Investigating Metabolomic Time of Death Using a Novel High-Resolution Orbitrap-based GC-MS/MS System
Investigating Metabolomic Time of Death Using a Novel
High-Resolution Orbitrap-based GC-MS/MS System
Broadcast on September 17, 2015
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Metabolomics aims to characterize and quantify the complete small molecule complement, or metabolome, of a biological system. The metabolome consists of a diverse mixture of small molecules, including amino acids, sugars and phosphosugars, biogenic amines and lipids.
Untargeted metabolomics is exceptionally challenging because one must identify and quantify hundreds of different compounds with limited a priori knowledge of the metabolites. These studies benefit from a detection system that is not only capable of untargeted, sensitive detection of specific molecules, but can also provide accurate mass information for confident confirmation and structural elucidation of unknowns.
Gas chromatography-mass spectrometry (GC-MS) is routinely used for metabolomics applications due to its chromatographic resolution, reproducibility, peak capacity, and convenient spectral libraries. GC provides excellent chromatographic separation capability for biomarker discovery using untargeted metabolomics, but has previously been hampered by the lack of high-end mass spectrometry support to analyze very complex samples, such as mammalian muscle tissue.
One area in which this type of untargeted metabolomics might be beneficial is in forensic investigation of post-mortem interval (PMI). Current methods to determine PMI are inaccurate and primarily based on visual inspection of the body. Untargeted metabolomics has the potential to identify a robust biomarker for PMI that might be used in a laboratory-based method to assist in these investigations.
A GC-MS configuration using an Orbitrap-based MS detector enables the ultra-high mass resolution, sub-ppm mass accuracy, large dynamic range and scan rate needed for the efficient quantitive analysis of highly complex metabolomic samples to make determination of PMI metabolic biomarkers possible.
This work demonstrates:
- The application of a complete untargeted metabolomics workflow using a novel Thermo Scientific™ Orbitrap™ MS-based GC to detect biomarkers for time of death in a rat model.
- The high mass resolution, sub-ppm mass accuracy, a large dynamic range, and a scan rate commensurate with the efficient quantitative analysis of highly complex metabolomic samples that Orbitrap technology provides.
- A laboratory-based method, using a robust biomarker for PMI, would assist forensic investigation.
Key learning objectives
Attendees will learn how to:
- Use high resolution and high mass accuracy to investigate metabolic changes in complex samples.
- Apply a complete untargeted metabolomics workflow using a novel Thermo Scientific™ Orbitrap™ MS-based GC to detect biomarkers.
- Achieve higher throughput analyses using automation, assess reproducibility and account for variation in large scale studies.
Who should attend?
- Analysts and laboratory managers from both routine commercial and research laboratories.
Head of Metabolomics
University of Glasgow, UK
Karl Burgess: Biography
Karl Burgess is the Head of Metabolomics at Glasgow Polyomics, the University of Glasgow. His research interests focus on the use of mass spectrometry in biomedical research, particularly in the understanding of infectious disease. This multidisciplinary research area builds on his fruitful collaborations with cell biologists, engineers, bioinformaticians, instrumentation developers and clinicians. Karl obtained a Bachelor degree in Pathobiology from Reading University. He then went on to develop his bioinformatics skills with an MSc at Birkbeck College, University of London, followed by an MRes in Biomedical and Life Sciences at the University of Glasgow. After being introduced to mass spectrometry during his MRes, he remained at Glasgow for a PhD in proteomic methods development. After a short post-doc on the RASOR proteomics grant, he became head of the newly established, SULSA-funded, Glasgow University Metabolomics Facility, where he remains. He also obtained a Wellcome Trust ISSF fellowship in 2012, where he studies the mechanisms of adherence in pathogenic biofilms.
Senior Mass Spectrometry Applications Specialist
Chromatography and Mass Spectrometry Division
Thermo Fisher Scientific
Cristian Cojocariu: Biography
Cristian is a Senior Mass Spectrometry Applications Specialist working in the Chromatography and Mass Spectrometry Division at Thermo Fisher Scientific, Runcorn, UK. Cristian is an experienced analytical chemist and mass spectrometrist responsible for the applications and methods development using GC-MS technology, particularly GC high resolution Orbitrap-based mass spectrometers. Cristian has worked in both academia and industry gaining strong hands-on experience with GC-MS and LC-MS systems used to investigate trace chemicals in both biological and environmental samples.