丹参乙酸镁活性代谢产物在大鼠体内的药代动力学特征

Pharmacokinetic characteristics of the active metabolites of magnesium lithospermate B in rats

目的研究丹参乙酸镁代谢产物M1(3-′O-monomethyl-lithospermic acid B)和M2(3,′3′-′O-dimethyl-lithosper-mic acid B)在大鼠体内的药代动力学特征。方法大鼠静脉注射丹参乙酸镁代谢产物M1或M2,液质联用法进行MRM扫描分析,测定代谢物M1和M2血药浓度,计算药代动力学参数。结果采用该液质联用色谱测定血浆样品中丹参乙酸镁代谢物的方法,血浆内源性物质均不干扰样品峰,相对回收率为:87%-101.4%,日间和日内相对变异系数(CV%)均小于9.77%,血浆中的最低定量限为1μg/L(S/N≥3),线性范围为16-4 096μg/L。M1和M2的t1/2z分别为(1.54±0.81)h和(1.52±0.42)h,MRT(0-t)分别为(0.46±0.07)h和(0.33±0.05)h,AUC(0-tn)分别为(13.63±2.7)(mg.h)/L和(14.96±2.54)(mg.h)/L。结论M1和M2静脉注射的体内代谢过程符合二室模型,消除较快。

To study the pharmacokinetics of two main metabolites of magnesium lithospermate B, 3＂-O-monomethyl-lithospermic acid B and 3＂, 3-O-dimethyl-lithospermic acid B, in Sprague-Dawley rats. Methods Serum was collected from rats at various times after animals were intravenously administered with M1 or M2, respectively. The analysis of M1 and M2 was performed in the MRM model by liquid chromatography/tandem mass spectrometry method and their pharmacokinetic parameters were calculated. Results In this method, the determination was not distracted by endogenous factors. Recovery of M1 and M2 was 87%- 101.4%, intra- and inter^assay CVs were lower than 9.77% ,LOQ was 1 ,ug/L（S/N^3）. Calibrations between 16-4 096 ,ug/L exhibited consistent linearity and reproducibility. The main parameters of pharmacokinetics of M1 and M2 were as follows： t/2z of M1 and M2 was （1.54±0.81）h and （1.52±0.42）h, MRT of M1 and M2 was （0.46±0.07）h and （0.33±0.05）h, AUC（0-tn） of M1 andM2 was （13.63±2.7）（mg·h）/L and （14.96±2.54） （mg·h）/L, respectively. Oonclusion The pharmacokinetic characteristics of M1 and M2 by intravenous administration in rats is described by a two-compartment model. M1 and M2 were rapidly eliminated.