Rapid determination of seven bioactive components in rat plasma by UPLC-MS/MS and its application to pharmacokinetic compatibility study of Jinlingzi San

Jinlingzi San (JLZS), composed of Fructus Toosendan (FT) and Rhizoma Corydalis (RC), is a classical traditional Chinese medicine prescription for regulating Qi to relieve pain. The present study investigated the pharmacokinetic compatibility of FT and RC in JLZS. A fast, selective and sensitive UPLC-MS/MS method for simultaneous determination of one limonoid (toosendanin), four tertiary alkaloids (corydaline, tetrahydropalmatine, tetrahydrocoptisine, tetrahydroberberine) and two quaternary alkaloids (palmatine, dehydrocorydaline) in rat plasma was established and fully validated. The plasma samples were pretreated by a fast protein precipitation and chromatographed using a 1.7-mu m C18 column and 0.1 % formic acid-water and acetonitrile via gradient elution with a run time of 3.7 min. Multiple reaction monitoring mode with positive electrospray ionization was adopted to detect the analytes and internal standard (diphenhydramine). The lower limits of quantification were 0.08-3.09 ng/mL using only 50 mu L of plasma sample. Using the proposed method, the pharmacokinetic differences of seven bioactive components in rats after administration of JLZS and the single herb (FT or RC) were investigated. The results showed that the elimination of toosendanin and alkaloids decreased significantly in the JLZS group (p < 0.05) compared with the single herb group, and the exposure of the alkaloids increased in some degree. The study demonstrated the synergistic effect of combining FT with RC on the pharmacokinetics of seven bioactive components and provided new information for a better understanding of the compatibility mechanism of JLZS. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

A study was conducted to investigate the pharmacokinetic compatibility of two components in the traditional Chinese medicine prescription Jinlingzi San. Results showed a decrease in elimination of one limonoid and alkaloids in the Jinlingzi San group compared to the single herb group, with an increase in exposure of the alkaloids to some extent. The study demonstrated a synergistic effect of combining Fructus Toosendan with Rhizoma Corydalis on the pharmacokinetics of seven bioactive components, providing new insights into the compatibility mechanism of Jinlingzi San.