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

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.     

Direct simultaneous analysis of plasma samples for a drug discovery compound and its hydroxyl metabolite using mixed-function column liquid chromatography-tandem mass spectrometry

A polymer-coated mixed-function (PCMF) column was evaluated for direct plasma injection for the simultaneous determination of a drug candidate and its hydroxyl metabolite by high-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS-MS) in support of pharmacokinetic studies. Each diluted monkey plasma sample containing internal standard was directly injected on to the PCMF column for sample clean-up, enrichment and chromatographic separation. The proteins and macromolecules were first eluted from the column while the drug molecules were retained on the bonded hydrophobic phase. The analytes retained on the column were then eluted with a strong mobile phase using a gradient separation technique at a constant flow rate of 1.0 ml min(-1). When not diverted, the column effluent was connected either to the atmospheric pressure chemical ionization (APCI) source or the electrospray ionization (ESI) source as part of the mass spectrometer system used for quantification. The calibration curve was linear over the range 5-2500 ng ml(-1) for both analytes. The retention times for the analytes and the internal standard were both consistent and no column deterioration was observed for at least 500 injections. The recovery through the column and reproducibility of the dosed compound and its hydroxyl metabolite in monkey plasma samples were > 90% (RSD < 6%). The total analysis time was < 8 min per sample. The analytical results obtained by the proposed direct plasma injection method were in good agreement with those obtained by the conventional LC-MS-MS method.     

Investigation of matrix effects in bioanalytical high-performance liquid chromatography/tandem mass spectrometric assays: application to drug discovery

A series of studies was performed to investigate some of the causes for matrix effects ('ion suppression' or 'ion enhancement') in bioanalytical high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) assays. Previous studies have reported that matrix effects are mainly due to endogenous components in biological fluids and are a greater concern for electrospray ionization (ESI) than for atmospheric pressure chemical ionization (APCI). In this report we demonstrate that: (1) matrix effects can also be caused by exogenous materials, such as polymers contained in different brands of plastic tubes, or Li-heparin, a commonly used anticoagulant; (2) matrix effects are not only ionization mode (APCI or ESI) dependent, but also source design (Sciex, Finnigan, Micromass) dependent; and (3) for at least one vendor's design, we found the APCI mode to be more sensitive to matrix effects than the ESI mode. Based on these findings, we have proposed the following simple strategies to avoid matrix effects: (1) select the same brand of plastic tubes for processing and storing plasma samples and spiked plasma standards; (2) avoid using Li-heparin as the anticoagulant; and (3) try switching the ionization mode or switching to different mass spectrometers when matrix effects are encountered. These three strategies have allowed us to use protein precipitation and generic fast LC techniques to generate reliable LC/MS/MS data for the support of pharmacokinetic studies at the early drug discovery stage.     

Production of high transverse momentum prompt photons and neutral pions in proton-proton interactions at 280 GeV/c

The inclusive cross sections for production of prompt photons and π⁰ s by 280 GeV/c protons incident on a liquid hydrogen target, have been measured forp _T in the range 4.0 to 6.5 GeV/c and for |x _F |<0.45. A quantitative comparison of the prompt photon cross section with next-to-leading order QCD predictions using Duke and Owens structure functions is performed. Phenomenological fits to the π⁰ and prompt photon cross sections are given.     

Study of the π+π+π-π- system centrally 0 produced by incident π+ andp beams at 85 GeV/c

The reactions π⁺ p→π⁺(π⁺π⁺π^-π^-)p andpp→p(π⁺π⁺π^-π^-)p, where the (π⁺ π⁺ π^- π^-) system is centrally produced have been studied at 85 GeV/c. The π⁺π⁺π^-π^- mass spectrum shows evidence for thef ₁ (1285) meson with a mass of 1278±2 MeV and width 41±12 MeV which decays mainly through ρ⁰(770)π⁺π^-. Thef ₁(1285) is also observed in the ηπ⁺π^- channel. There is no significant evidence for ηππ or 4π decay modes of thef ₁(1420). The ρ⁰ρ⁰ production is found to be small. A Dalitz plot analysis of the 3π system shows evidence fora ₂ (1320) production and for a large contribution of theJ ^PC=1⁺⁺ ρπ wave.     

Lentivirus-mediated transgene delivery to the hippocampus reveals sub-field specific differences in expression

Background  

In the adult hippocampus, the granule cell layer of the dentate gyrus is a heterogeneous structure formed by neurons of different ages, morphologies and electrophysiological properties. Retroviral vectors have been extensively used to transduce cells of the granule cell layer and study their inherent properties in an intact brain environment. In addition, lentivirus-based vectors have been used to deliver transgenes to replicative and non-replicative cells as well, such as post mitotic neurons of the CNS. However, only few studies have been dedicated to address the applicability of these widespread used vectors to hippocampal cells in vivo. Therefore, the aim of this study was to extensively characterize the cell types that are effectively transduced in vivo by VSVg-pseudotyped lentivirus-based vectors in the hippocampus dentate gyrus.     

Analysis of transverse momentum and event shape invN scattering

The transverse momentum distributions of hadrons produced in neutrino-nucleon charged current interactions and their dependence onW are analysed in detail. It is found that the components of the transverse momentum in the event plane and normal to it increase withW at about the same rate throughout the availableW range. A comparison withe ⁺ e ^? data is made. Studies of the energy flow and angular distributions in the events classified as planar do not show clear evidence for high energy, wide angle gluon radiation, in contrast to the conclusion of a previous analysis of similar neutrino data.     

Coherent production of π+ mesons in ν-neon interactions

The coherent production of π⁺ mesons by charged current neutrino interactions on neon nuclei in BEBC is compared to the predictions of the PCAC hypothesis and the meson dominance model. Good agreement is observed.     

Rapid determination of pharmacokinetic properties of new chemical entities: in vivo approaches

There is a continuing need for increased throughput in the evaluation of new chemical entities in terms of their pharmacokinetic (PK) parameters as part of new drug discovery. This review summarizes various approaches that have been used to increase throughput in this area. The article divides the approaches into two areas: assay enhancement and sample reduction.