The achiral reaction monitoring of the synthetic route for rosuvastatin was successfully performed utilizing an ACQUITY UPC2 System and ACQUITY QDa Detector employed in an Open Access environment. Combining the separation power of Trefoil Columns and the ACQUITY UPC2 System, a fast and sensitive method for determining enantiomeric excess was achieved. Trefoil CEL1 delivered very good separation of the enantiomers, while providing improved resolution and MS compatibility compared to the patented methodology. Using an ACQUITY QDa Detector for nominal mass confirmation, determining enantiomeric presence was achieved with high confidence. The Trefoil Column methodology proved to be linear at various injection volumes and free from injection solvent effects. This result provided greater confidence in the method development of the assay, which will be used for future routine use. The combined technologies of ACQUITY UPC,2 ACQUITY QDa, and Trefoil Columns work well to provide a fast and successful separations platform for achiral and chiral reaction monitoring.