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Identification of novel metabolites of abiraterone in human serum and their metabolic pathways.
Analytical Sciences ( IF 1.6 ) Pub Date : 2023-10-13 , DOI: 10.1007/s44211-023-00431-4
Shizuyo Horiyama 1 , Noboru Hayama 2 , Hiroki Yoneyama 2 , Yoshihide Usami 2 , Jun Haginaka 3
Affiliation  

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).

中文翻译:

人血清中阿比特龙新代谢物及其代谢途径的鉴定。

人血清中的两种新型阿比特龙(Abi、3β-OH-Abi)代谢物被鉴定为 3α-OH-Abi 和 Δ5-Abi (D5A)。与化学合成的真实化合物相比,这两种代谢物均通过 LC/MS 上的保留时间和 LC-MS/MS 上的产物离子质谱得到证实。这两种代谢物的可能代谢途径如下:Abi 首先被 3β-羟基类固醇脱氢酶 (3β-HSD) 氧化为 D5A,然后被 Δ5-Δ4 异构酶不可逆地转化为 Δ4-Abi (D4A)。据推测,D5A 检测很困难,因为它快速转化为 D4A 并且在血清样品中浓度较低。相比之下,低浓度的 3α-OH-Abi 是通过使用 3α-羟基类固醇脱氢酶 (3α-HSD) 还原剩余的 D5A 产生的。
更新日期:2023-10-13
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