Analysis of Genotoxic Impurities like Ethane Sulfonic acid esters in pharmaceutical substance by GC-MS/MS

Residual genotoxic impurities, and particularly alkyl esters of alkyl or aryl sulfonic acids, have been, and probably remain, a significant safety concern to drug regulators. Since the sulfonate moiety is readily displaced by a variety of nucleophiles, such esters can act as DNA alkylating agents in biological systems and have been shown to exert genotoxic effects in bacterial and mammalian cells. Chemicals like Ethane sulfonic acid used in the process of pharmaceutical synthesis are likely to generate Ethane Sulfonic acid ester with alcohols as a reaction by-products. These Ethane sulfonic acid esters (Esylates) that include Methyl Ethane Sulfonate and Ethyl Ethane Sulfonate are Potential Genotoxic Impurities (PGI's) and are of great concern to pharmaceutical manufacturers. A TTC (Threshold of Toxicological Concern) based acceptable intake of a mutagenic impurity of 1.5 μg per person per day is considered to be associated with a negligible risk and can, in general, be used for most pharmaceuticals as a default value, to derive an acceptable limit for control.