Metabolomics relative quantitation with mass spectrometry using chemical derivatization and isotope labeling

Article type: Research Article

Authors: O'Maille, Grace^; | Go, Eden P. | Hoang, Linh | Want, Elizabeth J. | Smith, Colin | O'Maille, Paul | Nordström, Anders | Morita, Hirotoshi | Qin, Chuan | Uritboonthai, Wilasinee | Apon, Junefredo | Moore, Richard | Garrett, James | Siuzdak, Gary^;

Affiliations: The Center for Mass Spectrometry and Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA | Jack H. Skirball Center for Chemical Biology and Proteomics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA | Becton Dickinson, Sparks, MD 21152, USA

Note: [] These authors contributed equally to this work.

Note: [] These authors contributed equally to this work.

Note: [] Corresponding author: E-mail: siuzdak@scripps.edu.

Abstract: Comprehensive detection and quantitation of metabolites from a biological source constitute the major challenges of current metabolomics research. Two chemical derivatization methodologies, butylation and amination, were applied to human serum for ionization enhancement of a broad spectrum of metabolite classes, including steroids and amino acids. LC-ESI-MS analysis of the derivatized serum samples provided a significant signal elevation across the total ion chromatogram to over a 100-fold increase in ionization efficiency. It was also demonstrated that derivatization combined with isotopically labeled reagents facilitated the relative quantitation of derivatized metabolites from individual as well as pooled samples.

Keywords: Metabolomics, human plasma, isotope labeling, quantitation, mass spectrometry

DOI: 10.3233/SPE-2008-0361

Journal: Spectroscopy, vol. 22, no. 5, pp. 327-343, 2008