An intelligent data acquisition system for simultaneous screening of microsomal stability and metabolite profiling by liquid chromatography/mass spectrometry

This paper describes the development of a mass spectrometer-based, intellig ent, programmable, sample-selection data acquisition system with two unique features. One is that the system allows automatic determination of the mas s to charge ratio (m/z) of an unknown compound and the utilization of the m olecular ion information to perform selective ion monitoring (SIM) experime nts for quantitation. The other is its decision-making capability to select intelligently different samples and perform different experiments during d ata acquisition. These features were demonstrated by the application of the system to simultaneous screening for the microsomal stability and metaboli te profiling of adatanserin. In this application, the data acquisition syst em continuously calculated the peak areas of adatanserin from SIM analyses of a batch of microsomal incubates stopped at various time points. Once the peak area of adatanserin had dropped to an arbitrarily predefined 60% of t he initial value, the system made a decision to perform metabolite profilin g of the sample. This decision initiated a series of automated operations, such as selecting a sample for re-analysis, changing the data acquisition t ime and liquid chromatographic gradient and switching the SIM mode to the d ata-dependent product ion scanning mode. The completed analysis of the batc h of samples provided information both on the microsomal stability and on t he metabolic profile of adatanserin. This simultaneous approach to investig ating microsomal stability and metabolite profiling significantly increases the throughput for drug discovery support. Copyright (C) 2001 John Wiley & Sons, Ltd.