A validated CE method for determining dimethylsulfate a carcinogen and chloroacetyl chloride a potential genotoxin at trace levels in drug substances

A simple and rapid capillary zone electrophoretic method was developed for determining dimethyl sulfate a possible human carcinogen and mutagen and chloroacetyl chloride a potential genotoxic agent at trace levels in pharmaceutical drug substances by indirect photometric detection. A systematic screening of various anionic probes was performed to obtain the best separation conditions and sensitivity. High sensitivities with low quantification and detection levels were achieved for dimethylsulfate and chloroacetyl chloride using a background electrolyte (BGE) containing 5 mM pyridine dicarboxylic acid as the probe ion. The method is specific, precise and accurate for the two genotoxins. The optimized method was validated for specificity, precision, linearity, accuracy and stability in solution. Calibration curves were linear (R > 0.999) for both dimethylsulfate and chloroacetyl chloride in the range LOQ – 300% of nominal concentrations. The CE method was effectively implemented for estimating dimethylsulfate and chloroacetyl chloride in two different active pharmaceutical ingredients (APIs).

► A capillary electrophoresis method was developed for determining genotoxic dimethyl sulfate and chloroacetyl chloride in APIs.
► The method uses pyridine dicarboxylic acid as probe ion in indirect-UV mode.
► The developed method is cost effective, highly selective and sensitive; and was fully validated.
► Trace levels of these genotoxins were determined in real time samples to address regulatory queries.
► Genotoxins are mostly determined using HPLC–UV/MS, GC–MS but CE can complement these techniques and open new horizons.