A sensitive analytical method has been developed for the analysis of 2-dimethylaminoethyl chloride (DMC) in bulk drug substances. The requirement of analytical data to be collected at a low level of DMC in isolated intermediates and final bulk drug substance to mitigate any associated risk has led to the development of this method. This method development involves a derivatization approach in combination with LC-MS detection. A series of derivatizing agents has been screened during method development. Indoline was found to be the most promising one and further development work was continued with it. DMC and indoline solutions were prepared separately in DMSO. Derivatives were prepared by mixing DMC and indoline solutions, heating at approximately 60 degree C for 30 minutes while stirring. The derivative solution was diluted with water and ACN before injecting into the reversed-phase LC system to avoid any solvent effect. DMC solutions were evaluated using an LC-MS system configured with ESI operating in the positive (+) ion mode, and the analyte was detected in the selected ion monitoring mode using a linear ion trap mass spectrometer. The method was linear in the range of 10-150 ppm DMC level and the linear correlation coefficient is &gt;0.99. Spike recovery with 50 ppm DMC solution in 1 mg/mL API solution was approximately 94%. This method was successfully employed to determine the DMC contents in isolated intermediates and bulk drug substance.

Method development of 2-dimethylaminoethyl chloride (DMC) at low ppm level via derivatization and (+) electrospray LC-MS

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