Metabolomics:Open Access

High Resolution Mass Spectrometry Improves Data Quantity and Quality as Compared to Unit Mass Resolution Mass Spectrometry in High- Throughput Profiling Metabolomics

Abstract

Evans AM, Bridgewater BR, Liu Q, Mitchell MW, Robinson RJ, Dai H, Stewart SJ, DeHaven CD and Miller LAD

Metabolomics is a technique in which the small molecule component from a biological source material is analyzed for changes resulting from some set of test conditions. Liquid chromatography tandem mass spectrometry (LC/MS/MS) methods are commonly used because of the sensitivity and specificity of the data collected. The sensitivity of these methods permit the detection of a large number of small molecules, leading to greater coverage of the biochemical pathways involved in the system being tested. The success of metabolomic studies are partially reliant upon instrumentation, but to what extent? Here we present an evaluation of the analytical attributes of a high resolution accurate mass (HRAM) orbitrap based mass spectrometer compared to a unit mass resolution (UMR) ion-trap mass spectrometer as applied to high-throughput, non-targeted metabolomics. To carry out this evaluation, different sets of samples were analyzed and the data evaluated for analytical performance. Two dilution series of authentic standards demonstrated that the HRAM data stream improved the limit of detection from several fold to several orders of magnitude and showed an increased linear dynamic range of an order of magnitude over the UMR data stream. Analysis of a biological serum sample set demonstrated that the HRAM data stream enabled the detection of 118 additional named/known compounds, leading to the detection of 531 tier 1 and tier 2 identified compounds in human serum, with decreased process variability, increased consistency and accuracy of detection and integration.