Development of an LC-MS/MS Method for Trace Level Quantification of 4-(bromomethyl) Benzoic Acid, a Potential Genotoxic Impurity in Imatinib Mesylate Drug Substance

Abstract: A reversed-phase selective and sensitive liquid chromatography coupled with tandem mass spectrometric (LC-MS/MS) method was developed and validated for the trace analysis of (0.5 ppm level) of 4- (bromomehtyl) benzoic acid genotoxic impurity in imatinib mesylate drug substance. The method obtained with Inertsil C18 column (250 mm4.6 mm, 5.0 m) with negative electrospray ionization in multiple reaction monitoring (MRM) detection mode. Mobile phase was 0.1 % formic acid in water and acetonitrile in the ratio of 3565 (v/v). Isocratic program was developed and the flow rate was 1.0 mL/min and elution was monitored by mass spectrophotometer. The method was validated as per International Conference on Harmonization (ICH) guidelines and was able to quantitate up to 0.5 ppm of 4-bromo mehtyl benzoic acid.

Keywords: Imatinib mesylate, LC-MS/MS, Genotoxic impurity, Multiple reaction monitoring MRM

Edition: Volume 6 Issue 7, July 2017,

Pages: 655 - 658