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口服给药后双酚S在小鼠体内的代谢

Metabolism of bisphenol S in mice after oral administration.

作者信息

Song Yuanyuan, Xie Peisi, Cai Zongwei

机构信息

State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, SAR, China.

School of Environmental Science and Engineering, Guangdong University of Technology, Guangzhou, China.

出版信息

Rapid Commun Mass Spectrom. 2018 Mar 30;32(6):495-502. doi: 10.1002/rcm.8051.

Abstract

RATIONALE

As an important substitute of bisphenol A (BPA), bisphenol S (BPS) shows comparable estrogenic effects. BPS is now widely used in consumer products with widespread human exposure. In order to evaluate the health risk of BPS, it is essential to develop a rapid method for the determination of BPS and its metabolites as well as its biotransformation capacity in vivo.

METHODS

Two major BPS phase II metabolites, BPS glucuronide (BPS-G) and BPS sulfate (BPS-S), were synthesized and used as standards for the development of a ultra-performance liquid chromatography/electrospray ionization tandem mass spectrometry (UPLC/ESI-MS/MS) method. Phase II metabolism of BPS in imprinting control region (ICR) female mice after oral administration with different dosages (10, 100, 1000 μg/kg body weight) was investigated.

RESULTS

Urinary elimination was the main excretion route for BPS, with the total recovery ranging from 52.8% to 78.1%. In urine, BPS-G was identified as the predominant metabolite, and the maximum concentrations of BPS-G and BPS-S were obtained at 6 h after the oral administration upon the adjustment by creatinine. BPS was the major compound existed in feces. Only trace amounts of BPS and its metabolites were detected in digestive and excretory related tissues (<1%).

CONCLUSIONS

The distribution and metabolic pathway of BPS in mice were assessed. More than 50% of BPS was excreted through phase II metabolism. Due to the biological inactivity of BPS-G and BPS-S, rapid metabolism of BPS to BPS-G and BPS-S may result in reduced toxicity of BPS in vivo.

摘要

原理

作为双酚A(BPA)的重要替代品,双酚S(BPS)具有类似的雌激素效应。BPS目前广泛应用于消费品中,人类普遍接触。为了评估BPS的健康风险,开发一种快速测定BPS及其代谢物以及其体内生物转化能力的方法至关重要。

方法

合成了两种主要的BPS II相代谢物,BPS葡糖醛酸苷(BPS-G)和BPS硫酸盐(BPS-S),并将其用作开发超高效液相色谱/电喷雾电离串联质谱(UPLC/ESI-MS/MS)方法的标准品。研究了不同剂量(10、100、1000μg/kg体重)口服给药后,印记控制区(ICR)雌性小鼠体内BPS的II相代谢。

结果

尿液排泄是BPS的主要排泄途径,总回收率在52.8%至78.1%之间。在尿液中,BPS-G被确定为主要代谢物,经肌酐校正后,口服给药后6小时获得BPS-G和BPS-S的最大浓度。BPS是粪便中存在的主要化合物。在消化和排泄相关组织中仅检测到痕量的BPS及其代谢物(<1%)。

结论

评估了BPS在小鼠体内的分布和代谢途径。超过50%的BPS通过II相代谢排泄。由于BPS-G和BPS-S的生物无活性,BPS快速代谢为BPS-G和BPS-S可能导致其在体内的毒性降低。

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