Metabolism of Five Bisphenol A Analogs Studied by LC-HRMS/MS.

Bisphenol A (BPA) structural analogs are increasingly used as alternatives in many industrial applications, due to growing evidence of BPA-related toxicity. Despite their widespread use, little is known about the biotransformation of these BPA analogs in the body. In this study, the metabolism of five BPA analogs (bisphenol AF, bisphenol F, bisphenol S, cumylphenol, and tetramethylbisphenol F) were investigated, using human and rat liver fractions, to evaluate the formation of phase I and phase II metabolites. Liquid chromatography high-resolution tandem mass spectrometry was employed to separate and characterize over 50 metabolites, many of which were not previously reported. The structures of all detected oxidative metabolites, dimers, GSH adducts, glucuronide, and sulfate conjugates were elucidated. A biphenyl solid-core chromatographic column was utilized for the separation of all metabolites, with a subsequent method, on a F5 column, specifically optimized for the separation of dimers formed via oxidative metabolism. There are several examples in this work where the combination of high chromatographic resolution and tandem mass spectrometry were necessary to distinguish between isomeric metabolites and conjugates.