Identification of Beauvericin metabolites using rat and human liver microsomes and in vivo urinary excretion study in rats for biomonitoring application

Beauvericin (BEA), an emerging mycotoxin, belongs to a class characterized by a cyclic depsipeptide ring structure, commonly produced by fungal species like Fusarium sp. and Beauveria bassiana. BEA is known for contaminating cereals and grains (wheat, maize). Humans might be exposed to BEA through contaminated food. Biomonitoring is a valuable method for assessing environmental and occupational exposure to specific chemicals. These studies measure chemical biomarkers to quantify exposure for public health risk assessment. However, identifying specific and sensitive chemical biomarkers for BEA exposure remains challenging. In the present study, metabolites of BEA were identified through in vitro metabolism studies conducted in the rat (RLM) and human liver microsomes (HLM) using the liquid chromatography-high resolution mass spectrometry (LC-HRMS) technique. Seventeen metabolites were characterized, showcasing products of oxidation, reduction, and deamination reactions. Predominantly, oxidative metabolites resulting from mono‑oxygenation, di‑oxygenation, and tri‑oxygenation were observed. The metabolites in RLM primarily consisted of mono and di‑oxygenated forms, while in HLM, tri‑oxygenated and demethylated products were also found. Furthermore, in vivo excretion study in rat urine samples confirmed the presence of oxygenated metabolites detected in the in vitro samples. Consequently, the study suggests that oxygenated metabolites of BEA could serve as useful biomarkers for conducting future biomonitoring studies.