Multiple-component covalent organic framework coated stainless steel fiber for efficient microextraction and determination of triazole antifungal drugs in human plasma.

Background: Triazole antifungal drugs are commonly used in clinical settings to treat life-threatening invasive fungal diseases. The development of an analysis method for the sensitive monitoring of antifungal drugs is crucial, given their narrow therapeutic index. Traditional plasma sample processing involves several complex steps. Some of the processes are time-consuming, may result in the loss of trace components, and increase the difficulty of detection. To address these limitations, this work focused on developing a multi-component covalent organic framework (COF) coated solid-phase microextraction (SPME) fiber for efficient extraction and determination of triazole antifungal drugs in human plasma.

Results: The multi-component COF TAPT-DMTP-TFTA was synthesized using 4,4',4''-(1,3,5-triazine-2,4,6-triyl)trianiline (TAPT), 2,3,5,6-tetrafluoroterephthaldehyde (TFTA), and 2,5-dimethoxyterephthalaldehyde (DMTP), which exhibited high surface areas, considerable regular porosity and multiple recognition sites, rendering it an ideal adsorbent for the efficient enrichment of antifungal drugs. The COF-based SPME fiber was integrated with a high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) system for the effective extraction of antifungal drugs from human plasma. With optimized conditions, the method showed excellent linearity for voriconazole (VOR), posaconazole (POS) and isavuconazole (ISA) in the concentration range of 0.01-20 μg/mL, and for itraconazole (ICZ) within 0.05-20 μg/mL, achieving correlation coefficients (R) of no less than 0.9923. The limits of detection (LODs) were in the range of 1.1-13.3 ng/mL. Satisfactory precision with relative standard deviations (RSDs) below 4.21 % were obtained. Through a combination of characterization results and theoretical simulations, multiple interactions between COF and analyte molecules were analyzed to elucidate the adsorption mechanism.

Significance And Novelty: The newly synthesized multi-component COF exhibited high specific surface area, well-defined pores, and multiple recognition sites. The SPME-HPLC-MS method utilizing a COF TAPT-DMTP-TFTA-coated fiber demonstrated simplicity, efficiency, and effective protein exclusion capabilities, thereby addressing the low enrichment efficiency and loading capacity of traditional methods, highlighting its great potential for the detection of antifungal drugs in biological fluids.