An Integrated Approach for an Ultra-High Throughput On-Line SPE-MS/MS System and its Applications to ADME Assays

摘要

We have successfully implemented RapidADME, which enhanced the usability of our first generation RapidFire~(TM) system and allowed it to be applied to a greater number of ADME assays. The system can now perform analyses in conjunction with triple quadrupole mass spectrometers controlled by Analyst or MassLynx data systems. Multiple acquisition methods containing MRM transitions customized for each test compound analyzed can be used within a run, and data acquired can be saved into multiple files. We have validated the RapidADME approach using samples from metabolic stability, plasma protein binding, and PAMPA permeability assays. Good correlation was obtained when comparing the data from RapidADME to those obtained from our standard LC/MRM approaches. A small number of outliers were likely due to matrix interferences. Future studies, including the use of APCI, will be conducted to further improve the success rate.