TABLE 1.

Mass spectrometry-based bulk metabolomics and nuclear magnetic resonance spectroscopy: strengths and weaknesses

Method	Description	Advantages	Limitations
MS	• Based on the analysis of gas-phase ions and measurement of the mass-to-charge ratio of the ions • Different configurations are available depending on:  – Ionization technique, used for generation of gaseous ions from the sample/extract  – Mass analyzer, used for separation of analytes according to mass-to-charge ratio  – Direct injection or coupled to separations-based techniques: gas chromatography, liquid chromatography, supercritical fluid chromatography or capillary electrophoresis	• High sensitivity and versatility • High throughput • Broad coverage of metabolites or tailored analysis associated with specific sample preparation, separation method, and chosen MS-configuration • Wide dynamic range • Low amount of sample	• Noninherently quantitative • Not equally sensitive for all the metabolites: the ionization efficiency differs among compounds • Matrix effect on complex samples such as hepatic tissue • High competition for the ionization of the metabolites, generating ion suppression of molecules less prone to be ionized • Destructive technique
NMR spectroscopy	• Based on the magnetic properties of atomic nuclei • It can be applied to the analysis of small molecules to large macromolecular complexes (ie, lipoprotein profiling):  – 1H NMR: distinctive signal for each proton or group of equivalent protons  – 31P NMR: analysis of phosphorylated compounds involved in central carbon and phospholipid metabolism  – 13C NMR: flux analysis	• Quantitative technique • High level of reproducibility and instrument stability • Low experimental variability between laboratories • Nondestructive • Minimal sample preparation of biofluids or analysis of intact tissue using 1H magic angle spinning NMR	• Low sensibility • Requires higher amount of sample • Lower metabolite coverage

Abbreviations: MS, mass spectrometry; NMR, nuclear magnetic resonance.