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

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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).

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Acknowledgements

This study was partially supported by JSPS KAKENHI (Grant no. 22K06571). We thank Dr. Taro Sakamoto of Bruker Japan for his help regarding MS/MS.

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Authors and Affiliations

  1. School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women’s University, 11-68, Koshien Kyuban-Cho, Nishinomiya, 663-8179, Japan

    Shizuyo Horiyama

  2. Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan

    Noboru Hayama, Hiroki Yoneyama & Yoshihide Usami

  3. Institute for Biosciences, Mukogawa Women’s University, 11-68, Koshien Kyuban-Cho, Nishinomiya, 663-8179, Japan

    Jun Haginaka

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  1. Shizuyo Horiyama
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Correspondence to Shizuyo Horiyama or Noboru Hayama.

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Horiyama, S., Hayama, N., Yoneyama, H. et al. Identification of novel metabolites of abiraterone in human serum and their metabolic pathways. ANAL. SCI. 40, 67–74 (2024). https://doi.org/10.1007/s44211-023-00431-4

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