This paper describes the application of high-flow (up to 2 mL/min) ion spray to the LC/MS determination of compounds of pharmaceutical and environmental interest with standard (HPLC) columns without established postcolumn splitting of the flow. It also illustrates the use of a nonvolatile mobilephase buffer, potassium phosphate, for the LC/MS determination of lysergic acid diethylamide (LSD). To achieve practicality and analytical ruggedness of the system, a liquid shield is placed between the sprayer and the ion sampling capillary, resulting in full-scan low-nanogram determination of quaternary ammonium drugs. The system also allows the use of gradients which is demonstrated for the analysis of carbamate pesticides and in particular for mexacarbate in pond water.