Simeprevir oxidative degradation product: Molecular modeling, in silico toxicity and resolution by synchronous spectrofluorimetry

Abstract

In this article, one of the potential degradation products of the novel antiviral drug simeprevir was isolated and characterized by means of infrared (IR) and mass spectrometry. Moreover, comparative molecular docking, ADMET (absorption, distribution, metabolism, excretion - toxicity) and insilico toxicity prediction studies were applied to evaluate the activity of simeprevir and its degradation product. Furthermore,a simple, accurate and selective second derivative synchronous spectrofluorimetric method was developed for the determination of simeprevir in the presence of its oxidative degradation product.The synchronous fluorescence spectra of both compounds were measured in ethanol at pH 2.0 usingΔλ of 140 nm and the peak amplitude of the second derivative spectra were measured at 442 nm. The method was rectilinear over the concentration range of 0.2 to 2.0 μg/ml and validated according to the ICH (International Conference on Harmonization) guidelines. Moreover, the method was statistically compared to the reverse-phase high-performance liquid chromatography (RP-HPLC) method and good results were obtained.

Keywords: in silico toxicity; molecular modeling; oxidative degradation product; simeprevir; synchronous spectrofluorimetric.