Author/Editor		Kračun, Matjaž; Grahek, Rok; Kocijan, Andrej; Lavrič, Anton; Kocjan, Darko; Zupančič-Kralj, Lucija
Title		Izolacija in identifikacija metabolitov atorvastatina
Type		članek
Source		In: Glavič P, Brodnjak-Vončina D, editors. Slovenski kemijski dnevi 2002. Zbornik referatov s posvetovanja. 2. del; 2002 sep 26-27; Maribor. Maribor: Univerza v Mariboru, Fakulteta za kemijo in kemijsko tehnologijo,
Publication year		2002
Volume		str. 628-33
Language		slo
Abstract		Atorvastatin is a synthetic HMG-CoA reductase inhibitor, lf lowers plasma cholesterol by inhibiting cholesterol biosynthesis. Atorvastatin is metabolized into o- and p- hydroxylated derivatives of atorvastatin, various beta-oxidation and unsaturated products. The hydroxylated derivatives are active metabolites with similar function as atorvastatin and they contribute to about 70% of the HMG-CoA reductase inhibition. In our study, rats were administered an oral dose of atorvastatin and their bile samples were collected. Atorvastatin and its metabolites were extracted from acidified bile samples by ethyl acetate. The ethyl acetate layer was analyzed by gradient reverse phase HPLC with UV and MS detection. A preparative HPLC method was developed in order to isolate individual metabolites. Fractions were obtained by preparative chromatography and analyzed. Fractions including atorvastatin metabolite of interest were pooled and returned to further purification procedure in order to get a pure product. For the confirmation of metabolite pure product is essential because MS detection can not differentiate between o- and phydroxylated derivatives. The structure of main isolated metabolite o- hydroxy atorvastatine was confirmed by MSIMS and NMR measurements.
Descriptors		HMG-COA REDUCTASE INHIBITORS BILE DRUG RESIDUES CHROMATOGRAPHY, HIGH PRESSURE LIQUID RATS