A Validated RP-HPLC Method for the Simultaneous Determination of Six High-Boiling Residual Solvents in Drug Substances and Its Implementation in Apis

A new method using high-performance liquid chromatography coupled with ultra violet detection was developed and validated for the simultaneous quantification of six high-boiling residual solvents-Acetic acid, N,N-dimethylformamide, Dimethyl sulfoxide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone and Benzyl alcohol in drug substances. This paper describes the development and validation of a simple and efficient RP-HPLC method for the determination of these high boiling residual solvents. Quantitation limits for Acetic Acid is 1000ppm (1000 μg/g of API), for Dimethylsulfoxide is 400 ppm (400 μg/g of API), for N, N dimethylformamide is 70 ppm (70 μg/g of API), for Dimethylacetamide is 80 ppm (80 μg/g of API), for N-methyl-2-pyrrolidone is 40 ppm (40 μg/g of API) and for Benzyl Alcohol is 60 ppm (60 μg/g of API) by this method. Several Active Pharmaceutical Ingredients were analyzed using the conditions of this method to evaluate and assess its versatility for the purpose of residual solvents analysis for a wide range of Active Pharmaceutical Ingredients. The results of this evaluation strongly indicate that this method can be readily used (as-is or with minor modifications) to determine high boiling residual solvents present in a wide range of Active Pharmaceutical Ingredients and other drug substances.