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Comparative Pharmacokinetic Studies of Paeoniflorin, Albiflorin and Oxypaeoniflorin Between Normal and Cerebral Ischemia–Reperfusion Rats Based on the Simultaneous Determinations Using an UPLC-MS–MS Method

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Abstract

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.

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All software used in this research were declared in the experimental section in the manuscript.

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Data that support this research were represented in Table attached to the manuscript.

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Acknowledgements

The authors express their thanks for the grants from the National Natural Science Foundation of China under Grant 81403177, the Science and Technology Planning Project of Shenyang Science and Technology Bureau under Grant F12-277-1-14, and the Innovative Talents Support Program of Liaoning Province under Grant LR2018047.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Liaoning University, Shenyang, 110036, People’s Republic of China

    Lijun Zhu, Shanshan Sun, Xin Li, Yanxi Hu & Yufeng Liu

  2. Department of Epidemiology, University of Florida, Gainesville, FL, 32608, USA

    Yancheng Li

  3. Natural Products Pharmaceutical Engineering Technology Research Center of Liaoning Province, Shenyang, 110036, People’s Republic of China

    Yufeng Liu

Authors
  1. Lijun Zhu
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  2. Shanshan Sun
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  3. Xin Li
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  4. Yanxi Hu
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by LZ, SS, YH, YL and XL. The manuscript was written and proved by LZ, YL, XL and YL. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yufeng Liu.

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This study has been approved by the ethics committee for research animals of Liaoning University, and all experimental operations were in accordance with the welfare of animals.

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All authors have made substantial contributions to this research. And all authors have drafted the work or revised it critically for important intellectual content.

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Zhu, L., Sun, S., Li, X. et al. Comparative Pharmacokinetic Studies of Paeoniflorin, Albiflorin and Oxypaeoniflorin Between Normal and Cerebral Ischemia–Reperfusion Rats Based on the Simultaneous Determinations Using an UPLC-MS–MS Method. Chromatographia 83, 1345–1354 (2020). https://doi.org/10.1007/s10337-020-03954-4

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