In vitro metabolism of sunscreen compounds by liquid chromatography/high‐resolution tandem mass spectrometry

Rationale 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. Methods 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. Results 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. Conclusions The results of this study will help better understand the metabolism and detoxification pathways of these xenobiotics.