SYNTHESIS AND CHARACTERIZATION OF QUATERNARY AMMONIUM-LINKED GLUCURONIDE METABOLITES OF DRUGS WITH AN ALIPHATIC TERTIARY AMINE GROUP

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: H-1 antihistamines, antipsychotic agents, and tricyclic antidepressants. Physical data such as HPLC retention times, and diagnostic fast-atom bombardment mass spectra and H-1 NMR spectra were obtained. These should aid in the characterization of compounds in samples isolated from biological media.