High-throughput chromatographic approaches to liquid chromatographic/tandem mass spectrometric bioanalysis to support drug discovery and development Review Article

Due to the fast paced nature of pharmaceutical research and development, and the important role that drug analysis plays in supporting this venture, significant resources have been invested in minimizing the time spent performing bioanalysis to support in vivo studies. These efforts have focused on sample preparation and chromatographic techniques, because mass spectrometric detection is usually not rate limiting. In this paper, liquid chromatographic strategies used to facilitate high-throughput liquid chromatography tandem mass spectrometry (LC/MS/MS) bioanalysis to support drug discovery and development are reviewed. Different analytical approaches that focus on chromatographic sample preparation and on reduction of the LC/MS cycle time are discussed. The techniques reviewed include the use of high flow rates and fast (ballistic) gradients, restricted access media (RAM), monolithic columns, turbulent flow chromatography (TFC), and column switching. Specific applications of each of these techniques are also reviewed.