Method Development, Validation, and Quantification of Residual Solvents in Sofosbuvir Using Flame Ionization Detector by Head Space Gas Chromatography Technique

The headspace gas chromatography technique is used to identify residual solvents in pharmaceutical samples. By good manufacturing practices, residual solvents (R.S.) must be quantified for the release testing of all Active Pharmaceutical Ingredients (API). Organic solvents such as methanol, Ethanol, Dichloromethane, ethyl acetate, tetrahydrofuran, Toluene, and diisopropyl ethylamine are frequently used in the pharmaceutical industry to produce API. From the International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH) guidelines, a headspace gas chromatographic (HS-GC) method for R.S. analysis in the sofosbuvir drug has been developed and validated for quantification of residual solvents. An Agilent Technologies 6890 series G.C. system and 7694 headspace Autosampler Gas chromatograph and Flame ionization detector (FID) were used to monitor residual solvents in APIs and marketed formulations. For this development, a DB-624 capillary column was used for separation in split mode by headspace method with dimensions of 30 m × 0.53 mm I.D. × 3.0 m film thickness, with Nitrogen as carrier gas. The described method here is simple, rugged, sensitive, dependable, and reproducible for quantifying methanol, Ethanol, Dichloromethane, ethyl acetate, tetrahydrofuran, Toluene, and di-isopropyl ethylamine in sofosbuvir pure drug and the marketed formulation at the residual level.