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大鼠口服三物汤后香豆素类化合物的高效液相色谱测定及药代动力学研究

High-performance liquid chromatography determination and pharmacokinetics of coumarin compounds after oral administration of Samul-Tang to rats.

作者信息

Hwang Youn-Hwan, Cho Won-Kyung, Jang Doorye, Ha Jeong-Ho, Ma Jin Yeul

机构信息

Korean Medicine-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, South Korea.

出版信息

Pharmacogn Mag. 2014 Jan;10(37):34-9. doi: 10.4103/0973-1296.126656.

Abstract

BACKGROUND

Samul-tang has been traditionally used for the treatment of cardiovascular, gynecologic, cutaneous, and chronic inflammation disorders. Although coumarin compounds do have various pharmacological activities and the same may be present in Samul-tang, however there is little information about it.

OBJECTIVE

A simple and sensitive high-performance liquid chromatography (HPLC) method has been developed for the determination of nodakenin, nodakenetin, decursin, decursinol, and decursinol angelate in rat plasma. To obtain a better understanding for pharmacological properties of Samul-tang, pharmacokinetic study of coumarin compounds was performed after oral administration of Samul-tang in rats.

MATERIALS AND METHODS

Chromatographic separation of the analytes was successfully achieved on a Phenomenex Luna C18 column (4.6 mm×250 mm, 5 μm) using a mobile phase composed of acetonitrile water with a gradient elution at a flow rate of 1 mL/min. Noncompartmental analysis was performed.

RESULTS

Calibration curves for all analytes had good linearity (r(2) <0.999) in a wide linear range. The lower limit of quantification (LLOQ) ranged from 0.05 to 0.1 μg/mL. The variation of intra- and interday assay was less than 15%. Nodakenin, nodakenetin, and decursinol were determined in rat plasma after oral administration of Samul-tang.

CONCLUSION

This developed and validated HPLC method was successfully applied to the pharmacokinetic study of three coumarin compounds in rats, given as a single oral administration of Samul-tang. These pharmacokinetic data of the nodakenin, nodakenetin, and decursinol could offer a new point of view to evaluate the pharmacological effects of Samul-tang.

摘要

背景

四君子汤传统上用于治疗心血管、妇科、皮肤及慢性炎症性疾病。尽管香豆素类化合物确实具有多种药理活性,且四君子汤中可能存在此类成分,但相关信息却很少。

目的

建立一种简单、灵敏的高效液相色谱(HPLC)法,用于测定大鼠血浆中紫花前胡苷、紫花前胡素、蛇床子素、异虎耳草素和异虎耳草素当归酸酯的含量。为更好地了解四君子汤的药理特性,在大鼠口服四君子汤后进行了香豆素类化合物的药代动力学研究。

材料与方法

采用Phenomenex Luna C18柱(4.6 mm×250 mm,5μm),以乙腈 - 水为流动相,梯度洗脱,流速为1 mL/min,成功实现了分析物的色谱分离。进行了非房室分析。

结果

所有分析物的校准曲线在较宽的线性范围内均具有良好的线性(r²>0.999)。定量下限(LLOQ)为0.05至0.1μg/mL。日内和日间测定的变异小于15%。大鼠口服四君子汤后,在血浆中检测到了紫花前胡苷、紫花前胡素和异虎耳草素。

结论

所建立并验证的HPLC方法成功应用于大鼠单次口服四君子汤后三种香豆素类化合物的药代动力学研究。这些紫花前胡苷、紫花前胡素和异虎耳草素的药代动力学数据可为评估四君子汤的药理作用提供新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb37/3969656/1c20fc3d83a4/PM-10-34-g001.jpg

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