dArtemisinin-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 C 18 column and a mobile phase consisting of
Extensive deployment of antimalarial drugs in the past 50 years has led to high selection pressure on human malaria parasites to evolve mechanisms of resistance. Plasmodium falciparum is now highly resistant to chloroquine (a one-time first-line antimalarial) and other antimalarials in most malaria-affected areas. Due to the relentless increase in resistance of malaria parasites to conventional drugs, many African countries have adopted the WHO recommendation to use artemisinin-based combination therapies (ACTs) as the first-line treatment for uncomplicated falciparum malaria (1). Artemisinin derivatives rapidly reduce the biomass of multidrug-resistant parasites, leaving the partner drugs, which usually have longer half-lives and therefore are eliminated more slowly, to kill the remaining residual parasites. The complete clearance of all parasites is therefore dependent on the partner drugs, such as amodiaquine (AQ), lumefantrine, piperaquine, and mefloquine, being effective and persisting at parasiticidal concentrations until all infecting parasites are killed. A fixed-dose combination (FDC) of AQ and artesunate (AS) tablets (Diasunate; Emzor, Lagos, Nigeria) was introduced to the Nigerian market to improve patient compliance and achieve a positive outcome of malaria treatment. Following oral administration of AQ, there is rapid and extensive metabolism of the AQ to its pharmacologically active derivative desethylamodiaquine (DAQ), which is assumed to be responsible for most of the therapeutic effect (2); in vitro studies (3-5), however, suggest synergism between AQ and DAQ (Fig. 1). This underscores the importance of routine therapeutic drug monitoring when artesunate is coadministered with AQ, to ensure not only appropriate drug dosing, but also that the dosing regimen results in concentrations in the blood sufficiently high to kill the residual parasites. A diseased state significantly alters the disposition of antimalarial drugs, yet several analytical techniques that reported the quantification of AQ and DAQ (2, 6-13) in various biological fluids demonstrated its applicability only either in healthy volunteers or in patients administered AQ as monotherapy. To our know...