State-of-the art liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis uses a constant electrospray (ESI) voltage for data acquisition. Modern qualitative and quantitative LC-MS/MS methods depend on highly efficient gradient elution chromatography. The changing chemical composition of mobile phase during gradient elution results in an inherent disconnect with single point ESI voltage optimization. A constant ESI voltage limits spray stability and compromises chromatographic peak area quantification, limiting total peak area and increasing peak area relative standard deviation (RSD). Using a nanospray source equipped with a digitally controlled stage and software for precise and reproducible emitter positioning for data acquisition we investigate the relationship between spray stability and data quality at flow rates of 200 nL/min, 500 nL/min and 1,000 nL/min (data not presented here).