文摘
Warfarin is a well-known anticoagulant agent that occurs in two enantiomers, (R)-(+)-warfarin and (S)-(?-warfarin, in which 4-hydroxycoumarin and benzalacetone are commonly found as impurities. Due to the lack of analytical reports for the simultaneous estimation on warfarin and its impurities in bulk drug and pharmaceuticals, we aim at the simultaneous estimation and optimization of the chromatographic separation of warfarin and its related substances employing experimental design. Central composite design was employed to evaluate the influence of two independent variables (concentration of organic modifier and flow rate) on the output responses: capacity factor (k 1), resolution of the peak (Rs 3,4), and retention time of the last peak (tR 5), as well as to model these responses. Further, the central composite design results were combined in a multicriteria decision-making approach in order to obtain a set of optimal experimental conditions leading to the most desirable compromise between resolution and analysis time.