Liquid chromatography–tandem mass spectrometry is one of the most sensitive tools for determination of trace amounts of analytes in metabolomics and proteomics. The highest sensitivity is achieved in selected reaction monitoring detection, which involves fragmentation of the molecular ion between two levels of mass selection. However, fragmentation of some compounds is complicated. Detection sensitivity of such analytes may be increased by derivatizing them with a specific moiety fragmentation of which results in product ion of high abundance. In this work, we reveal the influence of iminium ions' structures on their stability by comparing six nitrogen-containing cyclic compounds as derivatization reagents for tandem mass spectrometric analysis of amino group-containing analyte. Commercially available starting materials (piperidine, 2,6-dimethylpiperidine, 1-methylpiperazine, morpholine, pyrrolidine and 1-cyanomethyl-3-methylimidazolium ionic liquid) were used for the synthesis of corresponding carboxylic acids which were further used for derivatization of the model analyte tryptamine. Liquid chromatographic–mass spectrometric analysis of differently derivatized tryptamine was performed for the evaluation of release and stability of corresponding iminium ions under collision-induced dissociation conditions. As a result, morpholine moiety was shown being the most promising iminium ion source among tested compounds. Possible sub-fragmentation pathways of investigated iminium ions were discussed, and the structures of secondary product ions were proposed.
Selected Reaction Monitoring–Mass Spectrometric Immunoassay Responsive to Parathyroid Hormone and Related Variants