Research And Application Of Magnetic Solid Phase Extraction Of Heavy Metal And Nitrogen Heterocyclic Drugs By Fe₃O₄ Based Functionalized Materials

The extraction,separation and detection of heavy metals in pharmaceuticals and drugs in biological samples have been the important research contents in analytical chemistry.Heavy metals and drugs can be excreted through various metabolic pathways,eventually existed in the environment by transferring,accumulation and pollution.Due to low concentration and complex matrices in these components,appropriate pretreatment procedures by enrichment and separation methods are required before the analysis of complex matrix samples.Magnetic solid-phase extraction?MSPE?is a procedure based on the use of magnetic sorbents for the preconcentration of different inorganic or organic analytes from sample solutions.MSPE has been attracted much attention due to their well-known advantages,which include the high enrichment efficiency,convenient operation,timesaving and rapid processing,green and environment-friendly method.In this thesis,heavy metals in pharmaceuticals and nitrogen heterocyclic drugs in biological samples were selected as the research objects.Fe₃O₄-based functionalized materials were prepared and applied in the MSPE of heavy metals and nitrogen heterocyclic drugs.Combination of instrument analysis,simple and efficient sample pretreatments were successfully established.The main research content is as follows:?1?The nanoscale sorbent of glutaraldehyde cross-linked magnetic chitosannanoparticles?Fe₃O₄/GMCNs?was synthesized with Fe₃O₄ particles carrier by crosslinking reaction between glutaraldehyde and chitosan.The properties of the nanocomposites were characterized by Fourier transform infrared spectroscopy?FT-IR?,transmission electron microscope?TEM?and X-ray diffraction?XRD?.Fe₃O₄/GMCNs were used as an adsorbent for the dispersive solid-phase extraction of palladium?Pd?in active pharmaceutical ingredients?APIs?prior to analysis by flame atomic absorption spectrophotometer?FAAS?.The effects of experimental parameters affecting extraction recoveries like the adsorbent amount,pH of solutions,adsorption time,eluent solution and ions mutual interferences were examined.Under the optimized conditions,the calibration curve obtained showed a good linear correlation from 5.0 ?g/L to 500 ?g/L and relative recoveries of palladium in palonosetron hydrochloride and silodosin APIs was in the range of 91.7?97.6%.According to the fitting results of adsorption isothermal model,the Langmuir model was more suitable than Freundlich model for the adsorption of Pd on Fe₃O₄/GMCNs,and the maximum adsorption capacity was 23.9 mg/g.?2?Fe₃O₄/graphene magnetic nanoparticles?Fe₃O₄/G?were successfully prepared with graphene as raw materials by a simple chemical coprecipitation method.Thiosemicarbazide-thiophene formaldehyde Schiff base as complexing agent and Fe₃O₄/G as an adsorbent were used for enrichment and separation of copper and lead in Panax Notoginseng prior to analysis by FAAS.The effects of various parameters such as the adsorbent amount,pH,adsorption time,eluent solution and ions mutual interferences on the recovery were evaluated.The linear ranges of the calibration curve for the determination of copper and lead were 1.0?500 ?g/L and 5.0?750 ?g/L,respectively.The limits of detections?LODs?for Cu and Pb were 0.22 ?g/L and 0.87?g/L,respectively.The spiked recoveries for the target metal ions were in the range of 96.4?102.0%,with the relative standard deviations?RSD?in the range of 0.8?3.6%.According to the fitting results of adsorption isothermal model,the Langmuir model was suitable for the description of the adsorption of two metal ions on Fe₃O₄/G.The maximum adsorption capacities of copper and lead calculated from the Langmuir equation were 172.7 mg/g and 122.2mg/g,respectively.?3?A magnesium-aluminum layered double hydroxide coated on magnetic nanoparticles was synthesized and used as a sorbent to extract chromium?Cr?from gelatins and hollow capsules.The extracted chromium can be quickly separated by an external magnet and quantified by FAAS.According to Box-Behnken center combination experimental design principle,experimental parameters such as sorbent amount,solution pH and adsorption time were studied and optimized.The linearity range of the method was between 50 and 1000 ?g/L with the determination coefficient?R2?higher than 0.999.Relative standard deviations for intra-and inter-day precision for Cr were in the range of 1.7%and 2.8%,respectively.The limit of detection was 7.8 ?g/L.Relative recoveries higher than 92.1%with RSDs in the range of 1.1-4.2%were obtained in the analysis of gelatins and hollow capsules samples.The adsorption of chromium reached equilibrium at 30 min and followed the pseudo-second order kinetic equation.The equilibrium adsorption isotherm data well fitted the Langmuir model for Cr.This indicated that Fe₃O₄@SiO₂@Mg-Al LDH was an effective adsorbent for the dispersive solid phase extraction of chromium with quick separation.?4?Multi-walled carbon nanotubes functionalized with a HNO3/H2SO4 mixture?Fe₃O₄/MWCNTs?were prepared for MSPE coupled with UPLC-MS/MS to determine silodosin?SI?,imidafenacin?IM?and its metabolin?oxidative imidafenacin,OM?in biological samples.The optimum MSPE conditions were investigated by the single factor experiment design and Box-Behnken combination center experimental design in detail.Under the optimized conditions,the calibration curves were linear?R2?0.9960?over the concentration range of 1.0?800 ng/mL?SI?and 15.0?800 pg/mL?IM and OM?.The limits of detection were 0.3 ng/mL for SI,5.2 pg/mL for IM and 3.8 pg/mL for OM.The developed method showed satisfactory reproducibility with intra-day and inter-day relative standard deviations less than 13.6%.This MSPE method was successfully used for the extraction and determination of three nitrogen heterocyclic drugs in biological fluids?plasma and urine?with relative recoveries in the range of 91.4 to 111.8%.?5?Oleic acid modified Fe₃O₄ nanoparticles?Fe₃O₄/OA?were synthesized by chemical coprecipitation method and used as a magnetic sorbent to extract two nitrogen heterocyclic drugs a risperidone?RISP?and 9-hydroxyrisperidone?90HR?in plasma and saliva sample.Dispersion solid-phase extraction integrated with UPLC-MS/MS was applied to enrich RISP and 90HR using milligram-level sorbents with vibration for 6 min and detect the target analytes within 10 min.Under optimal conditions,good linearities?R2>0.995?for all calibration curves were obtained,and the LODs for RISP and 90HR were 0.06 and 0.04 ng/mL,respectively.Satisfactory recoveries?93.2?97.4%and 91.8?99.2%for RISP and 90HR?in the biological matrices were achieved.Fe₃O₄/OA successfully applied in the preconcentration and determination of RISP and 90HR suggested that the MSPE method could be a promising alternative for efficient and selective extraction of trace amounts of pharmaceuticals in bio-matrix samples.