HPLC-UV method for Crizotinib and its Impurities: Integration of AQbD and green chemistry principles

Crizotinib (CZB) demonstrates therapeutic efficacy in the treatment of ALK-positive non-small cell lung cancer (NSCLC). This study reports the first development of a stability-indicating HPLC-UV method for CZB and its related impurities using an integrated Analytical Quality by Design (AQbD) and green chemistry. Separation was accomplished using a ZORBAX Eclipse XDB - C18 column with a stepped gradient elution system, employing a mobile phase consisting of 0.02 M potassium phosphate buffer (pH adjusted to 7.5) and acetonitrile. The proposed HPLC-UV method utilized a 40 °C column, a mobile phase flow rate of 0.9 mL/min, and UV detection set to 215 nm. Forced degradation studies confirmed the method stability-indicating properties, which revealed no interference from degradation products in the accurate determination of CZB and its related impurities. Acceptable accuracy and precision were confirmed across the concentration ranges by validation employing accuracy profiles. The ecological footprint of the technique was appraised using established greenness metrics, while the RGBfast algorithm were used to gauge its overall sustainability and practicality. Also, the method has attained a well-rounded level of proficiency through Efficient Valid Green (EVG) framework. This method provided a reliable and environmentally sound approach for quality control analysis of CZB in both bulk materials and pharmaceutical preparations, fulfilling the demand for advanced analytical methodologies for this important therapeutic compound.