代谢分析

单向肠灌流法研究芍药苷和刺芒柄花苷的肠吸收特性

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  • 西安交通大学医学部药学院,西安 710061
第一作者 Tel:(029)82655134;E-mail:quqh@xjtu.edu.cn

修回日期: 2020-12-25

  网络出版日期: 2024-05-31

Study on intestinal absorption characteristics of paeoniflorin and ononin by in situ single-pass intestinal perfusion

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  • School of Pharmacy,Health Science Center,Xi'an Jiaotong University,Xi'an 710061,China

Revised date: 2020-12-25

  Online published: 2024-05-31

摘要

目的:采用在体单向肠灌流法研究芍药苷和刺芒柄花苷在大鼠不同肠段的吸收特性,探索复方给药对单一活性成分吸收的影响。方法:采用高效液相色谱法进行含量测定和方法学验证。色谱柱:Shim Pack ODS C18 (250 mm×4.6 mm,5 μm);流动相:测定芍药苷时为甲醇 - 乙腈 -1.0 mL·L -1 磷酸水溶液(15:15:70),测定刺芒柄花苷时为乙腈 -1.0 mL·L -1 甲酸水溶液(55:45);流速:1.0 mL·min -1 ;检测波长: 230 nm(芍药苷)、254 nm(刺芒柄花苷);柱温:30 ℃。通过对相同药物浓度在不同肠段、不同药物浓度对同一肠段有效渗透系数(Peff )的影响研究芍药苷和刺芒柄花苷的主要吸收途径,在灌流液中添加维拉帕米研究糖蛋白抑制剂对药物在十二指肠 Peff 的影响,通过比较单一成分与复方灌流后的 Peff 差异,研究复方形式对单一活性成分在肠道吸收的影响。结果:芍药苷和刺芒柄花苷的质量浓度均在 0.5~60 μg·mL -1 范围内,与相应的峰面积呈良好的线性关系,相关系数分别为 0.999 9 和 0.999 8;日内精密度 RSD 分别小于 2.5% 和 2.9%,日间精密度 RSD 均小于 3.1%,稳定性 RSD 分别小于 3.6% 和 3.3%。芍药苷和刺芒柄花苷在大鼠小肠的 Peff 由大到小顺序均为十二指肠、空肠、回肠。糖蛋白抑制剂维拉帕米对二者在十二指肠的吸收无显著影响,同时不同浓度的含药灌流液的 Peff 又具有显著的差别,具有浓度饱和现象,复方灌流液补阳还五汤中芍药苷和刺芒柄花苷的 Peff 高于单一成分灌流。结论:十二指肠为芍药苷和刺芒柄花苷最佳吸收肠段,以复方形式给药能够提高部分有效成分在肠道的吸收。

本文引用格式

屈清慧, 周莉, 张继业 . 单向肠灌流法研究芍药苷和刺芒柄花苷的肠吸收特性[J]. 药物分析杂志, 2021 , 41(1) : 64 -71 . DOI: 10.16155/j.0254-1793.2021.01.07

Abstract

Objective: To study the absorption characteristics of paeoniflorin and ononin in different intestinal segments of rats and explore the effect of compound administration on the absorption of single active ingredient by in situ single-pass intestinal perfusion. Methods: An HPLC system was utilized to determine the contents of paeoniflorin and ononin. Shim Pack ODS C18 column (250 mm×4.6 mm,5 μm) was adopted;the mobile phases were methanol-acetonitrile-1.0 mL·L -1 phosphoric acid aqueous solution (15:15:70) for paeoniflorin, and acetonitrile-1.0 mL·L -1 formic acid aqueous solution(55:45) for ononin,respectively;the flow rate was 1.0 mL·min -1 ;the detection wavelength was 230 nm for paeoniflorin and 254 nm for ononin,respectively; the column temperature was 30 ℃.The main absorption pathway was investigated by comparing the effective permeability coefficient (Peff) values from the same drug concentration in different intestinal segments,and the different drug concentration in the same intestinal segment. Verapamil was added in the perfusion to study the influence of glycoprotein inhibitor on duodenal Peff . The influence of difference administration form on the absorption of single active ingredient was compared with compound form perfusion. Results: The linear ranges of paeoniflorin and ononin were both 0.5-60 μg·mL -1 ,and the peak area showed a good linear relationship with the concentration of corresponding compounds,r 1 =0.999 9 for paeoniflorin and r2 =0.999 8 for ononin;intra-day precision RSDs were less than 2.5% and 2.9%,inter-day precision RSDs were all less than 3.1%,stability RSDs was less than 3.6% and 3.3%,respectively. The order of Peff value in rat small intestine from large to small was duodenal,jejunum and ileum. Verapamil had no significant influence on the Peff of paeoniflorin and ononin in the duodenum. There were significant differences in Peff of different concentrations of perfusion fluid,with the phenomenon of concentration saturation. Peff of paeoniflorin and ononin with compound perfusion (Buyang Huanwu decoction) were higher than those of single component perfusion. Conclusion: Duodenum is the best intestinal segment for the absorption of paeoniflorin and ononin. Compound administration can improve the absorption of some effective components in the intestinal tract.

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