Peptides and other biological molecules such as proteins and monoclonal antibodies are becoming increasingly popular in many therapeutic areas such as drug discovery, medical diagnostics, and precision medicine1, 2. Because the initial stages of drug discovery often require only small amounts of target compound, fast and efficient product isolation is a key element to meeting aggressive development timelines. While traditional peptide isolation is generally performed using UV detection, mass-directed isolation makes the purification process easier with better clarity between target peptide and the contaminants formed during synthesis and cleavage. In addition, developing a separation that utilizes both mass and UV detection ensures a more complete chromatographic sample profile. Compounds that do not ionize, or ionize poorly, will often be detected with low wavelength UV. Conversely, peptides with very low UV extinction will usually be detected with mass analysis. The fluidically-optimized flow path of the UPLC combined with a specially-designed low dispersion fraction collector enable the mass-directed isolation of sharp, narrow product peaks. In this study, we illustrate the utility of the ACQUITY UPLC H-Class and Waters Fraction Manager-Analytical (WFM-A) Systems for the analysis and isolation of a synthetic peptide at the small scale. Fast, targeted isolation increases purification efficiency by reducing unnecessary sample handling while generating just enough product for future experiments.