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Objective: The current study focused on the development, validation, and characterization of forced degradation products using LC-MS/MS. Methods: A simple, selective, validated and well-defined isocratic HPLC methodology for the quantitative determination of Tucatinib at a wavelength of 239 nm. An isocratic elution of samples was performed on an Inertsil ODS (250x4.6 mm, 5m) column with a mobile phase of 70:30v/v Acetonitrile and formic acid (0.1%) delivered at a flow rate of 1.0 ml/min. MS/MS was used to characterize degradation products formed in the forced degradation study. The validation and characterization of forced degradation products were performed in accordance with ICH guidelines. Results: Over the concentration range of 5-100μg/ml, a good linear response was obtained. Tucatinib's LOD and LOQ were determined to be 0.05 and 0.5, respectively. According to standard guidelines, the method was quantitatively evaluated in terms of system suitability, linearity, precision, accuracy, and robustness, and the results were found to be within acceptable limits. The drug was degraded under acidic, alkaline, and reduction conditions in forced degradation studies. Conclusion: The method was found to be applicable for routine tucatinib analysis. Because no LC-MS/MS method for estimating tucatinib and its degradation products has been reported in the literature. There is a need to develop a method for studying the entire tucatinib degradation pathway.

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 C 18 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.

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