Stability study, method for the quantitation of a new antifilovirus agent in biological fluids and a preliminary study of its pharmacokinetics

The stability of the new antifiloviral agent AS-358 consisting of borneol and 3-(piperidin-1-yl)propanoic acid, was studied in the blood and blood plasma of rats in vitro. It was found that in both matrices stabilized by EDTA or heparin, the compound is rapidly hydrolyzed at the ester bond. When sodium fluoride was added, the decomposition of the compound was significantly slowed down. This made it possible to develop and validate a method for the quantitative determination of the agent in whole rat blood. Analysis was performed by HPLC-MS/MS method using reverse phase chromatography. The developed method was used for a preliminary study of the pharmacokinetics of the agent AS-358 after its oral administration to rats, and it was shown that the concentration of AS-358 in the blood of animals reached 550 ng/ml after 1 hour, despite its instability in blood. Analogues of the agent which contain ether linker have been synthesized and their metabolic stability has been shown.