Design and application of graphene oxide-based molecularly imprinted covalent organic framework for simultaneous and precise recognition of bile acid metabolites.

In this study a bile acid (BA)-imprinted covalent organic framework (COF) was constructed via Schiff base reactions, which integrated the advantages of both inherent structural stability of COF and exceptional selectivity of molecular imprinting technology. Besides, it was found that the addition of graphene oxide (GO) effectively increased the dispersibility of nanoparticles, ultimately resulting in a GO-based molecularly imprinted COF (GO@MICOF). The GO@MICOF was identified with the characteristics of excellent mass transfer performance (20.09 mg g), specific surface area (152.35 m g), selectivity (IFs = 2.4), and regeneration ability (n ≥ 10). By coupling the GO@MICOF-based pretreatment method with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, sensitive and accurate validation results (LOQs, 0.01-2.5 µmol L; extraction efficiency, 81.1-118.9%) were obtained. Notably, the application of the proposed pretreatment techniques to metabolomics analysis holds great significance for the precision of metabolomics results. Sixteen BA metabolites were successfully quantified in rat liver and fecal samples, and some potential biomarkers and related metabolic pathways associated with postmenopausal osteoporosis had been identified. Therefore, the integrated analysis strategy has significant advantages in purifying complex biological samples and has great application prospects in targeted metabolomics research.