Publication detail

Investigation of the Metabolism of Monepantel in Ovine Hepatocytes by UHPLC/MS/MS

Year: 2013

Type of publication: článek v odborném periodiku

Name of source: Analytical and Bioanalytical Chemistry

Publisher name: Springer

Page from-to: 1705-1712

Titles:

Language	Name	Abstract	Keywords
cze	Identifikace metabolismu monepantelu v ovčích hepatocytech s využitím UHPLC/MS/MS	Práce se zabývá charakterizací metabolismu monepantelu, nového léčiva proti parazitům, pomocí UHPLC/MS/MS. Vysoká správnost určení přesné hodnoty m/z v základních i tandemových spektrech umožnila určit elementární složení všech přítomných iontů. Výsledky ukázaly, že preferované metabolické reakce I. fáze jsou S-oxidace na sulfoxid a následně sulfon, aromatická hydroxylace. Co se týká metabolitů II. fáze, ve vzorcích byla identifikována glukuronidace, sulfatace a konjuace s acetylcysteinem.	Monepantel; UHPLC/MS/MS; Biotransformace; Metabolismus léčiv
eng	Investigation of the Metabolism of Monepantel in Ovine Hepatocytes by UHPLC/MS/MS	Monepantel (MOP) belongs to a new class of anthelmintic drugs known as aminoacetonitrile derivatives. It was approved for use in veterinary practice in Czech Republic in 2011. So far, biotransformation and transport of MOP in target animals have been studied insufficiently, although the study of metabolic pathways of anthelmintics is very important for the efficacy of safety of therapy and evaluation of the risk of drug-drug interactions. The aim of this study was to identify MOP metabolites and to suggest the metabolic pathways of MOP in sheep. For this purpose, primary culture of ovine hepatocytes was used as a model in vitro system. After incubation, medium samples and homogenates of hepatocytes were extracted separately using solid-phase extraction. Analysis was performed using a hybrid quadrupole-time-of-flight analyzer with respect to high mass accuracy measurements in full scan and tandem mass spectra for the confirmation of an elemental composition. The obtained results revealed S-oxidation to sulfoxide and sulfone and arene hydroxylation as MOP phase I biotransformations. From phase II metabolites, MOP glucuronides, sulfates, and acetylcysteine conjugates were found. Based on the obtained results, a scheme of the metabolic pathway of MOP in sheep has been proposed.	Monepantel; Aminoacetonitrile derivatives; Ultrahigh-performance liquid chromatography/mass spectrometry; Biotransformation; Drug metabolism

Search

Login for students

Login for employees

Publication detail

Departments

Other Parts

Map

Services

Popular Links