Table 1.

Methods for the evaluation of matrix effects.

Name of the Method	Description of the Method	Limits	References
Post-column infusion method	The post-column infusion method provides a qualitative assessment of matrix effects. It permits the identification of the retention time zones in a chromatographic plot most likely to experience phenomena of ion enhancement or suppression. It consists in a constant flow through the LC-MS column of the mobile phase or blank, and the post column injection through a T-piece of the analyte standard. ME can be assessed as suppression or enhancement of the analyte signal in specific regions of the chromatogram.	Only qualitative results Inefficiency for highly diluted samples. The concentration of the analyte should be in the analytical range being investigated Laborious and time-consuming procedure, especially for multiresidue analysis Blank matrix not always available	[7,10,12,25,29,30,31,32,33,34,35,36,37,38,39]
Post-extraction spike method	In the post-extraction spike method, the response of the analyte in a standard solution is compared to that of the analyte spiked into a blank matrix sample at the same concentration. Deviations from the responses of the two solutions are identified as ion enhancement or suppression. This method is able to provide a quantitative assessment of matrix effect.	Blank matrix not always available	[26,40,41,42,43,44]
Slope Ratio Analysis	It allows a semi-quantitative screening of matrix effect. It exploits spiked samples and matrix-matched calibration standards at different calibration levels. This modified approach evaluates the same parameters obtained by post-extracion addition method in an entire selected range of concentrations instead of a single level.	Only semi-quantitative results	[28]
Relative MEs evaluation	It permits the evaluation of the variability of MEs lot by lot	Laborious	[3,26,45,46,47,48,49]