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Acceleration Time-of-flight (acceleration + time-of-flight)

Distribution by Scientific Domains
Chemistry100%

Kinds of Acceleration Time-of-flight

  • orthogonal acceleration time-of-flight
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    Selected Abstracts

    Automated software-guided identification of new buspirone metabolites using capillary LC coupled to ion trap and TOF mass spectrometry

    JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 2 2006
    Anabel S. Fandiño
    Abstract The identification and structure elucidation of drug metabolites is one of the main objectives in in vitro ADME studies. Typical modern methodologies involve incubation of the drug with subcellular fractions to simulate metabolism followed by LC-MS/MS or LC-MSn analysis and chemometric approaches for the extraction of the metabolites. The objective of this work was the software-guided identification and structure elucidation of major and minor buspirone metabolites using capillary LC as a separation technique and ion trap MSn as well as electrospray ionization orthogonal acceleration time-of-flight (ESI oaTOF) mass spectrometry as detection techniques. Buspirone mainly underwent hydroxylation, dihydroxylation and N -oxidation in S9 fractions in the presence of phase I co-factors and the corresponding glucuronides were detected in the presence of phase II co-factors. The use of automated ion trap MS/MS data-dependent acquisition combined with a chemometric tool allowed the detection of five small chromatographic peaks of unexpected metabolites that co-eluted with the larger chromatographic peaks of expected metabolites. Using automatic assignment of ion trap MS/MS fragments as well as accurate mass measurements from an ESI oaTOF mass spectrometer, possible structures were postulated for these metabolites that were previously not reported in the literature. Copyright © 2006 John Wiley & Sons, Ltd. [source]

    High-throughput metabolic stability studies in drug discovery by orthogonal acceleration time-of-flight (OATOF) with analogue-to-digital signal capture (ADC)

    RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2010
    David G. Temesi
    Screening assays capable of performing quantitative analysis on hundreds of compounds per week are used to measure metabolic stability during early drug discovery. Modern orthogonal acceleration time-of-flight (OATOF) mass spectrometers equipped with analogue-to-digital signal capture (ADC) now offer performance levels suitable for many applications normally supported by triple quadruple instruments operated in multiple reaction monitoring (MRM) mode. Herein the merits of MRM and OATOF with ADC detection are compared for more than 1000 compounds screened in rat and/or cryopreserved human hepatocytes over a period of 3 months. Statistical comparison of a structurally diverse subset indicated good agreement for the two detection methods. The overall success rate was higher using OATOF detection and data acquisition time was reduced by around 20%. Targeted metabolites of diazepam were detected in samples from a CLint determination performed at 1,µM. Data acquisition by positive and negative ion mode switching can be achieved on high-performance liquid chromatography (HPLC) peak widths as narrow as 0.2,min (at base), thus enabling a more comprehensive first pass analysis with fast HPLC gradients. Unfortunately, most existing OATOF instruments lack the software tools necessary to rapidly convert the huge amounts of raw data into quantified results. Software with functionality similar to open access triple quadrupole systems is needed for OATOF to truly compete in a high-throughput screening environment. Copyright © 2010 John Wiley & Sons, Ltd. [source]

    Development of a liquid chromatographic time-of-flight mass spectrometric method for the determination of unlabelled and deuterium-labelled , -tocopherol in blood components

    RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 24 2003
    Wendy L. Hall
    A method is described for the analysis of deuterated and undeuterated , -tocopherol in blood components using liquid chromatography coupled to an orthogonal acceleration time-of-flight (TOF) mass spectrometer. Optimal ionisation conditions for undeuterated (d0) and tri- and hexadeuterated (d3 or d6) , -tocopherol standards were found with negative ion mode electrospray ionisation. Each species produced an isotopically resolved single ion of exact mass. Calibration curves of pure standards were linear in the range tested (0,1.5,,M, 0,15,pmol injected). For quantification of d0 and d6 in blood components following a standard solvent extraction, a stable-isotope-labelled internal standard (d3- , -tocopherol) was employed. To counter matrix ion suppression effects, standard response curves were generated following identical solvent extraction procedures to those of the samples. Within-day and between-day precision were determined for quantification of d0- and d6-labelled , -tocopherol in each blood component and both averaged 3,10%. Accuracy was assessed by comparison with a standard high-performance liquid chromatography (HPLC) method, achieving good correlation (r2,=,0.94), and by spiking with known concentrations of , -tocopherol (98% accuracy). Limits of detection and quantification were determined to be 5 and 50,fmol injected, respectively. The assay was used to measure the appearance and disappearance of deuterium-labelled , -tocopherol in human blood components following deuterium-labelled (d6) RRR - , -tocopheryl acetate ingestion. The new LC/TOFMS method was found to be sensitive, required small sample volumes, was reproducible and robust, and was capable of high throughput when large numbers of samples were generated. Copyright © 2003 John Wiley & Sons, Ltd. [source]