Application of Capillary Electrophoresis for High-Throughput Screening of Drug Metabolism

摘要

Pharmaceutical industry currently needs to screen extensive compound libraries within preclinical stages of drug development. Capillary electrophoresis has become a well-established analytical technique during the last two decades. In spite of the fact that capillary electrophoresis offers a number of favorable features for high-throughput analytical assays, it is still less important than chromatographic techniques in drug development programs. Hence, the main aim of this chapter is to discuss the practical limitations of capillary electrophoresis utilization and suggest ways to overcome these constraints. This is illustrated with a practical example namely the introduction of a method allowing rapid characterization of a compound's stability against human liver microsomes. NADP+ production monitoring was adopted to ensure generic applicability of the method. The fast stability screening of 12 chosen probe drugs and determination of apparent kinetic parameters for the lidocaine/human liver microsomes system were performed in order to demonstrate the potential of the final method. The results were in a good agreement with the literature data determined by different methods