Jinhongtang granule (JHT) is a traditional Chinese medicine formula used for treatment of infection diseases including severe COVID-19. However, pharmacokinetics of JHT was unknown, especially in infection condition. A liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed to simultaneously quantify ten active components form JHT in rat plasma. MS detection was performed by MRM scanning operating in the negative ionization mode. The method showed good linearity (r > 0.997). The accuracy, precision, matrix effect, recovery and stability were all satisfactory with current criterion. The method was successfully applied to compare the pharmacokinetic difference between normal and sepsis rats. The pharmacokinetic behaviors of analytes in sepsis rats were significantly different from those in normal rats. Cmax and AUC of rhein, emodin, aloe emodin, rhein-8-glucoside, aloe emodin 8-glucoside, protocatechuic acid, epicatechin and salidroside, were significantly increased in sepsis rats, except for 4-hydroxycinnamic acid and ferulic acid. In vitro intestinal absorption study using everted intestinal sac preparations indicated that the intestinal permeability was altered under sepsis. In conclusion, pharmacokinetic difference of JHT between normal and sepsis rats were evaluated for the first time, which provided useful information for the clinical application of JHT as an integrative therapy for severe and critical COVID-19.

中文翻译：

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LC-MS/MS 法同时测定大鼠血浆中金红汤颗粒中的十种活性成分及其在正常和脓毒症大鼠体内外药代动力学比较研究中的应用

金红汤颗粒（JHT）是一种中药配方，用于治疗包括重症 COVID-19 在内的感染性疾病。然而，JHT 的药代动力学尚不清楚，尤其是在感染情况下。开发了一种液相色谱-串联质谱 (LC-MS/MS) 方法来同时量化大鼠血浆中 JHT 的十种活性成分。MS 检测通过在负电离模式下运行的 MRM 扫描进行。该方法显示出良好的线性(r＞0.997)。准确度、精密度、基质效应、回收率和稳定性均符合现行标准。该方法成功应用于比较正常和脓毒症大鼠的药代动力学差异。分析物在脓毒症大鼠体内的药代动力学行为与正常大鼠有显着差异。除 4-羟基肉桂酸和阿魏酸外，大黄酸、大黄素、芦荟大黄素、大黄酸 8-葡萄糖苷、芦荟大黄素 8-葡萄糖苷、原儿茶酸、表儿茶素和红景天苷的 Cmax 和 AUC 在脓毒症大鼠中显着增加。使用外翻肠囊制剂进行的体外肠道吸收研究表明，在脓毒症下肠道通透性发生了改变。总之，首次评估了JHT在正常和脓毒症大鼠之间的药代动力学差异，这为JHT作为重症和危重症COVID-19的综合治疗的临床应用提供了有用的信息。使用外翻肠囊制剂进行的体外肠道吸收研究表明，在脓毒症下肠道通透性发生了改变。总之，首次评估了JHT在正常和脓毒症大鼠之间的药代动力学差异，这为JHT作为重症和危重症COVID-19的综合治疗的临床应用提供了有用的信息。使用外翻肠囊制剂进行的体外肠道吸收研究表明，在脓毒症下肠道通透性发生了改变。总之，首次评估了JHT在正常和脓毒症大鼠之间的药代动力学差异，这为JHT作为重症和危重症COVID-19的综合治疗的临床应用提供了有用的信息。