Evaluating human serum for trace levels of lipophilic organic chemicals: A novel GC-(Q)Orbitrap methodology

The exposome encompasses all environmental exposures across the lifespan, with chemical pollutants representing a major component. A robust sample preparation and multiresidue analytical method based on GC-(Q)Orbitrap technology was developed and validated for comprehensive characterization of the human chemical exposome in serum. The method demonstrated high accuracy and satisfactory performance at validation levels of 2 and 10 ng mL^-1, enabling the simultaneous quantification and confirmation of 198 GC-amenable compounds from diverse physicochemical properties (e.g., OPEs, PCBs, PAHs, and alkyl-PAHs). The validated methodology was applied to 24 serum samples from pregnant women participating in the INSULIN cohort (Hospital Joan XXIII, Tarragona, Spain), detecting ten chemicals (three PAHs, six alkyl-PAHs, and one synthetic antioxidant) at concentrations between 1 and 4 ng mL^-1. Furthermore, nontarget screening tentatively identified 64 additional compounds from various chemical families, highlighting the potential of GC-(Q)Orbitrap for broad-spectrum non-target analysis and holistic exposome characterization. This approach overcomes LC-based analytical limitations by enabling detection of low-to-medium polarity and semi-volatile compounds, demonstrating its value for expanding chemical coverage in human biomonitoring. Overall, this validated methodology provides a powerful tool for exposome-wide association studies (ExWAS) and public health assessments by enabling more comprehensive evaluation of human chemical exposures.