Determination of Three Potential Genotoxic Impurities in Imatinib Mesylate by Gas Chromatography—Mass Spectrometry

ABSTRACT

Two sensitive methods are reported for the determination of potential genotoxic impurities in imatinib mesylate by gas chromatography-mass spectrometry. The methods were used for the determination of hydrazine, 3-acetylpyridine, and 2-methyl-5-nitroaniline in imatinib mesylate. Hydrazine was quantified following its conversion into a volatile derivative with n-hexadecane as the internal standard. 3-Acetylpyridine and 2-methyl-5-nitroaniline were determined at low ppm levels using 1-eicosanol as the internal standard. Liquid extraction procedures were used for sample preparation. Mass spectrometry detection provided good sensitivity and specificity using selected ion-monitoring mode. The limits of detection for hydrazine, 3-acetylpyridine, and 2-methyl-5-nitroaniline were 0.11, 0.026, and 0.025 µg g⁻¹, respectively. The developed methods provided suitable figures of merit for the analysis of imatinib mesylate.

KEYWORDS:

• Gas chromatography-mass spectrometry
• hydrazine
• 2-methyl-5-nitroaniline
• 3-acetylpyridine