Background: Mass spectrometry (MS) is being introduced into a large number of clinical laboratories. It provides specificity because of its ability to monitor selected mass ions, sensitivity because of the enhanced signal-to-noise ratio, and speed because it can help avoid the need for intensive sample cleanup and long analysis times. However, MS is not without problems related to interference, especially through ion suppression effects. Ion suppression results from the presence of less volatile compounds that can change the efficiency of droplet formation or droplet evaporation, which in turn affects the amount of charged ion in the gas phase that ultimately reaches the detector.

Content: This review discusses materials shown to cause ion suppression, including salts, ion-pairing agents, endogenous compounds, drugs, metabolites, and proteins. Experimental protocols for examining ion suppression, which should include, at a minimum, signal recovery studies using specimen extracts with added analyte, are also discussed, and a more comprehensive approach is presented that uses postcolumn infusion of the analyte to evaluate protracted ionization effects. Finally, this review presents options for minimizing or correcting ion suppression, which include enhanced specimen cleanup, chromatographic changes, reagent modifications, and effective internal standardization.

Summary: Whenever mass spectrometric assays are developed, ion suppression studies should be performed using expected physiologic concentrations of the analyte under investigation.