丹参乙酸镁活性代谢产物在大鼠体内药代动力学特征.docVIP

丹参乙酸镁活性代谢产物在大鼠体内药代动力学特征 　 作者：王王乐，陆优丽 ，杨鼎，薛智谋，王逸平 【摘要】 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lithospermic 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16-4096μg/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。 【关键词】 丹参乙酸镁；代谢物；液质联用；大鼠；药物代谢动力学 　　Pharmacokinetic characteristics of the active metabolites of　magnesium lithospermate B in rats 　　ABSTRACT: Objective 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 1μg/L(S/N≥3). Calibrations between 16-4096μg/L exhibited consistent linearity and reproducibility. The main parameters of pharmacokinetics of M1 and M2 were as follows: t1/2z of M1 and M2 was (1.54±0.81)h and (1.52±0.42)h, MRT(0-t) of M1 and M2 was (0.46±0.07)h and (0.33±0.05)h, AUC(0-tn) of M1 and M2 was (13.63±2.7)(mg·h)/L and (14.96±2.54) (mg·h)/L, respectively. Conclusion 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. 　　KEY WORDS: lithospermic acid B; metabolite; liquid chromatography/mass spectrometry; rat; pharmacokinetics 　　丹参乙酸镁(mag