Box-Behnken design in optimization of the green liquid chromatographic method for the quantification of Afatinib in drug product: AQbD approach

Abstract

The aim of this research work was to quantitatively determine the tyrosine kinase inhibitor, Afatinib, in tablets using an eco-friendly chromatographic method. The development of a green liquid chromatographic method using analytical quality-by-design (AQbD) approach principles to estimate Afatinib via Box-Behnken design. A simple and effective green liquid chromatographic method was developed and validated. The analysis was done on the Zodiac C18 column by isocratic elution mode. Mobile phase composed of pH 3.0 potassium dihydrogen phosphate buffer and ethanol in the ratio of 65:35%V/V. The flow rate was set to 0.6 mL/min. with an injection volume of 10 µL and at detection wavelength of 254 nm. The optimized method was found to be specific, linear, precise, accurate, and robust. Established linearity in the range of 24.6 to 73.9 µg/mL. The developed method exhibited excellent greenness. Based on the greenness assessment tools, the analytical eco-score value of 94 and the pictograms of NEMI, Modified NEMI, GAPI, Complex GAPI, AGREE, and AGREE prep expressed the method’s greenness. Hence, the AQbD approach based green method and the validation data indicate that the method can be employed in routine analysis for the determination of Afatinib in pharmaceutical dosage form in quality control laboratory use.