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大鼠静脉注射丹酚酸B后代谢产物的鉴定及血浆药动学研究

The identification and pharmacokinetic studies of metabolites of salvianolic acid B after intravenous administration in rats

  • 摘要: 目的:鉴定丹酚酸B静注后在大鼠体内的代谢产物并对主要代谢物进行定量。方法:应用LC-IT/TOF-MS对大鼠胆汁、血浆和尿液中的代谢产物进行分析鉴定;应用LC-MS/MS对两个主要代谢产物进行定量,得到血浆药时曲线。结果:在大鼠胆汁、血浆和尿液中,共发现了九种代谢产物,包括丹酚酸B的甲基化产物,紫草酸及紫草酸的脱羧和甲基化产物,丹酚酸S及其脱水产物;药动学研究表明紫草酸和单甲基-丹酚酸B的t1/2都较小,单甲基-丹酚酸B与紫草酸相比有较大的AUC。结论:丹酚酸B静注后,在大鼠体内共发现了9种代谢产物,绘制了代谢通路图并对紫草酸和单甲基-丹酚酸B的药物代谢动力学进行了研究,阐明了丹酚酸B在大鼠体内主要的代谢方式是甲基化。

     

    Abstract: AIM:To identify and quantify the major metabolites of salvianolic acid B(SAB) after intravenous injection in rats.METHODS:LC-IT/TOF-MS was used to identify the metabolites in rat bile,plasma,and urine;LC-MS/MS was used to quantify the two major metabolites.RESULTS:In rat bile,plasma,and urine,nine metabolites were identified,including methylated metabolites of SAB,lithospermic acid(LSA),the decarboxylation and methylation metabolites of LSA,salvianolic acid S(SAS),and dehydrated-SAS.The t1/2 of monomethyl-SAB and LSA were both very short,and monomethyl-SAB had a larger AUC than LSA in rats.CONCLUSION:Nine metabolites were found,the metabolic pathway was described,and the pharmacokinetic profiles of LSA and monomethyl-SAB were studied,thereby clarifying that methylation was the dominant metabolic pathway for SAB in rats.

     

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