ABSTRACT
Improvements to the design and operation of a Gilson 215 multiprobe liquid-handling system have resulted in a significant increase in the throughput for flow injection molecular weight characterization of combinatorial chemistry libraries. The rapid injection sequence, and subsequent increased sample throughput, is effected by directing the entire mobile-phase flow through each of the injection loops sequentially while isolating or "dead-ending" the remaining nonactive loops. This mode of operation was accomplished by incorporating column-switching valves prior to and following the set of eight parallel injectors. Analysis rates are achieved without sacrificing the integrity of the flow injection peak profile as baseline resolution is maintained for all samples. Using this system, the total analysis time for a 96-well microtiter plate has been reduced to approximately 5 min.
ABSTRACT
The evolution of high-throughput drug discovery is readily apparent as the pharmaceutical industry continues to stress the rapid progression of new chemical entities and biological agents through drug discovery and development pipelines. Mass spectrometry and high performance liquid chromatography-mass spectrometry have played an instrumental role in the support and advancement of all facets of high-throughput drug discovery. The introduction of new instrumentation has extended the breadth of mass spectrometric-based capabilities from the characterization of high-throughput organic synthesis products to early adsorption, distribution, metabolism and excretion profiling. Additionally, advances in the capacity and throughput of mass spectrometry systems have concurrently led to the introduction of data management tools to address automated data reduction, archival and mining, as well as analytical data integration to chemical and biological databases.
