Sample preparation strategies for mass spectrometry analysis in human exposome research: Current status and future perspectives

The exposome is the measure of total environmental exposures and has a significant impact on human health outcomes. Exposomics research typically examines complex biological samples and assesses 100s to 1,000s of small molecules associated with chemical exposure events. To acquire robust and comprehensive datasets encompassing a broad range of multi-class biomarkers of chemical exposures, high-resolution and tandem mass spectrometry have emerged as the preferred analytical tools in the field. Due to matrix effects and interferences associated with complex biological samples together with the presence of very low abundance analytes, sensitivity and reproducibility have plagued exposomic studies. This is especially true for large sample sets where adequate robustness is frequently lacking. A possible solution to this problem is the development of non-discriminatory sample preparation methods which can reduce interferences while increasing sensitivity and reproducibility. However, sample preparation techniques intrinsically result in a discrete loss of analytes leading to the outstanding analytical challenge of finding a proper balance. Therefore, approaches which decrease matrix interferences while preserving broad chemical coverage need to be developed. In this review, sample preparation procedures currently applied in exposome research and related fields are summarized and critically evaluated. This includes a comparison of advantages and limitations between different techniques such as solid-phase extraction, liquid extraction, QuEChERS, filters and dilute and shoot with a liquid chromatography-mass spectrometry analysis focus. Based on this evaluation, recommendations promoting balanced strategies for sample preparation in future exposome research applications are provided.