Design and Synthesis of Labeling Reagents (MS Probes) for Highly Sensitive Electrospray Ionization Mass Spectrometry and Their Application to the Detection of Carbonyl, Alcohol, Carboxylic Acid and Primary Amine Samples

Novel labeling reagents, called MS probes, which possess a positively charged quaternary amine moiety and can transform a neutral analyte into a charged compound by simply mixing with the analyte and allowing the mixture to stand from several minutes to 30 min at room temperature or while heating to 50°C, were designed and synthesized for the highly sensitive detection of carbonyl, alcohol, carboxylic acid and primary amine samples by electrospray ionization mass spectrometry (ESI-MS), The positively charged products can be detected with high sensitivity in an ESI-MS system, which is the most popular liquid MS instrument. All of the labeled products showed a remarkably large increase in the molecular-ion peak abundance detection sensitivity of over 500-fold at picomolar concentration levels compared to that of unlabeled analytes in an ESI-MS system. These MS probes, used together with liquid MS detection, are widely applicable as a convenient method for the highly sensitive detection of less than picomolar levels of analytes, and therefore greatly enhance the power of ESI-MS analysis.