Single dose pharmacokinetics of intravenous 3,4-dihydroxyphenylacetic acid and 3-hydroxyphenylacetic acid in rats

Fitoterapia. 2020 Apr:142:104526. doi: 10.1016/j.fitote.2020.104526. Epub 2020 Feb 22.

Abstract

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).

Keywords: 3,4-Dihydroxyphenylacetic acid (PubChem CID: 547); 3-HPAA; 3-Hydroxyphenylacetic acid (PubChem CID: 12122).; DOPAC; Pharmacokinetics; UHPLC-MS/MS; Validation.

Publication types

  • Validation Study

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / administration & dosage
  • 3,4-Dihydroxyphenylacetic Acid / pharmacokinetics*
  • Administration, Intravenous
  • Animals
  • Male
  • Phenylacetates / administration & dosage
  • Phenylacetates / pharmacokinetics*
  • Quercetin / metabolism
  • Rats, Sprague-Dawley

Substances

  • Phenylacetates
  • 3,4-Dihydroxyphenylacetic Acid
  • Quercetin
  • 3-hydroxybenzeneacetic acid