Study of the biotransformation of a new sydnonimine derivative with predominant cerebral vasodilatory activity

Introduction: Sydnonimines are a promising group of drugs for development of novel substances with predominant cerebral vasodilatory activity. One of them is experimental compound with laboratory code BBP20233. The mechanism of action of BBP2023 compound is tied to its metabolites. This study aims for identification of biotransformation products of BBP2023 using HPLC-MS/MS method. Materials and Methods: Identification of BBP2023 biotransformation products was performed in male rats and male rabbits after intragastric administration of BBP2023 in form of oil emulsion. Blood samples were collected before and 1 and 8 hours after administration. Urine samples from rats were collected before and 24 hours after administration. Additionally, complete liver isolation was performed in another group of rats to investigate liver’s role in BBP2023 metabolism. Identification of products was performed using HPLC-MS/MS method as well as UHR-TOF method. Results and Discussion: Analysis of rat plasma samples collected 1 hour after administration revealed the presence of parent compound, active metabolite SIN, geranamine and various isomers of OH-derivatives. Analysis of rat urine samples collected 24 hours after administration showed the presence of glucuronic acid conjugates of SIN and parent compound. Similar results were obtained from rabbit plasma samples, although with less variety of hydroxylated derivative isomers. Conclusion: Investigated features of BBP2023 biotransformation require detailed analysis of pharmacokinetics for both BBP2023 and its metabolites to determine their role in therapeutic effect and possible adverse effects.