Matrix effect (ME) in gas chromatography (GC) is usually due to undesired interactions with active sites in the inlet and column which can lead to analyte losses and/or peak tailing. Analyte protectants (APs) are compounds added individually or in combination to interact with the active sites and minimize errors related to ME. However, the current Aps mixtures/introducing approach cannot sufficiently compensate for ME in all cases. In this study, a comparison (based on sensitivity and peak shape) between thirteen different Aps (2,3-Butanediol, 3-O-ethylglycerol, d-Fructose, d-Gluconic acid γ-lactone, d-Glucose, d-Ribonic acid γ-lactone, d-Ribose, D-Sorbitol, l-Gulonic acid γ-lactone, Menthol, Polyethylene glycol, Triglycerol and Vanillinin) four different solvents (n-hexane, acetone, acetonitrile and ethyl acetate) for 224 pesticides is presented. The comparison was done between solvent based calibration and extracts of one selected difficult matrices (strawberry), prepared according to the citrate-buffered QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure. Each Ap had different behavior for each solvent. In general, acetonitrile showed the most susceptibility to polar Aps, followed by acetone, then ethyl acetate and then n-hexane. However, in the absence of Aps, peak shapes were best for n-hexane, then ethyl acetate, then acetone and then acetonitrile. Based on their results, a mixture of seven Aps was chosen. To ease their introduction, the sandwich injection approach (SIA) was used. Several factors were studied such as the calibration solvent, Aps solvent and Aps concentration. For acetonitrile calibration, the ME of 213/224 (95%) pesticides were ≤ 20% in one Aps mixture compared to 36 pesticides (16%) in non-protected mixtures. For n-hexane:acetone (9:1) calibration, the ME of 221/224 (99%) pesticides were ≤ 20% in one Aps mixture compared to 102 pesticides (45%) in non-protected mixtures.