Multi-Residue Analysis of Pesticides and Pharmaceuticals in Soil by QuEChERS–LC-HRMS: Validation, Occurrence in Northeastern Greece, and Ecological Risks

Emerging contaminants are increasingly recognized as persistent soil pollutants with often-unknown environmental effects, yet Mediterranean monitoring data remain scarce. This study compared three established sample preparation approaches and subsequently validated and applied the best-performing QuEChERS-based procedure coupled to LC–HRMS for the simultaneous determination of 29 pesticides and 7 pharmaceuticals in soil. The modified EN 15662:2018 QuEChERS approach exhibited the best overall analytical performance. Validation following SANTE 11312/2021 (v2026) guidelines showcased good linearity (R2 > 0.992), acceptable recoveries (86% within 70–120%), precision (RSDs ≤ 18.1%), and sensitivity (LOQs: 0.01–2.5 ng/g). Negligible matrix effects were observed for 78% of compounds, while measurement uncertainty remained below 50%. Preliminary application to pear samples demonstrated potential method applicability to fruit matrices, although further matrix-specific validation is required. Analysis of 16 samples from northeastern Greece revealed 15/36 compounds in 62.5% of samples, with carbamazepine and imidacloprid as the dominant residues and fungicides as the most prevalent class. Importantly, 27% of the detected compounds were no longer approved in the EU. Ecological risk assessment using toxicity exposure ratios (TERs) and risk quotients (RQs) identified imidacloprid, carbamazepine, and terbuthylazine as medium risks. This workflow supports soil monitoring under the EU Soil Monitoring Law and One Health strategy.