Comparative HPLC-MS/MS-based pharmacokinetic studies of multiple diterpenoid alkaloids following the administration of Zhenwu Tang and Radix Aconiti Lateralis Praeparata extracts to rats

Abstracts

1. Zhenwu Tang (ZWT) is a traditional Chinese medicine that is primarily composed of Radix Aconiti Lateralis Praeparata (FZ) and diterpenoid alkaloids are believed to be the pharmacologically active compounds of ZWT. In this study, the pharmacokinetic profiles of hypaconitine, mesaconitine, aconitine, benzoylmesaconitine, benzoylaconitine, and benzoylhypacoitine were assessed in rats following intragastric ZWT administration. Furthermore, differences in the pharmacokinetic profiles of these six alkaloids were assessed as a function of rat sex and the administration of ZWT or FZ extracts to these animals. Plasma levels of these alkaloids were quantified via HPLC-MS/MS.

2. Significant differences in key pharmacokinetic parameters were observed when comparing rats administered FZ or ZWT. Relative to FZ extract treatment, ZWT administration was associated with C_max and AUC_0–∞ values of benzoylmesaconitine that were about 3.5 and 5.5 times higher. Considerable variations in hypaconitine pharmacokinetic parameters were also revealed between female and male rats. The C_max and AUC_0–∞ of hypaconitine were about 2.5- and 2.7-fold elevated in female rats in comparison with male rats.

3. These results suggested that the other compounds within ZWT can enhance the absorption of benzoylmesaconitine, while hypaconitine exhibits higher bioavailability in female rats, as compared with male rats.

Keywords:

• Diterpenoid alkaloids
• Radix Aconiti Lateralis Praeparata
• Zhenwu Tang
• pharmacokinetics
• HPLC-MS/MS

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Y.H. L., H. S., C. L., Z. C. P., J. Z. W., M. D. X., and H. J. L. conducted the experiments. Y.X. Z., H.J. L., R.L. B., and D. J. participated in the data analyses. H.T. X. and D.H. L. contributed to the design and supervision of the project. Y.H. L. wrote the manuscript. All authors have approved the final version of the manuscript.

Additional information

Funding

This work was supported by the Youth Foundation of Wannan Medical College [Grant number WK2018F05] and the Scientific and Technological Innovation Team Scaled the Peak of Yjishan Hospital of Wannan Medical College [KPF-2019016].