Hydrophilic molecularly imprinted resin-hexagonal boron nitride composite as a new adsorbent for selective extraction and determination of a carcinoid tumor biomarker in urine

Abstract

Background: The detection of disease biomarkers in biological samples plays an important role in early diagnosis and treatment of carcinoid tumor. However, due to the complexity of biological samples and the extremely low concentration of disease biomarkers, sample pretreatment is still the bottleneck of achieving accurate quantitative determination. In this work, new hydrophilic molecularly imprinted resin-hexagonal boron nitride (HMIR-h-BN) composites were developed and used as a new solid phase extraction (SPE) adsorbent for selective detection of 5-hydroxyindoleacetic acid (5-HIAA), a biomarker of carcinoid tumor, in urine.

Results: Twenty-two types of HMIR-h-BN were successfully synthesized through growing hydrophilic molecularly imprinted resin on surface of activated two-dimensional h-BN nanosheets, and preparation parameters affecting the adsorption performance of HMIR-h-BN were investigated and optimized through adsorption experiments. HMIR-h-BN #19 (the ratio of resorcinol to hexamethylenetetramine: 6:3; the dosage of h-BN: 300 mg; the dosage of dummy template: 0.12 mmol; the imprinting time: 4 h) has demonstrated to be the optimal material for efficient separation and extraction of 5-HIAA. Combined with HPLC-UV, the limit of detection and the limit of quantification of 5-HIAA in real urine samples were 9.4 ng mL^-1 and 31.3 ng mL^-1, respectively, the coefficient of determination (R²) was 0.9996 in the linear range of 0.1-300 μg mL^-1 and the relative recoveries ranged from 86.9 % to 97.7 % with RSD ≤5.1 %. Moreover, after being processed by HMIR-h-BN-SPE, there are no interferences from other peaks at the peak position of 5-HIAA.

Significance: The HMIR-h-BN composite has been demonstrated to be capable of selective extraction of 5-HIAA from urine samples and have a significant purification effect. Based on the established HMIR-h-BN-SPE-HPLC-UV method, accurate quantitative determination of 5-HIAA in urine samples was achieved, which is expected to be applied in the early diagnostic of carcinoid tumor.

Keywords: 5-Hydroxyindoleacetic acid; Biomarker; Hexagonal boron nitride; Hydrophilic molecularly imprinted resin; Solid phase extraction.