Abstract
A sensitive and selective liquid chromatography-mass spectrometry (LC-MS) method has been developed for the determination of a new antimalarial bisthiazolium salt, SAR97276, in mouse plasma and red blood cells (RBCs). A drug of the same chemical series as the test drug, T2, was used as internal standard. The method involved solid phase extraction of the compound and the internal standard from the two matrices using Oasis((R))HLB columns. LC separation was performed on a Zorbax eclipse XDB C8 column (5mum) with a mobile phase of acetonitrile containing trimethylamine (130mul/l, solvent A) and 2mM ammonium formate buffer (solvent B). MS data were acquired in single ion monitoring mode at m/z 227 for SAR97276 and m/z 326 for T2. The matrix had no influence on the detection of either SAR97276 or T2. The drug/internal standard peak area ratios were linked via quadratic relationships to plasma (1.65-1322ng/ml) and RBC concentrations (3.31-2644ng/ml). Precision was below 14% and accuracy was 91.4-104%. Dilution of the samples had no influence on the performance of the method. Extraction recoveries of SAR97276 were >/=90% in plasma and >/=60% in RBCs. The lower limits of quantitation were 1.65ng/ml in plasma and 3.31ng/ml in RBCs. Stability tests under various conditions were also investigated. The method was successfully used to determine the pharmacokinetic profile of SAR97276 in healthy mouse.