Synthesis and characterization of quaternary ammonium-linked glucuronide metabolites of drugs with an aliphatic tertiary amine group

J Pharm Sci. 1992 Nov;81(11):1079-83. doi: 10.1002/jps.2600811107.


A synthetic approach was developed to make the quaternary ammonium-linked glucuronide metabolites of compounds with an aliphatic tertiary amine group. The key step involved quaternization of the compound with methyl (2,3,4-tri-O-acetyl-alpha-D-glucopyranosyl bromide)uronate and sodium bicarbonate in a two-phase system of water and an organic solvent. The synthetic approach successfully yielded quaternary ammonium-linked glucuronides of 20 drugs and two of their phase I metabolites. The drugs were from various pharmacological classes: H1 antihistamines, antipsychotic agents, and tricyclic antidepressants. Physical data such as HPLC retention times, and diagnostic fast-atom bombardment mass spectra and 1H NMR spectra were obtained. These should aid in the characterization of compounds in samples isolated from biological media.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemical synthesis*
  • Chromatography, High Pressure Liquid
  • Glucuronates / chemical synthesis*
  • Magnetic Resonance Spectroscopy
  • Pharmacokinetics
  • Quaternary Ammonium Compounds / chemical synthesis*
  • Spectrometry, Mass, Fast Atom Bombardment


  • Amines
  • Glucuronates
  • Quaternary Ammonium Compounds