If the availability of different sources of matrix is limited, the concentration factor of a single matrix could be varied to test the ability of the PCIS to correct for the matrix effect induced by the increased matrix (Method 2 in Scheme 1). When applied to the endocannabinoid example, plasma with a concentration factor (CF) between 5 and 0.25 (= four times diluted plasma) was spiked with SIL standards. As the left plot in the Method 2 pane shows for d4-LEA, the plasma CF clearly affected the uncorrected peak area. The matrix effect logarithmically decreased with increasing the CF, in line with previous studies . Looking at the summary plot at the right, 2F-AEA had the most difficulty to correct for NADA and 2-AG, agreeing with the initial exploration. For the other compounds the PCIS correction improved the matrix effect from 9% -98% to 86% -118%.