GC-FID Quantification of N, N-Dimethyl Aminopropyl Chloride, a Genotoxic Impurity, in Imipramine Hydrochloride and Clomipramine Hydrochloride

Abstract

Background: Early antidepressant Active Pharmaceutical Ingredients (API) like Imipramine hydrochloride and Clomipramine hydrochloride have not been assessed for Genotoxic Impurities (GTI) as per ICHM7. Objective: The main aim of the study was to develop a new simple and sensitive method for the determination of genotoxic impurities in Imipramine hydrochloride and Clomipramine hydrochloride active pharmaceuticals ingrediens. Methods: A simple, selective, and sensitive gas chromatography (GC) liquid injector method was developed for the quantitative determination of N, N-Dimethyl amino propyl chloride (DAPC) in API s. This method provided an excellent sensitivity and a typical target analyte level of 4.0 ppm. The DPAC content in the sample was analyzed on ZB-624, 30m x 0.53mm x 3.0μm column interfaced with a flame ionization detector (FID). The developed method was validated as per ICH guidelines. Results: The validated method showed good linearity over the concentration range of LOQ to 120% (1.18ppm to 4.8ppm) with a correlation coefficient of 0.9986. Limit of detection (LOD) and limit of quantitation (LOQ) were found to be 0.36 ppm and 1.18 ppm, respectively. This method showed high sample recovery (>90.0%). Conclusion: The developed method was a simple and sensitive gas chromatography liquid injector method. This method was validated as per ICH guidelines and could be very useful for the determination of a potential genotoxic impurity (DAPC) in imipramine hydrochloride and clomipramine hydrochloride active drug substance quality checking and ensuring safety of the patients.