title: The isomeric metabolites of doxepin in equine serum and urine.
abstract: Due to its tranquilizing properties, the tricyclic antidepressant doxepin may be misused as a doping agent in competition horses. Therefore, efficient analytical procedures are required to detect this drug in samples submitted for doping control. To screen for parent doxepin in equine blood and urine, a less specific method has been accepted employing gas chromatography (GC) combined with electron impact (EI) mass spectrometry (MS). The aim of this study was identification of doxepin metabolites providing more specific MS data to verify positives resulting from screening. Thus, after a horse was given doxepin-HCl (1 mg/kg, i.v.), blood and urine were analyzed for free or conjugated metabolites using GC combined with EI- and positive chemical ionization (PCI) MS. In both of the sample materials, cis- and trans-isomers of desmethyldoxepin were detected for up to 48 h after treatment using trifluoracetylation and GC/EI-MS. Following enzymic hydrolysis of urine and propionylation of extracts, each four isomers of hydroxy desmethyldoxepin and hydroxydoxepin were recovered for up to 24 and 48 h, respectively. These compounds were characterized by their EI- and PCI-mass spectra. Although distinct positions of the hydroxyl groups could not be determined, the presence of each two cis/trans-isomeric pairs of differently monohydroxylated metabolites may be assumed. Results reported here suggest, that screening horses for parent doxepin should be completed by analysis of its major isomeric metabolites, desmethyldoxepin and hydroxydoxepin, providing MS data specific enough for confirmatory analysis.
authors.affiliation: Institute of Pharmacology, Toxicology and Pharmacy, Veterinary Faculty, University of Munich, Königinstrasse 16, D-80539 Munich, Germany.
authors.forename: Heinz-Werner
authors.initials: HW
authors.lastname: Hagedorn
authors.forename: Heribert
authors.initials: H
authors.lastname: Meiser
authors.forename: Heidrun
authors.initials: H
authors.lastname: Zankl
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Schulz
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000378:metabolism* / Q000652:urine; D002849:Chromatography, Gas / Q000379:methods*; D004300:Doping in Sports; D004316:Doxepin / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005260:Female; D006736:Horses; D013058:Mass Spectrometry / Q000379:methods*; D013237:Stereoisomerism
chemical_list: D000929:Antidepressive Agents, Tricyclic; D004316:Doxepin; C028701:desmethyldoxepin