Keywords
lumefantrine
PRISMA
methodological validation
risk of bias
quality control
systematic review
pharmacosurveillance
How to Cite
Abstract
Introduction
The fixed-dose combination (FDC) of artemether (ARM) and lumefantrine (LUM) is the global standard for treating uncomplicated Plasmodium falciparum malaria. Maintaining the analytical quality of AL formulations is critical to ensure therapeutic efficacy and combat the rise of substandard and falsified antimalarials.
Purpose
This systematic review aims to identify, evaluate, and synthesize the analytical methods developed and validated for the simultaneous determination of ARM and LUM in pharmaceutical dosage forms and biological matrices between 2010 and 2025.
Methods
A systematic search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework across PubMed, ScienceDirect, and Google Scholar. Studies were included if they provided formal validation data according to the International Council for Harmonisation (ICH) Q2(R1) or M10 guidelines. The risk of bias was formally assessed for all included studies. A total of 35 primary studies were analyzed.
Results
Quantitative synthesis demonstrates that reversed-phase high-performance liquid chromatography (RP-HPLC-UV) at 210 nm remains the standard for tablet assays, offering a mean precision relative standard deviation (RSD) of 1.88% and 98.0%–102.0% accuracy. Stability-indicating ultra-performance liquid chromatography (UPLC) and gas chromatography–mass spectrometry (GC-MS) platforms yield high resolution with limit of quantitation (LOQ) ranges of 0.01–0.10 µg/mL. For pharmacokinetic studies, liquid chromatography–tandem mass spectrometry (LC-MS/MS) provides high sensitivity with LOQ ranges of 1.5–8.0 ng/mL in plasma alongside a mean precision RSD of 5.37%. Alternative derivative spectrophotometry and high-performance thin-layer chromatography (HPTLC) densitometry report LOQ ranges of 0.35–3.80 µg/mL with moderate specificity.
Conclusion
The analytical landscape for ARM and LUM has evolved toward higher resolution and sensitivity. While HPLC remains dominant for routine quality control (QC), integrating mass spectrometry and stability-indicating protocols is essential for advanced clinical research and regulatory surveillance. Future perspectives include developing portable, solvent-free diagnostic tools to enhance global antimalarial security.
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