Pharmaceutical Research Center, Second Affiliated Hospital, Dalian Medical University, Dalian 116023, China.
College of Pharmacy, Institute of Integrative Medicine, Dalian Medical University, Dalian 116044, China.
J Chromatogr Sci. 2023 May 30;61(5):440-452. doi: 10.1093/chromsci/bmac043.
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.
金宏塘颗粒（JHT）是一种用于治疗感染性疾病的中药方剂，包括严重的 COVID-19。然而，JHT 的药代动力学尚不清楚，尤其是在感染情况下。本研究建立了一种同时定量测定大鼠血浆中 JHT 的十种活性成分的液相色谱-串联质谱（LC-MS/MS）方法。MS 检测采用负电离模式下的 MRM 扫描操作。该方法具有良好的线性（r>0.997）。目前的标准表明，该方法的准确度、精密度、基质效应、回收率和稳定性均令人满意。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。脓毒症大鼠分析物的药代动力学行为与正常大鼠明显不同。除 4-羟基肉桂酸和阿魏酸外，脓毒症大鼠中大黄酸、大黄素、芦荟大黄素、大黄素-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 均显著增加。采用外翻肠囊法进行的体外肠吸收研究表明，在脓毒症下，肠通透性发生改变。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，为 JHT 作为严重和危重症 COVID-19 的综合治疗的临床应用提供了有用信息。
