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Development of a sensitive UPLC-MS/MS method for simultaneous determination of 15 Bisphenol A analogues in human serum and urine: Application of paired samples and global exposure assessment.

Authors (7)
Guangting HuKey Laboratory of Public Health Safety, MOE, School of Public Health, Fudan University, Shanghai 200032, China.
Zhichun ZhangKey Laboratory of Public Health Safety, MOE, School of Public Health, Fudan University, Shanghai 200032, China.
Yi HuangKey Laboratory of Public Health Safety, MOE, School of Public Health, Fudan University, Shanghai 200032, China.
Deyu FangKey Laboratory of Public Health Safety, MOE, School of Public Health, Fudan University, Shanghai 200032, China.
Journal of chromatography. A
Unknown
Published
Oct 13, 2025
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Abstract

The global replacement of Bisphenol A (BPA) with structurally similar yet understudied analogues demands precise biomonitoring tools to assess human exposure and health risks. To bridge critical gaps, we developed a novel ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous quantification of 15 emerging BPA analogues including Bisphenol AF (BPAF), Bisphenol AP (BPAP), Bisphenol B (BPB), Bisphenol C (BPC), Bisphenol E (BPE), Bisphenol F (BPF), Bisphenol G (BPG), Bisphenol FL (BPFL), Bisphenol M (BPM), Bisphenol P (BPP), Bisphenol pH (BPPH), Bisphenol S (BPS), Bisphenol TMC (BPTMC), Bisphenol Z (BPZ), and Bisphenol A diglycidyl ether (BFDGE)-in human serum and urine matrices. The method achieved ultrahigh sensitivity with limits of detection (LODs) of 0.008-0.032 μg/L in urine and 0.010-0.030 μg/L in serum, high accuracy (recoveries: 84.58-113.53 %), and reproducibility (relative standard deviation (RSD) ≤14.7 %). Rigorous validation was conducted through uncertainty assessment and green chemistry metrics (GAC) evaluation. The following scores were obtained: Analytical GREEnness metric approach (AGREE):0.65, Analytical GREEnness Metric for Sample Preparation (AGREEprep):0.64, Modified Green analytical procedure index (MoGAPI) :72, Complex modified Green analytical procedure index (ComplexMoGAPI):73, RGB model: 74.2 %, Blue Applicability Grade Index (BAGI):60, Click Analytical Chemistry Index (CACI):69 and Carbon Footprint Reduction Index (CaFRI):71, respectively. These results confirm the method's reliability and environmental sustainability. Applied to 44 paired samples from Chinese children, the study revealed serum biomarkers (BPPH + BPTMC) as superior indicators of internal exposure compared to urinary metabolites, providing the first-reported paired biospecimen data for these analogues. Furthermore, dual-matrix biomonitoring (serum + urine) significantly improved cumulative exposure assessment accuracy. This work establishes a robust analytical framework for tracking emerging BPA substitutes, supporting evidence-based chemical regulation and advancing environmental health research.

Keywords

BiomonitoringBisphenolsGlobal exposure assessmentPaired samplesUPLC-MS/MS

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