In this paper, high throughput analysis with 3 minute, rapid gradient conditions is described using the ionKey/MS™ System with an integrated ACQUITY UPLC® M-Class System and the Xevo® G2-XS QTof Mass Spectrometer. Extensive testing of representative small molecules and a peptide shows that the system is well-tolerated and exhibits excellent reproducibility and linear response. The iKey™ HSS T3 Separation Device used is robust, withstanding ~2200 injections of prepared human plasma with excellent peak shape and system pressure profile. A 99% solvent savings was realized when compared with an analytical system using a 2.1 mm column with flow rate ranging from 0.6 mL/min to 1.5 mL/min. These data, coupled with examples from the literature, illustrate that the ionKey/MS System with Xevo G2-XS QTof can be used as a full service platform for high throughput analysis and high sensitivity analysis to support all phases of drug discovery and development.