Abstract

A SELECTIVE APPROACH TOWARDS QUANTIFICATION OF POTENTIAL GENOTOXIC AND CARCINOGENIC IMPURITIES IN DABIGATRAN ETEXILATE MESYLATE (DEM)

Prasad P. Talekar*, Dr. Rakesh Shrivastav and Dr. Swarup Prabhune

ABSTRACT

Dabigatran Etexilate Mesylate (DEM) is a direct oral anticoagulant widely used in the prevention and treatment of thromboembolic disorders. The presence of genotoxic and carcinogenic impurities in drug substance presents serious health risks, necessitating accurate and sensitive analytical methods for their detection. This study aimed to develop and validate a gas chromatography-mass spectrometry (GC-MS) method for the identification, characterization, and quantification of potential genotoxic and carcinogenic impurities Methyl methanesulfonate (MMS), Ethyl methanesulfonate (EMS), and Propyl methanesulfonate (PMS) in Dabigatran Etexilate Mesylate (DEM). The developed GC-MS method successfully detected MMS, EMS, and PMS with retention times of 3.00 minutes, 6.00 minutes, and 8.90 minutes, respectively. Mass fragmentation patterns were verified usingthe National Institute of Standards and Technology (NIST) spectral database to confirm compound identities. The method showed excellent system suitability and high sensitivity, with minimal interference from excipients or formulation components. Limits of detection (LOD) and quantification (LOQ) were sufficiently low to ensure precise analysis, meeting the requirements of International Council for Harmonisation (ICH) guidelines. Linearity studies demonstrated high correlation coefficients (r²), indicating reliable quantification across tested concentrations. Recovery rates between 98.15% and 103.30% confirmed the method’s accuracy. Chromatographic separation produced well-resolved peaks for all analytes, highlighting the method’s robustness and reproducibility. The validated GC-MS method offers a precise, accurate, and sensitive approach for quantifying Methyl methanesulfonate (MMS), Ethyl methanesulfonate (EMS), and Propyl methanesulfonate (PMS) in Dabigatran Etexilate Mesylate. Its compliance with regulatory standards ensures reliable quality control and enhances pharmaceutical safety by enabling effective monitoring of genotoxic and carcinogenic impurities.

Keywords: Mass spectrometry (MS), Electron Ionization (EI), Selective Ion Monitoring (SIM), genotoxic impurities (GTI), carcinogenic impurities, Limit of detection (LOD), Limit of quantification (LOQ).