Most SPE methods for analyzing drugs of abuse in oral fluid incorporate a strong acid in order to achieve high recoveries of basic drugs using strong cation exchange sorbent. However, there have been reports1 that this acid may lead to conversion of cannabidiol (CBD) to tetrahydrocannabinol (THC). In this research study, we used mixed mode XTR tips without the addition of a strong acid in order to avoid possible conversion of CBD to THC. This study focuses on analyzing 45 drugs of abuse commonly found in driving-under-the-influence (DUI) cases. The analysis uses a single extraction method and high performance liquid chromatography with tandem mass spectrometry (LC-MS/MS). A separate LC-MS/MS method is also presented for differentiation of delta-8 and delta-9 THC (for positive THC cases). We evaluated whether XTR™ tips for INTip SPE could be used for simultaneously extracting a 45 drug/metabolite panel from Quantisal™-collected oral fluid suitable for Driving Under the Influence of Drugs (DUID) testing.