Inclusion of emerging contaminants into water quality monitoring programs can serve as an additional layer for protecting water resources against deterioration. Based on prior non-target screening using LC-QTOF, a direct injection liquid chromatography-electrospray ionization-tandem mass spectrometry with multiple reaction monitoring method was developed for the determination of 23 micropollutants in natural waters. The combination of methodological simplicity, flexibility, environmental compatibility, and demonstrated performance under real-world monitoring conditions represents a significant advancement over existing chromatographic strategies for the determination of relevant and emerging pollutants. The method provides high sensitivity and reliability, enabling the simultaneous quantification of target analytes (pesticides, pharmaceuticals and products of their transformation) spanning a wide polarity range (XLogP3 0.3-6.1) and extending the applicability of multianalytes chromatographic analysis to complex environmental matrices. The limits of detection and quantification and linearity were evaluated in deionized water, groundwater, and surface water, while accuracy in terms of recovery and precision were determined in surface water. Pesticides provided satisfactory recoveries ranging from 83 to 120%, with quantification limits between 0.02 µg L-1 and 0.18 µg L-1, whereas pharmaceuticals displayed recoveries of 83-119%, with quantification limits of 0.03-0.20 µg L-1 in different types of water. Using the developed method, 599 water samples were analyzed between 2023 and 2025. The most frequently detected compounds at concentrations above the limit of quantification were terbumeton-desethyl, prometon and benzenesulfonamide in groundwater; fluconazole and sulfamethoxazole in surface water; and propazine-2‑hydroxy, terbuthylazine-2‑hydroxy and carbamazepine in both types of water samples.