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Abstract

The metabolism of clemastine was studied in dogs, horses, and humans after a single dose of Tavegyl ((R)). The urine collected was extracted by solid-phase extraction or hydrolyzed with beta-glucuronidase and then extracted by liquid-liquid extraction, prior to analysis for unchanged drug and phase I and II metabolites by liquid chromatography/tandem mass spectrometry. The metabolites were identified by their molecular mass and interpretation of the product ion spectra, since no standard substances were available. Unchanged drug was recovered in urine samples from dogs and humans, but not from horses. In dogs and humans, the phase I metabolite, norclemastine, was identified, and clemastine metabolites with one and two additional oxygens were found in all three species. In horses and dogs monohydroxylation on one of the aromatic rings or the adjacent methyl group was favored while, in humans, the additional oxygen was positioned on either the aromatic or the aliphatic part of the structure, and the aliphatic reaction seemed to result in at least three isomers. In the metabolites with two additional oxygens, both the oxygens were found on the aliphatic fragment in humans and dogs, whereas they were situated on the aromatic part of the structure in horses. In human patients, glucuronidated monohydroxyclemastine was recovered, and in urine from horses both mono- and dihydroxyclemastine glucuronides were identified, while phase II metabolites could not be recovered from the dog urine. Clemastine metabolism in dogs and horses has, to our knowledge, not been studied before, and new metabolites from humans are presented in this article. Thus, the metabolites described in the present work have not been previously reported in the literature. Copyright (C) 2004 John Wiley Sons, Ltd.

Keywords

clemastine metabolites; dogm horse; human urine; liquid chromatography/tandem mass spectrometry

Published in

Rapid Communications in Mass Spectrometry
2004, volume: 18, number: 19, pages: 2267-2272
Publisher: JOHN WILEY & SONS LTD

SLU Authors

UKÄ Subject classification

Analytical Chemistry

Publication identifier

  • DOI: https://doi.org/10.1002/rcm.1622

Permanent link to this page (URI)

https://res.slu.se/id/publ/4571