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Journal article
Development of a Rapid Microbore Metabolic Profiling Ultraperformance Liquid Chromatography-Mass Spectrometry Approach for High-Throughput Phenotyping Studies
Analytical chemistry (Washington), Vol.88(11), pp.5742-5751
2016
PMID: 27116471
Abstract
A rapid gradient microbore ultraperformance liquid chromatography–mass spectrometry (UPLC–MS) method has been developed to provide a high-throughput analytical platform for the metabolic phenotyping of urine from large sample cohorts. The rapid microbore metabolic profiling (RAMMP) approach was based on scaling a conventional reversed-phase UPLC–MS method for urinary profiling from 2.1 mm × 100 mm columns to 1 mm × 50 mm columns, increasing the linear velocity of the solvent, and decreasing the gradient time to provide an analysis time of 2.5 min/sample. Comparison showed that conventional UPLC–MS and rapid gradient approaches provided peak capacities of 150 and 50, respectively, with the conventional method detecting approximately 19 000 features compared to the ∼6 000 found using the rapid gradient method. Similar levels of repeatability were seen for both methods. Despite the reduced peak capacity and the reduction in ions detected, the RAMMP method was able to achieve similar levels of group discrimination as conventional UPLC–MS when applied to rat urine samples obtained from investigative studies on the effects of acute 2-bromophenol and chronic acetaminophen administration. When compared to a direct infusion MS method of similar analysis time the RAMMP method provided superior selectivity. The RAMMP approach provides a robust and sensitive method that is well suited to high-throughput metabonomic analysis of complex mixtures such as urine combined with a 5-fold reduction in analysis time compared with the conventional UPLC–MS method.
Details
- Title
- Development of a Rapid Microbore Metabolic Profiling Ultraperformance Liquid Chromatography-Mass Spectrometry Approach for High-Throughput Phenotyping Studies
- Authors/Creators
- Nicola Gray - Imperial College LondonKyrillos Adesina-Georgiadis - Imperial College LondonElena Chekmeneva - Imperial College LondonRobert S. Plumb - Imperial College LondonIan D. Wilson - Imperial College LondonJeremy K. Nicholson - Hammersmith Hospital
- Publication Details
- Analytical chemistry (Washington), Vol.88(11), pp.5742-5751
- Publisher
- Amer Chemical Soc
- Number of pages
- 10
- Grant note
- Bruker Biospin MC_PC_12025 / UK Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Metabometrix LTD Imperial College MC_PC_12025 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission Waters Corporation National Institute of Health Research (England); National Institute for Health Research (NIHR) MC_PC_12025 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
- Identifiers
- 991005600059307891
- Copyright
- © 2016 American Chemical Society
- Murdoch Affiliation
- Centre for Computational and Systems Medicine
- Language
- English
- Resource Type
- Journal article
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- Citation topics
- 2 Chemistry
- 2.211 Mass Spectrometry
- 2.211.990 Metabolomics
- Web Of Science research areas
- Chemistry, Analytical
- ESI research areas
- Chemistry