Method Development Combined with in silico Therapeutic and Toxicology Studies on Palbociclib and its Degradation Products to Assist in Discovery of New Molecule

Background: Palbociclib is anti-cancer drug which interacts with cyclindependent kinase. There are no methods repoRTed for the characterization of palbociclib together with degradation products (DPs). The main aim of the study is to develop method combined with in silico therapeutic and toxicology studies on palbociclib and its DPs which assist in discovery of new molecule. Methods: A new analytical method was developed for the identification, characterization of palbociclib and DPs formed when subjected to forced degradation, using symmetry C18 column, 150mm x 4.6mm, 3.5µm in isocratic mode with acetonitrile: formic acid (0.1%) (50:50). In silico toxicity for drugs and DPs were predicted using the Swiss ADME web tool and StarDrop Derek Nexus software for all DPs. Results: Validation: LOD and LOQ were 0.01 and 0.1 μg/ml. which shows accuracy data at three different concentrations of 50, 100, and 150 % in triplicate analysis. The % RSD for intra-day and intermediate precision was 0.47% and 0.33%, respectively, indicating the method was sufficiently precise. Mass spectrums (LC-MS/MS) of drug with m/z 447(RT= 4.075 min), DPI with [M+H] + at m/z 503(RT= 1.328 min), DPII with [M+H] +at m/z 540 (RT= 2.371 min), DPIII with m/z 46 (RT= 3.741 min) are reported. In docking studies, PS2 showed a higher docking score -12.289. Conclusion: The drug was found to degrade under forced degradation and DPs are characterized. All the DPs were found to be toxic except the major fragment ions (PS2), showed higher binding affinity than drug without toxicity. This is the lead molecule for further drug discovery.