A Sensitive Azeotropic Solvent Screening Head Space Gas Chromatographic Method for Teriflunomide Drug Substance Check Access

The International Council for Harmonization (ICH) has classified methanol and toluene as class-2 solvents, whose use must be limited as they may cause irreversible toxicity. A simple validated Head Space Gas Chromatographic (HSGC) method using flame ionization detector was developed for determination of azeotropic residual solvent; methanol and toluene in teriflunomide drug substance. The column DB-624 with specifications (30m X 0.53mm X 3.0 μm) was used. The flow rate of nitrogen carrier gas was 2.0 mL/min with analysis run time of 26 minutes. The HSGC conditions were optimized for determination of residual screening for methanol and toluene in the drug substance. The linearity were assessed for methanol and toluene mixture from 0.65–180 μg/mL and 0.24 –54 μg/mL respectively. The limit of detection for methanol and toluene were 5.5 ppm and 2.0 ppm and limit of quantification for methanol and toluene were 16.3 ppm and 6.0 ppm respectively. The solution stability study indicated that there was no significant variation in the ppm levels of specified solvents up to 48 hours at room temperature. The ICH has limited the concentrations of class-2 solvents; methanol and toluene in pharmaceutical drug substances as 3000 ppm and 890 ppm respectively. Limit of Quantification’s for methanol and toluene in this study were satisfactory for the detection of ICH concentration limits in teriflunomide drug substance.