# ZIF-8 Selective Dispersive Solid-Phase Extraction-LC-MS/MS Method for the Determination of Aconitine alkaloids in Rat Plasma: Application in Pharmacokinetic Studies

## TL;DR

This study developed a new method using ZIF-8 to efficiently extract and analyze toxic aconitine alkaloids in rat blood for safer use of Fuzi in medicine.

## Contribution

A novel ZIF-8-based d-SPE–LC–MS/MS method for quantifying aconitine alkaloids in plasma is introduced.

## Key findings

- The method showed strong linearity for five aconitine alkaloids with correlation coefficients over 0.99.
- The detection limit was as low as 0.104 ng/mL, enabling sensitive analysis.
- Benzoylaconitine was rapidly absorbed, reaching peak concentration in 0.25 hours.

## Abstract

Objective: Aconitine alkaloids, as the principal bioactive constituents of Fuzi, pose a significant challenge to its clinical application due to their toxicity. This study aimed to establish a rapid, efficient, and stable method for quantifying monoester-type and diester-type alkaloids in raw Fuzi using zeolitic imidazolate framework-8 (ZIF-8). The method was subsequently applied to pharmacokinetic studies in rats, offering valuable insights into the safe clinical use of Fuzi.

Methods: Synthetic ZIF-8 was employed as the microextraction adsorbent, with optimization of extraction parameters such as ZIF-8 content, shaker speed, extraction time, and sodium ion concentration to maximize enrichment efficiency. A dispersive solid-phase extraction–liquid chromatography–tandem mass spectrometry (d-SPE–LC–MS/MS) method, based on ZIF-8, was developed and validated for method performance. The pharmacokinetics of five aconitine alkaloids in Fuzi were investigated, ensuring efficient extraction and analysis.

Results: Under the optimized conditions, the d-SPE method demonstrated robust enrichment of aconitine alkaloids. A strong linear relationship was established for aconitine, hypaconitine, mesaconitine, lappaconitine, and benzoylaconitine within the concentration range of 0.3125–1000 ng/mL, with correlation coefficients exceeding 0.99. The LC–MS/MS assay achieved a detection limit as low as 0.104 ng/mL. Additionally, the pharmacokinetic analysis revealed rapid absorption of the five alkaloids, with benzoylaconitine exhibiting a Tmax of 0.25 h.

Conclusion: This study introduces a novel d-SPE–LC–MS/MS method based on ZIF-8 for the analysis of aconitine alkaloids in plasma, facilitating pharmacokinetic studies of Fuzi. These findings substantially contribute to a deeper understanding of the in vivo pharmacokinetics of aconitine alkaloids.