Quaternary N-glucuronides of 10-hydroxylated amitriptyline metabolites in human urine.
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.
Breyer-Pfaff
U
U
Department of Toxicology, University of Tübingen, FRG.
Becher
B
B
Nusser
E
E
Nill
K
K
Baier-Weber
B
B
Zaunbrecher
D
D
Wachsmuth
H
H
Prox
A
A
D000328:Adult; D000639:Amitriptyline / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005260:Female; D005965:Glucuronates / Q000652:urine*; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008875:Middle Aged; D015394:Molecular Structure
D005965:Glucuronates; C061039:amitriptyline N-glucuronide; C066142:10-hydroxyamitriptyline-N-glucuronide; D000639:Amitriptyline