Artemisinin-based combination
therapies (ACTs) have been adopted by most African countries, including Nigeria, as first-line treatments for uncomplicated
falciparum malaria. Fixed-dose combinations of these ACTs,
amodiaquine-artesunate (FDC AQAS) and
artemether-lumefantrine (AL), were introduced in Nigeria to improve compliance and achieve positive outcomes of
malaria treatment. In order to achieve clinical success with AQAS, we developed and validated a simple and sensitive high-performance liquid chromatography (HPLC) method with UV detection for determination of
amodiaquine (AQ) and
desethylamodiaquine (
DAQ) in plasma using liquid-liquid extraction of the drugs with
diethyl ether following
protein precipitation with
acetonitrile. Chromatographic separation was achieved using an Agilent Zorbax C18 column and a mobile phase consisting of distilled water-
methanol (80:20 [vol/vol]) with 2% (vol/vol)
triethylamine, pH 2.2, at a flow rate of 1 ml/min. Calibration curves in spiked plasma were linear from 100 to 1,000 ng/ml (r > 0.99) for both AQ and
DAQ. The limit of detection was 1 ng (sample size, 20 μl). The intra- and interday coefficients of variation at 150, 300, and 900 ng/ml ranged from 1.3 to 4.8%, and the biases were between 6.4 and 9.5%. The mean extraction recoveries of AQ and
DAQ were 80.0% and 68.9%, respectively. The results for the pharmacokinetic parameters of
DAQ following
oral administration of FDC AQAS (612/200 mg) for 3 days in female and male patients with uncomplicated
falciparum malaria showed that the maximum plasma concentrations (C max) (740 ± 197 versus 767 ± 185 ng/ml), areas under the plasma concentration-time curve (AUC) (185,080 ± 20,813 versus 184,940 ± 16,370 h · ng/ml), and elimination half-life values (T 1/2) (212 ± 1.14 versus 214 ± 0.84 h) were similar (P > 0.05).