Practical HPLC methods for the quantitative determination of common antimalarials in Africa.

This article describes high-performance liquid chromatographic assays for the quantification of sulfadoxine (SDX), pyrimethamine (PYM), chloroquine (CQ), amodiaquine (AQ) and desethylamodiaquine (AQM) from whole blood. All four assays were set up and validated in Malawi using a common high-performance liquid chromatography platform and column and involved the use of simple mobile phase and extraction reagents. Calibration curves were linear (r(2)>0.95) in the ranges 5-100microg/ml, 50-1000, 150-1500, 100-1000 and 100-1000ng/ml for SDX, PYM, CQ, AQ and AQM, respectively. Intra-assay and inter-assay coefficients of variation were <15% at 3 points spanning the concentration range and <20% at the lower limit of quantification. The assays were specific with no interference from the other antimalarials described in this report. All four assays use liquid-liquid extraction, reversed-phase chromatography and UV detection and require between 50 and 200microl of blood. Because the assays share common instruments and reagents, they are cost-efficient and could be used to optimise antimalarial drug therapies in other resource poor settings.

Population pharmacokinetics of sulfadoxine and pyrimethamine in Malawian children with malaria.

In addition to parasite resistance, inadequate levels of exposure to antimalarial drugs may contribute to treatment failure. We developed population pharmacokinetic (PK) models to describe the distribution of sulfadoxine (SDX) and pyrimethamine (PYM) in children with uncomplicated malaria in Malawi. The concentration levels of antimalarial drugs in whole blood were determined using high-performance liquid chromatography. We found no evidence of underdosing in children as compared with adults; the children had drug exposure levels similar to those described in adults. Treatment failure was more likely in children with lower PYM concentrations on day 14 (P = 0.024), and there was a trend for lower SDX concentrations on day 14 (P = 0.061). SDX and PYM concentrations at levels predictive of treatment failure have been identified at day 14. Less than one-third of the children displayed drug concentration levels above these thresholds after receiving the recommended SDX-pyrimethamine (SP) dose. Our findings suggest that PK factors contributed to the observed high rate of treatment failure, and we therefore recommend a higher SP dose for children under the age of 5 years.