Abstract
Protoapigenone, a unique class of natural flavonoid, exerted significant cytotoxic and antitumoral activities. A simple, sensitive, and rapid LC–MS/MS method for the quantification of protoapigenone in plasma was developed and validated to obtain the pharmacokinetic profile of protoapigenone in beagle dogs. Ethyl acetate-10% ammonium hydroxide (2:1, v/v) was employed for liquid–liquid extraction (recovery > 90%). Under optimal conditions, chromatographic resolution was achieved on a C18 column using acetonitrile and 10 mM ammonium formate in water (9:1, v/v), as mobile phase at a flow rate of 0.5 ml/min. The established method presented good linearity, selectivity, accuracy, and precision in the range of 0.2–100 ng/ml. Finally, this method was successfully applied to a pharmacokinetic study in beagle dogs following oral administration of protoapigenone.
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Funding
This study was funded by the National Natural Science Foundation of China (81401718, 81773811, 81803841), Fujian Provincial Key Laboratory of Innovative Drug Target Research (FJ-YW-2020KF01), and Major Basic Research Development Program of Hubei Province (2020BCB045).
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CQ and AHW participated in all the laboratory work. AHW also contributed to collection and identification of plant material, as well as in the isolation and purification of the tested compound. XJ, XYY, and YPL were involved in animal experiments. Data were organized, analyzed, and validated by WYL, LQS, and JGH. YJZ and AHW contributed to experimental design and critical review of the paper. All authors have read the final manuscript and approved the submission.
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The authors declare that no experiments were performed on humans. All studies of animal experiments were approved by the Institutional Animal Care and Use Committee, Tongji Medical College, Huazhong University of Science and Technology (No. 2447), and conducted in accordance with the guidelines of the Committee on the Care and Use of Laboratory Animals in China.
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Qin, C., Zhang, Y., Jiang, X. et al. Determination of Protoapigenone in Beagle Dog Plasma by LC–MS/MS: Application to a Pharmacokinetic Study. Rev. Bras. Farmacogn. 31, 772–778 (2021). https://doi.org/10.1007/s43450-021-00205-x
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DOI: https://doi.org/10.1007/s43450-021-00205-x