Quaternary N-glucuronides of 10-hydroxylated amitriptyline metabolites in human urine

Xenobiotica. 1990 Jul;20(7):727-38. doi: 10.3109/00498259009046888.

Abstract

1. Conjugated metabolites were isolated from the urine of patients receiving amitriptyline treatment using a combination of solid-phase extraction, h.p.l.c. and t.l.c. 2. By n.m.r. and mass spectrometry, N-glucuronides of E- and Z-10-hydroxyamitriptyline and of trans-10,11-dihydroxyamitriptyline were identified in addition to the previously described O-glucuronides of E- and Z-10-hydroxyamitriptyline and -nortriptyline and amitriptyline-N-glucuronide. 3. The quaternary ammonium glucuronides proved to be resistant to acid hydrolysis, but could be cleaved enzymatically. 4. In urine samples from three patients, 35-60% of conjugated 10-hydroxyamitriptyline was found in the form of N-glucuronides. 5. A volunteer given an i.v. infusion of amitriptyline-N-glucuronide excreted E- and Z-10-hydroxyamitriptyline-N-glucuronide; following ingestion of E-10-hydroxyamitriptyline its N-glucuronide could be measured in urine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amitriptyline / analogs & derivatives
  • Amitriptyline / pharmacokinetics*
  • Amitriptyline / urine
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Female
  • Glucuronates / urine*
  • Humans
  • Hydroxylation
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Middle Aged
  • Molecular Structure

Substances

  • Glucuronates
  • amitriptyline N-glucuronide
  • 10-hydroxyamitriptyline-N-glucuronide
  • Amitriptyline