The goal of the ongoing effort is to create and validate a quick, sensitive, and easy-to-use RP-HPLC method for the quantification of the anticancer drug curcumin benzothiazole analogue in human plasma using the Quality by Design methodology. Materials and method: The investigation employed a Waters Alliance HPLC system with a PDA detector and a Phenomenax C18 column. By using 33 factorial designs, Box-Behnken Design rationally optimised the process. Retention time, theoretical plate area, and wavelength were chosen as dependent variables; the mobile phase, pH, and wavelength were selected as independent variables.