罗丹宁衍生物Lj0104在大鼠体内的代谢产物研究

In vivo metabolism of a rhodanine derivative Lj0104 in rats

目的研究罗丹宁衍生物Lj0104在大鼠体内的主要代谢产物。方法对雄性SD大鼠采用口服和静脉注射两种给药方式,给药剂量为5.0 mg/kg(口服)和1.0 mg/kg(静脉注射)。在24 h内眼眶取血,采用质谱方法对血浆中母体化合物及代谢产物进行分析。结果发现Lj0104有3种主要代谢产物。结论化合物Lj0104主要代谢为水解和羟基化产物。该研究为进一步对该化合物进行结构改造提供了实验及理论依据。

Objective To study the metabolites of rodanine derivative Lj0104 in rat plasma in parti- cular. Method Verapamil is utilized as the internal standard （IS）. Male Sprague-Dawley rats were ad- ministered with compound Lj0104 by po. 5.0 mg/kg and iv. 1.0 mg/kg. Plasma concentration of the parent compound and the metabolites were analyzed using LC-MS/MS. Result Three major metabolites were discovered. Conclusion The major metabolites of Lj0104 are hydroxylation and hydrolysis prod- ucts. This study provides guidance for further modification of Lj0104.