title: An intelligent data acquisition system for simultaneous screening of microsomal stability and metabolite profiling by liquid chromatography/mass spectrometry.
abstract: This paper describes the development of a mass spectrometer-based, intelligent, programmable, sample-selection data acquisition system with two unique features. One is that the system allows automatic determination of the mass to charge ratio (m/z) of an unknown compound and the utilization of the molecular ion information to perform selective ion monitoring (SIM) experiments for quantitation. The other is its decision-making capability to select intelligently different samples and perform different experiments during data acquisition. These features were demonstrated by the application of the system to simultaneous screening for the microsomal stability and metabolite profiling of adatanserin. In this application, the data acquisition system 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 the initial value, the system made a decision to perform metabolite profiling of the sample. This decision initiated a series of automated operations, such as selecting a sample for re-analysis, changing the data acquisition time and liquid chromatographic gradient and switching the SIM mode to the data-dependent product ion scanning mode. The completed analysis of the batch of samples provided information both on the microsomal stability and on the metabolic profile of adatanserin. This simultaneous approach to investigating microsomal stability and metabolite profiling significantly increases the throughput for drug discovery support.
authors.affiliation: Wyeth-Ayerst Research, CN 8000, Princeton, New Jersey 08543, USA. ming.gu@bms.com
authors.forename: M
authors.initials: M
authors.lastname: Gu
authors.forename: H K
authors.initials: HK
authors.lastname: Lim
mesh_terms: D000465:Algorithms; D000818:Animals; D001185:Artificial Intelligence; D001711:Biotransformation; D002853:Chromatography, Liquid; D001330:Electronic Data Processing; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000737:chemistry* / Q000378:metabolism; D010879:Piperazines / Q000737:chemistry / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism; D051381:Rats
chemical_list: D007202:Indicators and Reagents; D010879:Piperazines; D011743:Pyrimidines; C081272:WY 50324