Measurement of piperaquine in plasma by liquid chromatography with ultraviolet absorbance detection

Piperaquine (PQ) is an antimalarial drug enjoying a resurgence of use in combination with an artemisinin derivative because of parasite resistance to standard treatments. Its pharmacokinetic properties have not been characterised. An assay for PQ in plasma was developed using solvent extraction and liquid chromatographic separation on a Waters XTerra™ RP18 column, with a mobile phase of 7% acetonitrile in water (containing 0.025% trifluoroacetic acid, 0.1% NaCl and 0.008% triethylamine) and UV detection at 340 nm. The assay was linear up to 1000 μg/l. Intra- and inter-day relative standard deviations were <10% (5–500 μg/l) and <21% (5–500 μg/l), respectively. Inter-day limits of quantitation and detection were 5 μg/l and 3 μg/l, respectively. A preliminary pharmacokinetic study in a patient who received 2.56 g of PQ phosphate orally with dihydroartemisinin as four doses over 32 h found an apparent steady-state volume of distribution of 447 l/kg, an apparent oral clearance 0.93 l/h/kg and a terminal half-life of 17.3 days.