Tissue samples, such as bovine muscle and liver, are typically extracted with an acetonitrile based solvent for LC-MS determination of veterinary drug residues. Among the most significant co-extracted substances are fats and polar lipids, particularly phospholipids (lecithin). Bovine liver typically contains about 45 mg of fat and about 25 mg of phospholipids per gram of tissue. Fats can be effectively removed from the acetonitrile based tissue extracts by liquid extraction with hexane or with SPE with octadecyl silica (C18). However, these defatting procedures are not effective for removal of phospholipids. Excessive amounts of phospholipids can shorten LC column life, contribute to ion-suppression, and contaminate the mass-spectrometer. In this study a novel reversed-phase sorbent is used for highly effective removal of both phospholipids and fats from bovine liver extracts prior to LC-MS/MS analysis. Greater than 95 % of phospholipids and greater than 85 % of fats were effectively removed from the tissue extracts after the simple pass-through SPE procedure. Recoveries of 45 compounds with published MRLs in beef liver averaged 83% with only a few compounds under 60%.