Negative mode nanostructure-initiator mass spectrometry for detection of phosphorylated metabolites

The chemical complexity of the metabolome requires the development of new detection methods to enlarge the range of compounds detectable in a biological sample. Recently, a novel matrix-free laser desorption/ionization method called nanostructure-initiator mass spectrometry (NIMS) [Northen et al., Nature 449(7165):1033-1036, 2007] was reported. Here we investigate NIMS in negative ion mode for the detection of endogenous metabolites, namely small phosphorylated molecules. 3-Aminopropyldimethylethoxysilane was found to be suitable as initiator for the analytes studied and a limit of detection in the tens of femtomoles was reached. The detection of different endogenous cell metabolites in a yeast cell extract is demonstrated.