Demonstration of the capabilities of a parallel high performance liquid chromatography tandem mass spectrometry system for use in the analysis of drug discovery plasma samples.

There is a continuing need for increased throughput in the evaluation of new drug entities in terms of their pharmacokinetic (PK) parameters. This report describes an alternative procedure for increasing the throughput of plasma samples assayed in one overnight analysis: the use of parallel high performance liquid chromatography (HPLC) combined with tandem mass spectrometry (parallel LC/MS/MS). For this work, two HPLC systems were linked so that their combined effluent flowed into one tandem MS system. The parallel HPLC/APCI-MS/MS system consisted of two Waters 2690 Alliance systems (each one included an HPLC pump and an autosampler) and one Finnigan TSQ 7000 triple quadrupole mass spectrometer. Therefore, the simultaneous chromatographic separation of the plasma samples was carried out in parallel on two HPLC systems. The MS data system was able to deconvolute the data to calculate the results for the samples. Using this system, 20 compounds were tested in one overnight assay using the rapid rat PK screening model which includes a total of 10 standards plus samples and two solvent blanks per compound tested. This application provides an additional means of increasing throughput in the drug discovery PK assay arena; using this approach a two-fold increase in throughput can be achieved in the assay part of the drug discovery rat PK screening step.     

Carbon dioxide conversion to valuable chemical products over composite catalytic systems

This paper reports an experimental study on catalytic conversion of carbon dioxide to methanol,ethanol and acetic acid.Catalysts having different catalytic functions were synthesized and combined in different ways to enhance the selectivity to desired products.The combined catalyst system possessed the following functions:methanol synthesis,Fischer-Tropsch synthesis,water-gas-shift and hydrogenation.Results showed that the methods of integrating these catalytic functions played an important role in achieving the desired product selectivity.We speculate that if methanol synthesis sites were located adjacent to the C-C chain growth sites,the formation rate of C₂ oxygenates would be enhanced.The advantage of using a high temperature methanol catalyst PdZnAl in the combined catalyst system was demonstrated.In the presence of PdZnAl catalyst,the combined catalyst system was stable at 380°C.It was observed that,at high temperature,kinetics favored oxygenate formation.The results implied that the process can be intensified by operating at high temperature using Pd-based methanol synthesis catalyst.Steam reforming of the byproduct organics was demonstrated as a means to provide supplemental hydrogen.Preliminary process design,simulation,and economic analysis of the proposed CO₂ conversion process were carried out.Economic analysis indicates how ethanol production cost was affected by the price of CO₂ and hydrogen.     

Liquid extraction surface analysis mass spectrometry (LESA-MS) as a novel profiling tool for drug distribution and metabolism analysis: the terfenadine example

Liquid extraction surface analysis mass spectrometry (LESA-MS) is a novel surface profiling technique that combines micro-liquid extraction from a solid surface with nano-electrospray mass spectrometry. One potential application is the examination of the distribution of drugs and their metabolites by analyzing ex vivo tissue sections, an area where quantitative whole body autoradiography (QWBA) is traditionally employed. However, QWBA relies on the use of radiolabeled drugs and is limited to total radioactivity measured whereas LESA-MS can provide drug- and metabolite-specific distribution information. Here, we evaluate LESA-MS, examining the distribution and biotransformation of unlabeled terfenadine in mice and compare our findings to QWBA, whole tissue LC/MS/MS and MALDI-MSI. The spatial resolution of LESA-MS can be optimized to ca. 1 mm on tissues such as brain, liver and kidney, also enabling drug profiling within a single organ. LESA-MS can readily identify the biotransformation of terfenadine to its major, active metabolite fexofenadine. Relative quantification can confirm the rapid absorption of terfendine after oral dosage, its extensive first pass metabolism and the distribution of both compounds into systemic tissues such as muscle, spleen and kidney. The elimination appears to be consistent with biliary excretion and only trace levels of fexofenadine could be confirmed in brain. We found LESA-MS to be more informative in terms of drug distribution than a comparable MALDI-MS imaging study, likely due to its favorable overall sensitivity due to the larger surface area sampled. LESA-MS appears to be a useful new profiling tool for examining the distribution of drugs and their metabolites in tissue sections.     

Search for disoriented chiral condensate in 158<Emphasis Type="Italic">A</Emphasis> GeV Pb+Pb collisions in WA98 experiment

The current status of the search for localized domains of disoriented chiral condensates (DCC) in Pb+Pb collisions at 158A GeV/c are presented. A new method based on the discrete wavelet transformation (DWT) technique along with an analysis of correlation between charged and neutral particles has been used for the search of localized DCC domains. We show that both the methods indicate the presence of non-statistical fluctuations in data.     

A laser extraction/combustion technique for in situ delta(13)C analysis of organic and inorganic materials

A CO(2) laser extraction system is described for in situ delta(13)C analysis of organic and inorganic materials. Carbonaceous compounds volatilized by the laser are quantitatively converted to CO(2) gas by a combustion furnace mounted after the sample chamber. Gases produced by the laser and combustion processes are swept by helium carrier gas and separated by a packed gas chromatography column prior to their introduction to an isotope ratio monitoring mass spectrometer. A sample of lentil bean was analyzed at a spatial resolution of 200 μm and yielded delta(13)C values with precision of +/- 0.3 per thousand. The accuracy of delta(13)C measurements was better than +/- 0.5 per thousand from NBS 22 (mineral oil), USGS 24 (graphite), and IAEA CO-1 (calcium carbonate). Copyright 1999 John Wiley & Sons, Ltd.     

Coherent production ofρ − mesons in charged current antineutrino-neon interactions in BEBC

Coherent production ofρ ^? mesons in charged current antineutrino interactions on neon nuclei is studied in the BEBC bubble chamber exposed to the CERN SPS wide band beam. The cross section is measured to be (95±25)·10^?40 cm² per neon nucleus, averaged over the beam energy spectrum. The distributions of kinematical variables and the absolute value of the cross section are in agreement with theoretical predictions based on the CVC hypothesis and the vector meson dominance model.     

Evidence for higher twist effects in fast π− production by antineutrinos in neon

Evidence for a significant higher twist contribution to highz π^? production in antineutrino scattering is presented. In events withW>3 GeV andQ ²>1 GeV² in our data, it accounts for (51 ±8)% of all π^? withz above 0.5. It is consistent with thez?Q ² correlations of Berger's higher twist prediction. The data are inconclusive concerning the predictedy?z correlation andp _T dependence. Thez ?Q ² correlation is not adequately described by the Lund Monte-Carlo.     

Confirmation of heptachlor epoxide and octachlor epoxide in milk via fused silica gas chromatography/negative ion chemical ionization mass spectrometry

A method for the mass spectral confirmation of heptachlor epoxide and octachlor epoxide in milk is described. The method includes the use of a 30 m × 0.25 mm DB-1701 fused silica gas chromatography column combined with negative ion chemical ionization mass spectrometry. By using this technique, confirmation of these compounds in milk can be performed at a level of 0.1 parts-per-million in milk fat.