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.

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

“…Validation of the proposed method was done according to the ICH (International Conference on Harmonization) guidelines. [20] The linearity of the developed method was determined over the concentration range of0.2to 2.0 μg/ml.…”

Microenvironment improvement protocol for the sensitive spectrofluorimetric determination of an hepatitis C virus antiviral (Simeprevir): application to human plasma

“…Merospevir ® capsules that contain SPV were analyzed using the proposed method. The obtained results were statistically compared with the results from the reported method . The comparison revealed no significant difference between both methods with respect to accuracy and precision.…”

“…These methods included four liquid chromatographic methods for analysis of SPV in plasma using different types of detectors such as tandem mass, UV and diode array detectors . In addition to chromatography, a synchronous spectrofluorimetry and two spectrophotometric methods were also reported.…”

Identification, isolation, structural characterization, in silico toxicity prediction and in vitro cytotoxicity assay of simeprevir acidic and oxidative degradation products

“…Three stability-indicating methods have been reported for the quantication of simeprevir in the presence of its degradation products, and these methods used HPLC-DAD, 18 spectrophotometry 19 and spectrouorometry. 20 Although there are several reported analytical methods for the determination of simeprevir, there have been no detailed studies on its degradation products, especially because simeprevir is a non-pharmacopeial drug, and its stability and the identities of its degradation products require further study.…”