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 pharmaceutical ingredients.
Methods: A simple, selective, and sensitive Gas Chromatography (GC) liquid injector method was developed for the quantitative determination of N, N-Dimethyl Aminopropyl Chloride (DAPC) in APIs. 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% (1.18 ppm to 4.8 ppm), with a correlation coefficient of 0.9986. Limit Of Detection (LOD) and Limit Of Quantification (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 found to be 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 substances, thus ensuring the safety of the patients.
Keywords: Genotoxic impurity, N, N-Dimethylaminopropyl chloride, imipramine hydrochloride, clomipramine hydrochloride, method development, validation, gas chromatography
Graphical Abstract
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