RESUMEN
This study describes, for the first time, the experimental and computational investigations for evaluation of kolliphor RH 40 as a fluorescence enhancer surfactant in development of a spectrofluorimetric method for determination of lapatinib (LAP), a tyrosine kinase-inhibitor drug approved for targeted therapy of breast cancer. The investigations involved the ability of kolliphor RH 40 to form micelles with LAP and its enhancing effect on the weak native fluorescence of LAP at 420 nm after its excitation at 292 nm. Different variables were experimentally investigated: types of organized media, diluting solvent, buffer type and its pH value. The optimum values of the most influencing variables on the interaction of kolliphor RH 40 with LAP were refined by the computational response surface methodology (RSM). Under the optimized conditions, it was found that kolliphor RH 40 forms micelles with LAP, and its fluorescence enhancing ability was higher than other surfactants tested by ~ 10-folds. This micellar-enhanced effect of kolliphor RH 40 was employed in the development of a new sensitive spectrofluorimetric method for the accurate determination of LAP. The method was validated according to the guidelines of the International Conference on Harmonization (ICH) for validation of analytical procedures. The relative fluorescence intensity (RFI) was in excellent linear relationship (correlation coefficient was 0.998) with the LAP concentrations in the range of 50-1000 ng/mL. The method limit of detection (LOD) was 27.31 ng/mL and its accuracy was ≥ 99.82%. The method was successfully applied to the determination of LAP in its pharmaceutical tablets, tablets dissolution testing and content uniformity. The method application was extended to the determination of LAP in urine samples with an accuracy of 99.82 ± 3.45%. The method is considered as an eco-friendly green approach and more efficient alternative method to the existing analytical methodologies for determination of LAP.