LC-MS/MS Method Development and Validation of Lenvatinib and its Related Impurities in Rat Plasma: Application to a Pharmacokinetic Study

Abstract

Background: Lenvatinib is a potent drug utilized in the medication of thyroid cancer and it acts as a tyrosine kinase inhibitor. Thus, the development and validation of Lenvatinib and allied impurities in rat plasma, and its pharmacokinetic study, are one of the most significant areas of modern pharmaceutical analysis. Objective: The current study conducts bioanalytical system validation and pharmacokinetic analysis of Lenvatinib and associated impurities in rat plasma with LC-MS/MS. Methods: The current study involves bioanalytical system validation and pharmacokinetic analysis of Lenvatinib and associated impurities in rat plasma using LC-MS/MS. Gradient elution of Lenvatinib with a flow rate of 1 mL/min and an X-Bridge phenyl column (150x4.6 mm, 3.5μ) was used in the optimized process. In this method, buffer (1 mL formic acid in 1 liter of water) and acetonitrile mixture was used as the mobile phase. Results: By using Carfilzomib as the internal norm and impurity-4 as the active metabolite and 30 minute run time, Lenvatinib and its associated impurities were separated. The linearity was in the range of 10 percent to 200 percent of rat plasma, and each analyte R2 value was found to be 0.999. Conclusion: This work indicates that all parameters, such as precision, recovery, accuracy, and stability, were achieved as per USFDA guidelines. This approach can be used to investigate Lenvatinib impurities and conduct pharmacokinetic studies involving rat plasma.