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

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 T max 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.