Abstract
The combination of large volume injection and mixed-mode chromatography was performed for direct ultra-trace LC-MS/MS analysis of seven artificial sweeteners with varying physicochemical properties in surface water samples.•The injection volume was raised from 10 µL to 500 µL, while the overall analysis time was only increased by ≈5 min compared to the initial method.•Online column head refocusing and concentration of analytes enabled detection in sub-ng L(-1) concentration range without elaborate sample preparation steps.•Relative standard deviations <7% despite multiple injection into the loop.