Intrinsic stability of the antiviral drug umifenovir by stress testing and DFT studies

Abstract

Umifenovir is an antiviral drug approved in China and Russia for the treatment of influenza. The available dosage form consists of capsules marketed under the brand name Arbidol®. Due to its broad spectrum, umifenovir may also be used in other viral contexts, alone or combined with other antiviral drugs. Although knowledge of umifenovir intrinsic stability may be useful for any potential development of other pharmaceutical forms for other routes of administration and for quality risk management, no data regarding this matter is available to date. In this study, the exploration of the molecule's behaviour under hydrolytic, oxidative and photolytic conditions was carried out experimentally and supported by density functional theory (DFT) studies. It comes out that umifenovir is sensitive to these stress conditions giving rise to 6 structurally characterized degradation products. The one-electron oxidation process produced on the sulphur atom is probably the main cause of umifenovir degradation with reference to the structures of the degradation products formed and the DFT data.

Keywords: Ab initio calculations; Degradation pathways; Hydrolysis; Mass spectrometry; Oxidation; Photolysis.