The two main techniques used to determine the degree ofmatrix effects on an HPLC–ESI–MS/MS method arepostextraction addition and postcolumn infusion. Thepostextraction addition technique requires sample extractswith the analyte of interest added postextraction comparedwith pure solutions prepared in mobile phase containingequivalent amounts of the analyte of interest [20,21,26–28].The difference in response between the postextractionsample and the pure solution divided by the pure solutionresponse determines the degree of matrix effect occurring tothe analyte in question under chromatographic conditions.