Green RP‐HPLC Method for Impurity Profiling of Desethynyl Erlotinib: A Process‐Related Impurity in Erlotinib

ABSTRACT Impurity profiling plays a vital role in ensuring the safety, efficacy, and regulatory compliance of pharmaceutical substances. In this study, a green, robust, and sensitive reverse‐phase high‐performance liquid chromatography (RP‐HPLC) method was developed and validated for the impurity profiling of Erlotinib, with a particular focus on its process‐related impurity, Desethynyl Erlotinib. The method employs a methanol:water (pH 3.1) mobile phase under gradient conditions and enables effective separation on a Shim‐pack GIST C18 column with detection at 251 nm. Validation as per International Council for Harmonisation (ICH) Q2(R2) and Q3A(R2) guidelines confirmed excellent linearity ( R 2 > 0.999), accuracy (98%–102% recovery), and precision (relative standard deviation [%RSD] < 2%). The method demonstrated high sensitivity, with limit of detection (LOD)/limit of quantification (LOQ) values of 0.0068/0.0206 µg/mL for Desethynyl Erlotinib, ensuring trace‐level detection and quantification. Additionally, the method showed strong robustness and minimal susceptibility to variations in analytical conditions. A greenness evaluation using the Analytical Greenness (AGREE) metric yielded a score of 0.82, endorsing the method's suitability for sustainable impurity profiling. Overall, this method offers a reliable and environmentally conscious tool for routine quality control and regulatory compliance of Erlotinib active pharmaceutical ingredient (API).