A bioassay for evaluating antimalarial activity and for measuring concentration in plasma

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Abstract:

Our objective was to develop a bioassay method based on the isotopic microtest of Desjardins and to validate it by comparing the results with high performance liquid chromatograph (HPLC). The bioassay was developed using a continuous culture of P. falciparum, and the test material consisted of 32 human serum samples from 22 Filipino patients treated only with chloroquine (CQ) for non-complicated malaria. A blind assay of the serum was done using the Desjardins method and HPLC. A good correlation (r2= 0.90, n = 32) was observed between the CQ plus monodesethylchloroquine (DCQ) concentrations obtained by HPLC and the equivalent CQ by bioassay. It was also shown that the antimalarial activity of CQ is practically identical to that of its main metabolite DCQ, the activity of DCQ being 0.9 times the activity of CQ. The bioassay is reliable, semi-automated, and reproducible. This method may be used as a complementary technique to HPLC for determining biological activity in serum and for measuring the kinetics of this activity, as well as to indicate the existence of new metabolites. The bioassay can be applied to other protozoans for which an in vitro model is available.

Keywords: Bioassay; HPLC; Plasmodium falciparum; chloroquine; in vitro test; monodesethylchloroquine

Document Type: Original Article

DOI: http://dx.doi.org/10.1046/j.1365-3156.1997.d01-150.x

Affiliations: 1: Laboratoire d'Epidémiologie et de Chimiorésistance du Paludisme, Service de Parasitologie, CHU Pitié Salpêtrière, Paris, France, 2: Marine Science Institute, University of the Philippines, Diliman, Manila, Philippines

Publication date: October 1, 1997

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