Hu Guangting, Zhang Zhichun, Huang Yi, Fang Deyu, Zhan Ming, Qu Weidong, Zhou Ying
Key Laboratory of Public Health Safety, MOE, School of Public Health, Fudan University, Shanghai 200032, China.
Department of Physics and Chemistry, Pudong New Area for Disease Control and Prevention, Shanghai 200136, China.
J Chromatogr A. 2025 Oct 11;1760:466217. doi: 10.1016/j.chroma.2025.466217. Epub 2025 Jul 18.
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.
用结构相似但研究较少的类似物全球替代双酚A（BPA），需要精确的生物监测工具来评估人类暴露情况和健康风险。为了填补关键空白，我们开发了一种新型超高效液相色谱-串联质谱（UPLC-MS/MS）方法，用于同时定量测定15种新兴的BPA类似物，包括双酚AF（BPAF）、双酚AP（BPAP）、双酚B（BPB）、双酚C（BPC）、双酚E（BPE）、双酚F（BPF）、双酚G（BPG）、双酚FL（BPFL）、双酚M（BPM）、双酚P（BPP）、双酚pH（BPPH）、双酚S（BPS）、双酚TMC（BPTMC）、双酚Z（BPZ）和双酚A二缩水甘油醚（BFDGE）——在人血清和尿液基质中。该方法实现了超高灵敏度，尿液中的检测限（LOD）为0.008 - 0.032μg/L，血清中的检测限为0.010 - 0.030μg/L，具有高准确度（回收率：84.58 - 113.53%）和重现性（相对标准偏差（RSD）≤14.7%）。通过不确定度评估和绿色化学指标（GAC）评估进行了严格验证。获得了以下分数：分析绿色度指标方法（AGREE）：0.65，样品制备的分析绿色度指标（AGREEprep）：0.64，改良绿色分析程序指数（MoGAPI）：72，复杂改良绿色分析程序指数（ComplexMoGAPI）：73，RGB模型：74.2%，蓝色适用性等级指数（BAGI）：60，点击分析化学指数（CACI）：69和碳足迹减少指数（CaFRI）：71。这些结果证实了该方法的可靠性和环境可持续性。应用于来自中国儿童的44对样本，该研究表明血清生物标志物（BPPH + BPTMC）作为内部暴露的指标优于尿液代谢物，提供了这些类似物的首次报告的配对生物样本数据。此外，双基质生物监测（血清 + 尿液）显著提高了累积暴露评估的准确性。这项工作建立了一个强大的分析框架，用于追踪新兴的BPA替代品，支持基于证据的化学监管并推进环境健康研究。
