In recent years, food safety laboratories have adopted new and simplified sample preparation methods designed to reduce analysis time and related costs, as well as to increase throughput. The QuEChERS methods for fruits and vegetables require only minutes for sample preparation, are suitable for effective recovery of hundreds of pesticides, and replace prior methods that took hours or days. In a similar fashion, effective acetonitrile based sample extraction methods have been developed for determination of multi-residue veterinary drugs in foodstuffs. In this poster, we will review fast and effective cleanup options for difficult matrices such as avocado, liver, and eggs, samples that are high in fats, phospholipids and extractable pigments. Excessive amounts of these substances in the injected sample can shorten LC or GC column life, contribute to ion-suppression, and contaminate the LC-MS or GC-MS. The goal of the cleanup is to remove as many of these interfering substances as possible from the sample extract without significant effect on the recovery of the multi-residue target compounds. Among the sorbents often used for dSPE cleanup are octadecyl silica (C18), primary/secondary amine silica (PSA), and graphitized carbon black (GCB). The advantages and limitations of these sorbents will be discussed with regard to both cleanup and recovery. We will show how many of the advantages are met and many of the disadvantages are overcome by use of a new rapid pas-through cleanup option, the Oasis PRiME HLB cartridge.