To explore the pharmacokinetic characteristics of the three monoterpene glycosides (paeoniflorin, albiflorin and oxypaeoniflorin) extracted from the Radix Paeoniae Rubra (RPR), we determined the plasma concentrations of these components in the cerebral ischemia–reperfusion (CIR) rats and the normal rats by a self-developed and validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS–MS) method. In this study, the CIR rats and the normal rats both underwent an intravenous administration of total paeony glucosides (TPG). The blood samples were collected from rats by eye puncture at a series of time points. Then, the pharmacokinetic parameters of the three components were calculated, including the half-life (t1/2), the area under curve of the concentration–time (AUC), the mean residence time (MRT), apparent volume of distribution (Vz) and the clearance (CL). Studies demonstrated that the Vz of albiflorin, the Vz of oxypaeoniflorin, the t1/2 of oxypaeoniflorin and the MRT of oxypaeoniflorin increased in the CIR rats versus the normal rats. Moreover, we found albiflorin and oxypaeoniflorin showed smaller AUC, longer MRT, larger Vz and larger CL than paeoniflorin both in CIR rats and normal rats. In conclusion, we used a validated method to determine the pharmacokinetic characteristics of three monoterpene glycosides in both CIR rats and normal rats simultaneously. These results demonstrated that there were meaningful differences among the pharmacokinetics of the three monoterpene glycosides in TPG either in normal rats or CIR rats. And the CIR model had influences on the in vivo process both of albiflorin and oxypaeoniflorin.

中文翻译：

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基于 UPLC-MS-MS 方法同时测定的芍药苷、白芍和氧化芍药苷在正常和脑缺血-再灌注大鼠之间的药代动力学比较研究

为了探索从赤芍 (RPR) 中提取的三种单萜苷（芍药苷、白芍和羟基芍药苷）的药代动力学特征，我们通过以下方法测定了这些成分在脑缺血再灌注（CIR）大鼠和正常大鼠中的血浆浓度一种自行开发和验证的超高效液相色谱-串联质谱 (UPLC-MS-MS) 方法。在这项研究中，CIR 大鼠和正常大鼠都接受了总芍药苷 (TPG) 的静脉注射。在一系列时间点通过眼睛穿刺从大鼠收集血液样品。然后计算三种组分的药代动力学参数，包括半衰期（t1/2）、浓度-时间曲线下面积（AUC）、平均停留时间（MRT）、表观分布容积 (Vz) 和间隙 (CL)。研究表明，与正常大鼠相比，CIR 大鼠白芍的 Vz、氧芍药苷的 Vz、氧芍药苷的 t1/2 和氧芍药苷的 MRT 增加。此外，我们发现白芍和氧化芍药苷在 CIR 大鼠和正常大鼠中均显示出比芍药苷更小的 AUC、更长的 MRT、更大的 Vz 和更大的 CL。总之，我们使用一种经过验证的方法同时测定了三种单萜糖苷在 CIR 大鼠和正常大鼠中的药代动力学特征。这些结果表明，无论是正常大鼠还是 CIR 大鼠，TPG 中三种单萜糖苷的药代动力学均存在显着差异。并且CIR模型对白花素和氧化芍药苷的体内过程都有影响。