{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:37:40Z","timestamp":1784205460372,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T00:00:00Z","timestamp":1609113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"Presidency of the Ministers Council, Department of Antidrug Policy","award":["F75J18000390005"],"award-info":[{"award-number":["F75J18000390005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>For more than ten years, new synthetic cathinones (SCs) mimicking the effects of controlled cocaine-like stimulants have flooded the illegal drug market, causing numerous intoxications and fatalities. There are often no data on the pharmacokinetics of these substances when they first emerge onto the market. However, the detection of SC metabolites is often critical in order to prove consumption in clinical and forensic settings. In this research, the metabolite profile of two pyrrolidinyl SCs, \u03b1-pyrrolidinohexaphenone (\u03b1-PHP) and 4\u2032\u2032-fluoro-\u03b1-pyrrolidinovalerophenone (4F-\u03b1-PVP), were characterized to identify optimal intake markers. Experiments were conducted using pooled human hepatocyte incubations followed by liquid chromatography\u2013high-resolution tandem mass spectrometry and data-mining software. We suggest \u03b1-PHP dihydroxy-pyrrolidinyl, \u03b1-PHP hexanol, \u03b1-PHP 2\u2032-keto-pyrrolidinyl-hexanol, and \u03b1-PHP 2\u2032-keto-pyrrolidinyl as markers of \u03b1-PHP use, and 4F-\u03b1-PVP dihydroxy-pyrrolidinyl, 4F-\u03b1-PVP hexanol, 4F-\u03b1-PVP 2\u2032-keto-pyrrolidinyl-hexanol, and 4F-\u03b1-PVP 2\u2032-keto-pyrrolidinyl as markers of 4F-\u03b1-PVP use. These results represent the first data available on 4F-\u03b1-PVP metabolism. The metabolic fate of \u03b1-PHP was previously studied using human liver microsomes and urine samples from \u03b1-PHP users. We identified an additional major metabolite (\u03b1-PHP dihydroxy-pyrrolidinyl) that might be crucial for documenting exposure to \u03b1-PHP. Further experiments with suitable analytical standards, which are yet to be synthesized, and authentic specimens should be conducted to confirm these results.<\/jats:p>","DOI":"10.3390\/ijms22010230","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T20:03:03Z","timestamp":1609185783000},"page":"230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Pyrrolidinyl Synthetic Cathinones \u03b1-PHP and 4F-\u03b1-PVP Metabolite Profiling Using Human Hepatocyte Incubations"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-9518","authenticated-orcid":false,"given":"Jeremy","family":"Carlier","sequence":"first","affiliation":[{"name":"Chemistry &amp; Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA"},{"name":"Department of Excellence of Biomedical Sciences and Public Health, Unit of Forensic Toxicology, Section of Legal Medicine, Marche Polytechnic University, 60126 Ancona, Italy"},{"name":"Department of Anatomical, Histological, Unit of Forensic Toxicology, Section of Legal Medicine, Forensic, and Orthopedic Sciences, Sapienza University of Rome, 00198 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6892-0861","authenticated-orcid":false,"given":"Xingxing","family":"Diao","sequence":"additional","affiliation":[{"name":"Chemistry &amp; Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA"},{"name":"Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2399-0396","authenticated-orcid":false,"given":"Raffaele","family":"Giorgetti","sequence":"additional","affiliation":[{"name":"Department of Excellence of Biomedical Sciences and Public Health, Unit of Forensic Toxicology, Section of Legal Medicine, Marche Polytechnic University, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco P.","family":"Busard\u00f2","sequence":"additional","affiliation":[{"name":"Department of Excellence of Biomedical Sciences and Public Health, Unit of Forensic Toxicology, Section of Legal Medicine, Marche Polytechnic University, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2137-4645","authenticated-orcid":false,"given":"Marilyn A.","family":"Huestis","sequence":"additional","affiliation":[{"name":"Chemistry &amp; Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA"},{"name":"Institute of Emerging Health Professions, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,28]]},"reference":[{"key":"ref_1","first-page":"268","article-title":"Synthetic cathinones related fatalities: An update","volume":"22","author":"Zaami","year":"2018","journal-title":"Eur. 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