Development and validation for the quantification of genotoxic impurities in Bempedoic acid drug by GC/MS

The assessment of potential genotoxic impurities in drug substances was treated as important as well as very challenging issue in the pharmaceutical world. As per European Medicines Agency (EMA), permissible daily exposer of potential genotoxic impurity given as acceptable limit 1.5 μg/day for the pharmaceutical products. In view of this, Bempedoic acid drug substances have been evaluated for the quantification of two genotoxic impurities like, Ethyl-7-bromo-2,2-dimethylheptanoate & 1,5-Dibromopentane, which are having structure alerts. The Gas chromatography-mass spectrometry (GCMS) was used for the determination of these impurities; The RTX-624 GC column used for better separation and selected ion monitoring (SIM) mode has been used to get the proper detection of both the impurities. GCMS method was validated as per ICH Q2 (R2) guidelines. The specific detection range of both impurities observed between 2.5-12.5 ppm, linearity observed with the exceed 0.990 correlation coefficient and found accuracy in terms of recovery between 82.0%-95.0% with the below 5.0% relative standard deviation of both the impurities. This technique has been successfully directed for determination at ppm level of both the impurities in Bempedoic Drug substances.