Preparation Of Novel Functionalized Magnetic Composites And Their Application In The Drug-set Enrichment Analysis

Biopharmaceutical analysis is an analytical methodology for studying the qualitative and quantitative changes of endogenous substances,drugs and metabolites in organisms.By analyzing the concentration of drugs in human or animal body fluids and tissue fluids,pharmacokinetics parameters of drugs are obtained to guide the clinical medication.However,the complex matrix effect of biological samples and the trace content of target drugs make the quantitative detection of target drugs in biological samples very difficult.On the other hand,drug contaminants are difficult to degrade in the environment,and their anti-biodegradability threatens the environment and human health.Therefore,it is of great significance to develop effective method for enriching and analyzing target drugs in biological and environmental samples.In the drug enrichment procedure,the enrichment material is the most critical part,which directly affects the sensitivity,selectivity and speed of the enrichment process.Functionalized magnetic composite materials have both the advantages of magnetic particles and functionalized modified materials,and have promising applications for the drug enrichment.The key to the construction of novel functionalized adsorbent material is to improve its surface functionalization properties on the basis of giving full play to the advantages of magnetic materials,so as to achieve the broad and specific enrichment of molecules for different types of target drugs.Therefore,this thesis focuses on improving the adsorption efficiency and selection characteristics of the adsorbent materials.By modifying the surface of magnetic particles and further grafting functionalized materials,we developed novel adsorbents material and established efficient and accurate drug enrichment analysis method.The main research contents are as follows:(1)Polydopamine was modified on the surface of the magnetic particles through dopamine self-polymerization reaction.The multi-walled carbon nanotubes were further coated on the polydopamine-modified magnetic particles.The prepared core-shell magnetic composite was applied to magnetic solid phase extraction(MSPE)of antiepileptic drugs.Different factors which affecting the extraction efficiency in the MSPE procedure were investigated and optimized.Under the optimized conditions,the analysis method of target drugs in plasma,urine and cerebrospinal fluid(CSF)matrices were established and the methodological parameters were investigated.The results showed that the matrix effect was significantly reduced and the target drugs had good response after the enrichment process.The linear correlation coefficient was above 0.992,the limit of detection was in the range of 0.4-3.1 μg L-1,and the relative standard deviations were<8.2%.These results indicate that the method has excellent linearity,high sensitivity and accuracy.The plasma and CSF clinical samples of epilepsy patients were analyzed,and the recovery of standard addition was in the range of 92.8-96.5%.The established analysis method is potential for the application of therapeutic drug monitoring of antiepileptic drug in future.(2)Based on the ligand structural tunability,the amino functionalized magnetic UiO-66-NH2 composite was prepared and used for the enrichment and adsorption of salicylic acid and acetylsalicylic acid.The amino functionalized magnetic UiO-66-NH2 material showed a significant increase in the enrichment efficiency of the target drugs.The mechanism of interaction between the adsorbent and the target drugs was investigated.Various synergistic force including hydrogen bonds,the affinity between the metal cluster and target molecule,and the electrostatic interaction due to the introduction of amino functional groups make the enrichment efficiency of the target drugs on the adsorbent material improved significantly.To illustrate the adsorption behavior of target drugs on the adsorbent,the adsorption kinetic model and isotherms of were investigated.The results showed that the adsorption process fitted well with the pseudo-second-order model and the isotherm could be explained by the Langmuir isotherm.Moreover,the adsorbent material maintained a high adsorption capacity after three times regeneration.This study provides a new route for preparing simple and efficient adsorbent materials for future application in the enrichment and removal of pharmaceuticals.(3)Through the mixed ligand strategy,original ligands and specific functionalized ligands were introduced to prepare boric acid-functionalized magnetic metal-organic framework composite,which were applied as adsorbents for the enrichment of cis-diol structure nucleoside molecules.The prepared material exhibited excellent acid-base resistance and chemical stability,and are chemically tolerant to the adsorption environment.Compared with the material without doping boric acid functional ligand,the enrichment efficiency of the doped material to the nucleoside molecule is significantly improved,which indicated the efficient selective recognition ability of boric acid ligand.In addition,the enrichment efficiency of adenosine and deoxyadenosine molecules on the composite was investigated.The results showed that the abundant boric acid active sites caused the selective capture of cis-diol structural adenosine molecules.Based on the efficient selective enrichment performance of the adsorbent,a method has been proposed for enrichment and liquid chromatographt analysis of nucleoside molecules in urine samples.The limit of detection was within 0.006-0.016 μg mL-1 range,and the linearity was within 0.02-10 μg mL-1 range.The method showed satisfactory accuracy and sensitivity,which opens up a new way for establishing accurate,efficient and selective analysis methods of drugs in complex samples.