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Structural Characterization of Electrochemically and in Vitro Biologically Generated Oxidation Products of Atorvastatin Using UHPLC/MS/MS

Autoři: Jirásko Robert | Mikysek Tomáš | Chagovets Vitaliy Viktorovich | Vokřál Ivan | Holčapek Michal

Rok: 2013

Druh publikace: článek v odborném periodiku

Název zdroje: Analytical and Bioanalytical Chemistry

Název nakladatele: Springer

Strana od-do: 7181-7193

Tituly:

Jazyk	Název	Abstrakt	Klíčová slova
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

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