Incorporating higher throughput analytical methods and enhancing the ability for data mining of in vitro ADME samples can greatly benefit drug discovery teams during lead optimization. Standard bioanalytical techniques generally rely on triple quadrupole mass spectrometers using the technique of multiple reaction monitoring (MRM) for quantification (QUAN). Although this conventional MRM approach can provide high specificity and sensitivity, this practice is also time-consuming since it is a two step process and requires the optimization of multiple parameters (cone voltage, collision energy, and Q1/Q3 m/z values) for each and every compound being analyzed. Furthermore, MRM techniques only detect the initial compound of interest and data mining for other, qualitative (QUAL) information (such as metabolite formation) is not possible. The use of a sensitive hybrid Q-Tof instrument in a full scan acquisition mode and subsequent narrow window mass eliminates the need for compound optimization while also providing both qualitative and quantitative (QUAL/QUAN) data to assist chemistry efforts in structure-property-relationships (SPR). The Xevo-Q-TOF mass spectrometer is a high resolution accurate mass instrument which possesses the speed, sensitivity, linearity, and wide mass range needed to screen in vitro ADME samples. The high resolution capabilities of Q-TOF-MS, combined with mass defect filtering and monitoring of isotopic peak patterns, allows for the discrimination against background noise when performing narrow window mass extraction from a full scan analysis. Samples were generated from multiple ADME assays including cellular (Caco-2) permeability, microsomal and hepatocyte stability, plasma stability, protein binding, and CYP450 inhibition of (known) metabolite formation. Chromatographic separations were obtained utilizing an Acquity UPLC and generic gradient conditions. Quantitative results obtained by narrow m/z windows were compared with traditional MRM analysis of the same samples analyzed using the high-sensitivity QTRAP 5500 system.. Data mining was then performed on the full scan analysis to identify known metabolites such as glucuronide, de-methylated, and hydroxylated metabolites from metabolic assays, as well as to determine possible non-hepatic compound instability and isomerization from in vitro plasma stability and permeability samples. Results indicate that the use of the Xevo-Q-TOF, combined with narrow window mass extraction and full scan analysis, gives comparable quantitative data (e.g. percent loss of parent compound) to conventional MRM techniques without the need for time-consuming compound optimization of new chemical entities (NCEs) or known CYP-dependent metabolites. In addition, valuable qualitative information could be obtained only from Xevo-Q-TOF full scans showing the susceptibility of reference compounds and NCEs for Phase I oxidative metabolism, Phase II conjugation, and non-hepatic, compound instability.