Non-target screening (NTS) plays a major role in the monitoring and management of water bodies. While the NTS of moderate to non-polar substances is well-established, the screening of highly polar chemicals remains challenging. In this study, a robust separation method for highly polar substances using zwitterionic hydrophilic interaction liquid chromatography coupled with high-resolution mass spectrometry (ZIC-HILIC-HRMS) was developed. This method was specifically designed for the NTS of industrial wastewater, with the objective of capturing a wide range of polar contaminants in each acquisition run. Method validation included assessing key parameters such as repeatability, reproducibility, linearity, and limit of detection (LOD). For repeatability and reproducibility, the average %RSD of intensity and retention time across all substances in different matrices-solvent, influent, and effluent-remained below 6% and 1%, respectively (n = 10). The method demonstrated good linearity (R2 > 0.99) for 75% of the substances, while LODs varied between 0.1 and 40µg/L depending on the compound tested. The method was then applied for NTS analysis of untreated wastewater at various locations within a chemical industrial park. Additionally, the overall influent and effluent of an industrial wastewater treatment plant (WWTP) were monitored over a 10-day period. Principal component analysis (PCA) was performed to interpret the data, identifying irregularities in the wastewater content. Moreover, the method demonstrated the WWTP's ability to achieve an average removal efficiency of approximately 90% for this category of substances in this period, while also detecting their degradation products in the effluent. Finally, the method was successfully integrated into the daily monitoring routine of the WWTP, ensuring continuous surveillance and improved management of wastewater treatment processes.
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