Preparation Of Magnetically Assisted Surface-enhanced Raman Substrates And Their Use In Drug Analysis In Vivo

Pharmaceutical analysis is an analytical methodology to investigate the level of drugs and their metabolites and endogenous substances in biological samples.Its main tasks include the study of methodological research,to provide data of drug monitoring for clinical treatment,detection of endogenous substances,and supervision of drug abuse.However,the biggest challenge in pharmaceutical analysis is that the composition of biological sample is complex and the concentration of the drug and its metabolites is always trace level.So the sensitivity of the analytical method must very good.Surface-enhanced Raman scattering(SERS)spectrum has many advantages including simple sample pretreatment,noninvasive detection,high sensitivity,and rich information of fingerprints.We can obtain the structure information of target molecular while obtaining high-sensitivity nondestructive results.Hence,SERS is becoming more and more popular in biopharmaceutical analysis.A good Raman signal enhanced substrate is integrant to the application of surface-enhanced Raman scattering spectroscopy.gold and silver nanoparticles are the most common SERS substrates.In order to be applied to the complex biological samples,traditional SERS substrates are functionalized by magnetic materials to prepare Au/magnetic composite substrate.So that under the effect of external magnetic field,it can achieve the separation of the substrate and complex samples quickly and easily.In this paper,three kinds of magnetic SERS substrates were prepared by in-situ synthesis of gold nanoparticles by using Fe@Fe3O4 core-shell structure,foam nickel and other magnetic materials as reductant templates,and tried to be used for detection serum concentration of endogenous dopamine and anti-cancer drug 6-mercaptopurine.It lays the foundation for more application of surface enhanced Raman spectroscopy in drug analysis.Specific work as follows:Endogenous biomarkers dopamine(DA)levels are associated with many neurological disorders,such as Alzheimer's disease,Parkinson's syndrome,etc.In this paper,Fe@Fe3O4 core-shell nanoparticles were synthesized by thermal decomposition method,and Au-Fe3O4 nanocomposites were synthesized in situ by reduction of chloroauric acid with iron nucleus as reducing agent.The detection limit of DA in serum was 5×10-9 M(S/N = 3).The method was simple,rapid and reproducible.The results were in good agreement with high-performance liquid chromatography(HPLC-MS),and realized the rapid and sensitive detection of endogenous substancesby surface-enhanced Raman scattering spectroscopy.Further,to simplify the magnetic optimization step of the substrate to obtain a clean SERS substrate,we used foam nickel as the in situ reduction template to synthesize Au/NFs composite magnetic SERS substrate.Foam Nickel is a sponge-like porous metal nickel material,its unique three-dimensional network structure can provide good adsorption and roughness.Not only the substrate preparation process and its fast and easy,very good magnetic moment to achieve magnetic separation operation,and SERS enhanced effect is ideal.Detection of drug molecules6-mercaptopurine the minimum detection limit of 1×10-9 M(S/N = 3).This study provides a new idea for the functionalization of SERS substrate.It is expected that a series of magnetic functional SERS substrates will be prepared for different practical applications in the future.Lastly,in order to balance the substrate clean operation and the substrate SERS performance and stability,and make full use of foam nickel porous structure to prepare more practical value of the SERS substrate,we introduced graphene material between foam nickel and gold nanoparticles.Graphene not only can improve the SERS enhancement performance(102-103)by charge transfer,but also has excellent adsorption of the molecules to be measured.Meanwhile,the excellent stability of graphene can also protect the surface of gold nanoparticles.The prepared Au/rGO/NFs magnetic SERS substrate detection probe molecule 4-MPy and drug molecule 6-MP have better performance than Au-NFs substrate,and have practical application value for surface-enhanced Raman spectroscopy.Pharceutical analysis provides the direction of effort.The results of this paper show that the surface-enhanced Raman scattering spectroscopy is a reliable method for the detection of dopamine and 6-mercaptopurine in the endogenous substances.The results are reliable and have some clinical reference value.Although there is still much work to be explored to improve the solution,we can still look forward to the future,Raman spectroscopy as a fast,non-destructive,safe detection technology,in vivo drug analysis and even clinical testing will have a very good application prospects.