<i>In Vivo</i> Solid-Phase Microextraction with Palladium-Doped Covalent Organic Framework-Coated Fiber for Enhanced Nicotine-Associated Metabolite Detection in Rat Brain Regions

Nicotine's neuroactive properties and influence on brain metabolism are not widely explored, particularly in spatially resolved contexts. This technical note presents an <i>in vivo</i> solid-phase microextraction method coupled with UHPLC-TOF/MS to investigate the temporo-spatial distribution of nicotine-associated metabolites in rat brain regions. The coating material, a Palladium-doped covalent organic framework (I-TFBPT-COF@Pd), exhibited a large surface area, suitable pore diameter, and good biocompatibility. The metabolite distribution pattern spectra demonstrated SPME's superior adsorption performance, as evidenced by a broader and more uniform distribution of metabolites. Principal component analysis and orthogonal partial least-squares discriminant analysis indicated that nicotine exposure induced a profound alteration in the metabolite composition of the experimental samples. In addition, 46 differential metabolites and 7 key pathways in the hippocampus and striatum were identified, which revealed the range of nicotine's influence on various biochemical processes, including neurotransmitter synthesis, energy metabolism, and inflammation regulation. This method provides an effective way to study the potential neural effects of nicotine in the brain, surpassing traditional sampling techniques, and it has broad application prospects in biomedicine.