In situ identification and quantification of genotoxic sulfonyl chloride impurity in topiramate (Topamax tablets) via...

This study reports a sensitive and selective method developed and validated for the detection of process-related genotoxic impurity (PGI) formed in situ during the synthesis of topiramate API. The method utilizes benzyl amine as a derivatizing agent to enhance sensitivity. of impurity. Chromatographic separation was performed on a Kromasil-C8 column (150 mm × 4.6 mm, 5 µm) with mobile phase A as 10 mM ammonium acetate containing 0.1 % formic acid in water and mobile phase B as acetonitrile (40:60 v/v). The flow rate was set at 1.2 mL/min and detection was carried out using an RI detector. Quantification was achieved using TQMS detection with electron spray ionization in MRM mode. The method exhibited excellent linearity in the range of 0.14-2.88 µg/mL with recovery between 96.82 % and 104.42 %. The method showed a detection limit of 0.0719 µg/mL and quantitation limit of 0.1438 µg/mL, making it suitable for trace-level analysis (< 1 ppm) of sulfonyl chloride in topiramate drug substance.•Derivatization with benzyl amine enhanced PGI detection sensitivity.•Separation using Kromasil-C8 column with acetonitrile/water buffer (40:60).•Detection via RI and quantification using TQMS in MRM mode.