A high capacity LC/MS system for the bioanalysis of samples generated fromplate-based metabolic screening

HPLC/MS is a linear technique characterized by serial injection and analysi s of individual samples. Parallel-format high-throughput screens for drugli ke properties present a significant analytical challenge. Analysis speed an d system ruggedness are key requirements for bioanalysis of thousands of sa mples per day. The tasks involved in LC/MS analysis are readily divided int o three areas, sample preparation/liquid handling, LC/MS method building/sa mple analysis, and data processing. Several automation and multitasking str ategies were developed and implemented to minimize plating and liquid handl ing errors, reduce dead times within the analysis cycle, and allow for comp rehensive review of data. Delivering multiple samples to multiple injectors allows the autosampler time to complete its wash cycles and aspirate the n ext set of samples while the previous set is being analyzed. A dual-column chromatography system provides column cycling and peak stacking and allows rapid throughput using conventional LC equipment. Collecting all data for a compound into a single file greatly reduces the number of data files colle cted, increases the speed of data collection, allows rugged and complete re view of all data, and provides facile data management. The described system s have analyzed over 40,000 samples per month for two years and have the ca pacity for over 2000 samples per instrument per day.