Combined host-guest complex with coffee-ring effect for constructing ultrasensitive SERS substrate for phenformin hydrochloride detection in healthcare products.

Phenformin hydrochloride (PHE), once used as a traditional anti-diabetic drug, has now been banned due to significant side effects. However, the phenomenon of the illegal addition of PHE to hypoglycemic healthcare products is still rampant. Thus, the detection of illegally added PHE is urgently needed. Surface-enhanced Raman scattering (SERS) is a promising candidate for this purpose, but the weak affinity between PHE and bare metal (Au or Ag) limits direct SERS detection of PHE. In this paper, we prepared Ag nanoparticles coated with β-cyclodextrin (AgNP@β-CD), which display the coffee-ring effect, that can be used for PHE sensing. β-CD-functionalized nanoparticles could capture the analyte and fix the molecular orientation in the hydrophobic cavity. The coffee-ring effect could improve the SERS effect through a higher concentration of the analyte, higher density of nanoparticles, and more hot spots. The SERS performance of the AgNP@β-CD substrate was characterized by using o-phenylenediamine dihydrochloride as a probe molecule. The excitation wavelength and pH value were optimized. A linear response for PHE detection is in the 7.0 × 10-8 -1.0 × 10-6  mol L-1 concentration range, and the limit of detection is as low as 8.0 × 10-9  mol L-1 . This AgNP@β-CD coffee-ring effect substrate was applied to the detection of PHE in healthcare products, with recoveries between 95.3 and 105.0% and relative standard deviations of less than 5.16%. It is anticipated that the AgNP@β-CD substrate will also have great potential for the monitoring of other aromatic drugs in healthcare products.