High-throughput quantitative bioanalysis by LC/MS/MS

This review article discusses the most recent significant advances in the s ample preparation and mass spectrometry aspects of high-throughput bioanaly sis by LC/MS/MS for the quantitation of drugs, metabolites and endogenous b iomolecules in biological matrices. The introduction and implementation of automated 96-well extraction has brought about high-throughput approaches t o the biological sample preparation techniques of solid-phase extraction, l iquid-liquid extraction and protein precipitation The fast-flow on-line ext raction technique is a different high-throughput approach that has also sig nificantly speeded up analysis by LC/MS/MS. The use of pierceable caps for biological tubes further enhances the analysis speed and improves the safet y in handling biological samples. The need for adequate chromatographic sep aration in order to eliminate interferences due to metabolites and/or matri x effects in LC/MS/MS is discussed. To highlight our limited understanding of atmospheric pressure ionization mass spectrometry, results from recent i nvestigations that appear to be counter-intuitive are presented. Looking ah ead to the future, multiplexed LC/MS/MS systems and capillary LC are presen ted as areas that can bring about further improvements in analysis speed an d sensitivity to quantitative bioanalysis by LC/MS/MS. Copyright (C) 2000 J ohn Wiley & Sons, Ltd.