Hierarchically porous covalent organic framework doped monolithic column for on-line chip-based array microextraction of nonsteroidal anti-inflammatory drugs in microlitre volume of blood

Abstract

Background

Traditional blood drug analysis involves large blood consumption and complicated operations and a further reduction in blood consumption is urgently needed. Chip-based monolithic column microextraction is a good strategy for the pretreatment of small-volume samples, and new monolithic materials is the critical factor. Covalent organic frameworks (COFs) are good adsorbents due to large specific surface area and rich conjugated structure. However, the poor dispersion ability of COFs in prepolymer solution severely hinders the preparation of COFs doped monolithic columns. Herein, high internal phase emulsion with viscoelastic properties was adopted to fixed COF particles.

Results

The COFs doped monolith exhibited a hierarchical porous structure and improved extraction efficiency for interest nonsteroidal anti-inflammatory drugs (NSAIDs) (68.2-77.3 vs 28.4-57.7%). A chip-based monolithic column array was fabricated and coupled with high-performance liquid chromatography (HPLC)-ultraviolet detection for online determination of five NSAIDs in microlitre volume of blood. The throughput of the developed method was approximately 3 h^-1, mainly determined by the separation time (22 min) of target NSAIDs in HPLC. Under the optimal conditions (200 μL sample solution, pH=3 at a sampling folw rate of 5 μL min^-1 and 20 μL of acetonitrile/10 mmol L^-1 NaOH (9/1, v/v) as desorbent), the detection limit of 4.39-15.5 μg L^-1 was obtained for target NSAIDs in blood with RSD of 7.8-15.3% and R² of 0.9943-0.9978. The method was applied to the analysis of human serum (20 μL) and dried blood spot, with recovery of 82.0-118% for target NSAIDs.

Significance

A method was proposed for the preparation of COF doped monolithic columns by emulsion polymerization, avoiding uneven distribution of COFs caused by their easy sedimentation in traditional free radical preparation of monolithic columns. Then a chip-based monolithic column array coupled with on-line HPLC-UV detection was established for the quantification of five NSAIDs in microlitre-blood samples. The developed method merits high automation and good anti-interference ability, with extremely low sample/reagents consumption.