The measurement of metabolites in biofluids offers valuable information concerning metabolism and general health. Numerous metabolites, such as amino acids and sugars, are measured routinely, and today over thirty-five diseases, including phenylketonuria in newborns, are monitored directly using electrospray ionization mass spectrometry (ESI-MS). The focus of the current screening methods is optimized for measuring one or a few metabolites. However, it can be advantageous to obtain a global view of the metabolites in the biofluid of interest in order to predict or detect disease states that are not yet characterized. In order to perform large-scale studies of total metabolite profiles, the development of efficient yet effective analysis techniques is crucial for reliable statistical analysis.

While many hundreds of metabolites are readily detected using liquid chromatography / ESI-MS (LC/ESI-MS), steroids, carbohydrates, and lipids often ionize poorly and therefore present a challenge for mass spectral analysis. All of these are important in cell signaling, and thus are potential targets for therapy, diagnosis, and screening. To extend the application of mass spectrometry to these types of metabolites, chemical modification procedures were applied to produce charged covalent adducts with enhanced ionization properties.

In addition to the analytical techniques, we have also developed a metabolite database to catalog and compare LC/ESI-MS data from biofluid samples. Our database tracts over a dozen variables from sample details to instrument settings; it is deployed on the web for free public access. This database, together with chemical derivation strategies provides a comprehensive approach to total metabolite profiling.