Shorter and Rugged Analytical GC Method for Residual Solvents Content in Active Pharmaceutical Ingredient.

This work describes the highly selective and sensitive robust analytical method (gas chromatography) for the qualitative and quantitative analysis of commonly used residual solvents (like methanol, ethanol, acetonitrile, dichloromethane, methyl tert-butyl ether, n-hexane, 1-propanol, ethyl acetate, tetrahydrofuran, N,N-diisopropylethylamine (DIPEA) and dimethylformamide), in an active pharmaceuticals ingredients. The developed method was optimized with good resolution (>1.9 between close eluting solvents) and a shorter run time (20 min). All the solvents were separated using GC column DB-624, 30-m length, 0.32-mm diameter, 1.8-μm particle size, nitrogen as a carrier gas and recorded the signals using flame ionization detector (FID). Further, analytical method validation has been performed for the developed analytical method and the validation results demonstrated its routine application for the determination of residual solvents content by GC-head space (HS). The practical application was demonstrated by the suitable API batch analysis (having sample Con. 40 mg/mL). The present developed method has more advantages than the other methods for the qualitative and quantitative applications, such as shorter runtime, selective for multiple solvents (11 organic solvents) analysis at a time, highly sensitive at ppm levels. This GC-HS method could be used for the qualitative and quantitative determination of the residual solvents content in APIs.