Untargeted search and identification of metabolites of antiviral agent camphecene in rat urine by liquid chromatography and mass spectrometry and studying their distribution in organs following peroral administration of the compound


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Abstract

Graphical abstractHighlightsMajor metabolites of a new antiviral agent camphecene were found and identified by HPLC-MS method followed by multivariate statistical analysis.Camphecene glucuronide, sulfate and iminoacid were found to be the metabolites excreting with urine along with intact compound.Distribution of camphecene and its metabolites in liver, kidney, lungs and brain after peroral administration to rats was studied.Major metabolites of camphecene, a new effective antiviral agent, formed after its oral administration to rats and excreted in the urine, were found and identified using liquid chromatography coupled to mass spectrometry as well as multivariate analysis of HPLC-MS data. The metabolites were found to be camphecene glucuronide, camphecene sulfate and the corresponding iminoacid. A study of the dynamics of accumulation of camphecene and its metabolites in the liver, kidneys, lungs and brain of animals was performed. Maximum concentration of camphecene in blood and organs was reached after 1.5–2 h of its administration, and the maximal content of the agent in the organs investigated was observed in the kidneys. The content of the substance in the lungs was comparable to that in the liver. Also, camphecene was found in brain in high concentration, thus allowing assumption of its ability to penetrate the blood-brain barrier and to exert its antiviral properties in the organ. Camphecene glucuronide and iminoacid had concentration-time profiles similar to that of their precursor, their content being maximal in kidney and liver and 2–3 orders of magnitude higher than in lungs and brain. The content of camphecene sulfate was of similar level in all organs studied. The results obtained made it possible to develop recommendations for therapy with the use of camphecene.

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