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Identification of metabolites of anthelminthics in helminth parasites using mass spectrometry
Komrska, Jan ; Vokřál, Ivan (referee) ; Skálová, Lenka (advisor)
If we want be successful in the treatment of parasitic disease, it is important to get the utmost information on the fate of given drug. The discovery of the metabolism of anthelmintics and in cosequence of participating enzymes can help us fight the rising resistance to given drugs. The aim of our work was to find and identify phase I and phase II metabolites of the anthelminthic drugs albendazole (ABZ), flubendazole (FLU) and mebendazole (MEB) formed in ex vivo incubations by parasitic helminth Dicrocoelium dendriticum, using liquid chromatography-mass spectrometric techniques. In the ex vivo study, D. dendriticum adults were incubated in cultivating medium in presence of benzimidazole drug for 24 hours. After incubation of parasites, both parasite homogenates and medium from the incubation were separately extracted using solid phase extraction. The extracts were analyzed using liquid chromatography-mass spectrometry (LC-MS). We detected in phase I albendazole sulphoxide, reduced flubendazole and reduced mebendazole. As for phase II metabolites, methylderivatives of flubendazole, reduced flubendazole and reduced mebendazole were observed.
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