LC-MS-based metabolomics

Fig. 8 An untargeted LC-MS-based metabolomics approach revealed that KIAA1363, an...

Untargeted LC-MS-based metabolomics in practice refers to LC-MS analysis that utilizes high-resolution mass spectrometry and generates large datasets that are subsequently subjected to multivariate statistical analysis to reduce data complexity and dimensionality and reveal salient trends. 

All such developments offer exciting opportunities, but a major obstacle in LC-MS-based metabolomics is the lack of standardization. In contrast to NMR or GC-MS, the application and the development of the field of LC-MS cannot rely on databases due to a number of important issues (1) correlation of LC-MS data or comparison of data obtained in different MS instruments is not possible, (2) adduct formation cannot be controlled, and (3) interlaboratory comparisons of full-scan MS data becomes very difficult. 

Burton, L. et al., Instrumental and experimental effects in LC-MS-based metabolomics, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 871(2), 227, 2008. 

Biomarker identification represents a major bottleneck in nontargeted MS-based metabolomics and in particular in LC-MS studies. This happens... 

Theodoridis, G., Gika, H.G., and Wilson, I.D., LC-MS based methodology for global metabolite profiling in metabonomics/metabolomics, Trends Anal. Chem., 27(3), 251, 2008. 

This approach differs from those discussed above in that measured analytes have been selected a priori, usually to address certain specific biological questions within a study. Furthermore, since the exact analytes are known, it is possible and desirable to measure their absolute concentrations with appropriate use of internal standards and calibration curves. The lines between targeted metabolomics and traditional LC—MS-based assay development are arguably ill defined. Certainly, no one would equate an MS assay developed to measure alanine with targeted metabonomics. However, a multiplex assay to measure 13 or 14 organic acids in a urine sample probably qualifies. Often, targeted approaches can be developed for specific compoimd classes such as... 

Lu W, et al. Analytical strategies for LC-MS-based targeted metabolomics. J Chromatogr B Anal Technol Biomed Life Sci 2008a 871 236—242. 

Metabolomics quality control uses different methods. In most cases for GC/LC/CE-MS-based nontargeted metabolomics, a pooled sample from the study serves as a quality-control sample and is injected prior to real samples to condition the chromatographic system and between samples for control of performance. Using this QC samples, retention time drifts or other alteration in performance can be monitored and possibly corrected. In targeted metabolomics retention time shifts, LOD and LOQ values and recovery rates of known materials are used similar to classic analytical chemistry. 

One last interesting point should be drawn to the combination of transcriptomics, proteomics, and metabolomics. Proteomics and metabolomics are both based on similar chemical analysis techniques LC-MS. It might be possible that in the future new work based on the combination of both or all three will be published. Virtually, high-resolution instruments such as the latest... 

Libraries and Database Resources for LC—MS Excellent compendiums of Web-based metabolomics resources that cover libraries, databases, and other... 

---