The need for unambiguous data to support milestone transition and compound selection for drug discovery and development has fueled an unrelenting desire for instruments with higher sensitivity. Consequently sensitivity enhancement has been a critical attribute in each evolution of modern LC-MS instrumentation.
Here, a variety of drugs in human plasma were analyzed using several configurations of the ionKey/MS System with the Xevo G2-XS Q-Tof. In the first series of experiments, the linearity and limits of quantitation (LOQ) were determined using direct injection and under Tof-MRM mode of operation. In the second set of experiments, a trap valve manager was configured to load samples onto the trap column for initial injection and wash, before being switched into the LC stream for compound elution, thus significantly increasing the injectable sample volume. Trapping using either single pump or dual pump configuration is described. The advantages of using trap-and-elute for optimum peak shape and higher sample volume is discussed.