Determination of Residual Solvents in Dapagliflozin Amorphous by Gas Chromatography with Static Head Space Method

摘要

The purpose of this research work was to develop a novel, sensitive and accurate analytical method for quantification of 12 residual solvents in Dapagliflozin Amorphous by using a static headspace gas chromatography (HSGC) coupled with flame ionization detector (FID). Methanol, Ethanol, Diethyl ether, Methyl acetate, Dichloromethane, Ethyl acetate, Tetrahydrofuran, Cyclohexane, Isopropyl acetate, Methyl isobutyl ketone, Toluene, Chlorobenzene as residual solvents were determined in Dapagliflozin Amorphous. The separations of 12 residual solvents were achieved on DB-624 (60 meters ×0.53 mm I.D, 3.0μm) column. Nitrogen was used as a carrier gas with constant pressure 7.0 psi. As a sample diluent in a headspace sampling, N-methyl-2-pyrrolidone was selected owing to its high capacity for dissolving Dapagliflozin Amorphous sample. Excellent correlation coeffient between peak responses and concentrations were 0.9936. The recoveries of all 12 solvents spiked in Dapagliflozin Amorphous were in the range from 97.1% to 103.0%. Limit of quantitation for all 12 solvents were sufficiently lower than limits specified by ICH. In the proposed method, USP resolutions between all the 12 solvents were more than 1.6. The method has validated as per International Conference on Harmonization (ICH) guidelines. A precise, accurate, linear and robust Headspace Gas Chromatography method was developed for the quantification of 12 residual solvents in Dapagliflozin Amorphous.