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

Article abstract of 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-α-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.