We have designed an efficient, integrated approach to incorporate in-vivo metabolic profiling data with quantitative pharmacokinetic (PK) assays for the determination of the liabilities of the NCE in early Discovery studies. This fills a much needed gap between in-vitro metabolic stability screening assays involving thousands of compounds to biotransformation studies focusing on fewer compounds identified for development. The integrated work-flow proposed does not compromise the speed or the quality of the exposure data used to support early discovery programs. In this presentation, we examine the main instrument parameters that are critical for the integration of UHPLC-QqTOF technology to existing bioanalytical workflows, in order to provide simultaneous quantitative and qualitative (quan/qual) bioanalysis of samples generated following in-vivo studies. A few case studies of simultaneous quan/qual approaches using TOF technology will be presented. Finally, important emerging TOF technologies that could potentially benefit early discovery in the semi-quantification of metabolites without synthesized standards will also be discussed.