Macromolecular Crowding Agents‐Assisted Imprinted Polymers For Analysis Of Glycocholic Acid In Human Plasma And Urine

Abstract

Glycocholic acid (GCA) is a newly identified biomarker for hepatocellular carcinoma (HCC) patients. In this study, a method based on macromolecular crowding strategy has been applied for preparation of a molecularly imprinted polymer (MIP), which possesses high adsorption capacity for GCA. Polymethyl methacrylate was used as a macromolecular crowding agent, N-(3-aminopropyl)-methacrylamide hydrochloride as a functional monomer and ethylene dimethacrylate as a cross-linker. The morphology and binding characteristics of MIP were assessed by scanning electron microscopy and absorption experiments. The MIP was used as an adsorbent material to separate GCA, and the molecularly imprinted solid-phase extraction (MISPE) was carefully optimized. The MISPE combined with high-performance liquid chromatographic analysis was successfully used to determine the GCA in plasma and urine samples. When spiked levels ranged from 0.2 to 20 μmol L , the recoveries were between 94.3 and 100.5%. As a proof of principle, this proposed method has been validated on a small subset of HCC patients (n = 10) and healthy volunteers (n = 10). The average GCA concentrations of HCC patients in plasma and urine were about 25 and 2.8 times than that of healthy volunteers. Copyright © 2016 John Wiley & Sons, Ltd.

Diagnosis of hepatocellular carcinoma using a novel anti‑glycocholic acid monoclonal antibody‑based method

“…The present study data also indicates that GCA may be used as a sensitive biomarker in HCC, which is consistent with the results from other groups (13,46). A number of studies have reported that there is a linear association between GCA and the severity of hepatocyte dysfunction (37,43).…”

“…Additionally, the level of glycocholic acid (GCA) in patients with HCC is significantly increased, compared with healthy individuals (11). GCA has been identified as a specific and sensitive biomarker for HCC in urine and serum (12,13).…”

“…GCA, a secondary bile acid and one of the main components of bile acids, is formed by the conjugation of cholic acid and glycine, which assists in the digestion and the absorption of fat in food, in addition to being located in the bile as a sodium salt (14). Numerous studies reported that GCA may serve as a superior clinical marker to detect liver diseases, compared with the traditional markers, including serum alpha fetoprotein, blood enzymology and metabolomics (13,15,16). Analysis of GCA in combination with other diagnostic indicators provides a more sensitive background for the diagnosis, treatment and prognosis of liver diseases (17).…”

“…Additionally, the level of GCA is also a vital diagnostic indicator for various biliary system diseases, including intrahepatic cholestasis and alcoholic liver injury (18). Currently, a number of methods have been reported for the analysis of GCA, including liquid chromatography-mass spectrometry (19), ultra-performance liquid chromatography-quadrupole time-of-flight-high-definition mass spectrometry (12), liquid chromatography-tandem mass spectrometry (20) and macromolecular crowding agents-assisted imprinted polymers (13). However, these methods come with a high cost as they require a well-equipped laboratory and well-trained professionals (19,20).…”

Isolation of sinapic acid from broccoli using molecularly imprinted polymers

“…The proper selection of the cross linker is essential as the CL has a high impact on the stability, morphology, and recognition properties of the imprinted polymer , more details in Supporting Information Section 3.5.…”