Construction Of Functionalized Silver Nanoparticles SERS Substrates And Their Application In Detection Of Illegally Added Chemical Drugs

As a kind of molecular vibrational spectroscopy,surface-enhanced Raman Scattering（SERS）technique can provide rich“fingerprint information”with high sensitivity,enabling rapid in-situ nondestructive analysis,and has been widely used in food safety,environmental analysis,biomedicine and drug testing and so on.Based on the great superiority of SERS technology in analysis and detection,it is used for the determination of illegally added chemical drugs in healthcare products.In this paper,two kinds of functionalized silver nanoparticles were prepared as SERS substrates for qualitative analysis and quantitative detection of different kinds of chemical drugs.Metal-organic frameworks-silver nanoparticles（MOFs-AgNPs）with SERS activity were successfully prepared via in situ synthesis AgNPs on the MOFs surface.By virtue of the adsorptivity of MOFs,the MOFs-AgNPs could effectively concentrate the drug molecules on the electromagnetic enhancement areas of AgNPs to generate SERS signals.The SERS performance of the substrate was estimated by using crystal violet（CV）as probe molecule,which demonstrated the high sensitivity and uniformity of MOFs-AgNPs substrate.The MOFs-AgNPs substrate was used for SERS determination of sildenafil（SIL）and pioglitazone hydrochloride（PIO）.The linear range of SIL and PIO were 1.0×10^-7-1.0×10^-5mol L^-1and 8.0×10^-7-3.0×10^-5mol L^-1,respectively.The limits of detection（LOD）of SIL and PIO were 4.8×10^-8mol L^-1and 1.4×10^-7 mol L^-1,respectively.The designed SERS method realized the determination of SIL and PIO in commercial drug tablets and healthcare products with recoveries of 93.8-108.0%and 93.0-104.0%,respectively,with relative standard deviation（RSD）less than 4.2%.β-cyclodextrin functionalized silver nanoparticles（CD-AgNPs）were synthesized usingβ-CD as reducing agent and protective agent.The introduction ofβ-CD with hydrophobic cavity can capture drug molecules with hydrophobic groups to form host-guest complex,making the drug molecules closer to SERS hot spots of AgNPs,thereby enhancing the SERS signal intensity of drug molecules.The SERS performance of CD-AgNPs was evaluate using crystal violet（CV）as the probe molecule,and the calculated enhancement factor（EF）was 7.2×10~6.The experimental parameters were optimized,including the concentration of CD-AgNPs,the p H value and the incubation time.Under the optimal conditions,SERS quantitative determination of antihypertensive drugs irbesartan（IRB）and doxazosin mesylate（DOX）were carried out.The Raman characteristic peaks of IRB and DOX were assigned by density functional theory（DFT）calculation.The linear response was3.0×10^-7 to 1.0×10^-5 mol L^-1for IRB and 3.0×10^-7to 2.0×10^-5 mol L^-1for DOX,respectively.The obtained limits of detection of IRB and DOX were as low as7.5×10^-8 and 8.6×10^-8 mol L^-1,respectively.Furthermore,this analytical method was successfully appiled to detect IRB and DOX in commercial drug tablets,healthcare products and human urine samples.The recoveries of IRB and DOX in real samples were 90.8-115.7%and 90.0-113.5%,respectively,with relative standard deviation（RSD）less than 4.5%.