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: 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.
Luo
H
H
College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
Hawes
E M
EM
McKay
G
G
Midha
K K
KK
D000588:Amines / Q000138:chemical synthesis*; D002851:Chromatography, High Pressure Liquid; D005965:Glucuronates / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D010599:Pharmacokinetics; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis*; D016339:Spectrometry, Mass, Fast Atom Bombardment
D000588:Amines; D005965:Glucuronates; D000644:Quaternary Ammonium Compounds