Threshold of Toxicological Concern (TTC)

To estimate the level of Phenylhydrazine, a potential genotoxic impurity in Ondansetron Hydrochloride API, a new simple, sensitive and accurate method was developed using Liquid Chromatographic Mass Spectrometry (LC-MS/MS). The chromatographic separation was achieved on Inert Sustain Swift C18, 5µ (150 x 4.6) mm column with gradient programme and elution was monitored by mass spectrometer in Multiple Reaction Monitoring mode using electrospray ionization. The LOD and LOQ values found to be 5 ppm and 15 ppm for the impurity with respect to the test concentration 2 mg/ml. The method was linear (r2>0.99), precise (RSD<2%), accurate and well within acceptable ICH limits.

A new, simple, accurate and sensitive method was developed for the quantification of two potential genotoxic impurities 1-(2-methyl-5-nitro-phenyl)guanidine nitrate and  N-(2-methyl-5-nitro-phenyl)-4-(3-pyridyl)pyrimidin-2-amine at low level (2 ppm) in Imatinib using liquid chromatographic mass spectrometry. The chromatographic separation was achieved on Kromasil 100-3.5-C18 (150 x 2.1) mm column with gradient programme and elution was monitored by mass spectrometer in selective ion monitoring mode using electrospray ionization. The LOD and LOQ values found to be 0.2 ppm and 0.6 ppm for both the impurities with respect to the test concentration 5 mg/ml. The method was linear (r2>0.99), precise (RSD