Development of a new eco-friendly HPLC method and assessing the pharmacokinetics of pelitinib, a potent epidermal growth factor receptor inhibitor used for the treatment of non-small cell lung cancer associated with EML4-ALK mutant gene

Abstract

Pelitinib (PEL) is a potent drug which demonstrated clinical success in the treatment of non-small cell lung cancers harboring the mutant fusion gene EML4-ALK (echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase. The objective of this study was the development of eco-friendly HPLC method to refine the therapeutic findings, support pharmacokinetic assessments, and aid in the potential therapeutic monitoring of PEL. The chromatographic separation of PEL and levofloxacin as an internal standard (IS) was accomplished on a Shim-pack VP-ODS C18 HPLC column using a gradient elution with a mobile phase consisting of formic acid (0.1 %, v/v) in an acetonitrile–methanol mixture (80:20 %, v/v). The flow rate was 1.0 mL min^–1 and the detection wavelength was 260 nm. Validation of the method was conducted in accordance with ICH guidelines for bioanalytical method validation, and all parameters’ values were acceptable. The novelty of the proposed eco-friendly HPLC-UV method in terms of its adherence of the method's procedures to the requirements of the green analytical chemistry approaches was confirmed by three comprehensive metric tools. The method was successfully applied in studying the pharmacokinetics of PEL in rats. The findings revealed that PEL was absorbed and reached maximum plasma concentration of 182.08 ng mL⁻¹ after 4 h and had an eliminated rate constant of 0.072 h⁻¹. The volume of distribution was 0.064 L/kg. The clearance was found at 0.005 L/h/kg. The results presented this method as a valuable tool for realizing targeted therapeutic benefits and ensuring safety of PEL treatment.