High-performance metabolic profiling with dual chromatography-Fourier-transform mass spectrometry (DC-FTMS) for study of the exposome
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Studies of gene–environment (G × E) interactions require effective characterization of all environmental exposures from conception to death, termed the exposome. The exposome includes environmental exposures that impact health. Improved metabolic profiling methods are needed to characterize these exposures for use in personalized medicine. In the present study, we compared the analytic capability of dual chromatography-Fourier-transform mass spectrometry (DC-FTMS) to previously used liquid chromatography-FTMS (LC-FTMS) analysis for high-throughput, top-down metabolic profiling. For DC-FTMS, we combined data from sequential LC-FTMS analyses using reverse phase (C18) chromatography and anion exchange (AE) chromatography. Each analysis was performed with electrospray ionization in the positive ion mode and detection from m/z 85 to 850. Run time for each column was 10 min with gradient elution; 10 μl extracts of plasma from humans and common marmosets were used for analysis. In comparison to analysis with the AE column alone, addition of the second LC-FTMS analysis with the C18 column increased m/z feature detection by 23–36%, yielding a total number of features up to 7,000 for individual samples. Approximately 50% of the m/z matched to known chemicals in metabolomic databases, and 23% of the m/z were common to analyses on both columns. Database matches included insecticides, herbicides, flame retardants, and plasticizers. Modularity clustering algorithms applied to MS-data showed the ability to detection clusters and ion interactions. DC-FTMS thus provides improved capability for high-performance metabolic profiling of the exposome and development of personalized medicine.
KeywordsMetabolomics LC/MS Anion exchange Reverse phase Exposome Personalized medicine Predictive health FT-ICR Plasma
The authors thank Jennifer M. Johnson, M.S., for her technical help with the internal standard and acquisition of human reference samples. This work was supported by research NIH grants P01ES016731 (DPJ), R01AG038746 (DPJ), R01ES011195 (DPJ) and P51RR000168 (KGM).
- Evans, A. M., DeHaven, C. D., Barrett, T., Mitchell, M., & Milgram, E. (2009). Integrated, nontargeted ultrahigh performance liquid chromatography/electrospray ionization tandem mass spectrometry platform for the identification and relative quantification of the small-molecule complement of biological systems. Analytical Chemistry, 81, 6656–6667.PubMedCrossRefGoogle Scholar
- Haouala, A., Zanolari, B., Rochat, B., et al. (2009). Therapeutic Drug Monitoring of the new targeted anticancer agents imatinib, nilotinib, dasatinib, sunitinib, sorafenib and lapatinib by LC tandem mass spectrometry. Journal of Chromatography B. Analytical Technologies in the Biomedical and Life Sciences, 877, 1982–1996.CrossRefGoogle Scholar
- Hodel, E. M., Zanolari, B., Mercier, T., et al. (2009). A single LC-tandem mass spectrometry method for the simultaneous determination of 14 antimalarial drugs and their metabolites in human plasma. Journal of Chromatography B. Analytical Technologies in the Biomedical and Life Sciences, 877, 867–886.CrossRefGoogle Scholar
- Institute of Laboratory Animal Resources. (1996). Guide for the care and use of laboratory animals. Washington, DC: National Academy Press.Google Scholar
- Kaufman, L., & Rousseeuw, P. J. (2005). Finding groups in data: an introduction to cluster analysis. New York: Wiley.Google Scholar