Bioanalytical chemistry lacks sufficiently sensitive and selective detection methods to identify many compounds of emerging biological importance, including post-translationally modified proteins and metabolites generated from pharmaceuticals, environmental toxins, or other endogenous sources. To improve upon current structural identification methods for these compounds, we are incorporating the utility of functional group analysis, as typically obtained by IR spectroscopy, into another method that has considerably higher sensitivity and selectivity, mass spectrometry. Our initial goals are to design mass spectrometric assays that identify sulfate, phosphate, and carboxylate in biologically modified compounds, specifically, pharmaceutical metabolites. We achieve these goals through a variety of methods, including tandem mass spectrometry, ion-pairing, and chemo-selective derivatizations.
Recently, we have developed a set of rules that describe carboxylic acid fragmentation, in a quadrupole ion trap mass spectrometer. These rules had a 90% success rate at predicting fragementation for 20 acid-containing pharmaceuticals. (Anal Chem. 2004, 76,1746-1753.) These studies (along with our ongoing efforts in this area) will be useful to identify various classes of biotransformation products. We are currently interested in developing these studies to probe human sulfotransferase activity. Changes in sulfotransferase activity have been linked to several diseases, including arthritis and cystic fibrosis.