently used in the atmospheric community to determine atmospheric CO(2) concentrations. The APIMS/ILS and NDIR methods exhibit a decreased sensitivity for CO(2) in the presence of water vapor. Therefore, dryers such as a nafion dryer are used to remove water before detection. The APIMS/ILS method measures mixing ratios and demonstrates linearity and range in the presence or absence of a dryer. The NDIR technique, on the other hand, measures molar concentrations. The second half of this paper describes errors in molar concentration measurements that are caused by drying. An equation describing the errors was derived from the ideal gas law, the conservation of mass, and Dalton's Law. The purpose of this derivation was to quantify errors in the NDIR technique that are caused by drying. Laboratory experiments were conducted to verify the errors created solely by the dryer in CO(2) concentration measurements post-dryer. The laboratory experiments verified the theoretically predicted errors in the derived equations. There are numerous references in the literature that describe the use of a dryer in conjunction with the NDIR technique. However, these references do not address the errors that are caused by drying. PMID:18574165

  14. Accelerator mass spectrometry as a bioanalytical tool for nutritional research

    SciTech Connect

    Vogel, J.S.; Turteltaub, K.W.

    1997-09-01

    Accelerator Mass Spectrometry is a mass spectrometric method of detecting long-lived radioisotopes without regard to their decay products or half-life. The technique is normally applied to geochronology, but recently has been developed for bioanalytical tracing. AMS detects isotope concentrations to parts per quadrillion, quantifying labeled biochemicals to attomole levels in milligram- sized samples. Its advantages over non-isotopeic and stable isotope labeling methods are reviewed and examples of analytical integrity, sensitivity, specificity, and applicability are provided.

  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. Resonance Ionization Mass Spectrometry in biochemical analysis

    SciTech Connect

    Anderson, J.E.; Perez-Lopez, B.L.; Nogar, N.S.; Estler, R.C.; Conia, J.E.

    1992-08-01

    Resonance Ionization Mass Spectrometry (RIMS) is a form of laser-based mass that is finding increasing applications in elemental and isotopic analysis, particular in biochemical systems. Significant attributes include: (1) excellent sensitivity-- sub-fg, absolute; sub-ppb, relative (2) information on isotopic distributions (3) reduction of background (relative to conventional mass spectrometry) due to the sample matrix. The high sensitivity allows the use of very small sample sizes; this is potentially important in trace element analysis for infants, neonates, or other hard-to-obtain samples. Isotopic measurements can provide direct absolute signal calibration, as well as being applicable to kinetic analysis, such as trace metal uptake studies. The selectivity of RIMS provides for accurate measurements with little or no sample preparation. This, in turn, improves the speed and accuracy of the analysis. Furthermore, resonance ionization can be adapted for use with many pre-existing mass spectrometric systems. We report here on three applications of RIMS: the detection of trace levels of chromium; the quantification of trace chromium in urine; and, the uptake of copper by single cells.

  17. Measurement of ?18O, ?17O, and 17O-excess in water by off-axis integrated cavity output spectroscopy and isotope ratio mass spectrometry.

    PubMed

    Berman, Elena S F; Levin, Naomi E; Landais, Amaelle; Li, Shuning; Owano, Thomas

    2013-11-01

    Stable isotopes of water have long been used to improve understanding of the hydrological cycle, catchment hydrology, and polar climate. Recently, there has been increasing interest in measurement and use of the less-abundant (17)O isotope in addition to (2)H and (18)O. Off-axis integrated cavity output spectroscopy (OA-ICOS) is demonstrated for accurate and precise measurements ?(18)O, ?(17)O, and (17)O-excess in liquid water. OA-ICOS involves no sample conversion and has a small footprint, allowing measurements to be made by researchers collecting the samples. Repeated (514) high-throughput measurements of the international isotopic reference water standard Greenland Ice Sheet Precipitation (GISP) demonstrate the precision and accuracy of OA-ICOS: ?(18)OVSMOW-SLAP = -24.74 0.07 (1?) and ?(17)OVSMOW-SLAP = -13.12 0.05 (1?). For comparison, the International Atomic Energy Agency (IAEA) value for ?(18)OVSMOW-SLAP is -24.76 0.09 (1?) and an average of previously reported values for ?(17)OVSMOW-SLAP is -13.12 0.06 (1?). Multiple (26) high-precision measurements of GISP provide a (17)O-excessVSMOW-SLAP of 23 10 per meg (1?); an average of previously reported values for (17)O-excessVSMOW-SLAP is 22 11 per meg (1?). For all these OA-ICOS measurements, precision can be further enhanced by additional averaging. OA-ICOS measurements were compared with two independent isotope ratio mass spectrometry (IRMS) laboratories and shown to have comparable accuracy and precision as the current fluorination-IRMS techniques in ?(18)O, ?(17)O, and (17)O-excess. The ability to measure accurately ?(18)O, ?(17)O, and (17)O-excess in liquid water inexpensively and without sample conversion is expected to increase vastly the application of ?(17)O and (17)O-excess measurements for scientific understanding of the water cycle, atmospheric convection, and climate modeling among others. PMID:24032448

  18. Simple and accurate measurement of carbamazepine in surface water by use of porous membrane-protected micro-solid-phase extraction coupled with isotope dilution mass spectrometry.

    PubMed

    Teo, Hui Ling; Wong, Lingkai; Liu, Qinde; Teo, Tang Lin; Lee, Tong Kooi; Lee, Hian Kee

    2016-03-17

    To achieve fast and accurate analysis of carbamazepine in surface water, we developed a novel porous membrane-protected micro-solid-phase extraction (μ-SPE) method, followed by liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) analysis. The μ-SPE device (∼0.8 × 1 cm) was fabricated by heat-sealing edges of a polypropylene membrane sheet to devise a bag enclosing the sorbent. The analytes (both carbamazepine and isotope-labelled carbamazepine) were first extracted by μ-SPE device in the sample (10 mL) via agitation, then desorbed in an organic solvent (1 mL) via ultrasonication. Several parameters such as organic solvent for pre-conditioning of μ-SPE device, amount of sorbent, adsorption time, and desorption solvent and time were investigated to optimize the μ-SPE efficiency. The optimized method has limits of detection and quantitation estimated to be 0.5 ng L(-1) and 1.6 ng L(-1), respectively. Surface water samples spiked with different amounts of carbamazepine (close to 20, 500, and 1600 ng L(-1), respectively) were analysed for the validation of method precision and accuracy. Good precision was obtained as demonstrated by relative standard deviations of 0.7% for the samples with concentrations of 500 and 1600 ng kg(-1), and 5.8% for the sample with concentration of 20 ng kg(-1). Good accuracy was also demonstrated by the relative recoveries in the range of 96.7%-103.5% for all samples with uncertainties of 1.1%-5.4%. Owing to the same chemical properties of carbamazepine and isotope-labelled carbamazepine, the isotope ratio in the μ-SPE procedure was accurately controlled. The use of μ-SPE coupled with IDMS analysis significantly facilitated the fast and accurate measurement of carbamazepine in surface water. PMID:26920772

  19. Detection of Synthetic Testosterone Use by Novel Comprehensive Two-Dimensional Gas Chromatography Combustion Isotope Ratio Mass Spectrometry (GC×GCC-IRMS)

    PubMed Central

    Tobias, Herbert J.; Zhang, Ying; Auchus, Richard J.; Brenna, J. Thomas

    2011-01-01

    We report the first demonstration of Comprehensive Two-dimensional Gas Chromatography Combustion Isotope Ratio Mass Spectrometry (GC×GCC-IRMS) for the analysis of urinary steroids to detect illicit synthetic testosterone use, of interest in sport doping. GC coupled to IRMS (GCC-IRMS) is currently used to measure the carbon isotope ratios (CIR, δ13C) of urinary steroids in anti-doping efforts; however, extensive cleanup of urine extracts is required prior to analysis to enable baseline separation of target steroids. With its greater separation capabilities, GC×GC has the potential to reduce sample preparation requirements and enable CIR analysis of minimally processed urine extracts. Challenges addressed include on-line reactors with minimized dimensions to retain narrow peaks shapes, baseline separation of peaks in some cases, and reconstruction of isotopic information from sliced steroid chromatographic peaks. Difficulties remaining include long-term robustness of on-line reactors and urine matrix effects that preclude baseline separation and isotopic analysis of low concentration and trace components. In this work, steroids were extracted, acetylated, and analyzed using a refined, home-built GC×GCC-IRMS system. 11-hydroxy-androsterone (11OHA) and 11-ketoetiocolanolone (11KE) were chosen as endogenous reference compounds (ERC) because of their satisfactory signal intensity, and their CIR was compared to target compounds (TC) androsterone (A) and etiocholanolone (E). Separately, a GC×GC-qMS system was used to measure testosterone (T)/EpiT concentration ratios. Urinary extracts of urine pooled from professional athletes, and urine from one individual that received testosterone gel (T-gel) and one individual that received testosterone injections (T-shot) were analyzed. The average precisions of δ13C and Δδ13C measurements were SD(δ13C) approximately ± 1‰ (n=11). The T-shot sample resulted in a positive for T use with a T/EpiT ratio of > 9 and CIR measurements of Δδ13C > 5‰, both fulfilling World Anti-Doping Agency criteria. These data show for the first time that synthetic steroid use is detectable by GC×GCC-IRMS without need for extensive urine cleanup. PMID:21846122

  20. 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.

  1. [Mass spectrometry for steroid assays].

    PubMed

    Dufour-Rainfray, Diane; Moal, Valrie; Cloix, Lucie; Mathieu, Elisabeth; Gauchez, Anne-Sophie; Brossaud, Julie; Corcuff, Jean-Benot; Fraissinet, Franois; Collet, Christine; Boux de Casson, Florence; Guilloteau, Denis; Emond, Patrick; Reynier, Pascal

    2015-01-01

    Steroid hormone measurement, first developed with radioimmunoassay, is now becoming easier with the use of automated platforms of immunoassay. However, some hormones remain uneasily detectable because of their low blood concentration, their structural homology or the presence of interferences. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) can be considered as an alternative to immunoassays. This approach allows the simultaneous determination of several parameters thanks to its selectivity led by the detector mass spectrometer and the separate dimension of chromatography liquid. In addition, recourse to UHPLC (ultra high performance liquid chromatography) allows improving selectivity and sensitivity while limiting the samples volumes. The "ready-to-use" kits are now available and added to the "homemade" techniques developed by laboratories, thus giving opportunity for measurement of a wide steroid panel with only one sample. Finally, mass spectrometry methods, including a prior extraction step, allow the use of varied biological fluids (blood, urine, saliva). Also, several clinical indications could gain from mass spectrometry, especially when hormone levels are low, when several steroids have to be identified, when the sample volume is low. However, this technology represents an important financial investment and in-depth staff training. In addition, some steroids are not easily quantifiable by mass spectrometry. It is likely by immunoassay and mass spectrometry, well-matched technologies, that we could answer the best to clinical questions about steroids. PMID:25582724

  2. Characterization of diesel fuel by chemical separation combined with capillary gas chromatography (GC) isotope ratio mass spectrometry (IRMS).

    PubMed

    Harvey, Scott D; Jarman, Kristin H; Moran, James J; Sorensen, Christina M; Wright, Bob W

    2012-09-15

    The purpose of this study was to perform a preliminary investigation of compound-specific isotope analysis (CSIA) of diesel fuels to evaluate whether the technique could distinguish diesel samples from different sources/locations. The ability to differentiate or correlate diesel samples could be valuable for discovering fuel tax evasion schemes or for environmental forensic studies. Two urea adduction-based techniques were used to isolate the n-alkanes from the fuel. Both carbon isotope ratio (?(13)C) and hydrogen isotope ratio (?D) values for the n-alkanes were then determined by CSIA in each sample. The samples investigated had ?(13)C values that ranged from -30.1 to -26.8, whereas ?D values ranged from -83 to -156. Plots of ?D versus ?(13)C with sample n-alkane points connected in order of increasing carbon number gave well-separated clusters with characteristic shapes for each sample. Principal components analysis (PCA) with ?(13)C, ?D, or combined ?(13)C and ?D data was applied to extract the maximum information content. PCA scores plots could clearly differentiate the samples, thereby demonstrating the potential of this approach for distinguishing (e.g., fingerprinting) fuel samples using ?(13)C and ?D values. PMID:22967550

  3. Quantification of carcinogenic 4- to 6-ring polycyclic aromatic hydrocarbons in human urine by solid-phase microextraction gas chromatography-isotope dilution mass spectrometry.

    PubMed

    Campo, Laura; Fustinoni, Silvia; Bertazzi, Pieralberto

    2011-08-01

    Polycyclic aromatic hydrocarbons (PAHs) are pollutants found in living and working environments. The aim of this study was to develop a solid-phase microextraction (SPME) gas chromatography (GC)-isotope dilution mass spectrometry method for the quantification of 10 four- to six-ring PAHs in urine samples. Seven of the selected PAHs have been classified as carcinogenic. Under the final conditions, analytes were sampled with a 100-?m polydimethylsiloxane SPME fibre for 60 min at 80 C and desorbed in the injection port of the GC at 270 C. Fluoranthene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenzo[a,h]anthracene, indeno[1,2,3-cd]pyrene and benzo[ghi]perylene were separated using a highly arylene-modified phase capillary column and quantified by MS using eight deuterated PAHs as surrogate internal standards. Limits of quantification (LOQ) were in the 0.5- to 2.2-ng/L range. Validation showed linear dynamic ranges up to 340 ng/L, inter- and intra-run precisions <20%, and accuracies within 20% of spiked concentrations. Matrix effect evaluation and the use of control charts to monitor process performances showed that the isotope dilution approach allowed for the control of bias sources. Urinary PAHs were above or equal to LOQ, depending on different compounds, in 58-100% (min-max), 40-100% and 5-39% of samples from coke oven workers (n?=?12), asphalt workers (n?=?10) and individuals not occupationally exposed to PAHs (n?=?18), respectively. Chrysene was the most abundant PAH determined with median levels of 62.6, 6.9 and <0.6 ng/L, respectively. These results show that the method is suitable for quantifying carcinogenic PAHs in specimens from individuals with different levels of PAH exposure. PMID:21626187

  4. Validation of an isotope dilution gas chromatography-mass spectrometry method for combined analysis of oxysterols and oxyphytosterols in serum samples.

    PubMed

    Schtt, Hans-Frieder; Ltjohann, Dieter

    2015-07-01

    We describe the validation of a method for the analysis of oxysterols, i.e. oxycholesterols and oxyphytosterols, in human serum using gas chromatography-mass spectrometry selected ion monitoring (GC-MS-SIM). Concentrations of 7?- and 7?-hydroxy-, and 7oxo-cholesterol, -campesterol, and -sitosterol as well as 4?-hydroxycholesterol and side-chain oxygenated 24S-, 25-, and 27-hydroxycholesterol were determined by isotope dilution methodology. After saponification at room temperature the oxysterols were extracted, separated from their substrates, cholesterol, campesterol, and sitosterol, by solid phase extraction, and subsequently derivatised to their corresponding trimethylsilyl-ethers prior to GC-MS-SIM. In order to prevent artificial autoxidation butylated hydroxytoluene and ethylenediaminetetraacetic acid were added. The validation of the method was performed according to the International Conference on Harmonisation guidance, including limits of detection and quantification, ranges, recovery and precision. Due to improved instrumental settings and work-up procedure, limits of detection and quantification ranged between 8.0-202.0pg/mL and 28.0-674pg/mL, respectively. Recovery data in five calibration points varied between 91.9% and 116.8% and in serum samples between 93.1% and 118.1%. The mean coefficient of variation (CV) for the recovery of all compounds was <10%. Well satisfying CVs for within-day precision (2.1-10.8%) and for between-day precision (2.3-12.1%) were obtained. More than 20 samples could be processed in a single routine day and test series of about 300 samples can be realised without impairment of the validation parameters during a sequence. Comparison of oxysterol and oxyphytosterol content in serum and plasma revealed no difference. A fully validated isotope dilution methodology for the quantification of oxycholesterols and oxyphytosterols from human serum or plasma is presented. PMID:25701095

  5. Influence of relative abundance of isotopes on depth resolution for depth profiling of metal coatings by laser ablation inductively coupled plasma mass spectrometry.

    PubMed

    Farias, Juan C; Coedo, Aurora G; Dorado, Teresa

    2010-04-15

    A systematic study on the influence of relative abundance of isotopes of elements in the coating (A(c)) and in the substrate (A(s)) on both shape of time-resolved signals and depth resolution (Delta z) was performed for depth profile analysis of metal coatings on metal substrates by ultraviolet (266 nm) nanosecond laser ablation inductively coupled plasma quadrupole mass spectrometry. Five coated samples with coating thicknesses of the same order of magnitude (20-30 microm) were tested: nickel coating on aluminium, chromium and copper, and steel coated with copper and zinc. A laser repetition rate of 1 Hz and a laser fluence of 21 J cm(-2) were used. Five different depth profile types were established, which showed a clear dependence on A(c)/A(s) ratio. In general, depth profiles obtained for ratios above 1-10 could not be used to determine Delta z. We found that Delta z increased non-linearly with A(c)/A(s) ratio. The best depth profile types, leading to highest depth resolution and reproducibility, were attained in all cases by using the isotopes with low/medium A(c) values and with the highest A(s) values. In these conditions, an improvement of up to 4 times in Delta z values was achieved. The average ablation rates were in the range from 0.55 microm pulse(-1) for copper coating on steel to 0.83 microm pulse(-1) for zinc coating on steel, and the Delta z values were between 2.74 microm for nickel coating on chromium and 5.91 microm for nickel coating on copper, with RSD values about 5-8%. PMID:20188923

  6. Digital imaging mass spectrometry.

    PubMed

    Bamberger, Casimir; Renz, Uwe; Bamberger, Andreas

    2011-06-01

    Methods to visualize the two-dimensional (2D) distribution of molecules by mass spectrometric imaging evolve rapidly and yield novel applications in biology, medicine, and material surface sciences. Most mass spectrometric imagers acquire high mass resolution spectra spot-by-spot and thereby scan the object's surface. Thus, imaging is slow and image reconstruction remains cumbersome. Here we describe an imaging mass spectrometer that exploits the true imaging capabilities by ion optical means for the time of flight mass separation. The mass spectrometer is equipped with the ASIC Timepix chip as an array detector to acquire the position, mass, and intensity of ions that are imaged by matrix-assisted laser desorption/ionization (MALDI) directly from the target sample onto the detector. This imaging mass spectrometer has a spatial resolving power at the specimen of (84 ± 35) μm with a mass resolution of 45 and locates atoms or organic compounds on a surface area up to ~2 cm(2). Extended laser spots of ~5 mm(2) on structured specimens allows parallel imaging of selected masses. The digital imaging mass spectrometer proves high hit-multiplicity, straightforward image reconstruction, and potential for high-speed readout at 4 kHz or more. This device demonstrates a simple way of true image acquisition like a digital photographic camera. The technology may enable a fast analysis of biomolecular samples in near future. PMID:21953049

  7. Qualitative Metabolome Analysis of Human Cerebrospinal Fluid by 13C-/12C-Isotope Dansylation Labeling Combined with Liquid Chromatography Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Guo, Kevin; Bamforth, Fiona; Li, Liang

    2011-02-01

    Metabolome analysis of human cerebrospinal fluid (CSF) is challenging because of low abundance of metabolites present in a small volume of sample. We describe and apply a sensitive isotope labeling LC-MS technique for qualitative analysis of the CSF metabolome. After a CSF sample is divided into two aliquots, they are labeled by 13C-dansyl and 12C-dansyl chloride, respectively. The differentially labeled aliquots are then mixed and subjected to LC-MS using Fourier-transform ion cyclotron resonance mass spectrometry (FTICR MS). Dansylation offers significant improvement in the performance of chromatography separation and detection sensitivity. Moreover, peaks detected in the mass spectra can be readily analyzed for ion pair recognition and database search based on accurate mass and/or retention time information. It is shown that about 14,000 features can be detected in a 25-min LC-FTICR MS run of a dansyl-labeled CSF sample, from which about 500 metabolites can be profiled. Results from four CSF samples are compared to gauge the detectability of metabolites by this method. About 261 metabolites are commonly detected in replicate runs of four samples. In total, 1132 unique metabolite ion pairs are detected and 347 pairs (31%) matched with at least one metabolite in the Human Metabolome Database. We also report a dansylation library of 220 standard compounds and, using this library, about 85 metabolites can be positively identified. Among them, 21 metabolites have never been reported to be associated with CSF. These results illustrate that the dansylation LC-FTICR MS method can be used to analyze the CSF metabolome in a more comprehensive manner.

  8. An improved analytical method for the determination of urea nitrogen isotopomers in biological samples utilizing continuous flow isotope ratio mass spectrometry.

    PubMed

    Marini, Juan C; Attene-Ramos, Matias Sebastian

    2006-01-01

    Over the past few years numerous dual inlet isotope ratio mass spectrometry (IRMS) applications have been adapted to continuous flow systems which allow the automation of sample admission and a higher throughput. The isotopomer analysis of urea nitrogen by IRMS requires the offline conversion of urea into nitrogen gas before analysis. The oxidation of urea with LiOBr results in the monomolecular degradation of urea, which preserves the identity of the parent urea molecule, and has to be conducted under vacuum to prevent contamination with atmospheric nitrogen. We have developed an offline system of urea degradation utilizing disposable Exetainers, in which atmospheric nitrogen is displaced by helium. Recovery of urea nitrogen was linear within the range of the standards tested (0 to 420 microg nitrogen) and standard curves for 15N15N-urea standards showed high coefficients of determination (R2 > 0.9998). A small portion of urea degrades in a non-monomolecular fashion and has been shown to depend on the concentration of urea in the sample. Long-term storage of prepared samples showed a decline in 15N15N enrichment, suggesting air contamination. However, samples were stable for 24 h, which allows for the analysis of large sample batches. Interest in urea metabolism, particularly in ruminant species, has increased recently due to the environmental implications of urea and nitrogen excretion by farm animals. This novel analytical method will allow for accurate measurements and the rapid throughput needed in order to support these field studies. PMID:17099932

  9. Studies on the analysis of 25-hydroxyvitamin D3 by isotope-dilution liquid chromatographytandem mass spectrometry using enzyme-assisted derivatisation

    PubMed Central

    Abdel-Khalik, Jonas; Crick, Peter J.; Carter, Graham D.; Makin, Hugh L.; Wang, Yuqin; Griffiths, William J.

    2014-01-01

    The total serum concentration of 25-hydroxyvitamins D (25-hydroxyvitamin D3 and 25-hydroxyvitamin D2) is currently used as an indicator of vitamins D status. Vitamins D insufficiency is claimed to be associated with multiple diseases, thus accurate and precise reference methods for the quantification of 25-hydroxyvitamins D are needed. Here we present a novel enzyme-assisted derivatisation method for the analysis of vitamins D metabolites in adult serum utilising 25-[26,26,26,27,27,27-2H6]hydroxyvitamin D3 as the internal standard. Extraction of 25-hydroxyvitamins D from serum is performed with acetonitrile, which is shown to be more efficient than ethanol. Cholesterol oxidase is used to oxidize the 3?-hydroxy group in the vitamins D metabolites followed by derivatisation of the newly formed 3-oxo group with Girard P reagent. 17?-Hydroxysteroid dehydrogenase type 10 is shown to oxidize selectively the 3?-hydroxy group in the 3?-hydroxy epimer of 25-hydroxyvitamin D3. Quantification is achieved by isotope-dilution liquid chromatographytandem mass spectrometry. Recovery experiments for 25-hydroxyvitamin D3 performed on adult human serum give recovery of 102106%. Furthermore in addition to 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D3 and other uncharacterised dihydroxy metabolites, were detected in adult human serum. PMID:24486315

  10. Measurement of (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines in DNA in vivo by liquid chromatography/isotope-dilution tandem mass spectrometry

    SciTech Connect

    Jaruga, Pawel; Department of Clinical Biochemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz ; Xiao, Yan; Nelson, Bryant C.; Dizdaroglu, Miral

    2009-09-04

    Oxidatively induced DNA lesions (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines (R-cdA and S-cdA) are detectable and accumulate in vivo due to disease states and defects in DNA repair. They block transcription and inhibit gene expression, and may play a role in disease processes. Accurate measurement of these lesions in DNA in vivo is necessary to understand their biological effects. We report on a methodology using liquid chromatography/isotope-dilution tandem mass spectrometry to measure R-cdA and S-cdA in DNA. This methodology permitted the detection of these compounds at a level of 0.1 fmol on-column. Levels of R-cdA and S-cdA in mouse liver DNA amounted to 0.133 {+-} 0.024 and 0.498 {+-} 0.065 molecules/10{sup 7} DNA 2'-deoxynucleosides, respectively. The successful measurement of R-cdA and S-cdA in DNA in vivo suggests that this methodology will be used for understanding of their repair and biological consequences, and that these compounds may be used as putative biomarkers for disease states.

  11. Quantification of DNA damage products resulting from deamination, oxidation and reaction with products of lipid peroxidation by liquid chromatography isotope dilution tandem mass spectrometry

    PubMed Central

    Taghizadeh, Koli; McFaline, Jose L.; Pang, Bo; Sullivan, Matthew; Dong, Min; Plummer, Elaine; Dedon, Peter C.

    2009-01-01

    The analysis of damage products as biomarkers of inflammation has been hampered by a poor understanding of the chemical biology of inflammation, the lack of sensitive analytical methods, and a focus on single chemicals as surrogates for inflammation. To overcome these problems, we developed a general and sensitive liquid chromatographic tandem mass spectrometry (LC/MS-MS) method to quantify, in a single DNA sample, the nucleoside forms of seven DNA lesions reflecting the range of chemistries associated with inflammation: 2?-deoxyuridine, 2?-deoxyxanthosine, and 2?-deoxyinosine from nitrosative deamination; 8-oxo-2?-deoxyguanosine from oxidation; and 1,N2-etheno-2?-deoxyguanosine, 1,N6-etheno-2?-deoxyadenosine, and 3,N4-etheno-2?-deoxycytidine arising from reaction of DNA with lipid peroxidation products. Using DNA purified from cells or tissues under conditions that minimize artifacts, individual nucleosides are purified by HPLC and quantified by isotope-dilution, electrospray ionization LC/MS-MS. The method can be applied to other DNA damage products and requires 4-6 days to complete depending upon the number of samples. PMID:18714297

  12. Isotope dilution gas chromatography with mass spectrometry for the analysis of 4-octyl phenol, 4-nonylphenol, and bisphenol A in vegetable oils.

    PubMed

    Wu, Pinggu; Zhang, Liqun; Yang, Dajin; Zhang, Jing; Hu, Zhengyan; Wang, Liyuan; Ma, Bingjie

    2016-03-01

    By the combination of solid-phase extraction as well as isotope dilution gas chromatography with mass spectrometry, a sensitive and reliable method for the determination of endocrine-disrupting chemicals including bisphenol A, 4-octylphenol, and 4-nonylphenol in vegetable oils was established. The application of a silica/N-(n-propyl)ethylenediamine mixed solid-phase extraction cartridge achieved relatively low matrix effects for bisphenol A, 4-octylphenol, and 4-nonylphenol in vegetable oils. Experiments were designed to evaluate the effects of derivatization, and the extraction parameters were optimized. The estimated limits of detection and quantification for bisphenol A, 4-octylphenol, and 4-nonylphenol were 0.83 and 2.5 μg/kg, respectively. In a spiked experiment in vegetable oils, the recovery of the added bisphenol A was 97.5-110.3%, recovery of the added 4-octylphenol was 64.4-87.4%, and that of 4-nonylphenol was 68.2-89.3%. This sensitive method was then applied to real vegetable oil samples from Zhejiang Province of China, and none of the target compounds were detected. PMID:26698324

  13. Absolute quantification of Pru av 2 in sweet cherry fruit by liquid chromatography/tandem mass spectrometry with the use of a stable isotope-labelled peptide.

    PubMed

    Ippoushi, Katsunari; Sasanuma, Motoe; Oike, Hideaki; Kobori, Masuko; Maeda-Yamamoto, Mari

    2016-08-01

    Pru av 2, a pathogenesis-related (PR) protein present in the sweet cherry (Prunus avium L.) fruit, is the principal allergen of cherry and one of the chief causes of pollen food syndrome (oral allergy syndrome). In this study, a quantitative assay for this protein was developed with the use of the protein absolute quantification (AQUA) method, which consists of liquid chromatography/tandem mass spectrometry (LC/MS/MS) employing TGC[CAM]STDASGK[(13)C6,(15)N2], a stable isotope-labelled internal standard (SIIS) peptide. This assay gave a linear relationship (r(2)>0.99) in a concentration range (2.3-600fmol/μL), and the overall coefficient of variation (CV) for multiple tests was 14.6%. Thus, the contents of this allergenic protein in sweet cherry products could be determined using this assay. This assay should be valuable for allergological investigations of Pru av 2 in sweet cherry and detection of protein contamination in foods. PMID:26988485

  14. Multiresidue method for the determination of nitroimidazoles and their hydroxy-metabolites in poultry muscle, plasma and egg by isotope dilution liquid chromatography-mass spectrometry.

    PubMed

    Mitrowska, Kamila; Posyniak, Andrzej; Zmudzki, Jan

    2010-06-15

    A multiresidue analytical procedure for the determination of four nitroimidazoles (metronidazole, dimetridazole, ronidazole, ipronidazole) and their hydroxy-metabolites in poultry muscle, plasma and egg is presented. The procedure is based on ion-exchange solid phase extraction with acetonitrile as an extractant followed by liquid chromatography-mass spectrometry. The separation of analytes was performed on a C18 column using a mobile phase of 0.1% formic acid in acetonitrile and 0.1% formic acid in water with gradient elution. The electrospray ionization was used to obtain the protonated molecules [M+H](+) and two product ions were monitored for each compound. For the quantification stable isotope-labelled analogues of the analytes were used as internal standards. The whole procedure was evaluated according to EU Commission Decision 2002/657/EC requirements. Specificity, decision limit (CCalpha), detection capacity (CCbeta), recovery and precision were determined during validation process. The overall recoveries ranged between 93 and 103% with a good coefficient of variation, less than 14.0% under within-laboratory reproducibility conditions. CCalpha and CCbeta were 0.05-0.44 and 0.08-0.90microgkg(-1) depending on analyte and matrix. PMID:20441895

  15. Comparison of digestion procedures and methods for quantification of trace lead in breast milk by isotope dilution inductively coupled plasma mass spectrometry

    PubMed Central

    Amarasiriwardena, Chitra J.; Jayawardene, Innocent; Lupoli, Nicola; Barnes, Ramon M.; Hernandez-Avila, Mauricio; Hu, Howard

    2014-01-01

    Measurement of lead in breast milk is an important public health consideration and can be technically quite challenging. The reliable and accurate determination of trace lead in human breast milk is difficult for several reasons including: potential for contamination during sample collection, storage, and analysis; complexities related to the high fat content of human milk; and poor analytic sensitivity at low concentrations. Breast milk lead levels from previous published studies should therefore be reviewed with caution. Due to the difficulty in identifying a method that would successfully digest samples with 100% efficiency, we evaluated three different digestion procedures including: (1) dry ashing in a muffle furnace, (2) microwave oven digestion, and (3) digestion in high pressure asher. High temperature, high pressure asher digestion was selected as the procedure of choice for the breast milk samples. Trace lead analysis was performed using isotope dilution (ID) inductively coupled plasma mass spectrometry (ICP-MS). Measured lead concentrations in breast milk samples (n = 200) from Mexico ranged from 0.2 to 6.7 ng ml?1. The precision for these measurements ranged from 0.277.8% RSD. Use of strict contamination control techniques and of a very powerful digestion procedure, along with an ID-ICP-MS method for lead determination, enables us to measure trace lead levels as low as 0.2 ng ml?1 in milk (instrument detection limit = 0.01 ng ml?1). PMID:24808927

  16. Regional water-quality analysis of 2,4-D and dicamba in river water using gas chromatography-isotope dilution mass spectrometry

    USGS Publications Warehouse

    Thurman, E.M.; Zimmerman, L.R.; Aga, D.S.; Gilliom, R.J.

    2001-01-01

    Gas chromatography with isotope dilution mass spectrometry (GC-MS) and enzyme-linked immunosorbent assay (ELISA) were used in regional National Water Quality Assessment studies of the herbicides, 2,4-D and dicamba, in river water across the United States. The GC-MS method involved solid-phase extraction, derivatized with deutemted 2,4-D, and analysis by selected ion monitoring. The ELISA method was applied after preconcentration with solid-phase extraction. The ELISA method was unreliable because of interference from humic substances that were also isolated by solid-phase extraction. Therefore, GC-MS was used to analyzed 80 samples from river water from 14 basins. The frequency of detection of dicamba (28%) was higher than that for 2,4-D (16%). Concentrations were higher for dicamba than for 2,4-D, ranging from less than the detection limit (<0.05 ??g/L) to 3.77 ??g/L, in spite of 5 times more annual use of 2,4-D as compared to dicamba. These results suggest that 2,4-D degrades more rapidly in the environment than dicamba.

  17. Determination of Os by isotope dilution-inductively coupled plasma-mass spectrometry with the combination of laser ablation to introduce chemically separated geological samples

    NASA Astrophysics Data System (ADS)

    Sun, Yali; Ren, Minghao; Xia, Xiaoping; Li, Congying; Sun, Weidong

    2015-11-01

    A method was developed for the determination of trace Os in geological samples by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) with the combination of chemical separation and preconcentration. Samples are digested using aqua regia in Carius tubes, and the Os analyte is converted into volatile OsO4, which is distilled and absorbed with HBr. The HBr solution is concentrated for further Os purification using the microdistillation technique. The purified Os is dissolved in 10 μl of 0.02% sucrose-0.005% H3PO4 solution and then evaporated on pieces of perfluoroalkoxy (PFA) film, resulting in the formation of a tiny object (< 3 × 104 μm2 superficial area). Using LA-ICP-MS measurements, the object can give Os signals at least 100 times higher than those provided by routine solution-ICP-MS while successfully avoiding the memory effect. The procedural blank and detection limit in the developed technique are 3.0 pg and 1.8 pg for Os, respectively when 1 g of samples is taken. Reference materials (RM) are analyzed, and their Os concentrations obtained by isotope dilution are comparable to reference or literature values. Based on the individual RM results, the precision is estimated within the range of 0.6 to 9.4% relative standard deviation (RSD), revealing that this method is applicable to the determination of trace Os in geological samples.

  18. Innovative method for carbon dioxide determination in human postmortem cardiac gas samples using headspace-gas chromatography-mass spectrometry and stable labeled isotope as internal standard.

    PubMed

    Varlet, V; Smith, F; de Froidmont, S; Dominguez, A; Rinaldi, A; Augsburger, M; Mangin, P; Grabherr, S

    2013-06-19

    A novel approach to measure carbon dioxide (CO2) in gaseous samples, based on a precise and accurate quantification by (13)CO2 internal standard generated in situ is presented. The main goal of this study was to provide an innovative headspace-gas chromatography-mass spectrometry (HS-GC-MS) method applicable in the routine determination of CO2. The main drawback of the GC methods discussed in the literature for CO2 measurement is the lack of a specific internal standard necessary to perform quantification. CO2 measurement is still quantified by external calibration without taking into account analytical problems which can often occur considering gaseous samples. To avoid the manipulation of a stable isotope-labeled gas, we have chosen to generate in situ an internal labeled standard gas ((13)CO2) on the basis of the stoichiometric formation of CO2 by the reaction of hydrochloric acid (HCl) with sodium hydrogen carbonate (NaH(13)CO3). This method allows a precise measurement of CO2 concentration and was validated on various human postmortem gas samples in order to study its efficiency. PMID:23746406

  19. Benzylic rearrangement stable isotope labeling for quantitation of guanidino and ureido compounds in thyroid tissues by liquid chromatography-electrospray ionization mass spectrometry.

    PubMed

    Fan, Ruo-Jing; Guan, Qing; Zhang, Fang; Leng, Jia-Peng; Sun, Tuan-Qi; Guo, Yin-Long

    2016-02-18

    Benzylic rearrangement stable isotope labeling (BRSIL) was explored to quantify the guanidino and ureido compounds (GCs and UCs). This method employed a common reagent, benzil, to label the guanidino and ureido groups through nucleophilic attacking then benzylic migrating. The use of BRSIL was investigated in the analysis of five GCs (creatine, l-arginine, homoarginine, 4-guanidinobutyric acid, and methylguanidine) and two UCs (urea and citrulline). The labeling was found simple and specific. The introduction of bi-phenyl group and the generation of nitrogen heterocyclic ring in the benzil-d0/d5 labeled GCs and UCs improved the retention behaviors in liquid chromatography (LC) and increased the sensitivity of electrospray ionization mass spectrometry (ESI MS) detection. The fragment ion pairs of m/z 182/187 and m/z 210/215 from the benzil-d0/d5 tags facilitated the discovery of potential GCs and UCs candidates residing in biological matrices. The use of BRSIL combined with LC-ESI MS was applied for simultaneously quantitation of GCs and UCs in thyroid tissues. It was demonstrated that nine GCs and UCs were detected, six of which were further quantified based on corresponding standards. It was concluded that five GCs and UCs (l-arginine, homoarginine, 4-guanidinobutyric acid, methylguanidine, and citrulline) were statistically significantly different (p<0.05) between the para-carcinoma and carcinoma thyroid tissue samples. PMID:26826695

  20. An optimised method for the accurate determination of zeranol and diethylstilbestrol in animal tissues using isotope dilution-liquid chromatography/mass spectrometry.

    PubMed

    Han, Hyesun; Kim, Byungjoo; Lee, Sueg Geun; Kim, Jeongkwon

    2013-09-01

    Isotope dilution-liquid chromatography/mass spectrometry (ID-LC/MS) has been established as a candidate reference method for the accurate determination of growth promoters (zeranol, taleranol, and diethylstilbesterol) in raw meat samples. Sample preparation processes including an enzymatic hydrolysis, extraction, and SPE clean-up were optimised. The sensitivity difference of trans- and cis-diethylstilbestrol (isomerizing in sample preparation processes) by the LC/MS was measured by running a trans/cis mixture (ratio measured by a quantitative NMR) with and without sample matrices, and applied for the determination of total diethylstilbestrol. Validity, repeatability, and reproducibility of the analytical method were tested by measuring gravimetrically fortified samples (chicken breast, bovine muscles, and porcine muscle) in a number of different time periods. Measurement results agreed with the fortified values within their uncertainties. The method provided accurate results of the target analytes in the range of 0.05-15 ?g/kg with the relative expanded uncertainty of 2-15%. PMID:23578613

  1. Simplified Method for Quantifying Sulfur Mustard Adducts to Blood Proteins by Ultrahigh Pressure Liquid Chromatography−Isotope Dilution Tandem Mass Spectrometry.

    PubMed

    Pantazides, Brooke G; Crow, Brian S; Garton, Joshua W; Quiñones-González, Jennifer A; Blake, Thomas A; Thomas, Jerry D; Johnson, Rudolph C

    2015-02-16

    Sulfur mustard binds to reactive cysteine residues, forming a stable sulfur-hydroxyethylthioethyl [SHETE]adduct that can be used as a long-term biomarker of sulfur mustard exposure in humans. The digestion of sulfur mustard-exposed blood samples with proteinase K following total protein precipitation with acetone produces the tripeptide biomarker [S-HETE]-Cys-Pro-Phe. The adducted tripeptide is purified by solid phase extraction, separated by ultra high pressure liquid chromatography, and detected by isotope dilution tandem mass spectrometry. This approach was thoroughly validated and characterized in our laboratory. The average interday relative standard deviation was ≤ 9.49%, and the range of accuracy was between 96.1 and 109% over a concentration range of 3.00 to 250. ng/mL with a calculated limit of detection of1.74 ng/mL. A full 96-well plate can be processed and analyzed in 8 h, which is 5 times faster than our previous 96-well plate method and only requires 50 μL of serum, plasma, or whole blood. Extensive ruggedness and stability studies and matrix comparisons were conducted to create a robust, easily transferrable method. As a result, a simple and high-throughput method has been developed and validated for the quantitation of sulfur mustard blood protein adducts in low volume blood specimens which should be readily adaptable for quantifying human exposures to other alkylating agents. PMID:25622494

  2. [Preparation and certification of mussel reference material for organochlorine pesticides and polychlorinated biphenyls using isotope dilution-high resolution mass spectrometry].

    PubMed

    Lu, Xianbo; Chen, Jiping; Wang, Shuqiu; Zou, Lili; Tian, Yuzeng; Ni, Yuwen; Su, Fan

    2012-09-01

    A method for the preparation and certification of the reference material of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in mussel tissue is described. The mussel tissue from Dalian Bay was frozen-dried, comminuted, sieved, homogenized, packaged, and sterilized by 60Co radiation sterilization in turn. The certified values for 18 OCPs and 16 PCBs were determined by high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS) using isotope dilution and internal standard quantitation techniques. The certified values were validated and given based on seven accredited laboratories, and these values are traceable to the SI (international system of units) through gravimetrically prepared standards of established purity and measurement intercomparisons. The certified values of PCBs and OCPs in mussel span 4 orders of magnitude with a relative uncertainty of about 10%. This material is a natural biological material with confirmed good homogeneity and stability, and it was approved as the grade "primary reference material" (GBW10069) in June 2012 in China. This reference material provided necessary quality control products for our country to implement the Stockholm Treaty on the monitoring of persistent organic pollutants (POPs). The material is intended to be used for the method validation and quality control in the determination of OCPs and PCBs in biota samples. PMID:23285973

  3. Counting individual sulfur atoms in a protein by ultrahighresolution Fourier transform ion cyclotron resonance mass spectrometry: Experimental resolution of isotopic fine structure in proteins

    PubMed Central

    Shi, Stone D.-H.; Hendrickson, Christopher L.; Marshall, Alan G.

    1998-01-01

    A typical molecular ion mass spectrum consists of a sum of signals from species of various possible isotopic compositions. Only the monoisotopic peak (e.g., all carbons are 12C; all nitrogens are 14N, etc.) has a unique elemental composition. Every other isotope peak at approximately integer multiples of ∼1 Da higher in nominal mass represents a sum of contributions from isotope combinations differing by a few mDa (e.g., two 13C vs. two 15N vs. one 13C and one 15N vs. 34S, vs. 18O, etc., at ∼2 Da higher in mass than the monoisotopic mass). At sufficiently high mass resolving power, each of these nominal-mass peaks resolves into its isotopic fine structure. Here, we report resolution of the isotopic fine structure of proteins up to 15.8 kDa (isotopic 13C,15N doubly depleted tumor suppressor protein, p16), made possible by electrospray ionization followed by ultrahigh-resolution Fourier transform ion cyclotron resonance mass analysis at 9.4 tesla. Further, a resolving power of m/Δm50% ≈8,000,000 has been achieved on bovine ubiquitin (8.6 kDa). These results represent a 10-fold increase in the highest mass at which isotopic fine structure previously had been observed. Finally, because isotopic fine structure reveals elemental composition directly, it can be used to confirm or determine molecular formula. For p16, for example, we were able to determine (5.1 ± 0.3) the correct number (five) of sulfur atoms solely from the abundance ratio of the resolved 34S peak to the monoisotopic peak. PMID:9751700

  4. 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.

  5. Relative quantitation of protein nitration by liquid chromatographymass spectrometry using isotope-coded dimethyl labeling and chemoprecipitation

    PubMed Central

    Guo, Jia; Prokai-Tatrai, Katalin; Prokai, Laszlo

    2012-01-01

    Protein nitration has been recognized as an important biomarker for nitroxidative stress associated with various diseases. While identification of protein targets for nitration is important, its quantitative profiling also is necessary to understand the biological impact of this low-abundance posttranslational modification. We have previously reported an efficient and straightforward enrichment method for nitropeptides to reduce sample complexity and permit unambiguous site-specific identifications by LCMS analyses. This approach relies on two chemical derivatization steps: specifically reductive methylation of aliphatic amines and, then, conversion of nitrotyrosines to the corresponding aminotyrosines before their selective capture by a solid-phase reagent we introduced previously. Hence, the method inherently offers the opportunity for relative quantitation of nitropeptides by using isotopic variants of formaldehyde for reductive methylation. This simple method was tested via LCMS analyses of differently N-methylated nitropeptides and nitroubiquitin as a model nitroprotein enriched from human serum albumin digest and from human plasma, respectively. PMID:22285050

  6. Characterization of Diesel Fuel by Chemical Separation Combined with Capillary Gas Chromatography (GC) Isotope Ratio Mass Spectrometry (IRMS)

    SciTech Connect

    Harvey, Scott D.; Jarman, Kristin H.; Moran, James J.; Sorensen, Christina M.; Wright, Bob W.

    2011-09-15

    The purpose of this study was to perform a preliminary investigation of compound-specific isotope analysis (CSIA) of diesel fuels to evaluate whether the technique could distinguish between the diesel samples from different sources/locations. The ability to differentiate or correlate diesel samples could be valuable for detecting fuel tax evasion schemes. Two fractionation techniques were used to isolate the n-alkanes from the fuel. Both ?13C and ?D values for the n-alkanes were then determined by CSIA in each sample. Plots of ?D versus ?13C with sample n-alkane points connected in order of increasing carbon number gave well separated clusters with characteristic shapes for each sample. Principal components analysis (PCA) with ?13C, ?D, or combined ?13C and ?D data on the yielded scores plots that could clearly differentiate the samples, thereby demonstrating the potential of this approach for fingerprinting fuel samples using the ?13C and ?D values.

  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. Fit for purpose validated method for the determination of the strontium isotopic signature in mineral water samples by multi-collector inductively coupled plasma mass spectrometry

    NASA Astrophysics Data System (ADS)

    Brach-Papa, Christophe; Van Bocxstaele, Marleen; Ponzevera, Emmanuel; Qutel, Christophe R.

    2009-03-01

    A robust method allowing the routine determination of n( 87Sr)/ n( 86Sr) with at least five significant decimal digits for large sets of mineral water samples is described. It is based on 2 consecutive chromatographic separations of Sr associated to multi-collector inductively coupled plasma mass spectrometry (MC-ICPMS) measurements. Separations are performed using commercial pre-packed columns filled with "Sr resin" to overcome isobaric interferences affecting the determination of strontium isotope ratios. The careful method validation scheme applied is described. It included investigations on all parameters influencing both chromatographic separations and MC-ICPMS measurements, and also the test on a synthetic sample made of an aliquot of the NIST SRM 987 certified reference material dispersed in a saline matrix to mimic complex samples. Correction for mass discrimination was done internally using the n( 88Sr)/ n( 86Sr) ratio. For comparing mineral waters originating from different geological backgrounds or identifying counterfeits, calculations involved the well known consensus value (1/0.1194) 0 as reference. The typical uncertainty budget estimated for these results was 40 'ppm' relative ( k = 2). It increased to 150 'ppm' ( k = 2) for the establishment of stand alone results, taking into account a relative difference of about 126 'ppm' systematically observed between measured and certified values of the NIST SRM 987. In case there was suspicion of a deviation of the n( 88Sr)/ n( 86Sr) ratio (worst case scenario) our proposal was to use the NIST SRM 987 value 8.37861 0.00325 ( k = 2) as reference, and assign a typical relative uncertainty budget of 300 'ppm' ( k = 2). This method is thus fit for purpose and was applied to eleven French samples.

  9. [Determination of mono- to tri-chlorinated dibenzo-p-dioxins and dibenzofurans in stack gas using isotope dilution high resolution gas chromatography-high resolution mass spectrometry].

    PubMed

    Tang, Chen; Liu, Qipeng; Tian, Zhenyu; Xie, Huiting; Wang, Mengjing; Liu, Wenbin

    2014-09-01

    A method for the determination of mono- to tri-chlorinated dibenzo-p-dioxins and dibenzofurans (mono- to tri-CDD/Fs) in stack gas using isotope dilution high resolution gas chromatography-high resolution mass spectrometry (HRGC-HRMS) was developed. The sam- ples were extracted by Soxhlet extraction, and then the extracts were concentrated and purified using a multilayer silica gel column and a basic alumina column. The analytes were separated by HRGC on a DB-5MS column (30 m x 0.25 mm x 0.25 ?m) and determined by HRMS. The identi- fication of mono- to tri-CDD/Fs was based on the retention times of 13C-labelled standard and the abundance ratios of the two exacted mass-to-charge ratios. The quantitative analysis was performed using the ratios of the integrated areas of the 13C-labelled standards. This method had the recoveries ranging from 66.6% to 112.5% and the relative standard deviations (RSD) ranging from 19.9% to 40.5% (n = 5). The limits of detection (LODs) of this method for the mono- to tri-CDD/Fs were ranging from 0.027 to 0.485 ?g/L. Three stack gas samples from waste incinerators were measured using this method, with the recoveries ranging from 85.7% to 137.0% and the concentrations ranging from 11.4 to 9,183 pg/Nm3. The results indicated that the method can be applied to the precise determination of mono- to tri-CDD/Fs at trace level in stack gas. PMID:25752087

  10. Measurement of Sulfur Isotopic Composition (?34S) by Multiple-Collector Thermal Ionization Mass Spectrometry (MC-TIMS) Using a 33S/36S Double Spike

    NASA Astrophysics Data System (ADS)

    Mann, J. L.; Kelly, W. R.

    2006-05-01

    A new analytical technique for the determination of ?34S will be described. The technique is based on the production of singularly charged arsenic sulfide molecular ions (AsS+) by thermal ionization using silica gel as an emitter and combines multiple-collector thermal ionization mass spectrometry (MC-TIMS) with a 33S/36S double spike to correct instrumental fractionation. Because the double spike is added to the sample before chemical processing, both the isotopic composition and sulfur concentration are measured simultaneously. The accuracy and precision of the double spike technique is comparable to or better than modern gas source mass spectrometry, but requires about a factor of 10 less sample. ?33S effects can be determined directly in an unspiked sample without any assumptions about the value of k (mass dependent fractionation factor) which is currently required by gas source mass spectrometry. Three international sulfur standards (IAEA-S-1, IAEA-S-2, and IAEA-S-3) were measured to evaluate the precision and accuracy of the new technique and to evaluate the consensus values for these standards. Two different double spike preparations were used. The ?34S values (reported relative to Vienna Canyon Diablo Troilite (VCDT), (?34S () = 34S/32S)sample/(34S/32S)VCDT - 1) x 1000]), 34S/32SVCDT = 0.0441626) determined were -0.32 0.04 (1?, n=4) and -0.31 0.13 (1?, n=8) for IAEA-S-1, 22.65 0.04 (1?, n=7) and 22.60 0.06 (1?, n=5) for IAEA- S-2, and -32.47 0.07 (1?, n=8) for IAEA-S-3. The amount of natural sample used for these analyses ranged from 0.40 ?moles to 2.35 ?moles. Each standard showed less than 0.5 variability (IAEA-S-1 < 0.4, IAEA-S-2 < 0.2, and IAEA-S-3 < 0.2). Our values for S-1 and S-2 are in excellent agreement with the consensus values and the values reported by other laboratories using both SF6 and SO2. Our value for S-3 differs statistically from the Institute for Reference Materials and Measurement (IRMM) value and is slightly lower than the currently accepted consensus value (-32.3). Because the technique is based on thermal ionization of AsS+, and As is mononuclidic, corrections for interferences or for scale contraction/expansion are not required. The availability of MC-TIMS instruments in laboratories around the world makes this technique immediately available to a much larger scientific community who require highly accurate and precise measurements of sulfur.

  11. Femtosecond laser ablation molecular isotopic spectrometry for zirconium isotope analysis.

    PubMed

    Hou, Huaming; Chan, George C-Y; Mao, Xianglei; Zorba, Vassilia; Zheng, Ronger; Russo, Richard E

    2015-05-01

    Laser ablation molecular isotopic spectrometry (LAMIS) for rapid isotopic analysis of zirconium at atmospheric pressure was studied with a femtosecond-laser system operated under high repetition rate (1 kHz) and low pulse energy (160?J). The temporal evolution of zirconium neutral-atomic and ionic lines, as well as zirconium oxide molecular bands, were studied. Six molecular bands, belonging to the d(3)?-a(3)? (i.e., the ? system) and E(1)?(+)-X(1)?(+) transitions, were observed with appreciable isotopic shifts. The assignments of the isotopic bandheads were first based on theoretical predictions of the band origins and the associated isotopic shifts of various dipole-allowed ZrO electronic transitions, followed by an experimental confirmation with a (94)Zr-enriched ZrO2 sample. In this work, the ?(0,1) band from the d(3)?3-a(3)?3 subsystem was utilized for Zr isotope analysis based on a compromise between the magnitude of isotopic shifts in emission wavelengths, emission strengths, signal-to-background ratios, and spectral interferences. The analysis was performed in a standardless calibration approach; the isotopic information was extracted from the experimentally measured molecular spectra through theoretical spectral fitting. The results demonstrate the feasibility to obtain isotopic information for a spectrally complicated element like zirconium, without the need to use isotopically labeled calibration standards. The availability of comprehensive molecular constants will further improve the analytical accuracy of this standardless calibration approach. PMID:25821993

  12. High-precision measurements of uranium and thorium isotopic ratios by multi-collector inductively coupled plasma mass spectrometry (MC-ICPMS)

    NASA Astrophysics Data System (ADS)

    Wang, Lisheng; Ma, Zhibang; Duan, Wuhui

    2015-04-01

    Isotopic compositions of U-Th and 230Th dating have been widely used in earth sciences, such as chronology, geochemistry, oceanography and hydrology. In this study, five ages of different carbonate samples were measured using 230Th dating technique with U-Th high-precision isotopic measurements by multi-collector inductively coupled plasma mass spectrometry, in Uranium-series Chronology Laboratory, Institute of Geology and Geophysics, Chinese Academy of Sciences.In this study, the precision and accuracy of uranium isotopic composition were estimated by measuring the uranium ratios of NBS-CRM 112A, NBS-CRM U500 and HU-1. The mean measured ratios, 234U/238U = 52.86 (0.04) 10-6 and ?234U = -38.36 (0.77) 10-3 for NBS-CRM 112A, 234U/238U = 10.4184 (0.0001) 10-3, 236U/238U = 15.43 (0.01) 10-4 and 238U/235U = 1.00021 (0.00002) for NBS-CRM U500, 234U/238U = 54.911 (0.007) and ?234U = -1.04 (0.13) 10-3 for HU-1 (95% confidence levels). The U isotope data for standard reference materials are in excellent agreement with previous studies, further highlighting the reliability and analytical capabilities of our technique. We measured the thorium isotopic ratios of three different thorium standards by MC-ICPMS. The three standards (Th-1, Th-2 and Th-3) were mixed by HU-1 and NBS 232Th standard, with the 230Th/232Th ratios from 10-4 to 10-6. The mean measured atomic ratios, 230Th/232Th = 2.1227 (0.0024) 10-6, 2.7246 (0.0026) 10-5, and 2.8358 (0.0007) 10-4 for Th-1, Th-2 and Th-3 (95% confidence levels), respectively. Using this technique, the following standard samples were dated by MC-ICPMS. Sample RKM-4, collected from Babardos Kendal Hill terrace, was used during the first stage of the Uranium-Series Intercomparison Project (USIP-I). Samples 76001, RKM-5 and RKM-6 were studied during the second stage of the USIP program (USIP-II). Sample 76001 is a laminated flowstone, collected from Sumidero Terejapa, Chiapas, Mexico, and samples RKM-5 and RKM-6 are from the Babardos III terrace and the lower terrace (6 to 10m) of Curacao, respectively. China RCM GBW04412 was also analyzed. The ages of the five standard samples mentioned above are 1979701590 yr BP, 47520220 yr BP, 129300650 yr BP, 130830550 yr BP, and 86940300 yr BP for samples RKM-4, 76001, RKM-5, RKM-6 and GBW04412, respectively. The results are consistent with the data of the same samples analyzed in Institute of Global Environmental Change, Xi'an Jiaotong University and Department of Earth Sciences, University of Minnesota, USA within errors, which suggests that the technique in our lab is reliable.

  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. Quantitative determination of free and total bisphenol A in human urine using labeled BPA glucuronide and isotope dilution mass spectrometry.

    PubMed

    Kubwabo, Cariton; Kosarac, Ivana; Lalonde, Kaela; Foster, Warren G

    2014-07-01

    Bisphenol A (BPA) is a widely used industrial chemical in the manufacturing of polycarbonate plastic bottles, food and beverage can linings, thermal receipts, and dental sealants. Animal and human studies suggest that BPA may disrupt normal hormonal function and hence, potentially, have negative effects on the human health. While total BPA is frequently reported, it is recognized that free BPA is the biologically active form and is rarely reported in the literature. The objective of this study was to develop a sensitive and improved method for the measurement of free and total BPA in human urine. Use of a labeled conjugated BPA (bisphenol A-d6 β-D-glucuronide) allowed for the optimization of the enzymatic reaction and permitted an accurate determination of the conjugated BPA concentration in urine samples. In addition, a (13)C12-BPA internal standard was used to account for the analytical recoveries and performance of the isotope dilution method. Solid-phase extraction (SPE) combined with derivatization and analysis using a triple quadrupole GC-EI/MS/MS system achieved very low method detection limit of 0.027 ng/mL. BPA concentrations were measured in urine samples collected during the second and third trimesters of pregnancy in 36 Canadian women. Total maternal BPA concentrations in urine samples ranged from not detected to 9.40 ng/mL (median, 1.21 ng/mL), and free BPA concentrations ranged from not detected to 0.950 ng/mL (median, 0.185 ng/mL). Eighty-six percent of the women had detectable levels of conjugated BPA, whereas only 22 % had detectable levels of free BPA in their urine. BPA levels measured in this study agreed well with data reported internationally. PMID:24817354

  15. 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.

  16. Gold assay with Knudsen effusion mass spectrometry

    NASA Astrophysics Data System (ADS)

    Bardi, U.; Niccolai, F.; Tosti, M.; Tolstogouzov, A.

    2008-06-01

    Commercial 18 carat (ct) gold alloys along with pure coinage metals have been studied with Knudsen effusion mass spectrometry. Isotopic fractionation in vapour phase and the enthalpies of vaporization were estimated for Au, Ag and Cu samples. The assaying of the gold content was carried out by means of calibration with respect to standard reference alloys measured with energy dispersive X-ray spectroscopy. The accuracy of the gold determination resulted of about 1.5 wt.[per mille sign] in the ternary Au-Ag-Cu alloy.

  17. Effect of the detector dead-time uncertainty on the analytical result of minor elements in low-alloy steel by isotope dilution/ICP sector field mass spectrometry.

    PubMed

    Nonose, Naoko; Hioki, Akiharu; Chiba, Koichi

    2014-01-01

    In the present study the effects of the detector dead-time and its uncertainties on the accuracy and uncertainty of isotope dilution mass spectrometry (IDMS) were considered through an interlaboratory study on the analysis of low-alloy steel by using an ICP-sector field mass spectrometer. Also, an optimized mixing ratio of the sample and the spike to obtain highly precise results was theoretically and experimentally investigated. The detector dead-time used in the interlaboratory study showed a negative value. However, it less affected the trueness of the analytical result if the dead-time correction for the measured isotope ratio was done properly. As many researchers have pointed out, the detector dead-time showed a clear mass dependence. Therefore, it is desirable to check the dead-time in every target element by using assay standards or isotopic standards, which would lead to an accurate result even if the detector dead-time is a negative value. On the other hand, the effect of the uncertainty of the detector dead-time can be minimized when both isotope ratios and ICP-MS signals of the [sample + spike] blend in IDMS are equal to those of [spike + assay standard] in reverse IDMS. From standpoints of error magnification theory and the precision of the isotope ratio measurement, an optimized isotope ratio of the sample-spike blend would be 1.0 for an element with a large difference in ten times and more between the atomic fractions of two isotopes used for IDMS. In the case of an element with no significant difference between the atomic fractions of two isotopes, an optimized isotope ratio can be calculated by a formula expressed as a function of the atomic fractions of the sample and the spike as well as the signal of ICP-MS. PMID:25213815

  18. Application of the Reference Method Isotope Dilution Gas Chromatography Mass Spectrometry (ID/GC/MS) to Establish Metrological Traceability for Calibration and Control of Blood Glucose Test Systems

    PubMed Central

    Andreis, Elisabeth; Kllmer, Kai

    2014-01-01

    Self-monitoring of blood glucose (BG) by means of handheld BG systems is a cornerstone in diabetes therapy. The aim of this article is to describe a procedure with proven traceability for calibration and evaluation of BG systems to guarantee reliable BG measurements. Isotope dilution gas chromatography mass spectrometry (ID/GC/MS) is a method that fulfills all requirements to be used in a higher-order reference measurement procedure. However, this method is not applicable for routine measurements because of the time-consuming sample preparation. A hexokinase method with perchloric acid (PCA) sample pretreatment is used in a measurement procedure for such purposes. This method is directly linked to the ID/GC/MS method by calibration with a glucose solution that has an ID/GC/MS-determined target value. BG systems are calibrated with whole blood samples. The glucose levels in such samples are analyzed by this ID/GC/MS-linked hexokinase method to establish traceability to higher-order reference material. For method comparison, the glucose concentrations in 577 whole blood samples were measured using the PCA-hexokinase method and the ID/GC/MS method; this resulted in a mean deviation of 0.1%. The mean deviation between BG levels measured in >500 valid whole blood samples with BG systems and the ID/GC/MS was 1.1%. BG systems allow a reliable glucose measurement if a true reference measurement procedure, with a noninterrupted traceability chain using ID/GC/MS linked hexokinase method for calibration of BG systems, is implemented. Systems should be calibrated by means of a traceable and defined measurement procedure to avoid bias. PMID:24876614

  19. Achieving comparability with IFCC reference method for the measurement of hemoglobin A1c by use of an improved isotope-dilution mass spectrometry method.

    PubMed

    Liu, Hong; Wong, Lingkai; Yong, Sharon; Liu, Qinde; Lee, Tong Kooi

    2015-10-01

    The development of reference measurement methods for hemoglobin A1c (HbA1c) is important for quality assurance in diabetes management. The IFCC reference method using purified proteins as calibration standards is the recommended accuracy-based reference method for the standardization of HbA1c measurement. We developed a highly precise and accurate liquid chromatography-isotope-dilution tandem mass spectrometry (LC-IDMS/MS) procedure, which can serve as an alternative accuracy-based method for HbA1c measurement. In this method, enzymatic proteolysis was applied to sample preparation, followed by LC-IDMS/MS measurement of hemoglobin A0 (HbA0) and HbA1c, using two "signature" hexapeptides for calibration. The concentrations of the signature hexapeptide calibration solutions were, in turn, determined using a hydrolysis method with HCl, followed by LC-IDMS/MS measurement using amino acid solutions as calibration standards. These solutions were gravimetrically prepared from pure amino acid certified reference materials (CRMs). The developed LC-IDMS/MS method was used in participation in an IFCC ring trial for reference laboratories (RELA 2013 and 2014) for HbA1c, where our results were compared with those using the IFCC reference method. The deviations were found to be 0.4-1.7 mmol mol(-1) [or 0.04-0.16% in National Glygohemoglobin Standardization Program (NGSP) units], revealing good comparability with the IFCC reference method. The relative expanded uncertainty of the LC-IDMS/MS was in the range of 2.6% to 2.8% (1.6% to 2.2% after converting to NGSP units). With excellent method precision, good comparability with the IFCC reference method, and a small measurement uncertainty, the developed LC-IDMS/MS method may be used as an alternative accuracy-based reference method for HbA1c measurement. PMID:26302961

  20. Hydrogen radical removal causes complex overlapping isotope patterns of aromatic carboxylic acids in negative-ion matrix-assisted laser desorption/ionization mass spectrometry.

    PubMed

    Yamagaki, Tohru; Watanabe, Takehiro

    2012-01-01

    We studied the ionization process of aromatic carboxylic acids, including ones with or without hydroxy groups in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), because many natural products, metabolites, and drags contain those structural units. In the actual experimental data, benzoic acid was ionized as only deprotonated molecule [M-H](-). In contrast, both of negative molecular ion M(-) and deprotonated molecule [M-H](-) were generated from 2-naphthoic acid and 2-anthracenecarboxylic acid, and the ratio of negative molecular ion to deprotonated molecule M(-)/[M-H](-) was increased in 2-anthracenecarboxylic acid. In addition, the ratio of 2-anthracenecarboxylic acid was much higher than those of 1- and 9-anthracenecarboxylic acids among the three isomers. Therefore, 2-substitution induced the generation of the negative molecular ion M(-), which can made us prediction of the substituted positions from their overlapping peak isotope patterns. 2,5-Dihydroxybenzoic acid (2,5-DHBA) showed two deprotonated molecules, [M-H](-) and [M-H*-H](-), which was generated from a neutral hydrogen radical (H*) removal from a phenolic hydroxy group. The deprotonated molecule [M-H*-H](-) of 2,5-DHBA was the most abundant among six DHBAs and three hydroxybenzoic acids (hBAs). This observation raises the possibility that such a property of 2,5-DHBA could be a clue to explain its highest efficiency as a MALDI matrix. The order of the hydrogen radical removal from the phenolic hydroxy groups was the 3-<4-?5-positions in the DHBAs, and the 3-<4-positions in hBAs. We can distinguish among six DHBA isomers and three hBA isomers from their spectral pattern around the deprotonated molecules [M-H*-H](-) and [M-H](-). The intra-molecular hydrogen bonding between 1-carboxy and 2-hydroxy groups was an important factor in hydrogen radical removal in the hydroxylbenzoic acids and dihydroxybenzoic acids. PMID:24349906

  1. Simplified method for microlitre deuterium measurements in water and urine by gas chromatography-high-temperature conversion-isotope ratio mass spectrometry.

    PubMed

    Gucciardi, Antonina; Cogo, Paola E; Traldi, Umberto; Eaton, Simon; Darch, Tegan; Simonato, Manuela; Ori, Carlo; Carnielli, Virgilio P

    2008-07-01

    Deuterium (2H) in water and urine can be measured by off-line and, more recently, on-line techniques using isotope ratio mass spectrometry (IRMS). We describe a new simple on-line pyrolysis method for the analysis of 2H/1H in water and urine samples by continuous flow IRMS, normally used for 2H/1H measurements in organic compounds. A deactivated column connected the split injector to a high-temperature conversion reactor (TC HD), and 0.5 microL of sample was injected. Accuracy and precision were determined with Vienna Standard Mean Ocean Water (VSMOW), Standard Light Antarctic Precipitation (SLAP), and Greenland Ice Sheet Precipitation (GISP). The range of linearity was measured with a calibration curve of enriched water from 0 up to 0.1 atom percent excess (APE) (i.e. -72 up to 6323 delta per mil (deltaD per thousand)) with a precision of <5 per thousand and accuracy ranging between 1 and 55 per thousand. Blinded reanalysis of urine samples by an equilibration device (Gas Bench) and by a dedicated pyrolysis system (TC/EA) was performed and results compared by the Bland-Altman test. Enrichments ranged between 600 and 2400 per thousand deltaD(VSMOW) with a precision of +/-5 per thousand. Urine enrichments described by our method were strongly correlated with values obtained by Gas Bench and TC/EA (p < 0.0001). There was a significant memory effect that was reduced by injecting the sample 15 times and discarding the first 10 injections, together with accurate furnace conditioning and appropriate cleaning of the syringe. Data indicate that the method is accurate, and that it can be used for water and urine deuterium determination when a Gas Bench or TC/EA instrument is not available and the amount of sample is limited. PMID:18512843

  2. Determination of the H isotopic composition of individual components in fine-scale mixtures of organic matter and phyllosilicates with the nanoscale secondary ion mass spectrometry.

    PubMed

    Piani, Laurette; Remusat, Laurent; Robert, Franois

    2012-12-01

    When organic matter is mixed on a nanometer scale with clay minerals, the individual D/H ratios of the two H-bearing phases cannot be directly measured even with the nominal spatial resolution of nanoscale secondary ion mass spectrometry (NanoSIMS, 50-100 nm). To overcome this limitation, a new analytical protocol is proposed based on the deconvolution of the D(-)/H(-) and (16)OD(-)/(16)OH(-) ionic ratios measured by NanoSIMS. Indeed, since the yields of H(-) and (16)OH(-) are different for organics and clays, it should be theoretically possible to determine the mixing ratio of these two components in the area analyzed by the ion probe. Using organics with different D/H ratios, the interdependence of the D(-)/H(-) and (16)OD(-)/(16)OH(-) ionic ratios was determined in pure samples. Then using the H(-) and (16)OH(-) yields and the isotopic ratios measured on pure organic matter and clays, the expected D(-)/H(-) and (16)OD(-)/(16)OH(-) variations as a function of the mixing proportions were determined. These numerical predictions are consistent with measurements on laboratory prepared mixtures of D-rich organic matter and D-poor phyllosilicates, validating both the proposed experimental protocol and its use for meteorites. With an improvement of the precision of the ionic ratios by a factor of 10, it should possible to expend this protocol to samples having natural terrestrial D/H variations. Such an improvement could be attainable with the development of synthetic deuterated reference samples. PMID:23121456

  3. Application of the reference method isotope dilution gas chromatography mass spectrometry (ID/GC/MS) to establish metrological traceability for calibration and control of blood glucose test systems.

    PubMed

    Andreis, Elisabeth; Kllmer, Kai; Appel, Matthias

    2014-05-01

    Self-monitoring of blood glucose (BG) by means of handheld BG systems is a cornerstone in diabetes therapy. The aim of this article is to describe a procedure with proven traceability for calibration and evaluation of BG systems to guarantee reliable BG measurements. Isotope dilution gas chromatography mass spectrometry (ID/GC/MS) is a method that fulfills all requirements to be used in a higher-order reference measurement procedure. However, this method is not applicable for routine measurements because of the time-consuming sample preparation. A hexokinase method with perchloric acid (PCA) sample pretreatment is used in a measurement procedure for such purposes. This method is directly linked to the ID/GC/MS method by calibration with a glucose solution that has an ID/GC/MS-determined target value. BG systems are calibrated with whole blood samples. The glucose levels in such samples are analyzed by this ID/GC/MS-linked hexokinase method to establish traceability to higher-order reference material. For method comparison, the glucose concentrations in 577 whole blood samples were measured using the PCA-hexokinase method and the ID/GC/MS method; this resulted in a mean deviation of 0.1%. The mean deviation between BG levels measured in >500 valid whole blood samples with BG systems and the ID/GC/MS was 1.1%. BG systems allow a reliable glucose measurement if a true reference measurement procedure, with a noninterrupted traceability chain using ID/GC/MS linked hexokinase method for calibration of BG systems, is implemented. Systems should be calibrated by means of a traceable and defined measurement procedure to avoid bias. PMID:24876614

  4. Urinary profiling of cis-diol-containing metabolites in rats with bisphenol A exposure by liquid chromatography-mass spectrometry and isotope labeling.

    PubMed

    Li, Shangfu; Jin, Yibao; Wang, Jue; Tang, Zhi; Xu, Shunqing; Wang, Tiejie; Cai, Zongwei

    2016-02-01

    Exposure to bisphenol A (BPA), an environmental contaminant, has been linked to metabolic disorders. However, there are no reports describing the effects of BPA on the profiling of cis-diol metabolites. It is challenge to detect these metabolites in biological samples because of their low abundance, high polarity and serious matrix interference. In this study, a chemical isotope-labeling method was applied to solve these problems. Acetone and deuterated acetone (acetone-d6) were used as chemical tags to label the rat urine samples, respectively. The light and heavy labeling products were recognized using the ShiftedIonsFinder software. The selected cis-diol metabolite signals were used to build a data set. The data set was applied to evaluate the changes in the urinary profiling of cis-diol-containing metabolites in rats with BPA exposure. The results showed that chromatographic separation and mass spectrometry detection of cis-diol metabolites were improved after acetone labeling. Using this method, the cis-diol metabolites were recognized easily from the urine samples. By comparing different dose administration on rats, the influence of BPA exposure on cis-diol metabolites was investigated. The analytes showing noticeable differences were identified. It was found that high-dose BPA exposure had strong effects on the cis-diol compound metabolism. The influences were mostly related to the metabolism of galactose and nucleoside and its analogues. The disturbance of the galactose metabolism by BPA is reported for the first time, to the best of our knowledge. This may have some implications for exploring the toxic effects of BPA exposure. PMID:26739229

  5. Studies on the analysis of 25-hydroxyvitamin D{sub 3} by isotope-dilution liquid chromatography–tandem mass spectrometry using enzyme-assisted derivatisation

    SciTech Connect

    Abdel-Khalik, Jonas; Crick, Peter J.; Carter, Graham D.; Makin, Hugh L.; Wang, Yuqin; Griffiths, William J.

    2014-04-11

    Highlights: • New method for the analysis of 25-hydroxyvitamin D{sub 3} exploiting Girard P derivatisation. • Method also applicable to vitamin D{sub 3}, 1α,25- and 24,25-dihydroxyvitamin D{sub 3}. • By modification of the method 3-epi-25-hydroxyvitamin D{sub 3} can also be analysed. - Abstract: The total serum concentration of 25-hydroxyvitamins D (25-hydroxyvitamin D{sub 3} and 25-hydroxyvitamin D{sub 2}) is currently used as an indicator of vitamins D status. Vitamins D insufficiency is claimed to be associated with multiple diseases, thus accurate and precise reference methods for the quantification of 25-hydroxyvitamins D are needed. Here we present a novel enzyme-assisted derivatisation method for the analysis of vitamins D metabolites in adult serum utilising 25-[26,26,26,27,27,27-{sup 2}H{sub 6}]hydroxyvitamin D{sub 3} as the internal standard. Extraction of 25-hydroxyvitamins D from serum is performed with acetonitrile, which is shown to be more efficient than ethanol. Cholesterol oxidase is used to oxidize the 3β-hydroxy group in the vitamins D metabolites followed by derivatisation of the newly formed 3-oxo group with Girard P reagent. 17β-Hydroxysteroid dehydrogenase type 10 is shown to oxidize selectively the 3α-hydroxy group in the 3α-hydroxy epimer of 25-hydroxyvitamin D{sub 3}. Quantification is achieved by isotope-dilution liquid chromatography–tandem mass spectrometry. Recovery experiments for 25-hydroxyvitamin D{sub 3} performed on adult human serum give recovery of 102–106%. Furthermore in addition to 25-hydroxyvitamin D{sub 3}, 24,25-dihydroxyvitamin D{sub 3} and other uncharacterised dihydroxy metabolites, were detected in adult human serum.

  6. Determination of agmatine using isotope dilution UPLC-tandem mass spectrometry: application to the characterization of the arginine decarboxylase pathway in Pseudomonas aeruginosa.

    PubMed

    Dalluge, Joseph J; McCurtain, Jennifer L; Gilbertsen, Adam J; Kalstabakken, Kyle A; Williams, Bryan J

    2015-07-01

    A method has been developed for the direct determination of agmatine in bacterial culture supernatants using isotope dilution ultra performance liquid chromatography (UPLC)-tandem mass spectrometry (UPLC-MS/MS). Agmatine determination in bacterial supernatants is comprised of spiking culture or isolate supernatants with a fixed concentration of uniformly labeled (13)C5,(15)N4-agmatine (synthesized by decarboxylation of uniformly labeled (13)C6,(15)N4-arginine using arginine decarboxylase from Pseudomonas aeruginosa) as an internal standard, followed by derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBDF) to improve the reversed-phase chromatographic retention characteristics of agmatine, as well as the selectivity and sensitivity of UPLC-MS/MS detection of this amine in complex biologically derived mixtures. Intrasample precisions for measurement of agmatine in culture supernatants average 4.1% (relative standard deviation). Calibration curves are linear over the range 5 nM to 10 μM, and the detection limit is estimated at 1.5 nM. To demonstrate the utility of the method, agmatine levels in supernatants of overnight cultures of wild-type (UCBPP-PA14), as well as arginine decarboxylase and agmatine deiminase mutant strains of P. aeruginosa strain UCBPP-PA14 were measured. This method verified that the mutant strains are lacking the specific metabolic capabilities to produce and metabolize agmatine. In addition, measurement of agmatine in supernatants of a panel of clinical isolates from patients with cystic fibrosis revealed that three of the P. aeruginosa isolates hyper-secreted agmatine into the supernatant, hypothesized to be a result of a mutation in the aguA gene. Because agmatine has potential inflammatory activities in the lung, this phenotype may be a virulence factor for P. aeruginosa in the lung environment of cystic fibrosis patients. PMID:25957842

  7. Detection of triclocarban and two co-contaminating chlorocarbanilides in US aquatic environments using isotope dilution liquid chromatography tandem mass spectrometry

    SciTech Connect

    Sapkota, Amir; Heidler, Jochen; Halden, Rolf U. . E-mail: rhalden@jhsph.edu

    2007-01-15

    The antimicrobial compound triclocarban (TCC; 3,4,4'-trichlorocarbanilide; CAS-bar 101-20-2) is a high-production-volume chemical, recently suggested to cause widespread contamination of US water resources. To test this hypothesis, we developed an isotope dilution liquid chromatography electrospray ionization tandem mass spectrometry method for ultratrace analysis of TCC (0.9ng/L detection limit) and analyzed low-volume water samples (200mL) along with primary sludge samples from across the United States. All river water samples (100%) collected downstream of wastewater treatment plants had detectable levels of TCC, as compared to 56% of those taken upstream. Concentrations of TCC (mean+/-standard deviation) downstream of sewage treatment plants (84+/-110ng/L) were significantly higher (P<0.05; Wilcoxon rank sum test) than those of samples taken upstream (12+/-15ng/L). Compared to surface water, mean TCC concentrations found in dried, primary sludge obtained from municipal sewage treatment plants in five states were six orders of magnitude greater (19,300+/-7100{mu}g/kg). Several river samples contained a co-contaminant, identified based on its chromatographic retention time, molecular base ion, and MS/MS fragmentation behavior as 4,4'-dichlorocarbanilide (DCC; CAS-bar 1219-99-4). In addition to TCC and DCC, municipal sludge contained a second co-contaminant, 3,3',4,4'-tetrachlorocarbanilide (TetraCC; CAS-bar 4300-43-0). Both newly detected compounds were present as impurities (0.2%{sub w/w} each) in technical grade TCC (99%). Application of the new method for chlorocarbanilide analysis yielded TCC occurrence data for 13 US states, confirmed the role of sewage treatment plants as environmental inputs of TCC, and identified DCC and TetraCC as previously unrecognized pollutants released into the environment alongside TCC.

  8. Quantitation of the sulfur mustard metabolites 1,1'-sulfonylbis[2-(methylthio)ethane] and thiodiglycol in urine using isotope-dilution Gas chromatography-tandem mass spectrometry.

    PubMed

    Boyer, Anne E; Ash, Doris; Barr, Dana B; Young, Carrie L; Driskell, W J; Whitehead, Ralph D; Ospina, Maria; Preston, Kerry E; Woolfitt, Adrian R; Martinez, Rodolfo A; Silks, L A Pete; Barr, John R

    2004-01-01

    Sulfur mustard (HD), or bis(2-chloroethyl)sulfide, has several urinary metabolites that can be measured to assess human exposure. These metabolites include the simple hydrolysis product thiodiglycol (TDG) and its oxidative analogue, TDG-sulfoxide, as well as metabolites of the glutathione/b-lyase pathway 1,1'-sulfonylbis[2-(methyl-sulfinyl)ethane] (SBMSE) and 1-methyl-sulfinyl-2-[(methylthio)ethyl-sulfonyl]ethane (MSMTESE). Current methods focus on either the TDG or the b-lyase metabolites. We have developed a single method that measures products of both metabolic branches, with the reduced compound of SBMSE and MSMTESE, 1,1'-sulfonylbis [2(methylthio)ethane] (SBMTE), as the definitive analyte and TDG as a confirmation analyte. Sample preparation included b-glucuronidase hydrolysis for TDG-glucuronide conjugates, titanium trichloride reduction of sulfoxides to SBMTE and TDG, solid-phase extraction, and a chemical derivatization. We analyzed samples using gas chromatography-tandem mass spectrometry with quantitation using isotope-dilution calibration. The method limits of detection for TDG and SBMTE were 0.5 ng/mL and 0.25 ng/mL, respectively, with relative standard deviations of less than 10%. Urine samples from individuals with no known exposure to mustard agent HD had measurable concentrations of TDG, but no SBMTE was detected. The geometric mean concentration of TDG was 3.43 ng/mL, with concentrations ranging from < 0.5 ng/mL to 20 ng/mL. PMID:15239851

  9. Determination of the cardiac glycosides digoxin and digitoxin by liquid chromatography combined with isotope-dilution mass spectrometry (LC-IDMS)--a candidate reference measurement procedure.

    PubMed

    Kaiser, Patricia; Kramer, Udo; Meissner, Dieane; Kress, Michael; Wood, William Graham; Reinauer, Hans

    2003-01-01

    This article describes a method of high analytical sensitivity, reproducibility and trueness for the determination of digoxin and digitoxin in serum or plasma at therapeutic levels using a combination of high-pressure liquid chromatography (HPLC), isotope-dilution mass spectrometry (IDMS) and caesium-adduct formation. A method for threefold deuterium substitution in the glycosides was developed, which could be performed within 24 hours without distillation giving yields > 98% of the theoretical value. Extraction from a serum or plasma matrix was performed using a liquid-phase extraction with ammonium acetate buffer/tertiary butylmethyl ether/ethyl acetate at pH 9.5. The HPLC-separation used a 10 x 2 mm LiChrospher RP-18 5 microm guard column in combination with a 125 x 2 mm main column of the same material and a gradient containing methanol, caesium ions and formic acid. Quantification of digoxin and digitoxin was made with IDMS using deuterated internal standards and the system run in single ion monitoring (SIM) mode. The methods had a lower limit of determination of 0.25 microg/l for digoxin and digitoxin, a trueness between 97.5 and 104% for digoxin and between 98 and 101% for digitoxin, respectively and had a coefficient of variation of less than 3% in the therapeutic range for both glycosides. Maximally 1 ml serum or plasma was needed for the procedure. The method is used to set target values for materials used in external quality assessment surveys (EQAS) run by INSTAND as part of a national EQAS-programme.) PMID:12908733

  10. Adaptation of continuous-flow cavity ring-down spectroscopy for batch analysis of ?13C of CO2 and comparison with isotope ratio mass spectrometry.

    PubMed

    Berryman, E M; Marshall, J D; Rahn, T; Cook, S P; Litvak, M

    2011-08-30

    Measurements of ?(13)C in CO(2) have traditionally relied on samples stored in sealed vessels and subsequently analyzed using magnetic sector isotope ratio mass spectrometry (IRMS), an accurate but expensive and high-maintenance analytical method. Recent developments in optical spectroscopy have yielded instruments that can measure ?(13)CO(2) in continuous streams of air with precision and accuracy approaching those of IRMS, but at a fraction of the cost. However, continuous sampling is unsuited for certain applications, creating a need for conversion of these instruments for batch operation. Here, we present a flask (syringe) adaptor that allows the collection and storage of small aliquots (20-30 mL air) for injection into the cavity ring-down spectroscopy (CRDS) instrument. We demonstrate that the adaptor's precision is similar to that of traditional IRMS (standard deviation of 0.3 for 385 ppm CO(2) standard gas). In addition, the concentration precision (0.3% of sample concentration) was higher for CRDS than for IRMS (7% of sample concentration). Using the adaptor in conjunction with CRDS, we sampled soil chambers and found that soil-respired ?(13)C varied between two different locations in a pion-juniper woodland. In a second experiment, we found no significant discrimination between the respiration of a small beetle (~5 mm) and its diet. Our work shows that the CRDS system is flexible enough to be used for the analysis of batch samples as well as for continuous sampling. This flexibility broadens the range of applications for which CRDS has the potential to replace magnetic sector IRMS. PMID:21766378

  11. Development and validation of a stable-isotope dilution liquid chromatography-tandem mass spectrometry method for the determination of bisphenols in ready-made meals.

    PubMed

    Regueiro, Jorge; Wenzl, Thomas

    2015-10-01

    Due to their growing consumption, ready-made meals are a major dietary component for many people in today's society, representing an important potential route of human exposure to several food contaminants. The recent restrictions in the use of bisphenol A have led the plastic industry to look for alternative chemicals, most of them belonging to the same family of p,p'-bisphenols. The aim of the current work was to develop and validate a method based on stable-isotope dilution liquid chromatography-tandem mass spectrometry for the analysis of bisphenol A and its main analogs - bisphenol S, 4,4'-sulfonylbis(2-methylphenol), bisphenol F, bisphenol E, bisphenol B, bisphenol Z, bisphenol AF, bisphenol AP, tetrabromobisphenol A and bisphenol P - in solid foodstuffs, and particularly in ready-made meals. Extraction was carried out by ultrasound-assisted extraction after sample disruption with sand. A selective solid-phase extraction procedure was then applied to reduce potential matrix interferences. Derivatization of bisphenols with pyridine-3-sulfonyl chloride increased their ionization efficiency by electrospray ionization. Validation of the proposed method was performed in terms of selectivity, matrix effects, linearity, precision, measurement uncertainty, trueness and limits of detection. Satisfactory repeatability and intermediate precision were obtained; the related relative standard deviations were ≤7.8% and ≤10%, respectively. The relative expanded uncertainty (k=2) was below 17% for all bisphenol analogs and the trueness of the method was demonstrated by spike recovery experiments. Low limits of detection, in the range from 0.025μgkg(-1) to 0.140μgkg(-1), were obtained for all compounds. To demonstrate the applicability of the proposed method, it was eventually applied to several ready-made meals purchased from different supermarkets in Belgium. PMID:26456223

  12. Simultaneous determination of four sulfur mustard-DNA adducts in rabbit urine after dermal exposure by isotope-dilution liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhang, Yajiao; Yue, Lijun; Nie, Zhiyong; Chen, Jia; Guo, Lei; Wu, Bidong; Feng, Jianlin; Liu, Qin; Xie, Jianwei

    2014-06-15

    Sulfur mustard (SM) is a classic vesicant agent, which has been greatly employed in several wars or military conflicts. The most lesion mechanism is its strong alkylation of DNAs in vivo. Until now there are four specific DNA adducts of SM identified for further retrospective detection, i.e., N(7)-(2-hydroxyethylthioethyl)-2'-guanine (N(7)-HETEG), bis(2-ethyl-N(7)-guanine)thioether (Bis-G), N(3)-(2-hydroxyethylthioethyl)-2'-adenine (N(3)-HETEA) and O(6)-(2-hydroxyethylthioethyl)-2'-guanine (O(6)-HETEG), respectively. Here, a novel and sensitive method of isotope-dilution ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) combining with solid phase extraction was reported for the simultaneous determination of four SM-DNA adducts. A lower limit of detection of 2-5ngL(-1), and a lower limit of quantitation of 5-10ngL(-1) were achieved, respectively, and the recoveries ranged from 87% to 116%. We applied this method in the determination of four SM-DNA adducts in rabbit urine after dermal exposure by SM in three dose levels (2, 5, 15mgkg(-1)), so as to investigate the related metabolic behavior in vivo. For the first time, in SM exposed rabbit urine, our results revealed the relative accumulation abundance of four SM-DNA adducts, i.e., 67.4% for N(7)-HETEG, 22.7% for Bis-G, 9.8% for N(3)-HETEA, 0.1% for O(6)-HETEG, and significant dose and time dependent responses of these SM-DNA adducts. The four adducts were detectable after 8h, afterwards, their contents continuously increased, achieved maximum in the first two or three days and then gradually decreased till the end of one month. Meanwhile, the amounts of SM-DNA adducts were positively correlated with the exposure doses. PMID:24858262

  13. An optimized method for the accurate determination of patulin in apple products by isotope dilution-liquid chromatography/mass spectrometry.

    PubMed

    Seo, Miyeong; Kim, Byungjoo; Baek, Song-Yee

    2015-07-01

    Patulin, a mycotoxin produced by several molds in fruits, has been frequently detected in apple products. Therefore, regulatory bodies have established recommended maximum permitted patulin concentrations for each type of apple product. Although several analytical methods have been adopted to determine patulin in food, quality control of patulin analysis is not easy, as reliable certified reference materials (CRMs) are not available. In this study, as a part of a project for developing CRMs for patulin analysis, we developed isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC/MS/MS) as a higher-order reference method for the accurate value-assignment of CRMs. (13)C7-patulin was used as internal standard. Samples were extracted with ethyl acetate to improve recovery. For further sample cleanup with solid-phase extraction (SPE), the HLB SPE cartridge was chosen after comparing with several other types of SPE cartridges. High-performance liquid chromatography was performed on a multimode column for proper retention and separation of highly polar and water-soluble patulin from sample interferences. Sample extracts were analyzed by LC/MS/MS with electrospray ionization in negative ion mode with selected reaction monitoring of patulin and (13)C7-patulin at m/z 153→m/z 109 and m/z 160→m/z 115, respectively. The validity of the method was tested by measuring gravimetrically fortified samples of various apple products. In addition, the repeatability and the reproducibility of the method were tested to evaluate the performance of the method. The method was shown to provide accurate measurements in the 3-40 μg/kg range with a relative expanded uncertainty of around 1%. PMID:25925860

  14. Flavor authenticity studies by (2)h/(1)h ratio determination using on-line gas chromatography pyrolysis isotope ratio mass spectrometry.

    PubMed

    Hör, K; Ruff, C; Weckerle, B; König, T; Schreier, P

    2001-01-01

    Based on (2)H/(1)H ratio measurements of commercial synthetic and "natural" references, the recently developed on-line gas chromatography pyrolysis isotope ratio mass spectrometry (HRGC-P-IRMS) technique was used to determine the delta(2)H(SMOW) values of the flavor compounds decanal, linalool, and linalyl acetate, as well as those of E-2-hexenal and E-2-hexenol in foods and essential oils. In preceding model studies, the influence of sample preparation steps (simultaneous distillation extraction, SDE; solvent extraction, SE; liquid liquid extraction, LLE) on the delta(2)H values was found to be negligible. For decanal, the typical (2)H abundance, with higher content of (2)H for synthetic material (delta(2)H(SMOW) from -90 to -156 per thousand) and lower (2)H content for natural references (delta(2)H(SMOW) from -138 to -262 per thousand) was observed. Although the delta(2)H data recorded for linalool did not allow one to distinguish between synthetic (delta(2)H(SMOW) from -207 to -301 per thousand) and natural (delta(2)H(SMOW) from -234 to -333 per thousand) materials, the situation was somewhat more encouraging for linalyl acetate; delta(2)H(SMOW) values from -199 to -239 per thousand and from -213 to -333 per thousand were found for synthetic and natural samples, respectively. E-2-Hexenal and E-2-hexenol showed clear-cut origin-dependent differences in their (2)H/(1)H ratios; that is, delta(2)H(SMOW) values from -14 to -109 per thousand and from -263 to -415 per thousand as well as from -41 to -131 per thousand and from -238 to -348 per thousand were recorded for products from synthetic and natural origins, respectively. PMID:11170554

  15. Sulfur isotope analysis of cinnabar from Roman wall paintings by elemental analysis/isotope ratio mass spectrometry--tracking the origin of archaeological red pigments and their authenticity.

    PubMed

    Spangenberg, Jorge E; Lavric, Jost V; Meisser, Nicolas; Serneels, Vincent

    2010-10-15

    The most valuable pigment of the Roman wall paintings was the red color obtained from powdered cinnabar (Minium Cinnabaris pigment), the red mercury sulfide (HgS), which was brought from mercury (Hg) deposits in the Roman Empire. To address the question of whether sulfur isotope signatures can serve as a rapid method to establish the provenance of the red pigment in Roman frescoes, we have measured the sulfur isotope composition (?(34)S value in VCDT) in samples of wall painting from the Roman city Aventicum (Avenches, Vaud, Switzerland) and compared them with values from cinnabar from European mercury deposits (Almadn in Spain, Idria in Slovenia, Monte Amiata in Italy, Moschellandsberg in Germany, and Genepy in France). O