Washington University in St. Louis

The Patti Lab
Metabolomics to elucidate novel biochemical mechanisms of disease
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International Ring Trial of a High Resolution Targeted Metabolomics and Lipidomics Platform for Serum and Plasma Analysis

Thompson JW, Adams KJ, Adamski J, Asad Y, Borts D, Bowden JA, Byram G, Dang VD, Dunn WB, Fernandez FM, Fiehn O, Gaul DA, Huhmer A, Kalli A, Koal T, Koeniger S, Mandal R, Meier F, Naser FJ, O'Neil D, Pal A, Patti GJ, Pham-Tuan H, Prehn C, Raynaud FI, Shen T, Southam AD, St.John-Williams L, Sulek K, Vasilopoulou CG, Viant MR, Winder CL, Wishart DS, Zhang L, Zheng J, and Moseley MA
International Ring Trial of a High Resolution Targeted Metabolomics and Lipidomics Platform for Serum and Plasma Analysis
Anal. Chem., 91(22), 14407-14416, 2019
doi:10.1021/acs.analchem.9b02908

A challenge facing metabolomics in the analysis of large human cohorts is the cross-laboratory comparability of quantitative metabolomics measurements. In this study, 14 laboratories analyzed various blood specimens using a common experimental protocol provided with Biocrates AbsoluteIDQ p400HR kit, to quantify up to 408 metabolites. The specimens included human plasma and serum from male and female donors, mouse and rat plasma as well as NIST SRM 1950 reference plasma. The metabolite classes covered range from polar (e.g. amino acids and biogenic amines), to nonpolar (e.g. diacyl- and triacyl-glycerols), and span 11 common metabolite classes. The manuscript describes a strict system suitability testing (SST) criteria used to evaluate each laboratory’s readiness to perform the assay, and provides the SST Skyline documents for public dissemination. The study found approximately 250 metabolites were routinely quantified in the sample types tested, using Orbitrap instruments. Inter-laboratory variance for the NIST SRM-1950 has a median of 10% for amino acids, 24% for biogenic amines, 38% for acylcarnitines, 25% for glycerolipids, 23% for glycerophospholipids, 16% for cholesteryl esters, 15% for sphingolipids, and 9% for hexoses. Comparing to consensus values for NIST SRM-1950, nearly 80% of comparable analytes demonstrated bias of <50% from the reference value. The findings of this study result in recommendations of best practices for system suitability, quality control, and calibration. We demonstrate that with appropriate controls, high-resolution metabolomics can provide accurate results with good precision across laboratories, and the p400HR therefore is a reliable approach for generating consistent and comparable metabolomics data.

Washington University, Departments of Chemistry, Genetics, and Medicine. Saint Louis, Missouri 63110 USA