基于靶向和非靶向 LC-MS 分析的二至方及加味二至方化学成分与药代动力学的综合研究。
A Comprehensive Study on the Chemical Constituents and Pharmacokinetics of Erzhi Formula and Jiawei Erzhi Formula Based on Targeted and Untargeted LC-MS Analysis.
机构信息
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai, Tianjin 301617, P.R. China.
Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai, Tianjin 301617, P.R. China.
出版信息
Curr Drug Metab. 2023;23(14):1130-1142. doi: 10.2174/1389200224666230130093412.
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 and AUC 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 and AUC 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.
背景
二至丸（EZF）是一种中药方剂，已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 EZF 方中加入另外两味草药鸡血藤（SC）和牛膝（ABB），得到两种新的加味二至丸（JW-EZF）制剂。为阐明原方草药配伍的效果，检测了体内的化学成分和生物活性化合物。
方法
首先建立了一种高效灵敏的靶向和非靶向 UHPLC/ESI-Q-Orbitrap MS 方法，并结合质量缺陷过滤和前体离子列表，对不同 EZF 配方进行了分析。此外，还同时定量测定了大鼠血浆中的 11 种吸收化合物（芹菜素、芦丁、木樨草素、橄榄苦苷、wedelolactone、毛蕊花糖苷、獐牙菜苷、11-甲氧基葡萄糖苷、蜕皮甾酮 A、芒柄花素和β-蜕皮甾酮）。
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了 124、162 和 177 种化合物。三种配方中共有 110 种化合物为共有成分。此外，采用相同策略，在大鼠口服三种配方后，在血浆中还鉴定出 66 种原型。在 PK 研究中，对 66 种吸收成分中的 11 种进行了同时定量。与原 EZF 相比，JW-3-EZF 口服后，血浆 AUC 和 AUC 中芹菜素、11-甲氧基葡萄糖苷、木樨草素、芦丁、wedelolactone 和毛蕊花糖苷的含量明显增加，而 JW-4-EZF 给药后，血浆 AUC 和 AUC 中芹菜素、wedelolactone 和毛蕊花糖苷的含量也明显增加。
结论
该联合定性和定量方法为中药及其制剂的特征化和质量控制提供了一种潜在的方法。
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