Nitrogen-rich porous polymer as a solid-phase microextraction coating for the ultrasensitive analysis of nicotine and its metabolites in different rat brain regions

Nicotine, a major component of tobacco smoke, exerts complex effects on the brain, including dependence and potential neurotoxicity. Understanding its distribution and metabolism in different brain regions is crucial for elucidating its neurological impact. This study presents a new solid-phase microextraction (SPME) method using a nitrogen-rich porous polymer coating (BDTB-MBD) that simultaneously quantified nicotine and its six metabolites in different rat brain regions. The coating material exhibited excellent stability with a high surface area (1001.7 m 2 /g), suitable pore diameter (5.28 nm), and excellent hydrophilic and hydrophobic properties. Under optimal conditions, the SPME tandem ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS) method exhibited a wide linear range (0.01–100 μg L −1 ), low limits of detection ranging from 0.002–0.020 μg L −1 , limits of quantifications ranging from 0.006–0.070 μg L −1 , and satisfactory repeatability and reproducibility. The spiked recovery rates ranged from 77.1 % to 99.6 %, indicating that the established method was sensitive, accurate, and reliable. Density functional theory calculations revealed strong non-covalent interactions between BDTB-MBD and analytes, providing insights into the adsorption mechanism. The SPME-UPLC-MS/MS method successfully tracked the pharmacokinetics of nicotine in different rat brain tissues following intraperitoneal injection. The results demonstrated rapid absorption with a regional distribution of nicotine, followed by its gradual metabolism into cotinine, nornicotine, and other metabolites. Notably, the concentration profiles varied across brain regions, highlighting the importance of considering regional specificity in nicotine brain research. Compared with traditional techniques such as solid phase extraction, this approach offers a valuable tool for studying nicotine distribution and metabolism in the brain, with potential applications in neuroscience and drug monitoring.