Enhancing the Response of Alkyl Methylphosphonic Acids in Negative Electrospray Ionization Liquid Chromatography Tandem Mass Spectrometry by Post-Column Addition of Organic Solvents

A method to enhance the signal intensity and signal-to-noise of several alkyl methylphosphonic acids in negative electrospray ionization liquid chromatography tandem mass spectrometry (ESI LC-MS/MS) is presented. This class of compound represents the initial metabolites and environmental degradants of the nerve agents: VX, rVX (Russian VX), GB (Sarin), GF (Cyclosarin), and GD (Soman). Compared with the post-column addition of the mobile phase, the post-column addition of aprotic solvents and longer chain alcohols enhance the signal intensity and signal-to-noise ratio (S/N) of the chromatographic peaks by factors of up to 60 and 19, respectively. The post-column addition of water, methanol, and ethanol resulted in little or no relative signal enhancement. It is proposed that the post-column addition of these solvents do not result in the same enhancements due to stabilization of analyte solvation through hydrogen bonding.