Identification of some new clemastine metabolites in dog, horse, and human urine with liquid chromatography/tandem mass spectrometry.
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 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 2004 John Wiley & Sons, Ltd.
Publication Date: 2004-09-24 PubMed ID: 15384147DOI: 10.1002/rcm.1622Google Scholar: Lookup
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- Comparative Study
- Evaluation Study
- Journal Article
- Validation Study
Summary
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The study aims to explore how the drug clemastine is metabolized (broken down) in the bodies of dogs, horses, and humans after administering a single dose. The researchers discovered new metabolites (products of metabolism) in the urine samples from these species, indicating variations in how clemastine is metabolized among different species.
Metabolism Study and Methodology
- The study specifically examines how clemastine, a drug usually prescribed to treat allergies, is metabolized in dogs, horses, and humans after receiving a single dose.
- The researchers collected urine from the subjects and performed two types of extraction methods: solid-phase extraction and liquid-liquid extraction.
- The extracted samples were then analyzed using liquid chromatography/tandem mass spectrometry to identify and categorize the unchanged drug and both phase I and II metabolites. Metabolites are substances that are created during the metabolism process.
- The identification of these metabolites was done based on their molecular mass and the interpretation of product ion spectra.
Findings and Conclusions
- Clemastine in its unchanged form was found in the urine samples of dogs and humans, but not in horses.
- In humans and dogs, a phase I metabolite, norclemastine, was identified. In all three species, metabolites with one and two additional oxygens were found. The oxygen location varied by species, indicating differences in metabolic pathways.
- Glucuronidated monohydroxyclemastine, a product of phase II metabolism, was found in human urine. In horse urine, both mono- and dihydroxyclemastine glucuronides were identified. However, these phase II metabolites were not present in dog urine.
- The researchers conclude that the study not only provides a new understanding of clemastine’s metabolic fate in dogs and horses (which hasn’t been extensively studied before) but also identifies new human metabolites of the drug.
- The discovery of new metabolites and the variation of metabolic pathways in different species increases our understanding of clemastine’s efficacy and potential side effects across these species.
Cite This Article
APA
Tevell A, Bondesson U, Törneke K, Hedeland M.
(2004).
Identification of some new clemastine metabolites in dog, horse, and human urine with liquid chromatography/tandem mass spectrometry.
Rapid Commun Mass Spectrom, 18(19), 2267-2272.
https://doi.org/10.1002/rcm.1622 Publication
Researcher Affiliations
- Division of Analytical Pharmaceutical Chemistry, Uppsala University, BMC, SE-751 23 Uppsala, Sweden.
MeSH Terms
- Administration, Oral
- Animals
- Anti-Allergic Agents / administration & dosage
- Anti-Allergic Agents / urine
- Clemastine / administration & dosage
- Clemastine / analogs & derivatives
- Clemastine / classification
- Clemastine / urine
- Dogs
- Female
- Horses
- Humans
- Injections, Intravenous
- Male
- Reproducibility of Results
- Sensitivity and Specificity
- Species Specificity
- Urinalysis / methods
Citations
This article has been cited 4 times.- Abbasi MM, Valizadeh H, Hamishekar H, Mohammadnejad L, Zakeri-Milani P. Inhibitory effect of clemastine on P-glycoprotein expression and function: an in vitro and in situ study. Iran J Basic Med Sci 2016 Apr;19(4):423-9.
- Holcapek M, Kolárová L, Nobilis M. High-performance liquid chromatography-tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites. Anal Bioanal Chem 2008 May;391(1):59-78.
- Chen Y, Monshouwer M, Fitch WL. Analytical tools and approaches for metabolite identification in early drug discovery. Pharm Res 2007 Feb;24(2):248-57.
- Soni S, Kaur G. Emerging therapeutic application of clemastine: a review of recent patents updates. Naunyn Schmiedebergs Arch Pharmacol 2025 Aug;398(8):9609-9622.
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