{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T15:16:02Z","timestamp":1780413362351,"version":"3.54.1"},"reference-count":46,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The analysis of psychoactive substances in hair is of great importance for both clinical and forensic toxicologists since it allows one to evaluate past and continuative exposure to xenobiotics. In particular, a new challenge is represented by new psychoactive substances: Among this new class of drugs of abuse, synthetic cathinone and phenethylamine derivatives are often detected in biological samples. Hence, there is a growing need to develop new analytical procedures or improve old ones in order to conduct evaluations of these emerging substances. This study is a systematic review of all the instrumental and experimental data available in the literature. A total of 32 articles were included in the review. Acidic solvents proved to be the most reliable solutions for extraction. Gas chromatography and liquid chromatography coupled to tandem mass spectrometric and high-resolution mass spectrometric systems represent the majority of the involved instrumental techniques. Sensitivity must be maintained at the pg\/mg level to detect any occurrences up to occasional consumption. In total, 23 out of 32 articles reported real positive samples. The most frequently detected substance in hair was mephedrone, followed by butylone, methylone, MDPV, and \u03b1-pyrrolidinophenone-type substances.<\/jats:p>","DOI":"10.3390\/molecules26206143","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T06:38:41Z","timestamp":1634107121000},"page":"6143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["New Synthetic Cathinones and Phenylethylamine Derivatives Analysis in Hair: A Review"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3419-3002","authenticated-orcid":false,"given":"Vittorio","family":"Bolcato","sequence":"first","affiliation":[{"name":"Legal Medicine and Forensic Sciences Unit, Department of Public Health, Experimental and Forensic Science, University of Pavia, Via C. Forlanini 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Carelli","sequence":"additional","affiliation":[{"name":"Legal Medicine and Forensic Sciences Unit, Department of Public Health, Experimental and Forensic Science, University of Pavia, Via C. Forlanini 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Radogna","sequence":"additional","affiliation":[{"name":"Legal Medicine and Forensic Sciences Unit, Department of Public Health, Experimental and Forensic Science, University of Pavia, Via C. Forlanini 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Freni","sequence":"additional","affiliation":[{"name":"Legal Medicine and Forensic Sciences Unit, Department of Public Health, Experimental and Forensic Science, University of Pavia, Via C. Forlanini 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7420-9366","authenticated-orcid":false,"given":"Matteo","family":"Moretti","sequence":"additional","affiliation":[{"name":"Legal Medicine and Forensic Sciences Unit, Department of Public Health, Experimental and Forensic Science, University of Pavia, Via C. Forlanini 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4584-5552","authenticated-orcid":false,"given":"Luca","family":"Morini","sequence":"additional","affiliation":[{"name":"Legal Medicine and Forensic Sciences Unit, Department of Public Health, Experimental and Forensic Science, University of Pavia, Via C. Forlanini 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"ref_1","unstructured":"(2021, October 03). European Drug Report 2021: Trends and Developments. Available online: https:\/\/www.emcdda.europa.eu\/publications\/edr\/trends-developments\/2021_en."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s11419-017-0385-6","article-title":"The newest cathinone derivatives as designer drugs: An analytical and toxicological review","volume":"36","author":"Majchrzak","year":"2018","journal-title":"Forensic Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.forsciint.2017.08.031","article-title":"The analysis of 132 novel psychoactive substances in human hair using a single step extraction by tandem LC\/MS","volume":"279","author":"Boumba","year":"2017","journal-title":"Forensic Sci. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s11419-019-00485-y","article-title":"Development and validation of a GC\u2013MS\/MS method for the determination of 11 amphetamines and 34 synthetic cathinones in whole blood","volume":"38","author":"Banaszkiewicz","year":"2020","journal-title":"Forensic Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s12024-019-00209-z","article-title":"Detection and quantification of synthetic cathinones and selected piperazines in hair by LC-MS\/MS","volume":"16","author":"Niebel","year":"2020","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_6","first-page":"663","article-title":"Recent Trends in Analytical Methods to Determine New Psychoactive Substances in Hair","volume":"15","author":"Kyriakou","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1093\/jat\/bkx020","article-title":"Hair testing for drugs of abuse and new psychoactive substances in a high-risk population","volume":"41","author":"Salomone","year":"2017","journal-title":"J. Anal. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.neuropharm.2017.10.016","article-title":"Fentanyl, fentanyl analogs and novel synthetic opioids: A comprehensive review","volume":"134","author":"Armenian","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/dta.2936","article-title":"Hair analysis can support the follow-up addiction care after acute New Psychoactive Substances intoxication: Illustration by two cases","volume":"13","author":"Richeval","year":"2021","journal-title":"Drug Test. Anal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/dta.1338","article-title":"Prevalence of new psychoactive substances: A retrospective study in hair","volume":"4","author":"Rust","year":"2012","journal-title":"Drug Test. Anal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"107508","DOI":"10.1016\/j.drugalcdep.2019.06.011","article-title":"Prevalence of New Psychoactive Substances (NPS) and conventional drugs of abuse (DOA) in high risk populations from Paris (France) and its suburbs: A cross sectional study by hair testing (2012\u20132017)","volume":"204","author":"Larabi","year":"2019","journal-title":"Drug Alcohol Depend."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1093\/jat\/bkaa007","article-title":"A Retrospective of Prevalence of Drugs of Abuse by Hair Analysis in Shanghai using LC-MS-MS","volume":"44","author":"Wang","year":"2020","journal-title":"J. Anal. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1002\/dta.2043","article-title":"Multi-class analysis of new psychoactive substances and metabolites in hair by pressurized liquid extraction coupled to HPLC-HRMS","volume":"9","author":"Montesano","year":"2017","journal-title":"Drug Test. Anal."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.chroma.2014.10.106","article-title":"Screening for new psychoactive substances in hair by ultrahigh performance liquid chromatography-electrospray ionization tandem mass spectrometry","volume":"1372","author":"Odoardi","year":"2014","journal-title":"J. Chromatogr. A"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.forsciint.2014.04.038","article-title":"Toxicological findings in a fatal multidrug intoxication involving mephedrone","volume":"243","author":"Gerace","year":"2014","journal-title":"Forensic Sci. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.forsciint.2011.10.016","article-title":"Evidence of mephedrone chronic abuse through hair analysis using GC\/MS","volume":"218","author":"Martin","year":"2012","journal-title":"Forensic Sci. Int."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kintz, P. (2016). Evidence of 2 Populations of Mephedrone Abusers by Hair Testing. Application to 4 Forensic Expertises. Curr. Neuropharmacol., 15.","DOI":"10.2174\/1570159X14666161026152107"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/978-1-4939-8579-1_10","article-title":"Analysis of Drugs of Abuse in Hair Samples by Ultrahigh-Performance Liquid Chromatography\u2013Tandem Mass Spectrometry (UHPLC-MS\/MS)","volume":"1810","author":"Salomone","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_19","unstructured":"(2020). Recommended Methods for the Identification and Analysis of Synthetic Cathinones in Seized Materials. Manual for Use by National Drug Analysis Laboratories, United Nations Office on Drugs and Crime. ST\/NAR\/49-Rev.1."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6274","DOI":"10.1016\/j.chroma.2010.08.001","article-title":"Analysis of phenylpiperazine-like stimulants in human hair as trimethylsilyl derivatives by gas chromatography-mass spectrometry","volume":"1217","author":"Barroso","year":"2010","journal-title":"J. Chromatogr. A"},{"key":"ref_21","first-page":"200","article-title":"Analysis of amphetamines and synthetic cathinones in hair samples using LC-tandem mass spectrometry and solid-phase extraction","volume":"32","author":"Elian","year":"2014","journal-title":"LCGC Eur."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"360348","DOI":"10.1016\/j.chroma.2019.07.002","article-title":"Combination of pressurized liquid extraction with dispersive liquid liquid micro extraction for the determination of sixty drugs of abuse in hair","volume":"1605","author":"Vincenti","year":"2019","journal-title":"J. Chromatogr. A"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.forsciint.2013.11.004","article-title":"Development and validation of a single LC-MS\/MS assay following SPE for simultaneous hair analysis of amphetamines, opiates, cocaine and metabolites","volume":"234","author":"Imbert","year":"2014","journal-title":"Forensic Sci. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/dta.1948","article-title":"An LC-MS\/MS methodological approach to the analysis of hair for amphetamine-type-stimulant (ATS) drugs, including selected synthetic cathinones and piperazines","volume":"9","author":"Lendoiro","year":"2017","journal-title":"Drug Test. Anal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1002\/rcm.3010","article-title":"Simultaneous determination of psychotropic phenylalkylamine derivatives in human hair by gas chromatography\/mass spectrometry","volume":"21","author":"Kim","year":"2007","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.forsciint.2016.01.039","article-title":"Detection of 3-methylmethcathinone and its metabolites 3-methylephedrine and 3-methylnorephedrine in pubic hair samples by liquid chromatography-high resolution\/high accuracy Orbitrap mass spectrometry","volume":"265","author":"Frison","year":"2016","journal-title":"Forensic Sci. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jchromb.2013.10.021","article-title":"Simple segmental hair analysis for \u03b1-pyrrolidinophenone-type designer drugs by MonoSpin extraction for evaluation of abuse history","volume":"942\u2013943","author":"Namera","year":"2013","journal-title":"J. Chromatogr. B"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1007\/s00216-015-9247-4","article-title":"Determination of cathinones and other stimulant, psychedelic, and dissociative designer drugs in real hair samples","volume":"408","author":"Salomone","year":"2016","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1093\/jat\/bkv054","article-title":"Simultaneous determination of 11 illicit phenethylamines in hair by LC-MS-MS: In vivo application","volume":"39","author":"Nieddu","year":"2015","journal-title":"J. Anal. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1093\/jat\/bkx053","article-title":"Application of a urine and hair validated LC-MS-MS method to determine the effect of hair color on the incorporation of 25B-NBOMe, 25C-NBOMe and 25I-NBOMe into hair in the rat","volume":"41","author":"Nisbet","year":"2017","journal-title":"J. Anal. Toxicol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5125","DOI":"10.1007\/s00216-020-02462-6","article-title":"Development and validation of fast UHPLC-MS\/MS screening method for 87 NPS and 32 other drugs of abuse in hair and nails: Application to real cases","volume":"412","author":"Mannocchi","year":"2020","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1093\/jat\/bky047","article-title":"Distribution of the synthetic cathinone \u03b1-pyrrolidinohexiophenone in biological specimens","volume":"43","author":"Vignali","year":"2019","journal-title":"J. Anal. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jpba.2011.11.026","article-title":"Quantitative analysis of mephedrone using liquid chromatography tandem mass spectroscopy: Application to human hair","volume":"61","author":"Shah","year":"2012","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.toxlet.2010.12.014","article-title":"Drugs for youth via Internet and the example of mephedrone","volume":"201","author":"Vardakou","year":"2011","journal-title":"Toxicol. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.forsciint.2019.02.036","article-title":"A multi-analyte LC\u2013MS\/MS method for screening and quantification of 16 synthetic cathinones in hair: Application to postmortem cases","volume":"298","author":"Freni","year":"2019","journal-title":"Forensic Sci. Int."},{"key":"ref_36","unstructured":"Kintz, P., Salomone, A., and Vincenti, M. (2015). Hair Analysis in Clinical and Forensic Toxicology, Academic Press\/Elsevier Science Ltd.. Chapter 11."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1093\/jat\/bkw058","article-title":"Fatal combination with 3-methylmethcathinone (3-MMC) and Gamma-Hydroxybutyric Acid (GHB)","volume":"40","author":"Jamey","year":"2016","journal-title":"J. Anal. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.forsciint.2016.11.028","article-title":"Identification and quantification of 4-methylethcathinone (4-MEC) and 3,4-methylenedioxypyrovalerone (MDPV) in hair by LC\u2013MS\/MS after chronic administration","volume":"270","author":"Alvarez","year":"2017","journal-title":"Forensic Sci. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e33","DOI":"10.1016\/j.forsciint.2014.10.027","article-title":"Neonatal withdrawal syndrome after chronic maternal consumption of 4-methylethcathinone","volume":"245","author":"Pichini","year":"2014","journal-title":"Forensic Sci. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1093\/jat\/bkt001","article-title":"Postmortem tissue distribution of MDPV following lethal intoxication by \u201cbath salts\u201d","volume":"37","author":"Wyman","year":"2013","journal-title":"J. Anal. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7831","DOI":"10.1007\/s00216-015-8955-0","article-title":"Metabolism of the new psychoactive substances N,N-diallyltryptamine (DALT) and 5-methoxy-DALT and their detectability in urine by GC\u2013MS, LC\u2013MS n, and LC\u2013HR\u2013MS\u2013MS","volume":"407","author":"Michely","year":"2015","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.drugpo.2017.07.010","article-title":"Hair testing to assess both known and unknown use of drugs amongst ecstasy users in the electronic dance music scene","volume":"48","author":"Palamar","year":"2017","journal-title":"Int. J. Drug Policy"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.forsciint.2019.05.004","article-title":"Ethyl glucuronide hair testing: A review","volume":"300","author":"Biondi","year":"2019","journal-title":"Forensic Sci. Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.forsciint.2009.11.005","article-title":"Effect of bleaching on ethyl glucuronide in hair: An in vitro experiment","volume":"198","author":"Morini","year":"2010","journal-title":"Forensic Sci. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s12024-007-0011-8","article-title":"Treatments against hair loss may hinder cocaine and metabolites detection","volume":"3","author":"Zucchella","year":"2007","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/20\/6143\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:11:58Z","timestamp":1760166718000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/20\/6143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,12]]},"references-count":46,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["molecules26206143"],"URL":"https:\/\/doi.org\/10.3390\/molecules26206143","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,12]]}}}