IRUS Total

Quantitative lipoprotein subclass and low molecular weight metabolite analysis in human serum and plasma by 1H NMR spectroscopy in a multilaboratory trial

File Description SizeFormat 
acs.analchem.8b02412.pdfAccepted version1.94 MBAdobe PDFView/Open
Title: Quantitative lipoprotein subclass and low molecular weight metabolite analysis in human serum and plasma by 1H NMR spectroscopy in a multilaboratory trial
Authors: Jimenez, B
Holmes, E
Heude, C
Tolson, RFM
Harvey, N
Lodge, SL
Chetwynd, AJ
Cannet, C
Fang, F
Pearce, JTM
Lewis, MR
Viant, MR
Lindon, JC
Spraul, M
Schaefer, H
Nicholson, JK
Item Type: Journal Article
Abstract: We report an extensive 600 MHz NMR trial of a quantitative lipoprotein and small molecule measurements in human blood serum and plasma. Five centers with eleven 600 MHz NMR spectrometers were used to analyze 98 samples including: 20 QCs, 37 commercially sourced, paired serum and plasma samples and 2 National Institute of Science and Technology, NIST, reference material 1951c replicates. Samples were analyzed using rigorous protocols for sample preparation and experimental acquisition. A commercial lipoprotein subclass analysis was used to quantify 105 lipoprotein subclasses and 24 low molecular weight metabolites from the nuclear magnetic resonance, NMR, spectra. For all spectrometers, the instrument specific variance in measuring internal quality controls, QCs, was lower than the percentage described by the National Cholesterol Education Program, NCEP, criteria for lipid testing (triglycerides<2.7%, cholesterol<2.8%; LDL-cholesterol<2.8%; HDL-cholesterol<2.3%), showing exceptional reproducibility for direct quantitation of lipoproteins in both matrices. The average RSD for the 105 lipoprotein parameters in the 11 instruments was 4.6% and 3.9% for the two NIST samples while it was 38% and 40% for the 37 commercially sourced plasmas and sera, respectively, showing negligible analytical compared to biological variation. The coefficient of variance, CV, obtained for the quantification of the small molecules across the 11 spectrometers was below 15% for 20 out of the 24 metabolites analyzed. This study provides further evidence of the suitability of NMR for high-throughput lipoprotein subcomponent analysis and small molecule quantitation with the exceptional reproducibility required for clinical and other regulatory settings.
Issue Date: 16-Oct-2018
Date of Acceptance: 13-Sep-2018
URI: http://hdl.handle.net/10044/1/64760
DOI: https://dx.doi.org/10.1021/acs.analchem.8b02412
ISSN: 0003-2700
Publisher: American Chemical Society
Start Page: 11962
End Page: 11971
Journal / Book Title: Analytical Chemistry
Volume: 90
Issue: 20
Copyright Statement: © 2018 American Chemical Society
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: MC_PC_12025
Keywords: Science & Technology
Physical Sciences
Chemistry, Analytical
0301 Analytical Chemistry
0904 Chemical Engineering
0399 Other Chemical Sciences
Analytical Chemistry
Publication Status: Published
Conference Place: United States
Online Publication Date: 2018-09-13
Appears in Collections:Department of Surgery and Cancer