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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法比較羌活勝濕湯顆粒灌胃給藥后6種成分在正常和類(lèi)風(fēng)濕性關(guān)節(jié)炎大鼠體內(nèi)的藥代動(dòng)力學(xué)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勝濕湯顆粒劑（QSD）中6種代表性成分（紫花前胡苷、蛇床子素、5-O-甲基維斯阿米醇苷、阿魏酸、甘草素、甘草苷）在灌胃給藥的正常大鼠和類(lèi)風(fēng)濕關(guān)節(jié)炎（RA）大鼠體內(nèi)的藥代動(dòng)力學(xué)行為。 方法：建立了一種快速準(zhǔn)確的超高效液相色譜-串聯(lián)質(zhì)譜（LC-MS/MS）同時(shí)測(cè)定血漿中這6種成分的方法，該方法具有良好的專屬性、線性、日內(nèi)及日間精密度、重復(fù)性、提取回收率、穩(wěn)定性和基質(zhì)效應(yīng)。 結(jié)果：采用經(jīng)驗(yàn)證的LC-MS/MS方法成功比較了正常大鼠和RA大鼠灌胃QSD顆粒后6種成分的血漿藥代動(dòng)力學(xué)，發(fā)現(xiàn)兩種大鼠的藥代動(dòng)力學(xué)存在差異。紫花前胡苷、蛇床子素、5-O-甲基維斯阿米醇苷、甘草素和甘草苷在RA大鼠體內(nèi)的吸收速率低于正常組，而阿魏酸的吸收率在兩組中保持不變。與正常大鼠相比，病理狀態(tài)下紫花前胡苷的暴露濃度更高，除紫花前胡苷外的其余5種成分暴露濃度更低。另外，相比于正常大鼠，RA大鼠對(duì)紫花前胡苷、蛇床子素、5-O-甲基維斯阿米醇苷和甘草苷的吸收量增加，對(duì)阿魏酸和甘草素的吸收量減少。與正常大鼠相比，紫花前胡苷、阿魏酸和甘草苷在RA大鼠體內(nèi)的駐留時(shí)間減少，而蛇床子素、5-O-甲基維斯阿米醇苷和甘草素在RA大鼠體內(nèi)駐留時(shí)間延長(zhǎng)。與正常大鼠相比，紫花前胡苷在RA大鼠體內(nèi)的消除速率增加，除紫花前胡苷的其余5個(gè)成分消除速率降低。 結(jié)論：本研究結(jié)果表明，紫花前胡苷、蛇床子素、5-O-甲基維斯阿米醇苷、阿魏酸、甘草素、甘草苷6種成分在正常和病理狀態(tài)下大鼠體內(nèi)的藥動(dòng)學(xué)行為存在差異，本研究為解釋QSD顆粒在正常和病理狀態(tài)下的藥動(dòng)學(xué)行為提供了必要的實(shí)驗(yàn)數(shù)據(jù)，并為其臨床應(yīng)用提供了一定程度的參考。

    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.

    關(guān)鍵詞:
    LC-MS/MS;藥物動(dòng)力學(xué);羌活勝濕湯顆粒劑;類(lèi)風(fēng)濕性關(guān)節(jié)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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