Department of Pharmacy, University of Salerno, Fisciano, SA, Italy; PhD Program in Drug Discovery and Development, University of Salerno, Fisciano, SA, Italy.
Department of Pharmacy, University of Salerno, Fisciano, SA, Italy.
J Pharm Biomed Anal. 2021 Jul 15;201:114107. doi: 10.1016/j.jpba.2021.114107. Epub 2021 Apr 30.
Bitter acids are a class of prenylated phloroglucinol derivatives present in Humulus lupulus L., known for their multiple healthy properties, nevertheless, research regarding their metabolism and stability is lacking. This study was aimed to elucidate the metabolic stability of hop α- and β-acids and characterize I and II phase metabolites in vitro and in vivo. For this purpose, an ultra high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) method was developed and validated. Mice liver microsomes were used to assess metabolic stability; in vitro t and clearance values were calculated, showing a moderate metabolism for α-acids (t: 120.01 min, CL 11.96 μL/min/mg), while β-acids were metabolized faster (t: 103.01 min, CL: 13.83 μL/min/mg). I and II phase metabolites were characterized both in in vitro, and in vivo, in mouse plasma and urine after oral administration. A combined full scan/data dependent/precursor ion list-triggered neutral loss (FS/dd-MS/PIL-tNL) strategy was used to detect unknown and expected metabolites. As a result, 33 compounds were detected, including novel metabolites, such as 9 potential oxidized metabolites of humulones (M6-M14), and 10 glucuronide conjugates of α-acids, comprising 7 glucuronide derivatives of oxidized phase I metabolites (M26-M32). The proposed method extends the current knowledge regarding metabolization of hop α- and β-acids and could be applied for the comprehension of the metabolic fate of this class of compounds in different species, as well as for in vivo pharmacokinetic studies.
苦味酸是一种存在于啤酒花（Humulus lupulus L.）中的类prenylated 间苯三酚衍生物，具有多种健康特性，但关于其代谢和稳定性的研究还很缺乏。本研究旨在阐明啤酒花 α-和 β-酸的代谢稳定性，并在体外和体内对其 I 相和 II 相代谢物进行表征。为此，开发并验证了一种超高效液相色谱-高分辨率质谱（UHPLC-HRMS）方法。使用小鼠肝微粒体评估代谢稳定性；计算体外 t 和清除率值，结果表明 α-酸的代谢中等（t：120.01min，CL 11.96μL/min/mg），而 β-酸的代谢速度更快（t：103.01min，CL：13.83μL/min/mg）。在口服给药后，在体外和体内（在小鼠血浆和尿液中）对 I 相和 II 相代谢物进行了表征。采用全扫描/数据依赖/前体离子列表触发中性丢失（FS/dd-MS/PIL-tNL）综合策略来检测未知和预期的代谢物。结果共检测到 33 种化合物，包括新的代谢物，如 9 种潜在的黄腐酚氧化代谢物（M6-M14），以及 10 种 α-酸的葡萄糖醛酸缀合物，包括 7 种 I 相氧化代谢物的葡萄糖醛酸衍生物（M26-M32）。该方法扩展了有关啤酒花 α-和 β-酸代谢的现有知识，可用于理解此类化合物在不同物种中的代谢命运，以及体内药代动力学研究。
