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

Abstract

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<1225> 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%.