Rapid determination of twelve bioactive components in rat plasma by UHPLC-MS/MS and its application to pharmacokinetic and in vitro-in vivo correlation study of compound liquorice tablets

Compound liquorice tablets (CLQTs), composed of Licorice Extract (LE), Powered Poppy Capsule Extractive (PPCE), Camphor, Oleum Anisi Stellati and sodium benzoate, is widely used for antitussive and expectorant. A fast, selective and sensitive UHPLC-MS/MS method for determination of seven flavonoids (liquiritin, isoliquiritin, neoisoliquiritin, liquiritigenin, isoliquiritigenin, liquiritin apioside, and isoliquiritin apioside), two triterpene saponins (glycyrrhizic acid and glycyrrhetinic acid), two isoquinoline alkaloid (codeine and morphine), one aromatic (trans-anethole) in rat plasma was developed and validated. Then, the proposed method was used to investigate the pharmacokinetic differences of eleven bioactive components in rats after administration of CLQTs and the single herb (LE or PPCE). The results showed that LE acted synergistically with PPCE by prolonging the efficacy of CLQTs. Subsequently, based on an AUC-weighting approach, the integrated pharmacokinetics of twelve bioactive components was determined, which might provide a more comprehensive understanding of the relationship between the pharmacokinetic behaviors of herbal medicine. Additionally, in view of the synthetic effect of complex chemicals in traditional Chinese medicine, we put forward a flow-injection analysis method to determine the total components dissolution profile of CLQTs. Finally, the integral pharmacokinetic parameter (lnC) and the cumulative dissolution (Pmr(i)) were used to explore the in vitro-in vivo correlations preliminarily and the R2 was above 0.9383. This study provided more insight for further understanding of the compatibility mechanism of CLQTs and improved the safety and rationality of the clinical use of CLQTs.

Automated summary

A fast, selective and sensitive UHPLC-MS/MS method was developed to determine the bioactive components in Compound liquorice tablets and investigate their pharmacokinetics in rats. The results showed synergistic effects between Licorice Extract and Powered Poppy Capsule Extractive, prolonging the efficacy of the tablets. Integrated pharmacokinetics provided a comprehensive understanding of the relationship between the pharmacokinetic behaviors of herbal medicine.