Quantification of organic volatile impurities in Oseltamivir phosphate drug substances by head space gas chromatography

Abstract

AbstractBackgroundThe present work is aimed at quantification of organic volatile solvents like Methanol, Ethanol, Acetonitrile, Isopropyl alcohol (IPA), Dichloromethane (DCM), Methyl tert-butyl ether (MTBE), Hexane fractions, Ethyl acetate (EA), Tetra hydro furan (THF), 1,4-Dioxane, Dimethylformamide (DMF), and Toluene in Oseltamivir phosphate Active pharmaceutical ingredient (API) and pharmaceutical dosage forms. The method was developed using a thermal gradient elution program associated with a column having dimensions are DB-1,60 m × 0.32 mm × 5.0 μm with a flow rate of 1.0 mL/min and Nitrogen (N2) as a carrier gas. A flame ionization detector was used as a detector, and its temperature is at 290 °C whereas the injector temperature is at 180 °C. The total run time is 60.0 min. The developed method was validated according to International Council for Harmonization (ICH) guidelines.ResultsThe linearity of the calibration curve for twelve impurities in the concentration range of Limit of Quantification (LOQ) to 150% was good. The curve was linear for twelve residual impurities of Oseltamivir phosphate. Relative standard deviation values for twelve residual impurities are not more than 15%. Limit of detection (LOD) and LOQ for twelve residual impurities were found to be very low-level concerning specification level. We found good results for all validated parameters for twelve residual impurities.ConclusionsTo quantify the residual organic volatile solvents (organic volatile impurities) in the Oseltamivir phosphate API, a novel, specific, and elevated sensitive headspace gas chromatography method was developed to separate twelve solvents that are accompanying with fifteen peaks. Out of fifteen peaks, critical components are Hexane fractions, Ethyl acetate, MTBE, and DCM. So, our method has capable of separating and simultaneous quantification such critical components. So, it can be successfully applied for routine analysis of quantification of these twelve residual impurities in Oseltamivir phosphate bulk and pharmaceutical dosage forms.