Matrix Effect in Liquid Chromatography Mass Spectrometry

Matrix Effects are the suppressing or enhancing properties of a co-eluting compound from a biological matrix on the primary signal response of the target analyte. In several liquid chromatography-tandem mass spectrometry (LC-MS) biological studies, Matrix Effects can suppress the ion intensity by interfering with target analyte ionization. Compounds with high mass, polarity, and basicity are typical candidates to trigger matrix effects.

Matrix components can deprotonate and neutralize the analyte ions produced in the liquid phase, causing ion suppression. Matrix Effects may also be caused by co-precipitation of the analytes with less-volatile and heavy compounds. Under these circumstances, the efficiency of droplet formation in liquid phase gets affected. High viscosity interfering compounds in a biological matrix could increase the surface tension of the charged droplets and further prevent evaporation. Additionally, matrix compounds can reduce the stability of the analyte ions produced in the gas phase. Also, the accumulation of charged matrix components in front of a quadrupole mass analyzer entrance could lead to charging issues, thus preventing the analyte ions from moving into the mass analyzer.

Figure 1 below summarizes the proposed mechanisms of matrix effects in Electrospray Ionization (ESI).

P. Panuwet, R. Hunter, et al. Biological Matrix Effects in Quantitative Tandem Mass Spectrometry-Based Analytical Methods: Advancing Biomonitoring. Anal Chem. 2016;46 (2):93-105.