In the face of advancing technology in combinatorial synthesis and high-throughput screening, the drug discovery process continues to evolve. Drug metabolism and pharmacokinetics (DMPK) studies play a key role in lead identification and optimization. This fast-paced development process has imposed an enormous burden on the analytical chemist to design faster and more sensitive assay techniques to aid the drug discovery and development. Various strategies aimed at increasing the throughput and reducing sample numbers in discovery DMPK have been developed for both in vitro and in vivo experiments. However, quantity and speed, often associated with technology development, do not always guarantee quality but a clear strategic focus in the spirit of 'Fit for Purpose' approach is required to implement systems to generate high-quality data and to drive research in new directions.