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Application of 2H stable isotope labelling methodology and ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry for the metabolite identification of dehydroandrographolide in rats

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Abstract

Dehydroandrographolide (DA), one of the crucial diterpenoids of Andrographis paniculata (Burm.F.) Nees, which has been widely used clinically due to its excellent biological activities and pharmacological safety. Until now, various investigations about the biological activities, pharmacokinetic profiles, and in vitro metabolism of DA have been conducted. However, information about the in vivo biotransformation of DA was still not available. In this study, a rapid and reliable approach based on stable isotope labeling and UPLC-Q/TOF–MS was developed and applied for the first systematic research about the in vivo metabolism of DA. As a result, a total of 35 metabolites were identified in rat urine, bile, plasma, and feces samples after DA was orally administered at the dose of 95 mg/kg, and 33 of them were further verified based on stable isotope labeling. The major metabolic pathways for DA were hydroxylation, hydration, sulfonation, sulfate conjugation, and glucuronidation. Meanwhile, sulfonation, sulfate conjugation, and amino acids conjugation of DA were reported for the first time. This is the first systematic investigation of the in vivo metabolism of DA in rats, and the identification of these metabolites might provide scientific and reliable support for a full understanding of the metabolism of DA.

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Acknowledgements

This work was supported by grant from the National Natural Science Foundation of China (No.81873079).

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Author notes

  1. Xinchi Feng & Feng Qiu

    Present address: School of Chinese Materia Medica, and State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, 301617, China

Authors and Affiliations

  1. School of Chinese Materia Medica, and State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Jinghai District, Tianjin, 301617, China

    Pengpeng Bai, Kaixia Niu & Zhipeng Huo

  2. TCM Research Center, Tasly Academy, Tasly Holding Group Co.Ltd, Tianjin, China

    Zhipeng Huo

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  1. Pengpeng Bai
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  2. Kaixia Niu
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Correspondence to Xinchi Feng or Feng Qiu.

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On behalf of all authors, the corresponding author states that there is no conflict of interest. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Bai, P., Niu, K., Huo, Z. et al. Application of 2H stable isotope labelling methodology and ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry for the metabolite identification of dehydroandrographolide in rats. ANAL. SCI. 38, 977–988 (2022). https://doi.org/10.1007/s44211-022-00129-z

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