Simultaneous quantification of twenty-eight components of Shenfu Injection in rat plasma by UHPLC-QQQ MS and its application to a pharmacokinetic study

Abstract

Shenfu Injection (SFI), derived from the classical traditional Chinese medicine formula "Shenfu Decoction", is a modern preparation used to treat heart failure and shock in clinic. In this study, an ultra-high performance liquid chromatography-triple quadruple tandem mass spectrometry (UHPLC-QQQ MS) method was established to simultaneously quantify twenty-eight main active components of SFI in rat plasma, including eighteen ginsenosides and ten aconite alkaloids. Multi-reaction monitoring in positive and negative ionization switching modes is used for mass spectrometry analysis, and the whole analysis process was within 14 min. The developed method was well validated and successfully applied to the pharmacokinetic study of multiple components of SFI in rat plasma. Eight PPD-type ginsenosides Ra₂, Ra₃, Rb₁, Ra₁, Rc, Rb₂, Rb₃ and Rd presented relative high systemic exposure levels among ginsenosides with AUC_0-t larger than 10,000 μg h/L, while mesaconine and hypaconine possessed relative high plasma abundance among aconite alkaloids with AUC_0-t at 142.50 ± 17.42 μg h/L and 40.65 ± 5.61 μg h/L, respectively. Several PPT-type ginsenosides had obviously higher AUC_0-t levels (e.g. 639.70 ± 134.61 μg h/L for ginsenoside Re and 874.79 ± 188.87 μg h/L for ginsenoside Rg₁) than alkaloids but similar t_1/2 levels (0.14 ± 0.03 h for ginsenoside Re, 0.16 ± 0.03 h for ginsenoside Rg₁, 0.04-0.33 h for aconite alkaloids), indicating their quick elimination. Collectively, the pharmacokinetic research of ginsenosides and aconite alkaloids in SFI would provide a scientific basis for its clinical use and drug-drug interactions.

Keywords: Aconite alkaloids; Ginsenosides; Pharmacokinetics; Shenfu Injection; UHPLC-QQQ MS.