Facilitating Biomonitoring in Vulnerable Populations with Dried Blood Spots: A High-Throughput Kit-Based Approach for Bisphenol Analogues

Bisphenol analogues, widely used in consumer products, are emerging environmental contaminants with documented endocrine-disrupting effects. Conventional biomonitoring methods relying on venous blood or urine are logistically challenging, especially for vulnerable populations. Dried blood spot (DBS) sampling serves as a minimally invasive and logistically superior alternative, yet its application for trace-level bisphenol analogues analysis remains limited due to sensitivity issues, background contamination, and lack of standardization. Herein, we developed a high-throughput, kit-based method for the simultaneous quantification of 16 bisphenol analogues in DBS samples using protein precipitation combined with phospholipid removal, followed by UHPLC-MS/MS analysis. The method demonstrated high sensitivity, with method detection limits (MDLs) ranging from 0.04 to 1.17 μg/L, method quantitation limits (MQLs) ranging from 0.16 to 1.48 μg/L, and excellent accuracy and precision (recoveries: 70-128%; RSDs < 20%). Matrix effects were effectively compensated using stable isotope-labeled internal standards. The method's application to 33 authentic DBS samples indicated substantial exposure to bisphenol F (BPF), bisphenol A (BPA), bisphenol S (BPS), and diphenyl sulfone (DPS). This standardized, scalable workflow provides a robust tool for large-scale biomonitoring and epidemiological studies of bisphenol analogues.