Title:GC-FID Quantification of N, N-Dimethyl Aminopropyl Chloride, a Genotoxic
Impurity, in Imipramine Hydrochloride and Clomipramine Hydrochloride
Volume: 18
Issue: 9
Author(s): Panga Chinna, Shet Prakash M.*, Ramesha Andagar Ramakrishna, Swamy Sreenivasa and Yashbir Singh
Affiliation:
- Department of Studies and Research in Chemistry, Tumkur University, Tumakuru, India
Keywords:
Genotoxic impurity, N, N-Dimethylaminopropyl chloride, imipramine hydrochloride, clomipramine hydrochloride, method development, validation, gas chromatography.
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.
