A high performance liquid chromatographic assay of Mefloquine in saliva after a single oral dose in healthy adult Africans

A high performance liquid chromatographic method with UV detection at 220 nm for assaying mefloquine in saliva was developed and validated by comparing mefloquine concentrations in saliva and plasma samples from four healthy volunteers who received single oral dose of mefloquine. Verapamil was used as internal standard. Chromatographic separation was achieved using a Hypersil ODS column.Extraction recoveries of mefloquine in plasma or saliva were 76-86% or 83-93% respectively. Limit of quantification of mefloquine was 20 ng/ml. Agreement between salivary and plasma mefloquine concentrations was satisfactory (r = 0.88, p < 0.001). Saliva:plasma concentrations ratio was 0.42.Disposition of mefloquine in saliva paralleled that in plasma, making salivary quantification of mefloquine potentially useful in therapeutic drug monitoring.The morbidity and mortality associated with malaria is highest in African children with approximately one million deaths per year. The spread of drug resistant Plasmodium falciparum confounds malaria control efforts and has resulted in the widespread use of artemisinin based combination therapy (ACT) in the management of malaria in several sub-Saharan African countries [1]. Mefloquine-artesunate is a formulation of ACT recommended by the World Health Organization [1] and historically the first ACT used clinically. The combination remains an effective treatment for uncomplicated malaria [2-5]. The effectiveness of ACT is dependent on the different modes of action of the drugs in the combination. The artemisinin derivatives cause an initial rapid reduction in parasite biomass though they are rapidly eliminated while the partner drugs such as mefloquine, lumefantrine, piperaquine, or amodiaquine are more slowly eliminated and cause subsequent removal of the remaining parasites. Thus, when combinations of drugs with discordant half-lives are used, the patient in effect receives monotherapy with the longer lasting drug for the tail end of therapy