On-line Extraction Techniques Based On Novel Metal-organic Frameworks And Their Application In Urine Analysis

In order to isolate and preconcentrate the trace target analytes in complex biological samples,the selection of adsorbent with high extraction efficiency and good selectivity is the key to sample pretreatment.Metal-organic framework(MOFs)compounds are a new class of inorganic-organic hybrid porous material,in which metal ions(clusters)and organic linkers are self-assembled to build bulk blocks with various infinite network topologies,possessing many fascinating characters such as large specific surface areas,adjustable pore size,high thermal stability,good chemical stability and tailorable.Those advantages endow the material many application fields in catalysis,medicine,gas storage,etc.In sample pretreatment,the weak molecular recognition origine from the coordination between guest molecules and open metal sites,as well as the unique interaction forces in the frameworks.Micro-solid phase extraction(μ-SPE)and magnetic solid phase extraction(MSPE)are two novel sample pretreatment techniques.The required amount of sorbents forμ-SPE is less than conventional SPE methods,exhibiting the merit of the environmentally friendly method in the view of green chemistry.Besideds,the format ofμ-SPE shows other admirable features like good permeability,large extraction capacity and available automation.MSPE is based on magnetic material as adsorbent,make use of external magnet to separate and retrieve magnetic materials after ectraction adequately.The integration of sample pretreatment techniques with online chromatographic analytic methods can reduce the processing steps and human errors,save the labor and organic solvent,and improve the sensitivity and accuracy.A novel[Co2(5,4-PMIA)2(TPOM)0.5]n(Co-MOF)was synthesized by employing Co(Ⅱ)as metallic nodes,together with rigid organic ligands 5-(4-pyridyl)-methoxyl isophthalic acid(5,4-PMIA)and flexible linker Tetrakis(4-pyridyloxymethylene)methane(TPOM),constructing a three-dimentional porous crystal.Its excellent adsorption properties and physico-chemical stability show the Co-MOF is promising to the application of gas and liquid phase separation.Therefore,we empoyed Co-MOF and its magnetic composite Fe3O4@Co-MOF as the adsorbent of μ-SPE and In-tube MSPE respectively.By connecting those devices to liquid chromatography(LC),liquid chromatography-mass spectrometry(LC-MS),we established on-line analysis methods to detect metabolic biomarkers in human urine.The contents are as follows:1.A novel metal-organic framework Co-MOF was synthesized and packed as sorbent of micro-solid phase extraction(μ-SPE).A validated μ-SPE method for the determination of trace mono-hydroxyl polycyclic aromatic hydrocarbons(OH-PAHs)in human urine was developed by online coupling to liquid chromatography-mass spectrometry(LC-MS).High porosity and robust organic linkage endows Co-MOF excellent mechanical and solvent stability for at least 200 repeatable operations in high back pressure and large organic volume.The hydrophobicity and rich π electrons facilitate affinity between OH-PAHs and Co-MOF.The enrichment factors up to 63 and 113 were obtained for 3-hydroxyphenanthrene(3-PHEN)and 1-hydroxypyrene(1-PYR),respectively.Satisfactory sensitivity with detection limits(S/N=3)of 1.1-4.1 ng·L-1 and good precision with relative standard deviations(RSDs)of 1.12%-8.50%were obtained.3-PHEN was detected in urine samples from non-smokers residents who lived in different ecological environment.The results show the online μ-SPE-LC-MS method has the feature of rapidity,sensitivity and automation,and it had the potential to assess the human environmental exposure to PAHs.2.The mono-dispersive Fe3O4 nanoparticle was added into the mixed solution of nanocrystal to prepare a novel magnetic composite(Fe3O4@Co-MOF).Subsequently,the magnetic material was immobilized on the inner wall of stainless steel tube by external magnet force to realize automation of the magnetic solid phase extraction(MSPE)conveniently.Based on the open tubular extraction phase coated by magnetic Co-MOF on the inner surface,the In-tube MSPE coupling to high performance liquid chromatography(In-tube MSPE-HPLC)was developed to determine six aldehydes in human urine of lung cancer patients and healthy volunteers.Benefiting from the hydrophobicity and the high pecific surface area,the Fe3O4@Co-MOF adsorbent can resist the interference from sample matrixes and selectively capture targeted analytes.The on-line method reduced tedious operation steps and error sources when compared to off-line mode.The dynamic reverse elution ensured the adsorbed analytes was completely desorbed by mobile phase.Several parameters that influence the extraction efficiency were investigated systematically.Under the optimal conditions,the relative standard deviation values were lower than 19%(n=7).Moreover,satisfactory sensitivities with the limits of detection in the range of 0.0068-0.0491μmol/L and good linearity with excellent correlation coefficients(R2)being larger than 0.9917 had also been achieved.The results demonstrated that the aldehydes in urine were detected successfully and our method was expected to become a promising approach for the determination of trace aldehyde metabolites in complex biological samples.