A Selective and Sensitive Method Development and Validation by LC?MS/MS Approach for Trace Level Quantification of Potential Genotoxic Impurity IMT-01 in Imatinib Mesylate Drug Substance

Nelaturi Subbaiah, G. V. Subba Reddy

Abstract: A novel 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 ng/mL level) of N- (2-methtyl-5-nitrophenyl) -4- (pyridine-3-yl) -pyrimidine-2-amine (IMT-01) genotoxic impurity in imatinib mesylate drug substance. The method utilizes Inertsil C18 column (150 mm4.6 mm, 5.0 m) with electrospray ionization in multiple reaction monitoring (MRM) detection mode. Isocratic program was developed for rapid analysis and mobile phase was 0.1 % formic acid in water and acetonitrile in the ratio of 3070 (v/v). 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 ng/mL of IMT-01.

Keywords: Imatinib mesylate, LC-MS/MS, Genotoxic impurity, Isocratic program, multiple reaction monitoring MRM