Login for students

Login for employees

Publication detail

Structural Characterization of Electrochemically and in Vitro Biologically Generated Oxidation Products of Atorvastatin Using UHPLC/MS/MS
Authors: Jirásko Robert | Mikysek Tomáš | Chagovets Vitaliy Viktorovich | Vokřál Ivan | Holčapek Michal
Year: 2013
Type of publication: článek v odborném periodiku
Name of source: Analytical and Bioanalytical Chemistry
Publisher name: Springer
Page from-to: 7181-7193
Titles:
Language Name Abstract Keywords
cze Strukturní charakterizace elektrochemicky a in vitro biologicky generovaných oxidačních produktů atorvastatinu s využitím UHPLC/MS/MS Práce se zabývá elektrochemickým a in vitro biologickým generováním oxidačních produktů atorvastatinu. Pro jejich strukturní charakterizaci byla využita ultravysokoúčinná kapalinová chromatografie ve spojení s hmotnostní spektrometrií (UHPLC/MS/MS). Strukturní charakterizace; elektrochemická oxidace; UHPLC/MS/MS; atorvastatin; biotransformace léčiv
eng Structural Characterization of Electrochemically and in Vitro Biologically Generated Oxidation Products of Atorvastatin Using UHPLC/MS/MS Ultrahigh-performance liquid chromatography coupled with high-mass-accuracy tandem mass spectrometry (UHPLC-MS-MS) has been used for elucidation of the structures of oxidation products of atorvastatin (AT), one of the most popular commercially available drugs. The purpose of the study was identification of AT metabolites in rat hepatocytes and comparison with electrochemically generated oxidation products. AT was incubated with rat hepatocytes for 24 h. Electrochemical oxidation of AT was performed by use of a three-electrode off-line system with a glassy carbon working electrode. Three supporting electrolytes (0.1 mol L-1 H2SO4, 0.1 mol L-1 HCl, and 0.1 mol L-1 NaCl) were tested, and dependence on pH was also investigated. AT undergoes oxidation by a single irreversible process at approximately +1.0 V vs. Ag/AgCl electrode. The results obtained revealed a simple and relatively fast way of determining the type of oxidation and its position, on the basis of characteristic neutral losses (NLs) and fragment ions. Unfortunately, different products were obtained by electrochemical oxidation and biotransformation of AT. High-mass-accuracy measurement combined with different UHPLC-MS-MS scans, for example reconstructed ion-current chromatograms, constant neutral loss chromatograms, or exact mass filtering, enable rapid identification of drug-related compounds. beta-Oxidation, aromatic hydroxylation of the phenylaminocarbonyl group, sulfation, AT lactone and glycol formation were observed in rat biotransformation samples. In contrast, a variety of oxidation reactions on the conjugated skeleton of isopropyl substituent of AT were identified as products of electrolysis. Atorvastatin; Electrochemical generation; Ultrahigh-performance liquid chromatography-tandem mass spectrometry; Biotransformation; Drug metabolism

Departments

Other Parts

Map

en.mapy.cz

Services

Popular Links

© 2023 University of Pardubice, Studentská 95, 532 10 Pardubice 2
Phone: +420 466 036 111, 466 036 112, 466 036 113
Webmaster, RSS
Data box ID: f5vj9hu
Accessibility Statement
CC BY-NC-ND 4.0Creative CommonsAttributionNonCommercialNoDerivatives