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

Abstract

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-μm 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 μL 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.