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高效液相色谱-串联质谱法的建立与验证及其在蒙药森登-4大鼠血浆药代动力学研究中的应用

Development and validation of the HPLC-MS/MS method and its application to the pharmacokinetic study for the Mongolian drug Sendeng-4 in rat blood plasma.

作者信息

Bai Pu, Dong Yu

机构信息

Inner Mongolia Medical University, Hohhot, China.

Ordos School of Clinical Medicine, Inner Mongolia Medical University, Ordos, China.

出版信息

Front Pharmacol. 2025 Mar 19;16:1547415. doi: 10.3389/fphar.2025.1547415. eCollection 2025.

DOI:10.3389/fphar.2025.1547415
PMID:40176895
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11962723/
Abstract

ABSTRACT

Sendeng-4 is a Mongolian drug. The Mongolian people have been using it to treat rheumatoid arthritis. At present, an increasing number of Han people are paying attention to the anti-rheumatoid effect of Sendeng-4. However, information on the pharmacokinetics of Sendeng-4 is limited, which limits its wide application in China.

OBJECTIVE

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established to study the pharmacokinetics of Sendeng-4.

METHOD

MS/MS with a negative ionization mode (ESI-) and multiple reaction monitoring at m/z 300.95→193.09 and 317.08→192.10 were detected for (2R, 3R)-dihydromyricetin and myricetin, respectively. The pharmacokinetic parameters were analyzed by DAS 2.0.

RESULT

The results showed that the plasma concentration time (C-T) curves of (2R, 3R)-dihydromyricetin and myricetin showed double peaks. The T value of (2R, 3R)-dihydromyricetin and myricetin in both groups was 3 h. In absorption, the AUC values of (2R, 3R)-dihydromyricetin and myricetin in the normal group and the arthritis model group were 16.151 ± 2.670 mg·h/L vs. 11.331 ± 0.749 mg·h/L and 2.626 ± 0.400 mg·h/L vs. 2.213 ± 0.388 mg·h/L, respectively. In the distribution, the Vz/F values of (2R, 3R)-dihydromyricetin and myricetin in the normal group and the arthritis model group were 8.212 L/kg vs. 1.744 L/kg and 5.252 L/kg vs. 10.568 L/kg, respectively. In metabolism, the MRT (0-∞) values of (2R, 3R)-dihydromyricetin and myricetin in the normal group and the arthritis model group were 6.848 h vs. 3.476 h and 5.661 h vs. 8.959 h, respectively. In excretion, the CLz/F values of (2R, 3R)-dihydromyricetin and myricetin in the normal group and the arthritis model group were 0.021 vs. 0.024 L/min/kg and 0.018 vs. 0.021 L/min/kg, respectively. There were significant variations in the absorption levels, distribution levels, and elimination rate of (2R, 3R)-dihydromyricetin and myricetin after the administration of Sendeng-4.

CONCLUSION

The study laid the foundation for the subsequent study of pharmacokinetics of Sendeng-4 in humans. The results of this study will contribute to a better understanding of the activity and clinical application of Sendeng-4 and other related traditional Mongolian drug prescriptions.

摘要

摘要

森登-4是一种蒙药。蒙古族人民一直用它来治疗类风湿性关节炎。目前,越来越多的汉族人开始关注森登-4的抗类风湿作用。然而,关于森登-4药代动力学的信息有限,这限制了它在中国的广泛应用。

目的

建立液相色谱-串联质谱法(LC-MS/MS)研究森登-4的药代动力学。

方法

采用负离子模式(ESI-)的串联质谱,分别对(2R,3R)-二氢杨梅素和杨梅素进行m/z 300.95→193.09和317.08→192.10的多反应监测。采用DAS 2.0分析药代动力学参数。

结果

结果表明,(2R,3R)-二氢杨梅素和杨梅素的血药浓度-时间(C-T)曲线呈双峰。两组中(2R,3R)-二氢杨梅素和杨梅素的T值均为3小时。吸收方面,正常组和关节炎模型组中(2R,3R)-二氢杨梅素的AUC值分别为16.151±2.670mg·h/L和11.331±0.749mg·h/L,杨梅素的AUC值分别为2.626±0.400mg·h/L和2.213±0.388mg·h/L。分布方面,正常组和关节炎模型组中(2R,3R)-二氢杨梅素的Vz/F值分别为8.212L/kg和1.744L/kg,杨梅素的Vz/F值分别为5.252L/kg和10.568L/kg。代谢方面,正常组和关节炎模型组中(2R,3R)-二氢杨梅素的MRT(0-∞)值分别为6.848小时和3.476小时,杨梅素的MRT(0-∞)值分别为5.661小时和8.959小时。排泄方面,正常组和关节炎模型组中(2R,3R)-二氢杨梅素的CLz/F值分别为0.021和0.024L/min/kg,杨梅素的CLz/F值分别为0.018和0.021L/min/kg。给予森登-4后,(2R,3R)-二氢杨梅素和杨梅素的吸收水平、分布水平和消除率存在显著差异。

结论

该研究为后续森登-4在人体药代动力学研究奠定了基础。本研究结果将有助于更好地理解森登-4及其他相关蒙药传统方剂的活性和临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b1/11962723/9672565df5b9/fphar-16-1547415-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b1/11962723/9b6b8a308255/fphar-16-1547415-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b1/11962723/3321c08c52d8/fphar-16-1547415-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b1/11962723/98617f4779b0/FPHAR_fphar-2025-1547415_wc_sch1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b1/11962723/d3dac2b62636/fphar-16-1547415-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b1/11962723/2e7ef8d780d4/fphar-16-1547415-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b1/11962723/9672565df5b9/fphar-16-1547415-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b1/11962723/9b6b8a308255/fphar-16-1547415-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b1/11962723/3321c08c52d8/fphar-16-1547415-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b1/11962723/98617f4779b0/FPHAR_fphar-2025-1547415_wc_sch1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b1/11962723/d3dac2b62636/fphar-16-1547415-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b1/11962723/2e7ef8d780d4/fphar-16-1547415-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6b1/11962723/9672565df5b9/fphar-16-1547415-g005.jpg

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