Dimethyl carbamoyl chloride is a potential genotoxic impurity (PGI) that typically needs to be controlled down to low ppm level in pharmaceutical development based on regulatory requirement.  Direct analysis of this PGI by liquid chromatography-mass spectrometry (LC-MS) is very challenging as it has very poor ionization efficiency. A simple and efficient derivatization scheme was developed to convert this PGI to derivative amenable to LC-MS analysis by using primary amine as a pre-column derivatization reagent.  By using this simple primary amine reagent, this potentially genotoxic alkylating impurity can be easily derivatized at room temperature.  The derivatized product can be readily detected by LC-MS through positive electrospray ionization (ESI) under selected ion monitoring (SIM) mode. This new approach allows for the determination of dimethyl carbamoyl chloride at trace levels down to 1 ppm.  This method was qualified and applied as a generic method to determine dimethyl carbamoyl chloride for pharmaceutical process control and drug material release.<br/>

Simple and sensitive method for the determination of alkylating chloride by LC-MS

254th National Meeting (2017)

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