Determination of Lumefantrine after Capillary Sampling onto Sampling Paper

• The antimalarial lumefantrine was first synthesised and registered in China and is now commercially available as a coformulated product together with artemether (Coartem®/Riamet®). This combination is well tolerated and has proven highly efficacious for treatment of uncomplicated falciparum malaria. Lumefantrine is highly lipophilic with an extensive protein binding (99.9%). The day 7 plasma lumefantrine level has been shown to be an important determinant of treatment efficacy. To date no method has been published for the determination of lumefantrine after capillary sampling onto filter paper for field use. The aim of this work was to develop a method with adequate sensitivity for quantification of lumefantrine in capillary blood sampled onto filter paper. The method has been validated according to the current FDA guideline for bioanalytical method validation. Method: Whatman 31 ET Chr filter paper was pre-treated with an organic acid before sampling capillary blood to enable a high recovery of lumefantrine. Lumefantrine was extracted from the filter paper, then further purified using solid phase extraction and finally quantified with HPLC. Results: The between day variation is below 10 % over the range 0.4 to 25 µmol/l. The lower limit of quantification is 0.25 µmol/l in 100 µl capillary blood. No decrease in Lumefantrine concentration in dried blood spot is seen after 3 months at 37o C. The field sampling for lumefantrine assay with pre-treated Whatman 31 ET Chr has been tested in Tanzania with good results. Discussion: The field sampling for lumefantrine concentration assay with pre-treated Whatman 31 ET Chr has been evaluated and proven to be a valid method for field studies. The day 7 level after treatment can lumefantrine be accurately estimated in capillary blood to follow up compliance and efficacy. Validation data will be presented.

Keyword

Lumefantrine

Sampling paper; Dried blood spots; Capillary blood; Antimalarial drugs; Solid-phase extraction; Liquid chromatography

Publication and Content Type

ref (subject category)

kon (subject category)