A homogeneous binary matrix assisted laser desorption/ionization time-of-flight mass spectrometry assay for determination of artificial sweeteners in beverages

Artificial sweeteners have been widely used as additives in various beverages. Due to the safety risks associated with artificial sweeteners, it is essential to develop a simple, rapid, and high-throughput method for the analysis of artificial sweeteners. Here, we report a homogeneous binary matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) assay for the simultaneous analysis of sweeteners including aspartame (ASP), neotame (NEO), and advantame (ADV) with a simple dilution step. The combination of nanodiamonds with 2,5-dihydroxybenzoic acid effectively improved the signal response of sweeteners, decreased the background noise, and improved the "spot-to-spot" repeatability. After the optimization, the method exhibits low limits of detection (ASP: 20 nΜ; NEO: 10 nΜ; ADV: 5 nΜ), good linearity (r > 0.995), satisfactory accuracy (96.2-103.0%), and lower RSDs (1.5-5.8%). Finally, the target sweeteners in 17 soft beverages were successfully determined with this method, showing the potential for the routine analysis of artificial sweeteners.