Gas chromatography mass spectrometer determination of dimethylamine impurity in N,N‐dimethylformamide solvent by derivatization of N,N‐dimethylbenzamide with benzoyl chloride agent

This study describes the development of a reliable and linear analytical method for precisely determining dimethylamine impurity in N,N‐dimethylformamide solvent utilizing a benzoyl chloride derivatization reagent and a gas chromatography mass spectrometer. Benzoyl chloride was used to derivatize dimethylamine. At normal temperature, benzoyl chloride combined with dimethylamine, producing N,N‐dimethylbenzamide. This method separated N,N‐dimethylbenzamide using Rtx‐5 amine (30 m × 0.32 mm × 1.50 μm) as the stationary phase, helium as the carrier gas, argon as the collision gas, and methanol as the diluent. The column flow rate was 2 mL/min. The retention time of N,N‐dimethylbenzamide was determined to be 8.5 min. Precision, linearity, and accuracy were tested using ICH Q2 (R2) and USP guidelines. The percentage coefficient of variation (CV) for N,N‐dimethylbenzamide in the system suitability parameter was 1.1%. The correlation coefficient of N,N‐dimethylbenzamide was found to be >0.99. In the method precision parameter, the % CV for N,N‐dimethylbenzamide was found to be 1.9%, whereas the % CV for N,N‐dimethylbenzamide was 1.2% in intermediate precision. The percentage recovery of N,N‐dimethylbenzamide was determined to be between 80% and 98%.