Identification and characterization of the forced degradation products of lenvatinib mesylate by liquid chromatography-high resolution mass spectrometry

Abstract

Lenvatinib mesylate (LEN) is a new generation anti-cancer medication included under the class of multiple kinase inhibitor and approved for the treatment of differentiated thyroid cancers that have not responded to the conventional radioactive iodine. It is marketed under the trade name Lenvima®. Forced degradation studies play an important part in the drug development process by providing crucial information about the inherent stability of the molecule under various conditions that are representative of the drug life cycle. The present study focused on exposing the active pharmaceutical ingredient, LEN to various stress conditions as per the ICH guidelines. LEN was found to degrade under hydrolytic stress whereas relatively stable in the thermal, oxidative and photolytic stress conditions. All the degradation products were separated on a Waters Acquity PFP (100 × 2.1 mm, 1.7 µm) column with mobile phase consisting of ammonium acetate in water and acetonitrile in gradient elution mode. LEN produced a total of nine degradation products (L1 to L9) which were structurally characterized with the help of LC-QTof-MS. The developed method was validated as per the ICH Q2 (R1) guidelines and was found to be specific, precise, accurate, linear and robust. The developed method can be effectively used for the routine batch analysis of LEN in bulk drug and various dosage forms in the presence of its degradation products /impurities.