NanoUPLC-QTOF-MS/MS Determination of Major Rosuvastatin Degradation Products Generated by Gamma Radiation in Aqueous Solution.

Lucija Dončević,Branka Mihaljević,Luka Ozdanovac,Dorota Jarmużek,Iva Džeba,Amela Hozić,Ivana Tartaro Bujak,Donata Pluskota-Karwatka,Ema Svetličić,Mario Cindrić

doi:10.3390/ph14111160

Abstract

Rosuvastatin, a member of the statin family of drugs, is used to regulate high cholesterol levels in the human body. Moreover, rosuvastatin and other statins demonstrate a protective role against free radical-induced oxidative stress. Our research aimed to investigate the end-products of free radical-induced degradation of rosuvastatin. To induce the radical degradation, an aqueous solution of rosuvastatin was irradiated using different doses of gamma radiation (50–1000 Gy) under oxidative conditions. Rosuvastatin and related degradation products were separated on nanoC18 column under gradient elution, and identification was carried out on hyphenated nanoUPLC and nanoESI-QTOF mass spectrometer system. Elemental composition analysis using highly accurate mass measurements together with isotope fitting algorithm identified nine major degradation products. This is the first study of gamma radiation-induced degradation of rosuvastatin, where chemical structures, MS/MS fragmentation pathways and formation mechanisms of the resulting degradation products are detailly described. The presented results contribute to the understanding of the degradation pathway of rosuvastatin and possibly other statins under gamma radiation conditions.

Highlights

Introduction published maps and institutional affilRosuvastatin (RSV), chemically described as (E)-7-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamide)pyrimidin-5-yl)-3,5-dihydroxyhept-6-enoic acid, is a member of the class of statins [1]
The main objectives of this work were to investigate the degradation of an aqueous solution of RSV affected by gamma radiation at different radiation doses, identify produced degradation molecules, and suggest mechanisms of their formation
The obtained results of our research provide qualitative information about the structure of rosuvastatin degradation products, the design of the remediation process should aim to completely decompose the pollutant without creating harmful intermediates

Summary

Introduction

Introduction published maps and institutional affilRosuvastatin (RSV), chemically described as (E)-7-(4-(4-fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfonamide)pyrimidin-5-yl)-3,5-dihydroxyhept-6-enoic acid, is a member of the class of statins [1]. Statins are effective cholesterol-lowering drugs, most commonly prescribed in the treatment of hyperlipidemia, mixed dyslipidemia, and related conditions [2]. Statins act as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which is a rate-limiting enzyme in cholesterol synthesis, converting HMG-CoA to mevalonate [3]. Previous studies have demonstrated the antioxidant properties of RSV. It was hypothesized that RSV and other statins have a protective role against oxidative stress by reducing NAD(P)H oxidase and upregulating antioxidant enzyme superoxide dismutase [4,5]. Oxidative stress is defined as an imbalance between free radical reactions and a lack of defense against these reactions in living organisms. Among all free radicals, OH radical is one of the most reactive oxygen iations

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Conclusion