{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:42:11Z","timestamp":1790754131476,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,21]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\u03b1-Pyrrolidinohexiophenone (\u03b1-PHP) is a derivative of the class of \u03b1-pyrrolidinophenones, a subgroup of synthetic cathinones. These substances are the second most abused drugs of new psychoactive substances. Here, we report the toxicological investigation of a series of 29 authentic forensic and clinical cases with analytically confirmed intake of \u03b1-PHP including two cases of drug testing in newborns using meconium. The age range of subjects where serum samples were available was 23\u201351\u2009years (median 39.5), and 90% were male. Serum \u03b1-PHP concentrations, determined by a validated LC\u2013MS-MS method, showed a high variability ranging from 1 to 83\u2009ng\/mL (mean, 40\u2009ng\/mL; median, 36\u2009ng\/mL). Comprehensive toxicological analysis revealed co-consumption of other psychotropic drugs in almost all cases with frequent occurrence of opiates (60%), benzodiazepines (35%), cannabinoids (30%), and cocaine (20%). Hence, forensic and clinical symptoms like aggressive behavior, sweating, delayed physical response, and impaired balance could not be explained by the abuse of \u03b1-PHP alone but rather by poly-intoxications. Liquid chromatography-quadrupole time-of-flight mass spectrometry and gas chromatography-mass spectrometry were used to investigate the metabolism of \u03b1-PHP in vivo using authentic human urine samples. Altogether, 11 phase I metabolites and 5 phase II glucuronides could be identified by this approach. Apart from the parent drug, most abundant findings in urine were the metabolites dihydroxy-pyrrolidinyl-\u03b1-PHP and dihydro-\u03b1-PHP and, to a lesser extent, 2\u02b9-oxo-dihydro-\u03b1-PHP and 2\u02b9-oxo-\u03b1-PHP. Monitoring of these metabolites along with the parent drug in forensic and clinical toxicology could unambiguously prove the abuse of the novel designer drug \u03b1-PHP.<\/jats:p>","DOI":"10.1093\/jat\/bkac057","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T16:57:58Z","timestamp":1659545878000},"page":"162-174","source":"Crossref","is-referenced-by-count":21,"title":["Toxicological Investigation of a Case Series Involving the Synthetic Cathinone \u03b1-Pyrrolidinohexiophenone (\u03b1-PHP) and Identification of Phase I and II Metabolites in Human Urine"],"prefix":"10.1093","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9728-5767","authenticated-orcid":false,"given":"Marcel","family":"Grapp","sequence":"first","affiliation":[{"name":"Forensic Toxicological Laboratory, University Medical Center G\u00f6ttingen, Georg-August-University , Robert-Koch-Stra\u00dfe 40, G\u00f6ttingen 37075, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Forensic Toxicological Laboratory, University Medical Center G\u00f6ttingen, Georg-August-University , Robert-Koch-Stra\u00dfe 40, G\u00f6ttingen 37075, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannes M","family":"Schwelm","sequence":"additional","affiliation":[{"name":"Institute of Forensic Medicine, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg , Albertstr. 9, Freiburg 79104, Germany"},{"name":"Herrmann Staudinger Graduate School, University of Freiburg , Albertstr. 9, Freiburg 79104, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3826-2327","authenticated-orcid":false,"given":"Merja A","family":"Neukamm","sequence":"additional","affiliation":[{"name":"Institute of Forensic Medicine, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg , Albertstr. 9, Freiburg 79104, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"2023032310460285000_","volume-title":"European Drug Report 2021: Trends and Developments","author":"European Monitoring Centre for Drugs and Drug Addiction","year":"2021"},{"key":"2023032310460285000_","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/164_2018_178","article-title":"Neuropharmacology of synthetic cathinones","volume":"252","author":"Baumann","year":"2018","journal-title":"Handbook of Experimental Pharmacology"},{"key":"2023032310460285000_","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.annemergmed.2012.01.005","article-title":"Hyperthermia and multiorgan failure after abuse of \u201cbath salts\u201d containing 3,4-methylenedioxypyrovalerone","volume":"60","author":"Borek","year":"2012","journal-title":"Annals of Emergency Medicine"},{"key":"2023032310460285000_","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.amjmed.2012.02.019","article-title":"Psychoactive \u201cbath salts\u201d intoxication with methylenedioxypyrovalerone","volume":"125","author":"Ross","year":"2012","journal-title":"The American Journal of Medicine"},{"key":"2023032310460285000_","doi-asserted-by":"crossref","first-page":"499","DOI":"10.3109\/15563650.2011.590812","article-title":"Clinical experience with and analytical confirmation of \u201cbath salts\u201d and \u201clegal highs\u201d (synthetic cathinones) in the United States","volume":"49","author":"Spiller","year":"2011","journal-title":"Clinical Toxicology (Philadelphia, Pa.)"},{"key":"2023032310460285000_","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.neubiorev.2018.07.015","article-title":"Abuse potential and toxicity of the synthetic cathinones (i.e., \u201cbath salts\u201d)","volume":"110","author":"Riley","year":"2019","journal-title":"Neuroscience and Biobehavioral Reviews"},{"key":"2023032310460285000_","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.forsciint.2015.12.020","article-title":"GC-MS analysis of the designer drug \u03b1-pyrrolidinovalerophenone and its metabolites in urine and blood in an acute poisoning case","volume":"259","author":"Grapp","year":"2016","journal-title":"Forensic Science International"},{"key":"2023032310460285000_","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.forsciint.2009.05.001","article-title":"Mass and NMR spectroscopic characterization of 3,4-methylenedioxypyrovalerone: a designer drug with alpha-pyrrolidinophenone structure","volume":"190","author":"Westphal","year":"2009","journal-title":"Forensic Science International"},{"key":"2023032310460285000_","first-page":"1954","article-title":"Increased abuse of the Internet drug MDPV in V\u00e4stmanland. 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