Identification of novel metabolites of abiraterone in human serum and their metabolic pathways

Abstract

Two novel abiraterone (Abi, 3β-OH-Abi) metabolites in human serum were identified as 3α-OH-Abi and Δ⁵-Abi (D5A). Both metabolites were confirmed by their retention times on LC/MS and their product-ion mass spectra on LC-MS/MS compared to those of authentic compounds, which were chemically synthesized. The plausible metabolic pathways of these two metabolites are as follows: Abi is first oxidized to D5A by 3β-hydroxysteroid dehydrogenase (3β-HSD) and then irreversibly converted to Δ⁴-Abi (D4A) by ∆⁵-∆⁴ isomerase. Presumably, D5A detection is difficult because of its rapid conversion to D4A and its low concentration in serum samples. In contrast, the low concentration 3α-OH-Abi was generated by reducing the remaining D5A using 3α-hydroxysteroid dehydrogenase (3α-HSD).

Keywords: 3α-Hydroxysteroid dehydrogenase; Abiraterone; LC/MS; Metabolite.