Analytical method development for twenty-one analytically challenging and under-investigated pesticides in drinking...

Analytically challenging pesticides and biocides remain underrepresented in routine drinking water (DW) monitoring because of their diverse physicochemical properties and associated analytical constraints. Consequently, their occurrence and potential contribution to human exposure remain poorly documented. This study developed and validated complementary analytical methods for the determination of twenty-one under-investigated pesticides, including biocides, in DW. Twenty compounds were determined by online solid-phase extraction coupled to high performance liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS), while only one compound was analyzed by direct injection ion chromatography-tandem mass spectrometry (DI-IC-MS/MS). Method validation was performed according to NF T90-210 and ISO 21253 standards using six representative DW matrices. The validated methods demonstrated satisfactory analytical performance, with limits of quantification (LOQ) ranging from 1.2 to 100 ng L^-1, quadratic calibration models (R² > 0.98), relative recoveries generally between 80 and 120%, acceptable relative bias, intermediate precision below 30%, and expanded measurement uncertainties generally below 50%, although values of up to 60% were observed for some analytes. The methods were subsequently applied to 313 DW samples collected during a nationwide French monitoring campaign from DW systems supplying approximately 20-25% of the population. Among the twenty-one target compounds, only fluopyram was quantified, and only in a single sample, at 11 ng L^-1, while no other target compound was quantified among the samples for which a valid analytical result was available. These findings are consistent with national occurrence databases, which indicate extremely low quantification frequencies (QFs) for most investigated substances. The developed methods provide robust tools for routine monitoring of the investigated parent compounds and establish a framework for future studies incorporating relevant transformation products in DW.