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<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%.

Analytical determination of ethylenediamine impurity in tripelennamine hydrochloride by gas chromatography-mass spectrometry using phthalaldehyde as the derivatizing agent.

In the pharmaceutical industry, effective risk management and control strategies for potential genotoxic impurities are of paramount importance. The current study utilized GC-MS to evaluate a precise, linear, and accurate analytical method for quantifying ethylenediamine present in tripelennamine hydrochloride using phthalaldehyde as a derivatizing agent. When phthalaldehyde is sonicated for 10 min at room temperature, it reacts with ethylenediamine to form (1z,5z)-3,4-dihydrobenzo[f][1,4]diazocine. This approach minimizes matrix interference issues and resolves sample preparation difficulties encountered during ethylenediamine identification in GC-MS. In this method, helium serves as the carrier gas, while methanol acts as the diluent. The stationary phase consists of a DB-5MS column (30 m × 0.25 mm × 0.25 µm) with a flow rate of 1.5 mL/min. The retention time of (1z,5z)-3,4-dihydrobenzo[f][1,4]diazocine was determined to be 6.215 min. The method validation demonstrated limits of detection and quantification for (1z,5z)-3,4-dihydrobenzo[f][1,4]diazocine at 0.4 and 1.0 ppm, respectively, with a linearity range spanning from 1 to 30 ppm concentration with respect to the specification level. System suitability, precision, linearity, and accuracy of the current method were assessed in accordance with guidelines, yielding results deemed suitable for the intended use.