One such method is pulsed ultrafiltration which was invented and developed in our laboratory. Applications of pulsed ultrafiltration mass spectrometry include the screening of natural products and combinatorial libraries for drug discovery, the screening of directed libraries during lead optimization, drug metabolism profiling, toxicity screening of lead compounds for metabolic activation to electrophilic intermediates, and measurement of affinity constants. In summary, the mass spectrometry-based screening technique of pulsed ultrafiltration may be used to facilitate multiple stages of drug discovery and development. CT The HTS community continues to require technological and assay innovation, however novel approaches require a substantial development and validation period before achieving the status of a reliable screening tool. Once an innovative approach is identified, it needs to pass rigorous tests to ensure reliability, high information content, ability to automate, and scalability.
Scalability is particularly important.
Progress in target identification, in large part stimulated by the sequencing of the human genome, is beginning to swell the number of assays to be run at any given time. Chromatography shows promise for alleviating the pressures of a growing workload. This presentation will focus on the fundamentals of the approach and demonstrate their relevance to the needs of the HTS community. The technology will be demonstrated with a range of examples, including estrogen receptor, sorbitol dehydrogenase, b-galactosidase and thrombin assays. Innovations in the area of multiplexed assays will be described and illustrated, and the importance of mass spectrometry as a detection scheme will be emphasized.