Segmented post‐column analyte addition; a concept for continuous response control of liquid chromatography/mass spectrometry peaks affected by signal suppression/enhancement

A novel technique, "segmented post-column analyte addition", is proposed to visualize and compensate signal suppression/enhancement effects in electrospray ionization tandem mass spectrometry (ESI-MS/MS). Instead of delivering a constant flow of analyte solution between the liquid chromatography (LC) column exit and the ESI interface into the eluent resulting from LC separation of analyte-free matrix in order to determine retention time widows in which suppression/enhancement is unimportant (King et al., J. Am. Soc. Mass Spectrom. 2000; 11: 942), segmented packets of analyte-containing solvent and analyte-free solvent were infused into an LC eluent resulting from separation of an analyte-containing sample. The obtained, superimposed, periodic spikes are much narrower than the analyte peak eluting from the column. The height of the spikes is affected by signal suppression phenomena to the same extent as the analyte signal, and hence variations of the spike height can be used to correct the peak area of analyte peaks affected by signal suppression/enhancement.