Application of Covalent Organic Framework-Based Solid-Phase Microextraction for Efficient and Direct Analysis of Neurotransmitters in the Striatum of Nicotine-Addicted mice

This study developed and validated a novel solid-phase microextraction (SPME) method based on covalent organic framework (COF) for the simultaneous analysis of 10 neurotransmitters (NTs) in mice brain tissue using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The synthesized COF was utilized as SPME fiber coating, exhibited a suitable pore size and macromolecule exclusion capability, ensuring excellent thermal stability and high adsorption efficiency for NTs. This allowed direct extraction from brain homogenates, eliminating the need for protein precipitation. And the COF-based SPME fiber exhibited good reusability throughout eight successive recycling cycles. The SPME-UHPLC method demonstrated excellent linearity (correlation coefficients > 0.99), low intra- and inter-day precision (RSDs ≤ 9.5 % and ≤ 10.6 %, respectively), and acceptable matrix effects (ranging 84.3 % to 117.3 %). The developed method was then applied to analyze NTs in the striatum of nicotine-addicted mice, and the statistical analysis revealed significant shifts in the concentrations of dopaminergic, serotonergic, glutamatergic, addiction and deepened the understanding of addiction's neurobiology. This method offers a sensitive and efficient approach for extracting polar NT analytes in complex matrices, profiling NT alterations linked to addiction, and holds potential for early detection and treatment of addiction disorders. It could contribute significantly to addiction neurobiology and neurological disease research.