The chemical diversity of the metabolites is enormous in addition to a large dynamic concentration range. A wide variety of methods have been used to separate and quantify components of the metabolome, and no single analytical platform can capture all metabolites in one sample. For that reason only a technology platform consisting of several approaches based on different techniques offers a solution today.  The best choice of platform for your study depends heavily on your research question. Nowadays roughly two different strategies can be distinguished for metabolite investigations: ¹⁾metabolic profiling and ²⁾metabolic fingerprinting (Dettmer et al., 2007).

Metabolic profiling focuses on a group or category of metabolites of interest defined a priori (e.g. fatty acids, oxidized lipids, nucleosides etc.) and all these metabolites are precisely quantified. Metabolic profiling is a targeted way to study different aspects of metabolism and one should need the assemblage of a whole suite of quantitative methods to turn metabolic profiling into metabolomics.

In general, people refer to metabolic fingerprinting, where metabolite profiles are acquired and compared with limited a priori knowledge of the metabolites of interest. Semi quantitative data are acquired by high throughput generic analytical methods (such as LC-MS or 1H-NMR) and (bio)markers (ions or chemical shift signals) revealed by multivariate statistical tools. The identity of the signals of interest from the fingerprint can subsequently be revealed by metabolite identification procedures.

• Gas chromatography-mass spectrometry (GCMS) wikipedia  

Ionization of the molecules in GCMS can be done in different ways: 

-                      Electron ionization (positive and negative)

-                      Chemical ionization (positive and negative)

The fragment ions are detected by time-of-flight (TOF) or by quadruple mass spectrometry (MS). Often derivatisation methods are used to make metabolites more volatile.  

GCMS mainly separates metabolites that are smaller than 500 Dalton. Separation is based on boiling point and binding to the column. Many metabolites can be identified in the GCMS, such as sugars, fatty acids, organic acids and amino acids. GC-MS is poor for the analysis of substances, which are non-volatile due to their high molecular weight and/or polarity. GCMS is suitable as a broad metabolic profiling technique.

• Liquid chromatography-mass spectrometry (LCMS) wikipedia  

Different types of LCMS approaches:

-                      lipid LCMS

-                      ion pair LCMS

-                      polar (derivatised) LCMS

LCMS is the better choice for (semi) polar and non-volatile compounds. It can also be applied to profiling of polar compounds, but special (ion pair) agents need to be used or derivatisation in order to retain polar compounds on the column. In LCMS, more combinations of LC (Normal Phase, Reversed Phase, Ion Pair, Hilic,..) and MS (TOF, Ion trap, Quadrupole, FTMS instruments…) parts are available for different applications  However, the identification of metabolites is more difficult than with GCMS.  Often derivatisation methods are used to make metabolites better solvable. LCMS polar is a suitable technique when you would like to apply a fingerprinting procedure specifically on polar compounds. Lipid LCMS techniques are suitable as metabolic profiling techniques when you are specifically interested in lipid metabolism.

• Nuclear magnetic resonance (NMR) spectroscopy wikipedia  

1H NMR measures a wide spectrum of metabolites (all metabolites containing H atoms and that are almost all organic compounds). However, compared to GCMS and LCMS techniques NMR is a relatively insensitive method. Identification of metabolites is achieved by 2-D NMR techniques. NMR is a suitable technique when you would like to apply a fingerprinting procedure measuring a broad spectrum of the most abundant metabolites in the metabolome.

Literature

• Encyclopedia of separation science (Editor I.D. Wilson) link
• Current and emerging mass-spectrometry technologies for metabolomics (M. Bedaira and L.W. Sumner) link
• Dettmer K, Aronov PA, Hammock BD. (2007) Mass spectrometry-based metabolomics. Mass Spectrom Rev 26:51-78 link
• Kaddurah-Daouk R, Kristal BS, WeinshilboumRM. (2008) Metabolomics: a global biochemical approach to drug response and disease. Annu Rev Pharmacol Toxicol. 48:653-83 link
• Want E.J., Nordstrom A., Morita H. and Siuzdak G., (2007) From Exogenous to Endogenoeus: The Inevitable Imprint of Mass Spectrometry in Metabolomics, J. Proteome Res., 6, 459-468 link
• Lin H.M, Edmunds S.J, Helsby N.A, Ferguson L.R, Rowan D.D. (2009) Nontargeted Urinary Metabolite Profiling of a Mouse Model of Crohn's Disease. J Proteome Res. 8:2045-2057 link
• Kind T, Tolstikov V, Fiehn O, Weiss R.H. (2007) A comprehensive urinary metabolomic approach for identifying kidney cancer. Anal Biochem. 363:185-95. link