{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T16:03:06Z","timestamp":1772726586404,"version":"3.50.1"},"reference-count":25,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T00:00:00Z","timestamp":1692057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Effetti delle NPS: Sviluppo di una multicentrica di ricerca per il potenziamento informativo del Sistema di Allerta Precoce"},{"name":"SNAP"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Anamorelin, developed for the treatment of cancer cachexia, is an orally active medication that improves appetite and food intake, thereby increasing body mass and physical functioning. It is classified as a growth hormone secretagogue and strictly monitored by the World Anti-Doping Agency (WADA), owing to its anabolic enhancing potential. Identifying anamorelin and\/or metabolite biomarkers of consumption is critical in doping controls. However, there are currently no data available on anamorelin human metabolic fate. The aim of this study was to investigate and identify biomarkers characteristic of anamorelin intake using in silico metabolite predictions with GLORYx, in vitro incubation with 10-donor-pooled human hepatocytes, liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS\/MS) analysis, and data processing with Thermo Scientific\u2019s Compound Discoverer. In silico prediction resulted in N-acetylation at the methylalanyl group as the main transformation (score, 88%). Others including hydroxylation at the indole substructure, and oxidation and N-demethylation at the trimethylhydrazino group were predicted (score, \u226436%). Hepatocyte incubations resulted in 14 phase I metabolites formed through N-demethylation at the trimethylhydrazino group, N-dealkylation at the piperidine ring, and oxidation at the indole and methylalanyl groups; and two phase II glucuronide conjugates occurring at the indole. We propose four metabolites detected as specific biomarkers for toxicological screening.<\/jats:p>","DOI":"10.3390\/metabo13080949","type":"journal-article","created":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T11:15:08Z","timestamp":1692098108000},"page":"949","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Metabolism Study of Anamorelin, a GHSR1a Receptor Agonist Potentially Misused in Sport, with Human Hepatocytes and LC-HRMS\/MS"],"prefix":"10.3390","volume":"13","author":[{"given":"Prince Sellase","family":"Gameli","sequence":"first","affiliation":[{"name":"Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Marche Polytechnic University, Via Tronto 10\/a, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omayema","family":"Taoussi","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Marche Polytechnic University, Via Tronto 10\/a, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9602-4223","authenticated-orcid":false,"given":"Giuseppe","family":"Basile","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery, IRCCS Galeazzi Orthopedic Institute, Via Riccardo Galeazzi 4, 20161 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-9518","authenticated-orcid":false,"given":"Jeremy","family":"Carlier","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Marche Polytechnic University, Via Tronto 10\/a, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco Paolo","family":"Busard\u00f2","sequence":"additional","affiliation":[{"name":"Section of Legal Medicine, Department of Biomedical Sciences and Public Health, Marche Polytechnic University, Via Tronto 10\/a, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.2165\/11537530-000000000-00000","article-title":"Should Performance-Enhancing Drugs in Sport be Legalized under Medical Supervision?","volume":"41","author":"Wiesing","year":"2011","journal-title":"Sports Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.2147\/SAR.S53784","article-title":"Drug abuse in athletes","volume":"5","author":"Reardon","year":"2014","journal-title":"Subs. 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