Abstract
A new highly specific high-performance liquid chromatography with tandem mass spectrometry (LC–MS/MS) method coupled to microdialysis sampling was developed and validated for simultaneous determination of L-ephedrine, D-pseudoephedrine, L-methyl-ephedrine, cinnamic acid, liquiritin, amygdalin, and glycyrrhizic acid both in rat blood and brain after oral administration of Mahuang decoction in this paper. An Agilent Zorbax SB-C18 using the 0.1% formic acid water solution and acetonitrile as mobile phase with a gradient elution was applied to the chromatographic separation. The ion transitions were quantified in positive mode for D-pseudoephedrine, L-ephedrine, L-methylephedrine, and diphenhydramine (internal standard), while negative mode for liquiritin, glycyrrhizic acid, amygdalin, cinnamic acid, and prednisolone (internal standard). Several parameters of the method including linearity, accuracy, precision, stability, and matrix effect were within acceptable ranges. The results showed the LC–MS/MS method coupled to microdialysis sampling can be utilized for the pharmacokinetic studies of these seven ingredients in vivo. According to the pharmacokinetic results, the pharmacokinetic parameters of L-ephedrine, D-pseudoephedrine, L-methylephedrine, glycyrrhizic acid, cinnamic acid, liquiritin, and amygdalin were totally different in rat blood and brain, the bioavailability of ephedrine and amygdalin in the blood and brain was higher, while the MRT of ephedrine was the shortest. In the rat brain, the elimination rate of three Ephedra alkaloids was lower than that of the remaining four components. This research offered more basic pharmacokinetic information on the safety mechanisms of Mahuang decoction.
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Funding
This research was financially supported by the National Natural Science Foundation of China (No. 81573868, 81930111), Zhejiang Provincial Natural Science Foundation of China (No. LZ18H270001, LY16H280008), and Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents (No. 2014-108-24).
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Y He and HT Wan conceived and designed research. HY Wan, Y Wang, C Li, and L Yu performed all experiments. HY Wan, LJ Pan, and HF Zhou analyzed data. HY Wan, LJ Pan, and Y He wrote the manuscript. All the authors read and approved the manuscript.
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All animal experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals (NIH Publications, No.80–23, revised in 1996), and this research was approved by the Animal Ethics Committee of Zhejiang Chinese Medical University and performed according to its guidelines.
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Wan, H., Pan, L., Wang, Y. et al. Pharmacokinetics of seven major active components of Mahuang decoction in rat blood and brain by LC–MS/MS coupled to microdialysis sampling. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1559–1571 (2020). https://doi.org/10.1007/s00210-019-01786-0
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DOI: https://doi.org/10.1007/s00210-019-01786-0