Pharmaceutical Biology, Pharmacenter, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
Department of Pharmaceutics, College of Pharmacy, University of Florida, 1345 Center Drive, Gainesville, FL 32610, USA.
Fitoterapia. 2020 Apr;142:104526. doi: 10.1016/j.fitote.2020.104526. Epub 2020 Feb 22.
3,4-Dihydroxyphenylacetic acid (DOPAC) and 3-hydroxyphenylacetic acid (3-HPAA) are intestinal metabolites of the dietary flavonoid quercetin. DOPAC reportedly showed anxiolytic activity after i.p. administration in rats. The fate of these metabolites after consumption, and the pharmacological properties of 3-HPAA in the body are largely unknown. The aim of the current study was to characterize pharmacokinetic properties of DOPAC and 3-HPAA after intravenous bolus application in rats. UHPLC-MS/MS methods for quantification of DOPAC and 3-HPAA levels in lithium heparin Sprague Dawley rat plasma were developed and validated according to international regulatory guidelines. Non-compartmental and compartmental analyses were performed. Pharmacokinetic profiles of DOPAC and 3-HPAA followed a two-compartment body model, with a fast distribution into peripheral tissues (half-lives of 3.27-5.26 min) and rapid elimination from the body (half-lives of 18.4-33.3 min).
3,4-二羟基苯乙酸（DOPAC）和 3-羟基苯乙酸（3-HPAA）是膳食类黄酮槲皮素的肠道代谢物。据报道，DOPAC 经腹腔注射给药后具有抗焦虑活性。这些代谢物在消耗后的命运，以及 3-HPAA 在体内的药理特性在很大程度上是未知的。本研究的目的是描述静脉推注后 DOPAC 和 3-HPAA 在大鼠体内的药代动力学特征。根据国际监管指南，建立和验证了用于锂肝素 Sprague Dawley 大鼠血浆中 DOPAC 和 3-HPAA 水平定量的 UHPLC-MS/MS 方法。进行了非房室和房室分析。DOPAC 和 3-HPAA 的药代动力学特征符合双室体模型，快速分布到外周组织（半衰期为 3.27-5.26 分钟），并迅速从体内消除（半衰期为 18.4-33.3 分钟）。
