Synthesis and development of an eco-friendly HPLC method for detection of Neratinib and its related Impurity H

Neratinib is a tyrosine kinase inhibitor prescribed for the treatment of breast cancer. The key step for the synthesis of neratinib involves the coupling of 4-N,N-dimethylaminocrotonic acid with 6-amino-4-[3-chloro-4-(2-pyridinyl methoxy)-anilino]-3-cyano-7-ethoxy quinolone. Several potential process related impurities are formed during the synthesis, including unreacted starting materials, and degradation products. These impurities are monitored by high-performance liquid chromatography (HPLC) and mass spectrometry (MS) to ensure the purity and quality of the final product. This study highlights the synthesis of neratinib impurity-H, and its detection by a new HPLC method. The HPLC method employed a C18 column (150 x 4.6 mm, 5μm) with a gradient flow of 1 ml min-1 of ethanol and phosphate buffer (pH 3.40) as a green solvent. The AGREE score confirmed the environmental benefits of using ethanol in the development of the liquid chromatographic method.