Identification of some new clemastine metabolites in dog, horse, and human urine with liquid chromatography/tandem mass spectrometry

Rapid Communications in Mass Spectrometry : RCM
Annica TevellMikael Hedeland

Abstract

The metabolism of clemastine was studied in dogs, horses, and humans after a single dose of Tavegyl. 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 ...Continue Reading

References

Apr 10, 1999·The Journal of Pharmacy and Pharmacology·M H ChoiB C Chung
Apr 2, 2003·Journal of Veterinary Pharmacology and Therapeutics·K TörnekeH Broström
Jun 25, 2004·Veterinary Dermatology·H HanssonK Törneke

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Citations

Oct 19, 2006·Pharmaceutical Research·Yuan ChenWilliam L Fitch
Sep 1, 2009·Rapid Communications in Mass Spectrometry : RCM·Cuirong SunYuanjiang Pan
May 26, 2006·European Journal of Mass Spectrometry·Saifeng PeiYuanjiang Pan

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