In this work, a simple, high-throughput, and sensitive analytical method for simultaneously determining 270 pesticides and 13 mycotoxins from different chemical classes in raw coffee beans was developed. The modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) process mainly involved the effects of hydration volume, extraction solvent, extraction salt, and the type and amount of adsorbent used for sample extraction and purification. The samples were detected by liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-Q-TOF/MS) with a self-built database. The method effectively reduced matrix effects and the 283 compounds showed good linearity in their respective linear ranges (R2> 0.99). The screening detection limits (SDL) of the method were in the range of 0.1–20 μg/kg, and the limits of quantification (LOQ) were in the range of 0.2–20 μg/kg. The average recoveries of the 283 compounds at three spiked levels ranged from 72.1 % to 114.9 %, with intra-day and inter-day relative standard deviations less than 9.8 % and 17.1 %, respectively. The recoveries of all analytes ranged from 70.0 % to 120.0 % at three spiked levels (1×LOQ, 2×LOQ, and 10×LOQ), with relative standard deviations less than 20.0 %. The results were satisfactory according to the SANTE/11312/2021 guidelines. The method successfully analyzed 34 batches of actual samples, with concentrations ranging from 0.1 to 61.9 μg/kg for pesticides and 2.3–43.0 μg/kg for mycotoxins. This method provides a powerful tool for monitoring organic contaminants in raw coffee beans.
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