Simultaneous Determination of Ten Active Components From Jinhongtang Granule in Rat Plasma by LC–MS/MS and its Application to a Comparative Pharmacokinetic Study in Normal and Sepsis Rats In Vivo and In Vitro

Abstract

Abstract 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.