Mass spectrometry (MS) analysis of some biologically relevant compounds is limited because of their inherently poor ionization efficiency. This challenge can often be overcome by incorporating easily ionized moieties via functional-group-targeted chemical derivatization. However, the wide variety of derivatization agents and conditions can make method development cumbersome. In this study, we employ an automated high-throughput (HT) platform based on desorption electrospray ionization (DESI) MS to rapidly screen (1 sample per second) and select appropriate derivatization strategies for poorly ionized analytes leveraging accelerated on-the-fly microdroplet reactions. This approach allowed the rapid identification of efficient derivatization strategies that were then readily applied to the qualitative and quantitative analyses of molecules of biological importance. Specifically, hydroxysteroids (e.g., cholesterol, testosterone, and cholecalciferol) were imaged in tissue sections using 4-formyl-1-methylpyridinium benzenesulfonate without the loss of the intrinsic spatial resolution of DESI, while 4-borono-N,N,N-trimethylbenzenaminium allowed sensitive and HT quantitation of urinary 3-methoxy-4-hydroxyphenylglycol, a metabolite whose urine levels have been correlated with neurological disorders.
Feng et al. (Mon,) studied this question.