Bioanalytical method validation for quantitative determination of two antimalarial thiazolium compounds and its application to a pharmacokinetic study in rat
Malaria remains one of the largest global health-care problems of the 21st century. Currently it affects more than 40% of the world's population. The disaster of malaria is mainly due to the emergence of multi-drug resistant Plasmodium strains. The current limited antimalarial drug repertoire, resistance of mosquitoes to various insecticides and absence of efficient malaria vaccine indicate that new antimalarial compounds are desperately needed. Two potential antimalarial monothiazolium compounds (T1 and T2), mimicking the structure of choline and inhibiting de novo phosphatidylcholine biosynthesis in Plasmodium, have been developed and are under investigation. Liquid chromatography / electrospray ionisation – mass spectrometry methods with good precision and accuracy have been developed for the simultaneous quantitation of monothiazolium compounds, T1 and T2, in biological matrices. Full validation of T1 and T2 in human plasma and whole blood as well as partial validation in rat plasma and red blood cells (RBCs) were carried out. This highly sensitive, accurate and precise method was suitable to analyse plasma and RBC samples, collected during preclinical pharmacokinetic study carried out after intravenous administration of T2 in rat. The calculated pharmacokinetic parameters of T2 indicate that further developmental work of this potential class of antimalarial compounds is needed.
Advisor:Briedis, Vitalis; Bressolle, Francoise; Sapragonien?, Marija; Marksien?, R?ta; Kiliuvien?, Guoda; Savickas, Ar?nas; Janulis, Valdimaras; Vainauskas, Paulius; Tarasevi?ius, Eduardas; Radži?nas, Raimondas; Kaduševi?ius , Edmundas
Source Type:Master's Thesis
Keywords:Malaria, validation, pharmacokinetic study
Date of Publication:06/12/2007