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

Autor:	Tian Y; Qinghai-Tibetan Plateau Ethnic Medicinal Resources Protection and Utilization Key Laboratory of National Ethnic Affairs Commission of the People's Republic of China, Southwest Minzu University, Chengdu, China., Liu Y; Qinghai-Tibetan Plateau Ethnic Medicinal Resources Protection and Utilization Key Laboratory of National Ethnic Affairs Commission of the People's Republic of China, Southwest Minzu University, Chengdu, China., Kong Y; Qinghai-Tibetan Plateau Ethnic Medicinal Resources Protection and Utilization Key Laboratory of National Ethnic Affairs Commission of the People's Republic of China, Southwest Minzu University, Chengdu, China., Li L; Institute of Chinese Materia Medica Pharmacology and Toxicology, Sichuan Academy of Chinese Medicine Sciences, Chengdu, China., Yang Z; Qinghai-Tibetan Plateau Ethnic Medicinal Resources Protection and Utilization Key Laboratory of National Ethnic Affairs Commission of the People's Republic of China, Southwest Minzu University, Chengdu, China., Li W; Qinghai-Tibetan Plateau Ethnic Medicinal Resources Protection and Utilization Key Laboratory of National Ethnic Affairs Commission of the People's Republic of China, Southwest Minzu University, Chengdu, China., Li Q; Shimadzu China Co. LTD., Chengdu, China., Ren C; College of Resources and Environment, Aba Teachers College, Wenchuan, China., Sun W; Engineering Research Center for Pharmaceuticals and Equipments of Sichuan Province, School of pharmacy, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu, China., Huang Y; Qinghai-Tibetan Plateau Ethnic Medicinal Resources Protection and Utilization Key Laboratory of National Ethnic Affairs Commission of the People's Republic of China, Southwest Minzu University, Chengdu, China.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2024 Dec 06; Vol. 15, pp. 1474768. Date of Electronic Publication: 2024 Dec 06 (Print Publication: 2024).
DOI:	10.3389/fphar.2024.1474768
Abstrakt:	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 MS 2 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. Competing Interests: 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. (Copyright © 2024 Tian, Liu, Kong, Li, Yang, Li, Li, Ren, Sun and Huang.)
Databáze:	MEDLINE
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