Isolation, identification and structural interpretation of degradation impurities in idelalisib

Abstract

AbstractIdelalisib is a Quinazolinone derivative, phosphatidylinositol‐3‐kinase delta inhibitor that has been approved for the treatment of hematological malignancies. A liquid chromatography method was developed to study the degradation of Idelalisib. As per the International Conference on Harmonisation guidelines, Idelalisib was exposed to acid, base, oxidative, photolytic, and thermal degradation studies. Idelalisib was labile to acidic, basic, and oxidative stress conditions. It was stable in remaining conditions. Three degradation products were observed that were not yet reported in the literature. Degradation products are isolated by using preparative‐scale high‐pressure liquid chromatography apparatus with C18 column using gradient elution. Structural characterization done by using fragmentation pattern of high‐resolution mass spectroscopy and further confirmed by using extensive NMR spectroscopic studies. Degradation studies were performed to determine the intrinsic stability of a drug substance in formulation and to generate more stable formulation.