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Quinine is an antimalarial agent whose main mechanism of action on Plasmodium is to inhibit the transformation of toxic haem to polymeric non-toxic haemozoin. After oral and intramuscular administration, quinine is well absorbed, with peak plasma concentration reached in 1 to 3 hours. The pharmacokinetic of quinine differs depending on the severity of the disease: the volume of distribution and the clearance decrease proportionally to the infection, while the half-life increases. Plasma concentrations are approximately 50% higher in patients in the acute phase than in convalescence. Quinine is metabolized primarily by CYP3A4, implying changing the dosage when combined with inhibitors or inducers of CYP. The efficacy of quinine has been proved for residual concentrations above 5 mg/L (15 μmol/L) throughout the duration of treatment. Some side effects are concentration-dependent and a concentration of 20 mg/L (60 μmol/L) is considered as the threshold for toxicity. The 2007 consensus conference of the French Language Infectious Diseases Society calls for daily monitoring of plasma concentrations during the first 3 days of treatment targeting a trough concentration between 10 and 12 mg/L (30-36 μmol/L). For this compound, the level of evidence of the interest of therapeutic drug monitoring has been evaluated and the latter is recommended., (© 2011 Société Française de Pharmacologie et de Thérapeutique.)

We propose a method to quantify quinine in biological fluids using liquid chromatography. After alkalinisation, samples are extracted with a chloroform-isoamyl alcohol mixture; in the case of urinary samples, a preliminary enzymatic hydrolysis is performed. Extracts are analyzed by adsorption chromatography. A mobile phase composed of methanol-acetonitril-ammonia in used to elute. A post-column reaction with sulfuric acid allows a fluorimetric detection. With this method concentration as low as 0.05 mg/l can be measured. Variation coefficient is about 2.5 p. cent Quinine, its metabolites and dihydroquinine are well separated; thus it is a very useful method for pharmacokinetic and metabolic studies.

Antimalarial therapy is directed more and more towards the use of associated substances: Pyrimethamine, sulfadoxime, quinine et chloroquine. The authors propose a method of direct determination of these four molecules mixed in biological fluids. The recommended extraction process followed by a spectrophotometric UV determination is fast, reproductible and sufficiently sensitive to study the evolution of a therapy.