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

Area of Science:

• Analytical Chemistry
• Green Chemistry
• Pharmaceutical Analysis

Background:

• Chiral analysis often involves hazardous chemicals and significant waste generation.
• Developing environmentally friendly analytical methods is crucial for operator and environmental safety.
• Lumefantrine (LUME) enantiomer determination requires efficient and sustainable separation techniques.

Purpose of the Study:

• To develop and validate a green chiral high-performance liquid chromatography (HPLC) method for lumefantrine (LUME) enantiomer determination.
• To assess the eco-friendly profile of the developed chiral separation method.
• To elucidate the enantiomeric configuration and interaction mechanisms of LUME.

Main Methods:

• Chiral separation using a Chiralpak AD column with ethanol as the mobile phase.
• Optimization of column temperature for enantiomer retention.
• Validation of the method for selectivity, linearity, precision, accuracy, and robustness.
• Assessment of method greenness using AGREE and AGSA metrics.
• Electronic circular dichroism (ECD) and molecular docking for enantiomer identification and interaction studies.

Main Results:

• Successful chiral separation of lumefantrine (LUME) enantiomers was achieved.
• The developed HPLC method demonstrated excellent greenness, confirmed by AGREE and AGSA metrics.
• The method exhibited adequate validation parameters (selectivity, linearity, precision, accuracy, robustness).
• ECD analysis identified the R- and S-enantiomers based on elution order.
• Molecular docking suggested van der Waals and π-interactions between LUME and the Chiralpak AD column.

Conclusions:

• A green and validated chiral HPLC method for lumefantrine (LUME) enantiomer separation was successfully developed.
• The method is eco-friendly, contributing to sustainable practices in pharmaceutical analysis.
• The study provides insights into LUME enantiomer interactions, supporting greener chiral analysis development.