A Comprehensive Study on the Chemical Constituents and Pharmacokinetics of Erzhi Formula and Jiawei Erzhi Formula Based on Targeted and Untargeted LC-MS Analysis.

IF 2.1 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current drug metabolism Pub Date : 2023-01-01 DOI:10.2174/1389200224666230130093412

Tongtong Zhu, Wanning Chen, Chunyue Han, Zhijie Gao, Erwei Liu, Xiumei Gao, Zhifei Fu, Lifeng Han

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引用次数: 1

Abstract

Background: Erzhi formula (EZF) is a traditional Chinese medicine prescription, which has been widely used in the treatment of osteoporosis and premature ovarian failure.

Objective: To enhance curative effects, the other two herbal medicines, including Spatholobi Caulis (SC) and Achyranthes bidentata Blume (ABB), were added into the original EZF formula to obtain two new Jiawei-EZF (JW-EZF) preparations. To clarify the effect of the compatibility of herbs for original formulas, the chemical constituents and bioactive compounds in vivo were detected.

Methods: An efficient and sensitive targeted and untargeted UHPLC/ESI-Q-Orbitrap MS method, together with mass defect filter and precursor ion list, was established firstly for the profiling of different EZF formulas. Furthermore, eleven absorbed compounds (apigenin, luteoloside, luteolin, oleuropein, wedelolactone, acteoside, specnuezhenide, 11-methyloleoside, ecliptasaponin A, formononetin, and β-ecdysone) were simultaneously quantified in rat plasma.

Results: A total of 124, 162, and 177 compounds were identified or tentatively identified in EZF, JW-3-EZF (EZF+SC) and JW-4-EZF (EZF+SC+ABB), respectively. 110 compounds were found to be common constituents in the three formulas. Moreover, 66 prototypes were unambiguously identified in the rats' plasma after oral administration of the three formulas using the same strategy. 11 out of the 66 absorbed components were simultaneously quantitated in the pharmacokinetic (PK) study. Compared to the original EZF, the plasma AUC_(0-24h) and AUC_(0-∞) of apigenin, 11-methyloleoside, luteolin, luteoloside, wedelolactone, and acteoside were found to be significantly increased after oral administration of JW-3-EZF, and plasma AUC_(0-24h) and AUC_(0-∞) of apigenin, wedelolactone, and acteoside, were also found to be significantly increased after JW-4-EZF administration.

Conclusion: The combined qualitative and quantitative methods were used to provide a potential approach to the characterization and quality control of the Traditional Chinese Medicine (TCM) and its preparations.

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基于靶向和非靶向LC-MS分析的二痔方和加味二痔方化学成分及药代动力学综合研究

背景:二栀方是一种中药方剂，被广泛用于治疗骨质疏松症和卵巢早衰。目的:为提高疗效，在原配方中加入鸡血藤(SC)和牛膝(ABB)两种中草药，得到两种新的加味EZF (JW-EZF)制剂。为明确中药配伍对原配方的影响，对其体内化学成分和生物活性成分进行了检测。方法:首次建立了一种高效、灵敏的靶向和非靶向UHPLC/ESI-Q-Orbitrap质谱分析方法，结合质量缺陷过滤器和前驱体离子表对不同EZF配方进行定性分析。同时测定了大鼠血浆中芹菜素、木犀草苷、木犀草素、橄榄苦苷、维地内酯、毛蕊草苷、specnuezhenide、11-甲基油葵苷、黄花皂苷A、刺芒柄花素和β-蜕皮酮等11种吸收化合物的含量。结果:在EZF、JW-3-EZF (EZF+SC)和JW-4-EZF (EZF+SC+ABB)中分别鉴定或初步鉴定出124、162和177个化合物。在这三个分子式中发现了110种化合物的共同成分。此外，使用相同的策略口服三种配方后，在大鼠血浆中明确识别出66个原型。66种吸收成分中有11种同时进行药代动力学(PK)研究。与原始EZF相比，口服JW-3-EZF后，芹菜素、11-甲基油苷、木犀草素、木犀草苷、维德内酯和毛蕊花苷的血浆AUC(0-24h)和AUC(0-∞)显著升高，JW-4-EZF后，芹菜素、维德内酯和毛蕊花苷的血浆AUC(0-24h)和AUC(0-∞)也显著升高。结论:定性与定量相结合的方法为中药及其制剂的表征和质量控制提供了一种可行的方法。

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来源期刊

Current drug metabolism 医学-生化与分子生物学

CiteScore

4.30

自引率

4.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism, pharmacokinetics, and drug disposition. The journal serves as an international forum for the publication of full-length/mini review, research articles and guest edited issues in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the most important developments. The journal covers the following general topic areas: pharmaceutics, pharmacokinetics, toxicology, and most importantly drug metabolism. More specifically, in vitro and in vivo drug metabolism of phase I and phase II enzymes or metabolic pathways; drug-drug interactions and enzyme kinetics; pharmacokinetics, pharmacokinetic-pharmacodynamic modeling, and toxicokinetics; interspecies differences in metabolism or pharmacokinetics, species scaling and extrapolations; drug transporters; target organ toxicity and interindividual variability in drug exposure-response; extrahepatic metabolism; bioactivation, reactive metabolites, and developments for the identification of drug metabolites. Preclinical and clinical reviews describing the drug metabolism and pharmacokinetics of marketed drugs or drug classes.