Development and Optimization of UHPLC Method for the Quantification of Process‐Related Impurities of Palbociclib

ABSTRACT This work mainly focuses on development and validation of ultra‐high‐performance liquid chromatography (UHPLC) technique for quantifying palbociclib and its related impurities I, II, III, and IV. The method involved a systematic investigation of critical method parameters and their optimization using design of experiments principles. Percentage of organic modifier, column temperature, and flow rate were systematically optimized using Box–Behnken design. Developed method was assessed for specificity, system suitability, accuracy, precision, linearity, and detection limits. The results demonstrate strong specificity, with the analysis remaining accurate even in the presence of impurities. The developed method exhibits excellent precision, with repeatability and intermediate precision showing %RSD values ranging from 6.42% to 8.18% for impurities and 1.09% for palbociclib. Furthermore, the method displays exceptional linearity, covering a wide range of concentrations. The linear regression analysis yields high coefficients of determination ( r 2 , 0.9996–0.9998), confirming the linearity. Developed UHPLC method is well‐suited for the accurate and reliable analysis of palbociclib and its impurities, making it a valuable tool for quality control and pharmaceutical research applications.