Site-selective hydroxyl functionalization: A dual-functional strategy for fabricating porous cellulose molecularly...

Conventional pretreatment methods for in vivo drug analysis are limited by low recovery rates, matrix interference, and invasive sampling procedures. While solid-phase microextraction (SPME) with molecularly imprinted polymer (MIP) coatings presents a promising alternative, traditional MIPs suffer from inefficient mass transfer and buried recognition sites.

A novel dual-functional strategy combining boric acid affinity and silane coupling was developed to selectively modify hydroxyl groups on porous cellulose (PC), creating boric acid-modified PC-MIP (B-PCMIP) for SPME fiber fabrication (B-PCMIP-N). Specifically, phenylboronic acid was first used to occupy cis-diol groups on PC. Meanwhile, remaining hydroxyl groups in PC were silanized to introduce polymerizable sites for MIP synthesis. Under acidic conditions, cis-diol groups were then released and served as recognition monomers. Subsequently, B-PCMIP was fabricated using the modified PC as substrate-integrated functional monomer. Finally, B-PCMIP-N SPME fiber was prepared by immobilizing B-PCMIP onto stainless-steel needle. The dual-functional strategy of modified PC ensures surface-exposed sites for improving imprinting efficiency and selectivity. Compared with traditional MIP SPME fiber, B-PCMIP-N SPME fiber showed a 6.2-fold higher adsorption capacity and superior selectivity (selectivity coefficient up to 70.6). Hydrogen bonding energy between PC and piperacillin sodium (PS) increased from -272 to -13.0 kcal mol^-1. Coupled with HPLC/UPLC-MS/MS, B-PCMIP-N SPME fiber enabled in vivo monitoring of PS and its metabolite in rat liver, blood, and excretions.

This dual-functional strategy overcomes limitations of traditional pretreatment methods. The B-PCMIP-N SPME fiber based analytical method enables minimally invasive, excellent selectivity, and good accuracy, offering a promising approach for drug monitoring.