Characterization of forced degradation products and in silico toxicity prediction of Sofosbuvir: A novel HCV NS5B polymerase inhibitor

• Sofosbuvir is a novel nucleotide analog used in the treatment of Hepatitis C virus infection.
• This is the first report on the forced degradation studies of Sofosbuvir.
• The degradation products were characterized by LC-ESI-QTOF–MS/MS and their toxicities were predicted using in silico tools like TOPKAT and DEREK.
• The proposed analytical method was also validated as per ICH Q2(R1) guidelines to use it as a stability indicating assay method.

Sofosbuvir is a direct acting antiviral medication used to treat Hepatitis C viral infection. The present study focuses on the degradation behavior of the drug under various stress conditions (hydrolysis, oxidative, thermal and photolytic) as per International Conference on Harmonization (ICH Q1A (R2)) guidelines. A high performance liquid chromatographic system (HPLC) was used to develop a selective, precise and accurate method for separating all the degradation products. The separation was achieved on a Sunfire™ C18 (150 mm × 4.6 mm × 5 μm) stationary phase with a mobile phase of 10 mM ammonium acetate (pH 5.0) buffer and acetonitrile in gradient elution mode. A quadrupole-time of flight mass analyzer equipped with an electrospray ionization technique was used to propose the structural information based on the MS/MS and accurate mass measurements. Seven degradation products were identified and characterised by LC-ESI-QTOF–MS/MS. In silico toxicity of the drug and its degradation products was determined using TOPKAT and DEREK toxicity prediction softwares. The proposed method was validated as per the ICH Q2 guidelines.

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