LC-MS/MS method for quantification of 3,4-dihydroxyphenylglycol, a norepinephrine metabolite in plasma and brain regions

Bioanalysis. 2019 May;11(10):971-986. doi: 10.4155/bio-2019-0023.

Abstract

Aim: To evaluate suitability of the LC-MS/MS method to quantify 3,4-dihydroxyphenylglycol (DHPG) that is used as a biomarker for monoamine oxidase (MAO) inhibition. Methods: DHPG was extracted using alumina basic cartridges and quantified on a triple quadrupole mass spectrometer using negative electrospray ionization, without the use of derivatization reagents. Results: Modulation of DHPG levels was observed following administration of selective and nonselective MAO inhibitors and results were in correlation with historical MAO inhibition potential of compounds. Conclusion: The proposed method is sensitive enough to measure plasma DHPG levels and DHPG can be used as a biomarker to assess MAO inhibition potential of new therapeutic agents.

Keywords: 3,4-dihydroxyphenlyglycol; LC–MS/MS; MAO inhibition; alumina extraction; bioanalysis; biomarker; catecholamine; drug–drug interaction; monoamine oxidase; norepinephrine.

MeSH terms

  • Animals
  • Blood Chemical Analysis / methods*
  • Brain / drug effects
  • Brain / metabolism*
  • Chromatography, Liquid / methods*
  • Humans
  • Male
  • Methoxyhydroxyphenylglycol / analogs & derivatives*
  • Methoxyhydroxyphenylglycol / blood
  • Methoxyhydroxyphenylglycol / metabolism
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / pharmacology
  • Norepinephrine / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry / methods*

Substances

  • Monoamine Oxidase Inhibitors
  • Methoxyhydroxyphenylglycol
  • Monoamine Oxidase
  • 3,4-dihydroxyphenylglycol
  • Norepinephrine