Green Chiral HPLC Method for Lumefantrine Analysis: Method Development, Greenness Assessment, and Computational...

Currently, greening analytical methods have become of great interest to ensure operators' and environment health. Chiral analysis can commonly employ hazardous chemicals and large quantities of waste. In this context, this study presents a green chiral high-performance liquid chromatography (HPLC) method for the determination of lumefantrine (LUME) enantiomers. Chromatographic enantioseparation was achieved on a Chiralpak AD column with a mobile phase composed of ethanol at a flow rate of 1 mL/min. The effects of column temperature on the retention of the enantiomers were investigated, and the analysis temperature was set at 35°C. The method greenness profile was assessed using the Analytical GREEnness (AGREE) and Analytical Green Star Area (AGSA) metrics by which the method proved to be eco-friendly. The method was validated, showing adequate selectivity, linearity, precision, accuracy, and robustness over the range of 80-120 μg/mL per enantiomer. Electronic circular dichroism (ECD) analysis proposed that the first eluted peak was the R-enantiomer and the second eluted peak was the S-enantiomer. Molecular docking studies suggested that LUME may interact mainly through van der Waals and π-interactions on the Chiralpak AD. A green method was successfully developed for the chiral separation of LUME. The proposed work contributes to more environmentally friendly chiral approaches in pharmaceutical analysis.