Hernández-Contreras, JordiRoig-Rubio, JordiParra, MargaritaGil, SalvadorArroyo, PauSáez, José A.Lodeiro, CarlosGaviña, Pablo2025-06-202025-06-202025-050026-3672PURE: 118930729PURE UUID: cce14b09-659a-4175-9301-5ce35964ad9bScopus: 105001736412PubMed: 40175785WOS: 001458232500001PubMed: 40175785PubMedCentral: PMC11965150ORCID: /0000-0001-5582-5446/work/201987788http://hdl.handle.net/10362/184286Funding Information: The authors gratefully acknowledge grant PID2021-126304OB-C42 funded by the Spanish MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe, EU”, and grant PDC2022-133576-C22 funded by the Spanish MCIN/AEI/10.13039/501100011033 and by the European Union “NextGenerationEU/PRTR”. This work also received partial support and help from Associate Laboratory for Green Chemistry—LAQV which is financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020) through national funds. The PROTEOMASS Scientific Society (Portugal) is also acknowledged by the funding provided through the General Funding Grant 2023. SCSIE (Universidad de Valencia) is gratefully acknowledged for all the equipment employed. NMR was registered at the U26 facility of ICTS “NAMBIOSIS” at the Universitat of València. Publisher Copyright: © The Author(s) 2025.The illicit use of gamma-hydroxybutyrate (GHB) in drug-facilitated crimes underscores the urgent need for rapid and reliable detection technologies. This study introduces two innovative silica-based nanosensors that offer real-time, on-site detection of GHB in spiked beverages at concentrations typical of chemical submission cases. Both chemosensors are based on silica nanoparticles functionalized with 2-aminonaphtoxazole derivatives. The first nanosensor, modified with a p-nitroaniline chromogenic unit, enables a visible color change for immediate visual identification, while the second incorporates a fluorescein derivative for high-sensitivity detection via fluorescence. Both nanosystems demonstrate exceptional specificity to GHB, with minimal interference from other substances. Moreover, the solid-phase integration of these nanosensors onto hydrophobic cellulose-based substrates enhances their portability and user-friendliness, making them suitable for nightlife venues and forensic applications. Finally, chromogenic precursor 1 has proven to be an excellent chemosensor for the visual detection of GHB in oral fluid, with a calculated LOD of 19.2 μM, and a linear response in the 32–132 μM range.143275482engChemical submissionChromo-fluorogenic chemosensorsGamma-hydroxybutyrate (GHB)Oral fluidsSilica nanoparticlesSpiked drinksAnalytical ChemistrySDG 16 - Peace, Justice and Strong Institutionsjournal article10.1007/s00604-025-07134-9https://www.scopus.com/pages/publications/105001736412https://www.webofscience.com/wos/woscc/full-record/WOS:001458232500001