New psychoactive substances (NPS) are a class of artificially designed and synthesized chemical substances designed to mimic the pharmacological effects of traditional drugs. They are characterized by significant structural diversity and rapid iteration and have become a major public health challenge threatening global public health. This article systematically reviews the taxonomic characteristics, epidemiological status, and research progress of major testing and detection methodologies for NPS. Based on the classification framework established by the United Nations Office on Drugs and Crime (UNODC) and the European Union Drugs Agency (EUDA) this article systematically describes the chemical structure, pharmacological properties, and modes of abuse of representative NPS such as synthetic cathinones, synthetic cannabinoids, phenethylamines, synthetic opioids, and benzodiazepines; as well as the working principles, application scope, analytical efficacy, and methodological advantages and disadvantages of chromatography-mass spectrometry, spectroscopic techniques, immunoassay techniques, and novel rapid detection techniques. Addressing the key bottlenecks currently facing the NPS detection field, such as prominent structural diversity, complex metabolic pathways, and a lack of standards, this article further proposes future development directions for detection technologies, including the widespread application of high-resolution mass spectrometry, the construction of artificial intelligence-assisted compound identification systems, the promotion of microfluidic chip technology, and the integration of green analytical chemistry principles.
References
[1]
Patocka, J., Zhao, B., Wu, W., Klimova, B., Valis, M., Nepovimova, E., et al. (2020) Flakka: New Dangerous Synthetic Cathinone on the Drug Scene. International Journal of Molecular Sciences, 21, Article 8185. https://doi.org/10.3390/ijms21218185
[2]
Xu, P., Liu, M., Wang, Y., et al. (2018) Research Progress on the Abuse and Dependence Evaluation of Synthetic Cathinones. Chinese Journal of Drug Dependence, 27, 89-93, 98. (In Chinese)
[3]
Li, X.Y., Zhang, S.J., Qiu, Y., et al. (2019) Pharmacological Research Progress of Synthetic Cathinones. Chinese Journal of Forensic Medicine, 34, 279-284. (In Chinese)
[4]
Patel, M., Manning, J.J., Finlay, D.B., Javitch, J.A., Banister, S.D., Grimsey, N.L., et al. (2020) Signalling Profiles of a Structurally Diverse Panel of Synthetic Cannabinoid Receptor Agonists. Biochemical Pharmacology, 175, Article ID: 113871. https://doi.org/10.1016/j.bcp.2020.113871
[5]
Xu, P., Liu, K. and Gao, L. (2012) Research Progress of New Aromatic Drugs. Chinese Journal of Drug Dependence, 21, 406-410. (In Chinese)
[6]
Lin, K., Wang, J., Xu, D., et al. (2017) Research Progress on Detection Methods for Syn-thetic Cannabinoid Psychoactive Substances. Chemical Bulletin, 80, 334-340. (In Chinese)
[7]
Pereira, J.R.P., Antunes, M., Neng, N.R., Mustra, C., Franco, J. and Fonseca, S. (2026) Development and Validation of a Simple and Fast Method for Routine Analysis of New Synthetic Opioids and Hallucinogens in Whole Blood Using Protein Precipitation and UHPLC-MS/MS. Forensic Science International, 378, Article ID: 112713. https://doi.org/10.1016/j.forsciint.2025.112713
[8]
Liu, J., He, H.Y., Ni, C.F., et al. (2020) Simultaneous Detection of Four Cathinone-Type New Psychoactive Substances in Blood Samples by Ultra-High Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry. Journal of Analytical Testing, 39, 1521-1526. (In Chinese)
[9]
Jiang, F.L., Teng, X.M., Ni, C.F., et al. (2016) Screening of 150 Drugs and Toxins in Human Whole Blood by Ultra-High Performance Liquid Chromatography-Tandem Quadrupole Time-Of-Flight Mass Spectrometry. Physical and Chemical Testing (Chemical Section), 52, 417-426. (In Chinese)
[10]
Wang, L., Zhang, Y., Li, J., et al. (2025) Rapid UHPLC-MS/MS Method for Simultaneous Quantification of 22 Synthetic Opioids, Cannabinoids and Their Metabolites in Whole Blood. Journal of Analytical Toxicology, 49, 387-395. (In Chinese)
[11]
Zou, X., He, J., Li, Y., et al. (2026) Research Progress on Analytical Methods for New Psychoactive Substances in Complex Matrices. Chemical Reagents, 1-9. (In Chinese)
[12]
Chen, T.W. (2024) Application of Surface-Enhanced Raman Spectroscopy in the Detection of New Psychoactive Substances. Journal of Fuzhou University (Natural Science Edition), 52, 105-111. (In Chinese)
[13]
Tian, Y., Yan, Y., Wen, D. and Shi, Y. (2025) Research Progress of Novel Functional Materials in Rapid Detection of New Psychoactive Substances. Journal of Forensic Medicine, 41, 314-325.
[14]
Croce, E.B., Dimitrova, A., Di Milia, M.G., Pierotti, S., Arillotta, D., Barbaresi, M., et al. (2025) Postmortem Distribution of MDPHP in a Fatal Intoxication Case. Journal of Analytical Toxicology, 49, 137-141. https://doi.org/10.1093/jat/bkae092
[15]
Fan, S., Zang, C., Shih, P., Ko, Y., Hsu, Y., Lin, M., et al. (2020) A LC-MS/MS Method for Determination of 73 Synthetic Cathinones and Related Metabolites in Urine. Forensic Science International, 315, Article ID: 110429. https://doi.org/10.1016/j.forsciint.2020.110429
[16]
Dimitrova, A., Croce, E.B., Iaquinta, G., Ferri, E., Faccioli, S., Chiavacci, G., et al. (2024) Exploring Cerebrospinal Fluid: Validation of a New Method for Quantification of 39 Drugs of Abuse by LC-MS/MS. Forensic Sciences, 4, 546-554. https://doi.org/10.3390/forensicsci4040036
[17]
Raspini e Silva, L., da Silva, B.E., Inamassu, C.H. and Marchioni, C. (2026) Synthetic Cannabinoids: A Critical Review of Challenges and Advances in Biological Sample Preparation. Journal of Chromatography A, 1765, Article ID: 466530. https://doi.org/10.1016/j.chroma.2025.466530
[18]
Nowak, P.M., Wietecha-Posłuszny, R. and Pawliszyn, J. (2021) White Analytical Chemistry: An Approach to Reconcile the Principles of Green Analytical Chemistry and Functionality. TrAC Trends in Analytical Chemistry, 138, Article ID: 116223. https://doi.org/10.1016/j.trac.2021.116223
