Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec 6:15:1474768.
doi: 10.3389/fphar.2024.1474768. eCollection 2024.

Discovery of quality markers of Meconopsis quintuplinervia based on an absorption-based metabolite approach and rapid quantification using polarity-switching UPLC-QQQ-MS/MS

Yifan Tian #  1 , Yuan Liu #  1 , Yuanlin Kong  1 , Limin Li  2 , Zhengming Yang  1 , Wenbin Li  1 , Qiang Li  3 , Chaoqin Ren  4 , Wenxia Sun  5 , Yanfei Huang  1
Affiliations

Discovery of quality markers of Meconopsis quintuplinervia based on an absorption-based metabolite approach and rapid quantification using polarity-switching UPLC-QQQ-MS/MS

Yifan Tian et al. Front Pharmacol. .

Abstract

Background: Meconopsis quintuplinervia Regel (MQ) is a traditional Chinese medicine (TCM) used for clearing liver and lung heat in Tibetan medicine for over a thousand years. However, the lack of quality markers that correlate with pharmacological actions and absorption in vivo limits the safety and efficacy in its clinical application and on the drug market. Furthermore, a universal and rapid method for simultaneously determining quality markers in the MQ crude drug is still lacking.

Purpose: An absorption-based metabolite approach was used to discover and identify the quality markers of MQ. An efficient method based on polarity-switching ultra-performance liquid chromatography triple quadrupole mass spectrometry (UPLC-QQQ-MS/MS) was then established to determine the quality markers.

Methods: The absorbed compounds and metabolites were first characterized using UPLC plus Q-Exactive Orbitrap tandem mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) after giving oral MQ extract to rats. Subsequently, the absorbed compounds and precursors of metabolites correlating with the hepatocyte protection activity were screened as quality markers. Finally, a polarity-switching UPLC-QQQ-MS/MS method was developed for the quantitative analysis of the MQ crude drug, enabling the detection of quality markers in both negative and positive ion modes in a single run. The MS2 characteristics of target compounds were investigated to select appropriate product ions.

Results: A total of 13 absorbed compounds and 30 metabolites were characterized. Among these, nine compounds, including five absorbed compounds and four precursors of metabolites intimately correlated with hepatocyte protection activity and absorption in vivo, were considered the quality markers of MQ in the current study. The quantification of quality markers was conducted using an Acquity UPLC HSS T3 (2.1 × 100 mm, 1.8 μm) column, the mobile phase consisting of acetonitrile and 0.1% formic acid solution (containing 10 mmol/L ammonium acetate). The validated UPLC-QQQ-MS/MS method was successfully applied to quantify the quality markers in the MQ crude drug.

Conclusion: We defined the quality markers and established a universal and rapid method for simultaneously determining the quality markers of MQ, which will be helpful for further investigation of the quality evaluation of MQ in clinical application and the drug market.

Keywords: LC-MS; Meconopsis quintuplinervia Regel; content determination; metabolism; quality markers; traditional Chinese medicine.

PubMed Disclaimer

Conflict of interest statement

Author QL was employed by Shimadzu China Co. LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Chemical structures of the nine investigated compounds in MQ.
FIGURE 2
FIGURE 2
MS2 spectra of M5 (A) and M6 (B) and proposed fragmentation pathway of M5 and M6 (C).
FIGURE 3
FIGURE 3
Metabolites and proposed metabolic pathways of meconquintupline and caffeic acid in rats.
FIGURE 4
FIGURE 4
Extracted ion chromatogram of nine quality markers in the MRM mode (A) and secondary mass spectra of nine compounds (B–J). 1. Chlorogenic acid, 2. caffeic acid, 3. taxifolin, 4. protopine, 5. allocryptopine, 6. luteolin, 7. quercetin, 8. apigenin, and 9. isorhamnetin.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Ahmed E. S., Mohamed H. E., Farrag M. A. (2022). Luteolin loaded on zinc oxide nanoparticles ameliorates non-alcoholic fatty liver disease associated with insulin resistance in diabetic rats via regulation of PI3K/AKT/FoxO1 pathway. Int. J. Immunopathol. Pharmacol. 36, 03946320221137435. 10.1177/03946320221137435 - DOI - PMC - PubMed
    1. Chinese Pharmacopoeia Commission (1995). Herba Meconopsis in: pharmaceutical standards of the Ministry of Health of the people’s Republic of China.
    1. Duan S., Niu L., Yin T., Li L., Gao S., Yuan D., et al. (2020). A novel strategy for screening bioavailable quality markers of traditional Chinese medicine by integrating intestinal absorption and network pharmacology: application to Wu Ji Bai Feng Pill. Phytomedicine 76, 153226. 10.1016/j.phymed.2020.153226 - DOI - PubMed
    1. Guo Q., Bai R. F., Zhao B. S., Feng X., Zhao Y. F., Tu P. F., et al. (2016). An ethnopharmacological, phytochemical and pharmacological review of the genus Meconopsis. Am. J. Chin. Med. 44, 439–462. 10.1142/S0192415X16500257 - DOI - PubMed
    1. He J. S., Huang B., Ban X. Q., Tian J., Zhu L., Wang Y. W. (2012). In vitro and in vivo antioxidant activity of the ethanolic extract from Meconopsis quintuplinervia. J. Ethnopharmacol. 141, 104–110. 10.1016/j.jep.2012.02.006 - DOI - PubMed

LinkOut - more resources