Analytical detection of New Psychoactive Substances in biological samples: a Systematic Review


Resumo

Novas substâncias psicoativas (NSP) representam um desafio analítico significativo devido à sua diversidade estrutural e ao surgimento acelerado no mercado de drogas. Diante desse cenário, este trabalho teve como objetivo revisar sistematicamente os principais métodos analíticos validados recentemente para a identificação de NSP em matrizes biológicas, além das técnicas de preparo de amostras associadas. A revisão foi conduzida seguindo as diretrizes PRIMA-S, com seleção de estudos baseados nos critérios de inclusão e exclusão predefinidos, resultando na análise de 73 artigos. Entre as matrizes biológicas analisadas, o sangue e a urina foram as mais recorrentes, sendo a extração em fase sólida o método de preparo de amostra mais utilizado. Observou-se ainda uma tendência crescente na busca por procedimentos de preparo mais ágeis, simples e com menor toxicidade (redução no consumo de solventes tóxicos). Quanto às técnicas analíticas, a cromatografia líquida acoplada à espectrometria de massas de alta resolução, empregando especialmente com colunas C18, destacou-se pela sua seletividade e especificidade. Quanto às classes de NSP, os estimulantes foram os mais frequentes. Portanto, diante dos resultados apresentados nesta revisão, é fundamental ressaltar que não existe um método único ideal para a identificação de NSP. Dada a constante modificação estrutural dessas substâncias, uma abordagem combinada, utilizando diferentes ferramentas analíticas, torna-se frequentemente necessária. Além disso, a atualização contínua das técnicas pelas autoridades é essencial para acompanhar a evolução desses compostos.


Referências

  1. M.G. dos Santos, R.J.A. do Nascimento, F.C.L. Ferreira, H.D.M. Possas, V. Vescovi, Uncovering the universe of New Psychoactive Substances (NPS): understanding the mechanisms of action and adverse effects in an accessible and didactic way, Cad. Pedagógico. 21 (2024) e9158. https://doi.org/10.54033/cadpedv21n10-158.
  2. J.B. Zawilska, J. Wojcieszak, An expanding world of new psychoactive substances—designer benzodiazepines, Neurotoxicology. 73 (2019). https://doi.org/10.1016/j.neuro.2019.02.015.
  3. K. Netzer, M. Balmith, B. Flepisi, Factors affecting the control of new psychoactive substances, South African Gen. Pract. 3 (2022) 15–18. https://doi.org/10.36303/SAGP.2022.3.1.0106.
  4. Unodc, Drug Markets: Cocaine Amphetamine-Type Stimulants Substances Report, 2022. https://www.unodc.org/res/wdr2022/MS/WDR22_Booklet_4_french.pdf.
  5. A. Peacock, R. Bruno, N. Gisev, L. Degenhardt, W. Hall, R. Sedefov, J. White, K. V. Thomas, M. Farrell, P. Griffiths, New psychoactive substances: challenges for drug surveillance, control, and public health responses, Lancet. 394 (2019) 1668–1684. https://doi.org/10.1016/S0140-6736(19)32231-7.
  6. G. Vaccaro, A. Massariol, A. Guirguis, S.B. Kirton, J.L. Stair, NPS detection in prison: A systematic literature review of use, drug form, and analytical approaches, Drug Test. Anal. 14 (2022) 1350–1367. https://doi.org/10.1002/dta.3263.
  7. Unodc, Current NPS Threats, United Nations Off. Drugs Crime. VII (2024) 1–25. www.unodc.org/nps.
  8. A. Bruni, C. Rodrigues, C. dos Santos, J. de Castro, L. Mariotto, L. Sinhorini, Analytical Challenges for Identification of New Psychoactive Substances: A Literature-Based Study for Seized Drugs, Brazilian J. Anal. Chem. (2021). https://doi.org/10.30744/brjac.2179-3425.rv-41-2021.
  9. K.C. Chimalakonda, S.M. Bratton, V.-H. Le, K.H. Yiew, A. Dineva, C.L. Moran, L.P. James, J.H. Moran, A. Radominska-Pandya, Conjugation of Synthetic Cannabinoids JWH-018 and JWH-073, Metabolites by Human UDP-Glucuronosyltransferases, Drug Metab. Dispos. 39 (2011) 1967–1976. https://doi.org/10.1124/dmd.111.040709.
  10. O.J.C. Soares, G.A. Silva, R. da M. Macêdo, D.E.L. Lhama, V. Vescovi, R.J.A. do Nascimento, W.S. de Alencar, A.C.T. e Silva, J.A.S. de Sá, R.S. de Araújo, F.C.L. Ferreira, Estudo sobre técnicas de quimioluminescência utilizadas na identificação de vestígios de sangue em cenas de crimes, Res. Soc. Dev. 11 (2022) e126111738997. https://doi.org/10.33448/rsd-v11i17.38997.
  11. M.L. Rethlefsen, S. Kirtley, S. Waffenschmidt, A.P. Ayala, D. Moher, M.J. Page, J.B. Koffel, PRISMA-S: an extension to the PRISMA Statement for Reporting Literature Searches in Systematic Reviews, Syst. Rev. 10 (2021) 39. https://doi.org/10.1186/s13643-020-01542-z.
  12. M.E. Falagas, E.I. Pitsouni, G.A. Malietzis, G. Pappas, Comparison of PubMed, Scopus, Web of Science, and Google Scholar: strengths and weaknesses, FASEB J. 22 (2008) 338–342. https://doi.org/10.1096/fj.07-9492LSF.
  13. F.A. Esteve-Turrillas, S. Armenta, M. de la Guardia, Sample preparation strategies for the determination of psychoactive substances in biological fluids, J. Chromatogr. A. 1633 (2020). https://doi.org/10.1016/j.chroma.2020.461615.
  14. D. Vearrier, J.A. Curtis, M.I. Greenberg, Biological testing for drugs of abuse., EXS. 100 (2010). https://doi.org/10.1007/978-3-7643-8338-1_14.
  15. P. Adamowicz, Z. Bakhmut, A. Mikolajczyk, Screening procedure for 38 fentanyl analogues and five other new opioids in whole blood by liquid chromatography‐tandem mass spectrometry, J. Appl. Toxicol. 40 (2020) 1033–1046. https://doi.org/10.1002/jat.3962.
  16. M. Antunes, M. Sequeira, M. de Caires Pereira, M.J. Caldeira, S. Santos, J. Franco, M. Barroso, H. Gaspar, Determination of Selected Cathinones in Blood by Solid-Phase Extraction and GC–MS, J. Anal. Toxicol. 45 (2021) 233–242. https://doi.org/10.1093/jat/bkaa074.
  17. L. Banaszkiewicz, M.K. Woźniak, M. Kata, E. Domagalska, M. Wiergowski, B. Szpiech, A. Kot-Wasik, Rapid and simple multi-analyte LC–MS/MS method for the determination of benzodiazepines and Z-hypnotic drugs in blood samples: Development, validation and application based on three years of toxicological analyses, J. Pharm. Biomed. Anal. 191 (2020) 113569. https://doi.org/10.1016/j.jpba.2020.113569.
  18. L. Borovcová, V. Pauk, K. Lemr, Analysis of new psychoactive substances in human urine by ultra-high performance supercritical fluid and liquid chromatography: Validation and comparison, J. Sep. Sci. 41 (2018) 2288–2295. https://doi.org/10.1002/jssc.201800006.
  19. A. Orfanidis, H.G. Gika, G. Theodoridis, O. Mastrogianni, N. Raikos, A UHPLC–MS-MS Method for the Determination of 84 Drugs of Abuse and Pharmaceuticals in Blood, J. Anal. Toxicol. 45 (2021) 28–43. https://doi.org/10.1093/jat/bkaa032.
  20. I. Razavipanah, E. Alipour, B. Deiminiat, G.H. Rounaghi, A novel electrochemical imprinted sensor for ultrasensitive detection of the new psychoactive substance “Mephedrone,” Biosens. Bioelectron. 119 (2018) 163–169. https://doi.org/10.1016/j.bios.2018.08.016.
  21. A.M. Ares-Fuentes, R.A. Lorenzo, P. Fernández, A.M. Carro, An analytical strategy for designer benzodiazepines and Z-hypnotics determination in plasma samples using ultra-high performance liquid chromatography/tandem mass spectrometry after microextraction by packed sorbent, J. Pharm. Biomed. Anal. 194 (2021) 113779. https://doi.org/10.1016/j.jpba.2020.113779.
  22. A.G. Verstraete, Detection Times of Drugs of Abuse in Blood, Urine, and Oral Fluid, Ther. Drug Monit. 26 (2004) 200–205. https://doi.org/10.1097/00007691-200404000-00020.
  23. N. Fabresse, I.A. Larabi, T. Stratton, R. Mistrik, G. Pfau, G. Lorin de la Grandmaison, I. Etting, S. Grassin Delyle, J. Alvarez, Development of a sensitive untargeted liquid chromatography–high resolution mass spectrometry screening devoted to hair analysis through a shared MS2 spectra database: A step toward early detection of new psychoactive substances, Drug Test. Anal. 11 (2019) 697–708. https://doi.org/10.1002/dta.2535.
  24. P.O.M. Gundersen, O. Spigset, M. Josefsson, Screening, quantification, and confirmation of synthetic cannabinoid metabolites in urine by UHPLC–QTOF–MS, Drug Test. Anal. 11 (2019). https://doi.org/10.1002/dta.2464.
  25. S.N. Staeheli, V.P. Veloso, M. Bovens, C. Bissig, T. Kraemer, M. Poetzsch, Liquid chromatography–tandem mass spectrometry screening method using information‐dependent acquisition of enhanced product ion mass spectra for synthetic cannabinoids including metabolites in urine, Drug Test. Anal. 11 (2019) 1369–1376. https://doi.org/10.1002/dta.2664.
  26. G.D. Hernandez, C.M. Solinsky, W.J. Mack, N. Kono, K.E. Rodgers, C. Wu, A.R. Mollo, C.M. Lopez, S. Pawluczyk, G. Bauer, D. Matthews, Y. Shi, M. Law, M.A. Rogawski, L.S. Schneider, R.D. Brinton, Safety, tolerability, and pharmacokinetics of allopregnanolone as a regenerative therapeutic for Alzheimer’s disease: A single and multiple ascending dose phase 1b/2a clinical trial, Alzheimer’s Dement. Transl. Res. Clin. Interv. 6 (2020). https://doi.org/10.1002/trc2.12107.
  27. R. Gottardo, D. Sorio, G. Soldati, M. Ballotari, N.M. Porpiglia, F. Tagliaro, Optimization and validation of a new approach based on CE‐HRMS for the screening analysis of novel psychoactive substances (cathinones, phenethylamines, and tryptamines) in urine, Electrophoresis. 42 (2021) 450–459. https://doi.org/10.1002/elps.202000304.
  28. A. Aldubayyan, E. Castrignanò, S. Elliott, V. Abbate, A Quantitative LC–MS/MS Method for the Detection of 16 Synthetic Cathinones and 10 Metabolites and Its Application to Suspicious Clinical and Forensic Urine Samples, Pharmaceuticals. 15 (2022) 510. https://doi.org/10.3390/ph15050510.
  29. S. Pascual-Caro, F. Borrull, C. Aguilar, M. Calull, Development of a Liquid Chromatography–Tandem Mass Spectrometry Method for the Simultaneous Determination of 40 Drugs of Abuse in Human Urine: Application to Real Cases, J. Anal. Toxicol. 47 (2023) 33–42. https://doi.org/10.1093/jat/bkac020.
  30. J. Czerwinska, M.C. Parkin, P.I. Dargan, C. George, A.T. Kicman, V. Abbate, Stability of mephedrone and five of its phase I metabolites in human whole blood, Drug Test. Anal. 11 (2019) 586–594. https://doi.org/10.1002/dta.2525.
  31. G. Musile, M. Mazzola, K. Shestakova, S. Savchuk, S. Appolonova, F. Tagliaro, A simple and robust method for broad range screening of hair samples for drugs of abuse using a high-throughput UHPLC-Ion Trap MS instrument, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 1152 (2020) 122263. https://doi.org/10.1016/j.jchromb.2020.122263.
  32. F. Vincenti, C. Montesano, L. Cellucci, A. Gregori, F. Fanti, D. Compagnone, R. Curini, M. Sergi, Combination of pressurized liquid extraction with dispersive liquid liquid micro extraction for the determination of sixty drugs of abuse in hair, J. Chromatogr. A. 1605 (2019) 360348. https://doi.org/10.1016/j.chroma.2019.07.002.
  33. E. Olesti, J.A. Pascual, M. Ventura, E. Papaseit, M. Farré, R. de la Torre, O.J. Pozo, LC-MS/MS method for the quantification of new psychoactive substances and evaluation of their urinary detection in humans for doping control analysis, Drug Test. Anal. 12 (2020) 785–797. https://doi.org/10.1002/dta.2768.
  34. L. Anzillotti, F. Marezza, L. Calò, R. Andreoli, S. Agazzi, F. Bianchi, M. Careri, R. Cecchi, Determination of synthetic and natural cannabinoids in oral fluid by solid-phase microextraction coupled to gas chromatography/mass spectrometry: A pilot study, Talanta. 201 (2019) 335–341. https://doi.org/10.1016/j.talanta.2019.04.029.
  35. L. Calò, L. Anzillotti, C. Maccari, R. Cecchi, R. Andreoli, Validation of a Bioanalytical Method for the Determination of Synthetic and Natural Cannabinoids (New Psychoactive Substances) in Oral Fluid Samples by Means of HPLC-MS/MS, Front. Chem. 8 (2020) 1–11. https://doi.org/10.3389/fchem.2020.00439.
  36. A. Di Trana, G. Mannocchi, F. Pirani, N. La Maida, M. Gottardi, S. Pichini, F.P. Busardò, A comprehensive HPLC–MS-MS screening method for 77 new psychoactive substances, 24 classic drugs and 18 related metabolites in blood, urine and oral fluid, J. Anal. Toxicol. 44 (2020). https://doi.org/10.1093/jat/bkaa103.
  37. Á. López-Rabuñal, D. Di Corcia, E. Amante, M. Massano, A. Cruz-Landeira, A. de-Castro-Ríos, A. Salomone, Simultaneous determination of 137 drugs of abuse, new psychoactive substances, and novel synthetic opioids in meconium by UHPLC-QTOF, Anal. Bioanal. Chem. 413 (2021) 5493–5507. https://doi.org/10.1007/s00216-021-03533-y.
  38. A. Alexandridou, T. Mouskeftara, N. Raikos, H.G. Gika, GC-MS analysis of underivatised new psychoactive substances in whole blood and urine, J. Chromatogr. B. 1156 (2020) 122308. https://doi.org/10.1016/j.jchromb.2020.122308.
  39. B. Garneau, B. Desharnais, J. Laquerre, C. Côté, M.-P. Taillon, P.-Y. Martin, G. Daigneault, P. Mireault, A. Lajeunesse, A comprehensive analytical process, from NPS threat identification to systematic screening: Method validation and one-year prevalence study, Forensic Sci. Int. 318 (2021) 110595. https://doi.org/10.1016/j.forsciint.2020.110595.
  40. S.E. Hadland, S. Levy, Objective Testing, Child Adolesc. Psychiatr. Clin. N. Am. 25 (2016) 549–565. https://doi.org/10.1016/j.chc.2016.02.005.
  41. J.J. Palamar, A. Le, H. Guarino, P. Mateu-Gelabert, A comparison of the utility of urine- and hair testing in detecting self-reported drug use among young adult opioid users, Drug Alcohol Depend. 200 (2019). https://doi.org/10.1016/j.drugalcdep.2019.04.008.
  42. J. Musiał, J. Powierska-Czarny, J. Czarny, M. Raczkowski, N. Galant, B. Buszewski, R. Gadzała-Kopciuch, One-step extraction and determination of 513 psychoactive substances, drugs, and their metabolites from hair by LC–MS/MS, Arch. Toxicol. 96 (2022) 2927–2933. https://doi.org/10.1007/s00204-022-03343-w.
  43. J. Rubicondo, L. Scuffi, L. Pietrosemoli, M. Mineo, F. Terranova, M. Bartucca, C. Trignano, E. Bertol, F. Vaiano, A New Multi-Analyte LC–MS-MS Screening Method for the Detection of 120 NPSs and 49 Drugs in Hair, J. Anal. Toxicol. 46 (2023) e262–e273. https://doi.org/10.1093/jat/bkac093.
  44. J.M. Matey, M.D. Moreno de Simon, C. García-Ruiz, G. Montalvo, A validated GC–MS method for ketamine and norketamine in hair and its use in authentic cases, Forensic Sci. Int. 301 (2019) 447–454. https://doi.org/10.1016/j.forsciint.2019.04.039.
  45. G. Musile, C. Palacio, M. Murari, S. Appolonova, F. Tagliaro, Development and Validation of a Rapid Method for Identification of New Synthetic Cannabinoids in Hair Based on High-Performance Liquid Chromatography–Ion Trap Mass Spectrometry Using a Simplified User Interface, J. Anal. Toxicol. 47 (2023) 72–80. https://doi.org/10.1093/jat/bkac027.
  46. T. Gicquel, C. Richeval, V. Mesli, A. Gish, F. Hakim, R. Pelletier, R. Cornez, A. Balgairies, D. Allorge, J. Gaulier, Fatal intoxication related to two new arylcyclohexylamine derivatives (2F-DCK and 3-MeO-PCE), Forensic Sci. Int. 324 (2021) 110852. https://doi.org/10.1016/j.forsciint.2021.110852.
  47. A. Salomone, D. Di Corcia, P. Negri, M. Kolia, E. Amante, E. Gerace, M. Vincenti, Targeted and untargeted detection of fentanyl analogues and their metabolites in hair by means of UHPLC-QTOF-HRMS, Anal. Bioanal. Chem. 413 (2021) 225–233. https://doi.org/10.1007/s00216-020-02994-x.
  48. S. Mestria, S. Odoardi, G. Biosa, V. Valentini, G. Di Masi, F. Cittadini, S. Strano-Rossi, Method development for the identification of methoxpropamine, 2-fluoro-deschloroketamine and deschloroketamine and their main metabolites in blood and hair and forensic application, Forensic Sci. Int. 323 (2021) 110817. https://doi.org/10.1016/j.forsciint.2021.110817.
  49. N. La Maida, G. Mannocchi, S. Pichini, G. Basile, A. Di Giorgi, F.P. Busardò, E. Marchei, Targeted screening and quantification of synthetic cathinones and metabolites in hair by UHPLC-HRMS, Eur. Rev. Med. Pharmacol. Sci. 26 (2022) 5033–5042. https://doi.org/10.26355/eurrev_202207_29289.
  50. F. Pragst, M.A. Balikova, State of the art in hair analysis for detection of drug and alcohol abuse, Clin. Chim. Acta. 370 (2006) 17–49. https://doi.org/10.1016/j.cca.2006.02.019.
  51. V.A. Boumba, K.S. Ziavrou, T. Vougiouklakis, Hair as a Biological Indicator of Drug Use, Drug Abuse or Chronic Exposure to Environmental Toxicants, Int. J. Toxicol. 25 (2006) 143–163. https://doi.org/10.1080/10915810600683028.
  52. P. Kintz, Hair analysis in forensic toxicology, WIREs Forensic Sci. 1 (2019). https://doi.org/10.1002/wfs2.1196.
  53. P. Fernández, M. Regenjo, A. Ares, A.M. Fernández, R.A. Lorenzo, A.M. Carro, Simultaneous determination of 20 drugs of abuse in oral fluid using ultrasound-assisted dispersive liquid–liquid microextraction, Anal. Bioanal. Chem. 411 (2019) 193–203. https://doi.org/10.1007/s00216-018-1428-5.
  54. A. Sorribes-Soriano, F.A. Esteve-Turrillas, S. Armenta, P. Amorós, J.M. Herrero-Martínez, Amphetamine-type stimulants analysis in oral fluid based on molecularly imprinting extraction, Anal. Chim. Acta. 1052 (2019) 73–83. https://doi.org/10.1016/j.aca.2018.11.046.
  55. A. Sorribes-Soriano, A. Monedero, F.A. Esteve-Turrillas, S. Armenta, Determination of the new psychoactive substance dichloropane in saliva by microextraction by packed sorbent – Ion mobility spectrometry, J. Chromatogr. A. 1603 (2019) 61–66. https://doi.org/10.1016/j.chroma.2019.06.054.
  56. M.A. Huestis, S.D. Brandt, S. Rana, V. Auwärter, M.H. Baumann, Impact of Novel Psychoactive Substances on Clinical and Forensic Toxicology and Global Public Health, Clin. Chem. 63 (2017) 1564–1569. https://doi.org/10.1373/clinchem.2017.274662.
  57. S. Graziano, L. Anzillotti, G. Mannocchi, S. Pichini, F.P. Busardò, Screening methods for rapid determination of new psychoactive substances (NPS) in conventional and non-conventional biological matrices, J. Pharm. Biomed. Anal. 163 (2019) 170–179. https://doi.org/10.1016/j.jpba.2018.10.011.
  58. J. Gareri, J. Klein, G. Koren, Drugs of abuse testing in meconium, Clin. Chim. Acta. 366 (2006) 101–111. https://doi.org/10.1016/j.cca.2005.10.028.
  59. T.R. Gray, T. Kelly, L.L. LaGasse, L.M. Smith, C. Derauf, W. Haning, P. Grant, R. Shah, A. Arria, A. Strauss, B.M. Lester, M.A. Huestis, Novel Biomarkers of Prenatal Methamphetamine Exposure in Human Meconium, Ther. Drug Monit. 31 (2009) 70–75. https://doi.org/10.1097/FTD.0b013e318195d7cb.
  60. Á. López-Rabuñal, E. Lendoiro, M. Concheiro, M. López-Rivadulla, A. Cruz, A. De-Castro-Ríos, A LC-MS/MS method for the determination of common synthetic cathinones in meconium, J. Chromatogr. B. 1124 (2019) 349–355. https://doi.org/10.1016/j.jchromb.2019.06.030.
  61. E. Gallardo, J.A. Queiroz, The role of alternative specimens in toxicological analysis, Biomed. Chromatogr. 22 (2008) 795–821. https://doi.org/10.1002/bmc.1009.
  62. I. Zelner, J.R. Hutson, B.M. Kapur, D.S. Feig, G. Koren, False‐Positive Meconium Test Results for Fatty Acid Ethyl Esters Secondary to Delayed Sample Collection, Alcohol. Clin. Exp. Res. 36 (2012) 1497–1506. https://doi.org/10.1111/j.1530-0277.2012.01763.x.
  63. P. Liu, W. Liu, H. Qiao, S. Jiang, Y. Wang, J. Chen, M. Su, B. Di, Simultaneous quantification of 106 drugs or their metabolites in nail samples by UPLC-MS/MS with high-throughput sample preparation: Application to 294 real cases, Anal. Chim. Acta. 1226 (2022) 340170. https://doi.org/10.1016/j.aca.2022.340170.
  64. M.E.C. Queiroz, I.D. de Souza, Sample preparation techniques for biological samples, Sci. Chromatogr. 10 (2018). https://doi.org/10.5935/sc.2018.011.
  65. D. Pasin, A. Cawley, S. Bidny, S. Fu, Current applications of high-resolution mass spectrometry for the analysis of new psychoactive substances: a critical review, Anal. Bioanal. Chem. 409 (2017). https://doi.org/10.1007/s00216-017-0441-4.
  66. S.-Y. Fan, C.-Z. Zang, P.-H. Shih, Y.-C. Ko, Y.-H. Hsu, M.-C. Lin, S.-H. Tseng, D.-Y. Wang, A LC-MS/MS method for determination of 73 synthetic cathinones and related metabolites in urine, Forensic Sci. Int. 315 (2020) 110429. https://doi.org/10.1016/j.forsciint.2020.110429.
  67. Y. Lin, J. Sun, M. Tang, G. Zhang, L. Yu, X. Zhao, R. Ai, H. Yu, B. Shao, Y. He, Synergistic Recognition-Triggered Charge Transfer Enables Rapid Visual Colorimetric Detection of Fentanyl, Anal. Chem. 93 (2021) 6544–6550. https://doi.org/10.1021/acs.analchem.1c00723.
  68. M. Cláudia, A. Pedro, R. Tiago, C.R. Francisco, G. Eugenia, Determination of New Psychoactive Substances in Whole Blood Using Microwave Fast Derivatization and Gas Chromatography/Mass Spectrometry, J. Anal. Toxicol. 44 (2019) 92–102. https://doi.org/10.1093/jat/bkz053.
  69. J.M. Matey, A. López-Fernández, C. García-Ruiz, G. Montalvo, M.D. Moreno, M.A. Martínez, Potential of High-Resolution Mass Spectrometry for the Detection of Drugs and Metabolites in Hair: Methoxetamine in a Real Forensic Case, J. Anal. Toxicol. 46 (2022) e1–e10. https://doi.org/10.1093/jat/bkaa168.
  70. E.M.L. Goh, X.Q. Ng, C.Y. Yong, A. Hamzah, H.Y. Moy, Qualitative Confirmation of 94 New Psychoactive Substances and Metabolites in Urine Using Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry, J. Anal. Toxicol. 00 (2023). https://doi.org/10.1093/jat/bkad006.
  71. S. Souverain, S. Rudaz, J.-L. Veuthey, Protein precipitation for the analysis of a drug cocktail in plasma by LC–ESI–MS, J. Pharm. Biomed. Anal. 35 (2004) 913–920. https://doi.org/10.1016/j.jpba.2004.03.005.
  72. J. Sánchez-González, S. Odoardi, A.M. Bermejo, P. Bermejo-Barrera, F.S. Romolo, A. Moreda-Piñeiro, S. Strano-Rossi, HPLC-MS/MS combined with membrane-protected molecularly imprinted polymer micro-solid-phase extraction for synthetic cathinones monitoring in urine, Drug Test. Anal. 11 (2019) 33–44. https://doi.org/10.1002/dta.2448.
  73. N. Li, T. Zhang, G. Chen, J. Xu, G. Ouyang, F. Zhu, Recent advances in sample preparation techniques for quantitative detection of pharmaceuticals in biological samples, TrAC Trends Anal. Chem. 142 (2021) 116318. https://doi.org/10.1016/j.trac.2021.116318.
  74. J.M. Kokosa, A. Przyjazny, Green microextraction methodologies for sample preparations, Green Anal. Chem. 3 (2022). https://doi.org/10.1016/j.greeac.2022.100023.
  75. E. Tomczak, M.K. Woźniak, M. Kata, M. Wiergowski, B. Szpiech, M. Biziuk, Blood concentrations of a new psychoactive substance 4-chloromethcathinone (4-CMC) determined in 15 forensic cases, Forensic Toxicol. 36 (2018) 476–485. https://doi.org/10.1007/s11419-018-0427-8.
  76. S. Turfus, L.N. Rodda, High Performance Liquid Chromatography and Ultra‐High Performance Liquid Chromatography Including Liquid Chromatography–Mass Spectrometry, in: Anal. Tech. Forensic Sci., Wiley, 2021: pp. 365–405. https://doi.org/10.1002/9781119373421.ch14.
  77. B.S. Martins, M.F. de Oliveira, Química forense experimental, Ed. Cengage Learn. São Paulo. (2016).
  78. S. Júlio, R.A. Ferro, S. Santos, A. Alexandre, M.J. Caldeira, J. Franco, M. Barroso, H. Gaspar, Synthesis of emerging cathinones and validation of a SPE GC–MS method for their simultaneous quantification in blood, Anal. Bioanal. Chem. 415 (2023) 571–589. https://doi.org/10.1007/s00216-022-04440-6.
  79. A.Y. Simão, M. Antunes, H. Marques, T. Rosado, S. Soares, J. Gonçalves, M. Barroso, M. Andraus, E. Gallardo, Recent bionalytical methods for the determination of new psychoactive substances in biological specimens, Bioanalysis. 12 (2020) 1557–1595. https://doi.org/10.4155/bio-2020-0148.
  80. J.Y. Kim, S. Suh, J. Park, M.K. In, Simultaneous Determination of Amphetamine-Related New Psychoactive Substances in Urine by Gas Chromatography–Mass Spectrometry†, J. Anal. Toxicol. 42 (2018) 605–616. https://doi.org/10.1093/jat/bky037.
  81. W.-H. Hsu, K.-W. Cheng, T.-H. Feng, J.-Y. Chen, G.-Y. Chen, L.-Y. Chen, T. Weng, C.-C. Hsu, Rapid Screening of New Psychoactive Substances Using pDART-QqQ-MS, J. Am. Soc. Mass Spectrom. 35 (2024) 1370–1376. https://doi.org/10.1021/jasms.4c00124.
  82. J. Ji, Y. Zhang, Y. Zhang, J. Chang, A. Wang, H. Zhou, Y. Liu, J. Wang, Direct analysis in real‐time tandem mass spectrometry method for the rapid screening of 11 new psychoactive substances in blood and urine, Rapid Commun. Mass Spectrom. 37 (2023) 1–11. https://doi.org/10.1002/rcm.9515.
  83. Agência Nacional de Vigilância Sanitária - Anvisa, Relatório: novas drogas proibidas e controladas, (n.d.). https://www.gov.br/anvisa/pt-br/assuntos/noticias-anvisa/2019/relatorio-novas-drogas-proibidas-e-controladas.
  84. Agência Nacional de Vigilância Sanitária - Anvisa, Lista de substâncias sujeitas a controle especial no Brasil, (n.d.). https://www.gov.br/anvisa/pt-br/assuntos/medicamentos/controlados/lista-substancias (accessed May 5, 2025).
  85. C. Miliano, G. Margiani, L. Fattore, M.A. De Luca, Sales and advertising channels of new psychoactive substances (NPS): Internet, social networks, and smartphone apps, Brain Sci. 8 (2018). https://doi.org/10.3390/brainsci8070123.
  86. F. Schifano, A. Albanese, S. Fergus, J.L. Stair, P. Deluca, O. Corazza, Z. Davey, J. Corkery, H. Siemann, N. Scherbaum, M. Farre’, M. Torrens, Z. Demetrovics, A.H. Ghodse, L. Di Furia, L. Flesland, M. Mannonen, A. Majava, S. Pagani, T. Peltoniemi, M. Pasinetti, C. Pezzolesi, A. Skutle, P. Van Der Kreeft, A. Enea, G. Di Melchiorre, H. Shapiro, E. Sferrazza, C. Drummond, A. Pisarska, B. Mervo, J. Moskalewicz, L. Floridi, L.S.Y. Haugen, Mephedrone (4-methylmethcathinone; ’Meow meow’): Chemical, pharmacological and clinical issues, Psychopharmacology (Berl). 214 (2011). https://doi.org/10.1007/s00213-010-2070-x.
  87. E. Papaseit, E. Olesti, R. de la Torre, M. Torrens, M. Farre, Mephedrone Concentrations in Cases of Clinical Intoxication, Curr. Pharm. Des. 23 (2018). https://doi.org/10.2174/1381612823666170704130213.
  88. E. Olesti, M. Pujadas, E. Papaseit, C. Pérez-Mañá, Ó.J. Pozo, M. Farré, R. de la Torre, GC–MS Quantification Method for Mephedrone in Plasma and Urine: Application to Human Pharmacokinetics, J. Anal. Toxicol. 41 (2016). https://doi.org/10.1093/jat/bkw120.
  89. C.L. German, A.E. Fleckenstein, G.R. Hanson, Bath salts and synthetic cathinones: An emerging designer drug phenomenon, Life Sci. 97 (2014). https://doi.org/10.1016/j.lfs.2013.07.023.
  90. L.A. Nisbet, F.M. Wylie, B.K. Logan, K.S. Scott, Gas Chromatography-Mass Spectrometry Method for the Quantitative Identification of 23 New Psychoactive Substances in Blood and Urine, J. Anal. Toxicol. 43 (2019) 346–352. https://doi.org/10.1093/jat/bky109.
  91. A. Stachniuk, E. Fornal, Liquid Chromatography-Mass Spectrometry in the Analysis of Pesticide Residues in Food, Food Anal. Methods. 9 (2016) 1654–1665. https://doi.org/10.1007/s12161-015-0342-0.
  92. M. Ilić, M. Ačanski, K. Pastor, L. Popović, S. Jovanović-Šanta, New challenge in the lipophilicity determination and separation of biologically active 16,17-secoesterone derivatives by HPLC–Use of pentafluorophenyl-propyl column, J. Liq. Chromatogr. Relat. Technol. 43 (2020). https://doi.org/10.1080/10826076.2019.1674662.
  93. F. Vincenti, A. Gregori, M. Flammini, F. Di Rosa, A. Salomone, Seizures of New Psychoactive Substances on the Italian territory during the COVID-19 pandemic, Forensic Sci. Int. 326 (2021) 110904. https://doi.org/10.1016/j.forsciint.2021.110904.
  94. G.L. Losacco, J.L. Veuthey, D. Guillarme, Supercritical fluid chromatography – Mass spectrometry: Recent evolution and current trends, TrAC - Trends Anal. Chem. 118 (2019). https://doi.org/10.1016/j.trac.2019.07.005.
  95. Š. Zupančič, Z. Lavrič, J. Kristl, Stability and solubility of trans-resveratrol are strongly influenced by pH and temperature, Eur. J. Pharm. Biopharm. 93 (2015) 196–204. https://doi.org/10.1016/j.ejpb.2015.04.002.
  96. Y. Iwasaki, T. Sawada, K. Hatayama, A. Ohyagi, Y. Tsukuda, K. Namekawa, R. Ito, K. Saito, H. Nakazawa, Separation Technique for the Determination of Highly Polar Metabolites in Biological Samples, Metabolites. 2 (2012) 496–515. https://doi.org/10.3390/metabo2030496.
  97. EMCDDA, EU Drug Markets Report 2019, (2019). https://www.emcdda.europa.eu/publications/joint-publications/eu-drug-markets-report-2019_en (accessed April 19, 2022).
  98. M.K. Gupta, A. Ghuge, M. Parab, Y. Al-Refaei, A. Khandare, N. Dand, N. Waghmare, A comparative review on High-Performance Liquid Chromatography (HPLC), Ultra Performance Liquid Chromatography (UPLC) & High-Performance Thin Layer Chromatography (HPTLC) with current updates, Curr. Issues Pharm. Med. Sci. 35 (2022) 224–228. https://doi.org/10.2478/cipms-2022-0039.
  99. M. Pellegrini, E. Marchei, E. Papaseit, M. Farré, S. Zaami, Uhplc-hrms and gc-ms screening of a selection of synthetic cannabinoids and metabolites in urine of consumers, Med. 56 (2020). https://doi.org/10.3390/medicina56080408.
  100. A. Garcia-Romeu, B. Kersgaard, P.H. Addy, Clinical applications of hallucinogens: A review., Exp. Clin. Psychopharmacol. 24 (2016) 229–268. https://doi.org/10.1037/pha0000084.
  101. C. K., N. R., B. D., Club drugs: Review of the “rave” with a note of concern for the Indian scenario, Indian J. Med. Res. 133 (2011).
  102. H. Helena, V. Ivona, Ř. Roman, F. František, Current applications of capillary electrophoresis‐mass spectrometry for the analysis of biologically important analytes in urine (2017 to mid‐2021): A review, J. Sep. Sci. 45 (2022) 305–324. https://doi.org/10.1002/jssc.202100621.
  103. A.A. Aldubayyan, E. Castrignanò, S. Elliott, V. Abbate, Influence of long-term storage temperatures and sodium fluoride preservation on the stability of synthetic cathinones and dihydro-metabolites in human whole blood, Forensic Toxicol. 41 (2023) 81–93. https://doi.org/10.1007/s11419-022-00634-w.
  104. R. Barone, G. Pelletti, A. Giorgetti, S. Mohamed, J.P. Pascali, S. Sablone, F. Introna, S. Pelotti, Validation and application of a method for the quantification of 137 drugs of abuse and new psychoactive substances in hair, J. Pharm. Biomed. Anal. 243 (2024) 116054. https://doi.org/10.1016/j.jpba.2024.116054.
  105. R. Barone, A. Giorgetti, R. Cardella, F. Rossi, M. Garagnani, J.P. Pascali, S. Mohamed, P. Fais, G. Pelletti, Development and validation of a fast UPLC-MS/MS screening method for the detection of 68 psychoactive drugs and metabolites in whole blood and application to post-mortem cases, J. Pharm. Biomed. Anal. 228 (2023) 115315. https://doi.org/10.1016/j.jpba.2023.115315.
  106. C. Guo, H. Yan, W. Liu, P. Xiang, B. Di, M. Shen, Liquid chromatography with tandem mass spectrometric method for determination of 425 drugs and poisons in dried blood spots and application to forensic cases, Forensic Toxicol. 41 (2023) 241–248. https://doi.org/10.1007/s11419-023-00659-9.
  107. H.-W. Chen, H.-T. Liu, Y.-N. Kuo, D.-P. Yang, T.-T. Ting, J.-H. Chen, J.-Y. Chiu, Y.-C. Jair, H.-C. Li, P.-J. Chiang, W.-R. Chen, M.-C. Lin, Y.-H. Hsu, P.-S. Chen, Rapid and sensitive dilute-and-shoot analysis using LC-MS-MS for identification of multi-class psychoactive substances in human urine, J. Pharm. Biomed. Anal. 233 (2023) 115443. https://doi.org/10.1016/j.jpba.2023.115443.
  108. A.L. Fabris, A.F. Martins, J.L. Costa, M. Yonamine, A new application of the switchable hydrophilicity solvent-based homogenous liquid–liquid microextraction to analyze synthetic cannabinoids in plasma by LC-MS/MS, J. Pharm. Biomed. Anal. 234 (2023) 115588. https://doi.org/10.1016/j.jpba.2023.115588.
  109. A.L. Fabris, R. Lanaro, J.L. Costa, M. Yonamine, Development of a Dispersive Liquid–Liquid Microextraction for Synthetic Cathinones in Biological Fluids Based on Principles of Green Analytical Toxicology, J. Anal. Toxicol. 47 (2023) 353–365. https://doi.org/10.1093/jat/bkad003.
  110. A.L. Fabris, S. Pedersen-Bjergaard, E.L. Øiestad, G.N. Rossi, J.E.C. Hallak, R.G. dos Santos, J.L. Costa, M. Yonamine, Solvent-free parallel artificial liquid membrane extraction for drugs of abuse in plasma samples using LC-MS/MS, Anal. Chim. Acta. 1301 (2024) 342387. https://doi.org/10.1016/j.aca.2024.342387.
  111. G. Di Francesco, F. Vincenti, C. Montesano, I. Bracaglia, M. Croce, S. Napoletano, A. Lombardozzi, M. Sergi, Target and suspect screening of psychoactive substances in seizures and oral fluid exploiting retention time prediction and LC-MS/MS analysis, Anal. Chim. Acta. 1303 (2024) 342529. https://doi.org/10.1016/j.aca.2024.342529.
  112. P. García-Atienza, H. Martínez-Pérez-Cejuela, E.F. Simó-Alfonso, J.M. Herrero-Martínez, S. Armenta, Determination of synthetic cannabinoids in oral fluids by liquid chromatography with fluorescence detection after solid-phase extraction, MethodsX. 10 (2023) 102173. https://doi.org/10.1016/j.mex.2023.102173.
  113. Y. Huang, W. Jia, Y. Chen, C. Liu, S. Liu, M. Su, Z. Hua, A comprehensive analytical strategy based on characteristic fragments to detect synthetic cannabinoid analogs in seized products and hair samples, Talanta. 265 (2023) 124830. https://doi.org/10.1016/j.talanta.2023.124830.
  114. J.-N. Kleis, C. Hess, T. Germerott, J. Roehrich, Sensitive Screening of New Psychoactive Substances in Serum Using Liquid Chromatography–Quadrupole Time-of-Flight Mass Spectrometry, J. Anal. Toxicol. 46 (2022) 592–599. https://doi.org/10.1093/jat/bkab072.
  115. J. Kutzler, A.E. Polettini, S. Bleicher, C. Sauer, W. Schultis, M.A. Neukamm, V. Auwärter, Synthetic cannabinoids in hair—Prevalence of use in abstinence control programs for driver’s license regranting in Germany, Drug Test. Anal. 16 (2024) 518–531. https://doi.org/10.1002/dta.3578.
  116. E. Lesne, M. Muñoz-Bartual, F.A. Esteve-Turrillas, Determination of synthetic hallucinogens in oral fluids by microextraction by packed sorbent and liquid chromatography–tandem mass spectrometry, Anal. Bioanal. Chem. 415 (2023). https://doi.org/10.1007/s00216-023-04751-2.
  117. F. Machado, J. Franco, D.N. Vieira, C. Margalho, Development and Validation of a GC–MS-EI Method to Determine α-PHP in Blood: Application to Samples Collected during Medico-Legal Autopsies, J. Anal. Toxicol. 47 (2023) 271–279. https://doi.org/10.1093/jat/bkac104.
  118. M. Massano, C. Incardona, E. Gerace, P. Negri, E. Alladio, A. Salomone, M. Vincenti, Development and validation of a UHPLC-HRMS-QTOF method for the detection of 132 New Psychoactive Substances and synthetic opioids, including fentanyl, in Dried Blood Spots, Talanta. 241 (2022) 123265. https://doi.org/10.1016/j.talanta.2022.123265.
  119. J.P. Pascali, S. Dagoli, M. Antonioni, O. Facetti, L. Anzillotti, L. Calò, G.F. Affini, B. Cantarelli, R. Cecchi, Oral fluid analysis to monitor recent exposure to synthetic cannabinoids in a high‐risk subpopulation, J. Forensic Sci. 67 (2022) 1932–1937. https://doi.org/10.1111/1556-4029.15067.
  120. A. Salomone, M. Galletto, M. Massano, D. Di Corcia, J.J. Palamar, M. Vincenti, Detection of fentanyl, synthetic opioids, and ketamine in hair specimens from purposive samples of American and Italian populations, J. Forensic Sci. 68 (2023) 1698–1707. https://doi.org/10.1111/1556-4029.15348.
  121. M. Schüller, I. Lucic, Å.M.L. Øiestad, S. Pedersen-Bjergaard, E.L. Øiestad, High-throughput quantification of emerging “nitazene” benzimidazole opioid analogs by microextraction and UHPLC–MS-MS, J. Anal. Toxicol. 47 (2023) 787–796. https://doi.org/10.1093/jat/bkad071.
  122. A.Y. Simão, P. Oliveira, L.M. Rosendo, T. Rosado, M. Andraus, M. Barroso, E. Gallardo, Microextraction by Packed Sorbent as a Clean-up Approach for the Determination of Ketamine and Norketamine in Hair by Gas Chromatography--Tandem Mass Spectrometry, J. Anal. Toxicol. 47 (2023) 227–235. https://doi.org/10.1093/jat/bkac075.
  123. S.E. Walton, A.J. Krotulski, B.K. Logan, A Forward-Thinking Approach to Addressing the New Synthetic Opioid 2-Benzylbenzimidazole Nitazene Analogs by Liquid Chromatography–Tandem Quadrupole Mass Spectrometry (LC–QQQ-MS), J. Anal. Toxicol. 46 (2022) 221–231. https://doi.org/10.1093/jat/bkab117.
  124. C.-A. Yang, H.-C. Liu, R.H. Liu, D.-L. Lin, S.-P. Wu, Simultaneous Quantitation of Seven Phenethylamine-Type Drugs in Forensic Blood and Urine Samples by UHPLC–MS-MS, J. Anal. Toxicol. 46 (2022) 246–256. https://doi.org/10.1093/jat/bkab014.
  125. Y. Yang, B. Xu, D. Li, Q. Zhang, J. Zhang, L. Yang, Y. Ye, A comprehensive LC-MS/MS method for simultaneous analysis of 65 synthetic cannabinoids in human hair samples and application to forensic investigations, J. Forensic Leg. Med. 101 (2024) 102636. https://doi.org/10.1016/j.jflm.2023.102636.
  126. Y. Te Yen, S.L. Zhou, D.Y. Huang, S.H. Tseng, C.F. Wang, S.C. Chyueh, 2-Methyl-4’-(methylthio)-2-morpholinopropiophenone: A commercial photoinitiator being used as a new psychoactive substance, Forensic Sci. Int. 360 (2024) 112074. https://doi.org/10.1016/j.forsciint.2024.112074.
  127. W. Zhai, Z. Qiao, P. Xiang, Y. Dang, Y. Shi, A UPLC-MS/MS methodological approach for the analysis of 75 phenethylamines and their derivatives in hair, J. Pharm. Biomed. Anal. 229 (2023) 115367. https://doi.org/10.1016/j.jpba.2023.115367.
  128. L. Zhao, M. Qin, G. Wu, Y. Zhou, J. Zhu, H. Peng, Quantitative determination of amphetamine-type stimulants in sewage and urine by hybrid monolithic column solid-phase microextraction coupled with UPLC-QTRAP MS/MS, Talanta. 269 (2024) 125437. https://doi.org/10.1016/j.talanta.2023.125437.
  129. J.B. Zawilska, M. Kacela, P. Adamowicz, NBOMes–Highly Potent and Toxic Alternatives of LSD, Front. Neurosci. 14 (2020). https://doi.org/10.3389/fnins.2020.00078.
  130. J.D. Martinez, E. Arrieta, A. Naranjo, P. Monsalve, K.J. Mintz, J. Peterson, A. Arboleda, H. Durkee, M.C. Aguilar, D. Pelaez, S.R. Dubovy, D. Miller, R. Leblanc, G. Amescua, J.M. Parel, Rose Bengal Photodynamic Antimicrobial Therapy: A Pilot Safety Study, Cornea. 40 (2021). https://doi.org/10.1097/ICO.0000000000002717.
  131. V. Vescovi, W. Kopp, J.M. Guisán, R.L.C. Giordano, A.A. Mendes, P.W. Tardioli, Improved catalytic properties of Candida antarctica lipase B multi-attached on tailor-made hydrophobic silica containing octyl and multifunctional amino- glutaraldehyde spacer arms, Process Biochem. 51 (2016). https://doi.org/10.1016/j.procbio.2016.09.016.
  132. R. Solimini, M.C. Rotolo, M. Pellegrini, A. Minutillo, R. Pacifici, F.P. Busardò, S. Zaami, Adulteration Practices of Psychoactive Illicit Drugs: An Updated Review, Curr. Pharm. Biotechnol. 18 (2017). https://doi.org/10.2174/1389201018666170710184531.
  133. E. Sanabria, R.E. Cuenca, M.Á. Esteso, M. Maldonado, Benzodiazepines: Their use either as essential medicines or as toxics substances, Toxics. 9 (2021). https://doi.org/10.3390/toxics9020025.
  134. C. Springs, ANSI/ASB Standard 036, 1st Ed. 2019, (2019). ANSI/ASB Standard 036, First Edition 2019 - https://www.aafs.org/sites/default/files/media/documents/036_Std_e1.pdf.

Creative Commons License

Este trabalho está licenciado sob uma licença Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Copyright (c) 2025 Revista Brasileira de Criminalística

Compartilhe

Autor(es)