Hierarchical Self-Assembly of AgNS@Fe–MoS2 for Ultrasensitive SERS Detection of Multiple Illicit Drugs in Urine

In response to the urgent need for rapid and on-site detection of illicit drugs in complex biological matrices, this study proposed a novel coupling strategy that integrated iron-doped molybdenum disulfide (Fe–MoS2) nanosheets with silver nanostars (AgNS) to construct a hierarchical SERS platform for the label-free detection of illicit drugs in urine. First, Fe–MoS2 nanosheets were synthesized via a hydrothermal method, where the Fe doping content was optimized to modulate the band structure and maximize the chemical enhancement effect. Subsequently, they were assembled into a film and directly interfaced with a pre-assembled AgNS substrate, ultimately yielding an AgNS@Fe–MoS2 hybrid SERS platform. By coupling the dense electromagnetic “hot spots” generated by AgNS with the optimized charge transfer capability of Fe-MoS2, this platform exhibits exceptional SERS performance for illicit drug detection. Experimental results show that this substrate achieved limits of detection as low as 5.59 ppb for methamphetamine (MAMP), 48 ppb for heroin (HER), and 32 ppb for ketamine (KET) in standard solution, and also maintained robust linear response and anti-interference capability in binary mixture systems. The recovery rates of MAMP (90.66–98.85%) and KET (94.01–101.70%) in urine samples were highly consistent with LC–MS/MS results, confirming its feasibility in complex biological systems. Overall, this study presents a controllable self-assembly strategy for semiconductor materials, providing a reliable sensing platform and methodological support for the highly sensitive and on-site detection of illicit drugs, along with potential applications in environmental monitoring, food safety, and point-of-care diagnostics.