A great strength of the clinical pharmacology laboratory is its innovative and highly successful approach to bioanalytical method development, utilizing diverse sample preparation techniques (such as solid-phase extraction, liquid-liquid extraction, protein precipitation) in combination with LC-MS, LC-MS/MS and LC-UV for quantification of drugs and metabolites in biological fluids. Optimising the dose of antimalarial drugs, and assessing drug safety are critical to current control and elimination efforts. Drug measurement is an essential part of dose optimisation. Infants and children bear the greatest burden of malaria. Antimalarial dose regimens for this important group are often extrapolated from studies in adults. Infants and young children are usually excluded from pharmacokinetic (PK) studies, and there have been very few detailed pharmacovigilance assessments because of the practical and operational difficulties in conducting such studies in the rural tropics. Taking and storing venous blood samples is often simply too difficult.

Our aim is to develop and validate low volume, high throughput, and field applicable methods for the accurate measurement of antimalarial drugs. Dried blood spots for instance can be taken anywhere a malaria smear is performed. This will greatly expand the opportunities for drug measurement in therapeutic and pharmacovigilance studies, and allow optimal drug regimens to be developed, particularly for the very young. Venous blood sampling is a major constraint limiting the conduct and availability of antimalarial drug assays. Venepuncture, sample preparation, and sample storage may simply be impossible in many areas of the rural tropics. It is often not possible to perform multiple venous blood draws. Even if it is possible many patients or guardians refuse, particularly on behalf of young children. Dried blood spot methods would considerably facilitate pharmacokinetic studies under tropical field conditions where blood or plasma storage at –20 °C or colder is not feasible. Another advantage is that dried blood spots significantly reduce or eliminate the activity of HIV and other pathogens making handling the samples safer for the laboratory personnel. We have published bioanalytical methods for the determination of several of the antimalarials in capillary blood samples, but these have usually required a minimum 100 μl capillary blood applied onto paper. The sensitivity of these methods has traditionally been limited mainly because the methods have relied upon LC with UV detection. The introduction of sensitive mass spectrometers, such as the API5000, should allow high throughput analysis of antimalarials in dried blood spots. There are many analytical challenges, and standardization of sampling methods, paper and analytical procedures is essential, but we believe these obstacles can be overcome for most available drugs and valid methodologies developed.

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