Can hair concentrations of artemether-lumefantrine be used as a tool to retrospectively determine drug exposure during malaria treatment?

Background: Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated Plasmodium falciparum malaria, with cure rates exceeding 95 %. However, recrudescence occurs in 2–14 % of cases, often linked to inadequate lumefantrine exposure. Retrospective assessment of drug exposure in recrudescence cases is challenging, as lumefantrine levels are undetectable in blood after several weeks. Hair analysis may offer an alternative method to assess drug exposure over time. The objective of this proof-of-concept study was to assess whether artemether and lumefantrine, and their respective metabolites dihydroartemisinin and desbutyl-lumefantrine, could be detected and quantified in hair of falciparum malaria patients who completed an AL treatment course. Methods: Hair samples were collected from six patients with falciparum malaria at Amsterdam UMC, four weeks after treatment initiation. Samples were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Lumefantrine and its metabolite desbutyl-lumefantrine were detected in all hair samples, with quantifiable levels in five cases. Artemether and its active metabolite dihydroartemisinin were undetectable. No study participants developed recrudescence. Conclusions: This study demonstrates that lumefantrine and its metabolite can be detected in hair weeks after treatment, suggesting hair analysis may serve as a retrospective tool to assess drug exposure in recrudescent malaria cases. The absence of artemether and dihydroartemisinin was likely due to their short half-lives, preventing incorporation into hair. A larger study is warranted to evaluate correlations between lumefantrine hair and plasma concentrations. If validated, this approach could aid in distinguishing inadequate drug exposure from reduced parasite susceptibility to AL, optimizing malaria treatment strategies.