A method and system are provided for detecting the concentration of an analyte in a fluid sample. The method and system involve analysis of a volatilized, ionized fluid sample using a mass spectrometer or other ionic analyte detection device that provides a signal proportional in intensity to the quantity of ionized analyte detected. The improvement involves replacement of a necessary non-analyte component in the fluid sample with a substitute component that serves the same purpose as the original component but is either more volatile than the original component and/or the analyte or undergoes a reaction to provide lower molecular weight reaction products, and results in an increased intensity in signal and signal-to-noise ratio. Acoustic fluid ejection is a preferred method of generating nanoliter-sized droplets of fluid sample that are then volatilized, ionized, and analyzed. Also provided are zwitterionic compounds suitable as the substitute components that when ionized and heated decompose to provide carbonic dioxide, a nitrogenous species such as ammonia, an amine, or nitrogen gas, and a volatile aromatic compound.