Archive > Volume 16 Issue 3 > 2024,16(3):457-465. DOI:https://doi.org/10.1016/j.chmed.2023.07.005 Prev Next

基于HPLC-MS/MS法比较羌活胜湿汤颗粒灌胃给药后6种成分在正常和类风湿性关节炎大鼠体内的药代动力学研究

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Comparative pharmacokinetics of six components in normal and rheumatoid arthritis rats after intragastrical administration of Qianghuo Shengshi Decoction granules by LC-MS/MS

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    摘要:
    目的：本研究旨在研究羌活胜湿汤颗粒剂（QSD）中6种代表性成分（紫花前胡苷、蛇床子素、5-O-甲基维斯阿米醇苷、阿魏酸、甘草素、甘草苷）在灌胃给药的正常大鼠和类风湿关节炎（RA）大鼠体内的药代动力学行为。 方法：建立了一种快速准确的超高效液相色谱-串联质谱（LC-MS/MS）同时测定血浆中这6种成分的方法，该方法具有良好的专属性、线性、日内及日间精密度、重复性、提取回收率、稳定性和基质效应。 结果：采用经验证的LC-MS/MS方法成功比较了正常大鼠和RA大鼠灌胃QSD颗粒后6种成分的血浆药代动力学，发现两种大鼠的药代动力学存在差异。紫花前胡苷、蛇床子素、5-O-甲基维斯阿米醇苷、甘草素和甘草苷在RA大鼠体内的吸收速率低于正常组，而阿魏酸的吸收率在两组中保持不变。与正常大鼠相比，病理状态下紫花前胡苷的暴露浓度更高，除紫花前胡苷外的其余5种成分暴露浓度更低。另外，相比于正常大鼠，RA大鼠对紫花前胡苷、蛇床子素、5-O-甲基维斯阿米醇苷和甘草苷的吸收量增加，对阿魏酸和甘草素的吸收量减少。与正常大鼠相比，紫花前胡苷、阿魏酸和甘草苷在RA大鼠体内的驻留时间减少，而蛇床子素、5-O-甲基维斯阿米醇苷和甘草素在RA大鼠体内驻留时间延长。与正常大鼠相比，紫花前胡苷在RA大鼠体内的消除速率增加，除紫花前胡苷的其余5个成分消除速率降低。 结论：本研究结果表明，紫花前胡苷、蛇床子素、5-O-甲基维斯阿米醇苷、阿魏酸、甘草素、甘草苷6种成分在正常和病理状态下大鼠体内的药动学行为存在差异，本研究为解释QSD颗粒在正常和病理状态下的药动学行为提供了必要的实验数据，并为其临床应用提供了一定程度的参考。

    Abstract:
    Objective: To investigate the plasma pharmacokinetics of six representative components (nodakenin, osthole, 5-O-methylvisammioside, ferulic acid, liquiritigenin, and liquiritin), which were the ingredients of Qianghuo Shengshi Decoction (QSD) granules, in normal and rheumatoid arthritis (RA) rats administrated QSD granules intragastrically. Methods: A rapid and accurate ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of six components in plasma, and it showed a good specificity, linearity, intra-day and inter-day precision, intra-day and inter-day accuracy, extraction recovery, stability, and the less matrix effect. Results: The validated LC-MS/MS method was successfully used to compare the plasma pharmacokinetics of six ingredients between normal and RA rats after intragastrical administration of QSD granules and differences in the pharmacokinetics were found in two types of rats. The absorption rate in the RA rats was lower for nodakenin, osthole, 5-O-methylvisammioside, liquiritigenin and liquiritin than in the normal group, while the absorption rate of ferulic acid remained constant in two groups. In comparison with the normal rats, the exposure concentration of nodakenin was higher and that of other five components except for nodakenin was lower under pathological conditions. Additionally, the absorptive amount of nodakenin, osthole, 5-O-methylvisammioside and liquiritin was increased and that of ferulic acid and liquiritigenin was reduced in the RA rats than in the normal rats. Compared with the normal rats, the retention time of nodakenin, ferulic acid and liquiritin was reduced in vivo, whereas the retention time of osthole, 5-O methylvisammioside and liquiritigenin was raised in the body for the RA rats. In contrast to the normal rats, the data demonstrated an increase in the elimination velocity of nodakenin and a decrease in the elimination velocity of the other five components except for nodakenin in the pathological state. Conclusion: This study showed that the pharmacokinetic behavior of the six components, nodakenin, osthole, 5-O-methylvisammioside, ferulic acid, liquiritigenin, and liquiritin, is different in vivo between normal and pathological states of rats, and this research provided the necessary experimental data to explain the pharmacokinetics of QSD granules in both normal and pathological states and provide some references for its clinical application at some level.

    关键词:
    LC-MS/MS;药物动力学;羌活胜湿汤颗粒剂;类风湿性关节炎

    Keywords:


    Project Supported:
    This research was supported by the Science and Technology Program of Tianjin (No. 21ZYJDJC00020), ‘‘Youth Qi Huang Scholar” by State Administration of TCM, and the Science and Technology Program of Haihe Laboratory of Modern Chinese Medicine (No. 22HHZYSS00005).

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