Impurity profiling of anticancer preclinical candidate, IIIM-290

Abstract 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, impurityprofiling of pilot scale batches is one of the most important component of the CMC documentation. Herein, we report impurityprofiling, its quantification in different scale-up batches and analytical method validation. Three impuritiesranging 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 impuritieswere characterized by 1 H, 13 C NMR, FTIR and ESI–MS spectral data. Based on the characterization data, the sources of these impuritieswere identified as unreacted starting material ( Imp-A ), impurityfrom botanical raw material ( Imp-B ; impuritycarried from starting material) and the chemically transformedproduct ( Imp-F ) of Imp-B , respectively.