Impurity profiling of anticancer preclinical candidate, IIIM-290.

IIIM-290, an orally bioavailable preclinical candidate is effective in human xenograft models of leukemia, colon and pancreatic cancer. The promising preclinical data of this lead candidate has shown its potential for clinical development. As a part of its preclinical development, impurity profiling of pilot scale batches is one of the most important component of the CMC documentation. Herein, we report impurity profiling, its quantification in different scale-up batches and analytical method validation. Three impurities ranging from 0.09 to 1.25% in preclinical anticancer candidate, IIIM-290 were detected by validated HPLC method. The impurities (Imp-A, Imp-B and Imp-F) were isolated from the partially purified batch of IIIM-290 using semi-preparative HPLC. Isolated impurities were characterized by 1H, 13C NMR, FTIR and ESI-MS spectral data. Based on the characterization data, the sources of these impurities were identified as unreacted starting material (Imp-A), impurity from botanical raw material (Imp-B; impurity carried from starting material) and the chemically transformed product (Imp-F) of Imp-B, respectively.