The goal of this study was to improve the sample preparation for the analysis of drugs of abuse/pain management panels in oral fluids. The oral fluid samples were collected with Intercept® i2he™ Oral Fluid Collection Devices. The diluted oral fluid samples were filtered using Thompson Filter Vials, followed by LC/MS/MS analysis. The most critical aspects of reliable Oral Fluid analysis are the reduction of interferences from the sample matrix and analyte recovery. Traditionally, SPE, SLE and centrifugation have been used to reduce matrix interference prior to MS analysis. However, these techniques are time consuming, adversely impact recovery, require expensive consumables and equipment and use large amounts of solvent. Thomson eXtreme® Filter Vials (patented) offer multi-layer filtration for viscous samples and samples containing up to 30% solid particulates.