Micelle-enhanced direct spectrofluorimetric method for the determination of linifanib: Application to stability studies.

Abstract

A new simple stability-indicating spectrofluorimetric method has been developed and validated for the determination of the tyrosine kinase inhibitor, linifanib (LNF). The proposed method makes use of the native fluorescence characteristics of LNF in a micellar system. Compared with aqueous solutions, the fluorescence intensity of LNF was greatly enhanced upon the addition of Tween-80. The relative fluorescence intensity of LNF was measured in a diluting solvent composed of 2% Tween-80: phosphate buffer pH8.0 (20: 80, v/v) using excitation and emission wavelengths of 290 and 450nm, respectively. The proposed method was fully validated as per the ICH guidelines. The recorded fluorescence intensity of LNF was rectilinear over a concentration range of 0.3-2μg/ml with a high correlation coefficient (r=0.9990) and low limits of detection (0.091μg/ml) and quantitation (0.275μg/ml). The applicability of the method was extended to study the inherent stability of LNF under different stress degradation conditions including, alkaline, acidic, oxidative, photolytic and thermal degradation. Moreover, the method was utilized to study the kinetics of the alkaline and oxidative degradation of LNF. The pseudo-first order rate constants and half-lives were calculated.