Ultimately, LOD values were determined for detected pesticides in white and red wine samples, reaching the pg/ml to ng/ml range using an injection volume of 80 µL for both TOF MS and TOF MS/MS levels using the three activation methods. This highlights the advantage of selecting the most suitable method for optimal sensitivity. The approach described could also be beneficial for the general screening of pharmaceuticals and metabolites in plasma and urine or for lipid analysis.