Cleanup of matrices is the first, the most important, and the most critical step for both broad-spectrum screening and accurate determination of pesticides and their metabolites in vegetables,meats, drinks and fruits. In most cases, solid phase extraction (SPE) methods are used to clean up the extracts before the GC-MS analysis. The ideal SPE material(s) should remove the greatest number of food matrix interferences and offer truly high recoveries for a broad-spectrum of pesticides. Primary Secondary Amine (PSA) has been found as the most effective sorbent for removal of various matrices and significantly reducing matrix-enhancement effect. On the other hand, graphitized carbon black (GCB) is very useful for removal of coloring substances (i.e. pigments) and sterols. Therefore, PSA itself and/or combination of GCB/PSA dual layer should be most effective for sample cleanup.