Liquid chromatography/mass spectrometric identification of benzimidazole anthelminthics metabolites formed ex vivo by Dicrocoelium dendriticum
Jazyk angličtina Země Anglie, Velká Británie Médium print
Typ dokumentu hodnotící studie, časopisecké články, práce podpořená grantem
PubMed
19630029
DOI
10.1002/rcm.4170
Knihovny.cz E-zdroje
- MeSH
- anthelmintika analýza farmakokinetika MeSH
- benzimidazoly analýza farmakokinetika MeSH
- chromatografie kapalinová metody MeSH
- Dicrocoelium chemie účinky léků MeSH
- hmotnostní spektrometrie metody MeSH
- metabolická inaktivace MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- anthelmintika MeSH
- benzimidazole MeSH Prohlížeč
- benzimidazoly MeSH
With further use of chemical agents in the control of parasitic infections, an increased number of drug resistance occurrences to antiparasitic drugs has been reported. Induction of enzymes responsible for detoxification of given drugs can contribute to drug resistance development in a parasitic organism. The identification of formed metabolites allows the characterization of the enzymes participating in biotransformation and possibly in drug resistance development. The objective of our work was to find and identify phase I and phase II metabolites of the anthelminthic drugs albendazole, flubendazole and mebendazole formed in ex vivo incubations by the parasitic helminth Dicrocoelium dendriticum, a parasite of ruminants and other grazing animals, using liquid chromatography/mass spectrometric (LC/MS) techniques. In the ex vivo study, approximately 50 living D. dendriticum adults were incubated in 5 mL RPMI-1640 medium in the presence of 10.0 micromol L(-1) benzimidazole drug (5% CO(2), 38 degrees C) for 24 h. The bodies of the parasite were then removed from the medium. After homogenization of parasites, both parasite homogenates and medium from the incubation were separately extracted using solid-phase extraction. The extracts were analyzed using LC/MS with electrospray ionization. The results showed that D. dendriticum enzymatic systems are capable of phase I oxidation and reduction as well as phase II conjugation reactions. Detected phase I metabolites comprised albendazole sulfoxide, reduced flubendazole and reduced mebendazole. As for phase II metabolites, methyl derivatives of both reduced flubendazole and reduced mebendazole were observed.
Citace poskytuje Crossref.org
Biotransformation of anthelmintics in nematodes in relation to drug resistance
