Development and validation of liquid chromatography method using the principles of QbD for antimalarials used in Artemisinin based combination therapy

Abstract

The present work aims at developing a liquid chromatographic method for the determination of drugs in the artemisinin combination therapy. The method development utilised the principles of QbD (Quality by Design) and design space in order to provide a specific, accurate and precise method. The drugs used in the study were Amodiaquine (AMD), Mefloquine(MFQ),Lumefantrine (LFN), Artesunate (ART) and Artemether (AMR). Separations of the analytes were achieved on a UPLC system using a HSS Cyano column (100 x 2.1) mm, x 1.8 µm and mobile phase consisting of20mM Ammonium formate buffer (pH 6.5) as mobile phase A, 0.04% formic acid and methanol as mobile phase B in gradient elution program. The method development was based on the systematic trials suggested by the software using QbD. The design space of the experimental conditions was proposed to indicate the ruggedness of the analytical method using DoE. The proposed method was successfully applied to various formulations and thus was approved as good analytical method based on its applications. The method was thoroughly validated as per ICH guidelines. The developed method finds its application in bulk drug and formulations with its extension to quality control and also in investigation of counterfeit drugs.

Graphical Abstract

Keywords:

• Antimalarials
• design space
• method validation
• quality by design (QbD)
• UPLC

Acknowledgements

The authors thank KL University for immense support to publish this work. The authors wish to thank the management of USPIndia for providing the facilities to carry out the work.

Disclosure statement

The authors declare that there are no conflicts of interest.