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- W2108177498 abstract "A new class of antimalarial drugs targeting membrane biogenesis during intraerythrocytic Plasmodium falciparum development has been identified. The bisthiazolium salts T3 and T4 have superior in vitro and in vivo parasite-killing properties and need to be monitored.We used a liquid chromatography-electrospray ionization mass spectrometry method (positive mode) to quantify two bisthiazolium compounds (T3 and T4) and a related prodrug (TE4c) in human and rat plasma. Verapamil was used as internal standard. Verapamil and the TE4c compound were characterized by protonated molecules at m/z 455.7 and m/z 725.7, respectively. T3 and T4 were detected through two ions [(M2+)/2] at m/z 227.7 and m/z 241.8 and by their adducts with trifluoroacetic acid [M+TFA]+ at m/z 568 and m/z 596, respectively. The sample clean-up procedure involved solid-phase extraction. HPLC separation was performed on a reversed-phase column, using a water-acetonitrile gradient, with both solvents containing TFA. Stability under various conditions was also investigated.The peak-area ratios (drugs/internal standard) were linked to concentrations (6.4-1282 microg/L for T3; 6.5-1309.8 microg/L for T4; 20-2000 microg/L for TE4c) according to a quadratic equation. The accuracy ranged from 85% to 113.1%, and the imprecision from 2.2% to 15%. The mean extraction recoveries were 87%, 98%, and 80% for T3, T4, and TE4c, respectively. The lower limit of quantification was 6.4 mug/L for the two bisthiazolium compounds, whereas it was 20 mug/L for TE4c, the related lipophilic prodrug.This highly specific and sensitive method is suitable for analyzing samples collected during preclinical pharmacokinetic studies in rats and to determine the percentage binding of T3 and T4 to human plasma proteins." @default.
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- W2108177498 date "2005-03-01" @default.
- W2108177498 modified "2023-10-16" @default.
- W2108177498 title "Quantification of Antimalarial Bisthiazolium Compounds and Their Neutral Bioprecursors in Plasma by Liquid Chromatography-Electrospray Mass Spectrometry" @default.
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- W2108177498 doi "https://doi.org/10.1373/clinchem.2004.042580" @default.
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