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(英文)

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

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。

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 dehy- drated-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.