Preparation Of Magnetic Porous Organic Polymers Based On Azo Reaction And Their Hyphenation With HPLC For Drug Analysis

Drugs play a very important role in our daily life,however,drug abuse and drug residues will cause serious harm to human health and the environment.Therefore,drug analysis is of great significance.Due to the complex matrix and low drug content in real samples,appropriate sample pretreatment methods are often necessary before the instrumental analysis.Compared with traditional solid phase extraction,magnetic solid phase extraction（MSPE）has the advantages of fast separation,simple and rapid processing,and can handle samples with large volume.MSPE has been widely used in the field of pharmaceutical analysis in recent years.The ideal magnetic material should have abundant porosity,large specific surface area,good stability and anti-matrix interference ability.Porous organic polymers（POPs）are formed by covalent bonding of organic molecules.They have abundant porous structure,large specific surface area and good stability.They are ideal adsorbents.However,due to the low density of POPs,it is difficult to recycle,and the conventional synthesis processes are rigorous,which limits the application of POPs in sample pretreatment.The aim of this paper is to prepare magnetic POPs with high extraction efficiency and high extraction kinetics for interest drugs,and to establish methods of POPs-MSPE-high performance liquid chromatography（HPLC）for the analysis of trace drugs in biological and food samples.The main contents of this paper are described as follows:（1）Magnetic POPs were prepared by physical blending two monomers of POPs（benzidine and resorcinol）with Fe₃O₄@Si O₂in an aqueous solution.With the magnetic POPs as the adsorbent,seven cardiovascular drugs（lidocaine,metoprolol,mexiletine,labetalol,propranolol,carvedilol and propafenone）were adsorbed based on the interaction ofπ-πand electrostatic interaction,and the extraction efficiency of seven cardiovascular drugs was 78.8-91.2%.Based on this,a method of POPs-MSPE-HPLC-UV was established to monitor the metabolism of metoprolol in human urine in real time.Under the optimum experimental conditions,the detection limit was0.06-0.57μg/L,the relative standard deviation was 4.3-8.6%(c _PRO=1μg/L,c _{XYL,MEX,LAB,CAR,PPF}=2μg/L,c _MET=10μg/L,n=5),and the recovery of target analytes in blank urine was 89.0-112%.The metabolism of metoprolol in urine of two volunteers who took metoprolol tablets was monitored in real time,the maximum concentration was reached at 7 h（1510μg/L）and 13 h（1689μg/L）after drug administration.The method has the advantages of high extraction efficiency and fast extraction kinetics.（2）Based on the synthesis strategy of in situ growth mediated by monomers,Fe₃O₄was modified by amino group firstly,and then hydroquinone,one of the monomers of POPs,was grafted onto the surface of Fe₃O₄@Si O₂-NH₂.Fe₃O₄@POPs with core-shell structure were then prepared by mixing monomer grafted Fe₃O₄@Si O₂with 1,3,5-tris（4-aminophenyl）benzene and hydroquinone in an aqueous solution.The obtainted magnetic POPs withstand ultrasound and has good mechanical and chemical stability.It was used as the adsorbent to adsorb five fluoroquinolone antibiotics（ofloxacin,ciprofloxacin,enrofloxacin,lomefloxacin and difloxacin）based on the interaction ofπ-πand electrostatic interaction.Based on this,the extraction efficiency of five fluoroquinolone antibiotics was 87.6-91.7%,and a new POPs-MSPE-HPLC-FLD method was established to analyze target fluoroquinolones in honey.Under the optimum experimental conditions,the detection limit for target fluoroquinolones was 0.0015-0.0054μg/L,and the relative standard deviation was7.4-12.1%(c _{OFO,CIP,ENR,LOM}=0.05μg/L,c _DIF=0.02μg/L,n=5).The target analyte was not detected in honey samples,and the recovery was 79.4-95.8%.