当药苦苷体内向香豆素类化合物转化过程的研究

Study on the Transformation Process of Swertiamain in Medicine to Coumarins

目的:探究当药苦苷体内向香豆素类化合物转化的过程。方法:通过设计化学衍生化-LC/MS的方法对可能代谢物进行检测,当药苦苷的体外主要的代谢产物为红百金花内酯,于是采用衍生化的方法提高其检测灵敏度。再经过动物实验和肝微粒孵育进行验证。结果:样品处理后经LC/MS经色谱测定后,专属性、精密度和准确度、稳定性等均满足生物样品分析,大鼠血浆中ECR定量分析,平均最高血药浓度、最长吸收时间、最大药时曲线面积分别为425.8±127.6ng/m L,128.6min,38.8μg/m L·min。结论:大鼠灌胃当药苦苷后血浆经衍生化,成功在血浆中检测到了红百金花内酯,当药苦苷首先在体内被水解变成苷元,大部分苷元经重排变成红百金花内酯,一个二氢香豆素,首次阐明了当药苦苷的大鼠体内代谢产物,发现其可以由单萜类化合物转化为生物碱类和香豆素类化合物,并以代谢物的形式发挥药效。丰富了环烯醚萜类化合物的体内代谢研究方法。

Objective ： To explore the process of medicine of swertiamarin in vivo transformation to coumarins. Methods： Through the de- sign of chemical derivative method - LC/MS of metabolites were detected, Swertia bitter glycosides in vitro primary metabolites as erythrocentaurin, .so the use of derivative of the methods to improve the detection sensitivity. The animal experiment and the liver mi- crosomal incubation were carried out to verify the. Results： The specificity, precision, accuracy and stability of the samples were ana- lyzed by LC/MS, and the average blood concentration, the maximum absorption time and the maximum drug curve were 425.8 ＋ 127. 6ng/mL, 128.6min,38.8 Ixg/mL ~ min respectively. Conclusion： Rat irrigation stomach Swertia bitter glycosides by plasma via deriving biochemical, success in the plasma detected erythrocentaurin, Swertia bitter glycoside first in vivo was hydrolyzed into aglycones. Most of the aglycone by rearrangement into erythrocentaurin, a Dihydrocoumarin first clarify Swertia bitter glycosides of rats in vivo metabo- lites, found that it can into the monoterpene compounds of alkaloids, coumarins, and its metabolites in the form of play a pharmacody- namics. Study on the metabolism of the compounds in the body of the cyclic ethers.