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A method for detecting methamphetamine (MET), ketamine (KET), and morphine (MOP) molecules is presented using a reusable substrate based on SERS. The SERS substrate was prepared by etching the Au/Ag alloy film to synthesize a nanoporous Au membrane (AuNPM). By optimizing the preparation conditions and using rhodamine 6G (R6G) as an analyte, the AuNPM exhibited good SERS performance with a limit of detection (LOD) of 10 -9  mol L -1 . A competitive immunoassay category has been applied to the detection of MET, KET, and MOP. The MET, KET, and MOP antigens were functionalized on the surface of the AuNPM to specifically bind to the related drug antibodies. The Au nanoparticles (AuNPs) modified with 4-mercaptobenzoic acid (4-MBA) and antibodies against MET, KET, and MOP were used as nanotags. The 4-MBA served as the reporting molecule and drug antibodies were used to bind to free drug molecules in the target solution. The mixture of nanotags and target solution was dropped onto the antigen-modified AuNPM (antigen/AuNPM), and the free nanotags bind to the antigen/AuNPM. By comparing the SERS intensity of 4-MBA with the presence or absence of drug molecules, the drugs were qualitatively and quantitatively identified. Through this category, the LODs for detecting MET, KET, and MOP were 0.1, 1, and 1 ng mL -1 , respectively. This study proposes an effective method for constructing SERS-based detection of drug molecules with good potential for practical applications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)