摘要
Development of advanced in vivo sampling tools for the synchronous monitoring of drugs and endogenous biomarkers is critical for integrated pharmacokinetic-pharmacodynamic (PK-PD) studies. Herein, a novel solid-phase microextraction (SPME) fiber coating was engineered based on a zwitterionic covalent organic framework (EB-TTB-DABSA COF), strategically functionalized with sulfonate and quaternary ammonium groups. This rationally designed coating provides synergistic electrostatic, π–π, and hydrophobic interactions, enabling the efficient and simultaneous extraction of both cationic alkaloids and neurotransmitters. Coupled with LC-MS/MS, the developed platform achieved highly sensitive (limits of detection down to 3.3 × 10 −3 ng·mL −1 ), minimally invasive, and synchronous monitoring of these analytes in paired blood and brain matrices of living rats. Application in a Parkinson's disease (PSD) model revealed altered pharmacokinetics of Coptis chinensis alkaloids, including significantly increased area under the curve (AUC) values ( p < 0.01) and prolonged elimination half-lives compared to controls. These findings indicate enhanced systemic absorption and improved bioavailability of alkaloids under PSD conditions. Crucially, pharmacodynamic analysis showed that alkaloid administration triggered a synchronized restoration of key depleted neurotransmitters in PSD brains. A correlation with a characteristic hysteresis pattern further established a delayed neuroprotective relationship between alkaloid concentrations and neurotransmitter levels. This study not only introduces a robust zwitterionic COF-SPME platform for concurrent in vivo biosampling but also provides the first quantitative neuropharmacological perspective on Coptis chinensis alkaloids, offering a foundational framework for mechanistic research and therapeutic development in PSD.
危险品化学品经营许可证（带存储）