Chemistry Department, Université du Québec à Montréal, P.O. Box 8888, Downtown Station, Montréal, Québec, Canada.
Rapid Commun Mass Spectrom. 2020 Apr 30;34(8):e8679. doi: 10.1002/rcm.8679.
Exposure to UV light can induce adverse effects on human health, such as photo-aging, immunosuppression, and cancer. Sunscreens are used to prevent the absorption of UV rays, but certain UV-filtering compounds have been shown to disrupt endocrine systems or act as carcinogens. To assess the effects of the exposure to such compounds, it is important to study the pathways by which they are biotransformed in the body.
Liquid chromatography coupled to high-resolution tandem mass spectrometry (LC/HRMS/MS) was employed to evaluate the oxidative metabolism and, specifically, the formation of reactive metabolites of six active ingredients commonly used in sunscreen formulations: oxybenzone, avobenzone, homosalate, octisalate, octocrylene, and octinoxate. In vitro incubations were performed with human and rat liver microsomes in the presence of β-nicotinamide adenine dinucleotide phosphate and glutathione. An LC/HRMS/MS method was developed to identify metabolites employing a biphenyl reversed-phase column for separating parent molecules, metabolites, and glutathione (GSH) adducts.
Each tested compound resulted in the formation of several metabolites, including at least one GSH adduct. Compounds containing ester groups were hydrolyzed, and some metabolites of the free acid forms were also detected. High-resolution MS/MS data was crucial for the structural elucidation of metabolites and GSH adducts. Fragmentation pathways were proposed for all parent compounds, as well as each described metabolite and adduct.
The results of this study will help better understand the metabolism and detoxification pathways of these xenobiotics.
暴露在紫外线下会对人体健康产生不良影响，例如光老化、免疫抑制和癌症。防晒霜用于防止紫外线吸收，但某些紫外线过滤化合物已被证明会破坏内分泌系统或充当致癌物质。为了评估接触此类化合物的影响，研究它们在体内被生物转化的途径非常重要。
采用液相色谱-高分辨串联质谱（LC/HRMS/MS）评估了六种常用于防晒霜配方的活性成分的氧化代谢，特别是活性代谢物的形成：氧苯酮、阿伏苯宗、胡莫柳酯、奥克立林、奥克立酯和甲氧基肉桂酸辛酯。在存在β-烟酰胺腺嘌呤二核苷酸磷酸和谷胱甘肽的情况下，用人和大鼠肝微粒体进行体外孵育。建立了一种 LC/HRMS/MS 方法，使用联苯反相柱分离母体分子、代谢物和谷胱甘肽（GSH）加合物来识别代谢物。
每种测试的化合物都形成了几种代谢物，包括至少一种 GSH 加合物。含有酯基的化合物被水解，并且还检测到一些游离酸形式的代谢物。高分辨 MS/MS 数据对于代谢物和 GSH 加合物的结构阐明至关重要。提出了所有母体化合物以及每个描述的代谢物和加合物的碎裂途径。
这项研究的结果将有助于更好地了解这些外源性物质的代谢和解毒途径。
