{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:07:12Z","timestamp":1771459632544,"version":"3.50.1"},"reference-count":17,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010765","name":"Manfred Donike Institut f\u00fcr Dopinganalytik","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010765","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013934","name":"Bundesministerium des Innern, f\u00fcr Bau und Heimat","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013934","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2025,11,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>2\u2010Chloro\u20104\u2010[[(1R,2R)\u20102\u2010hydroxy\u20102\u2010methyl\u2010cyclopentyl]amino]\u20103\u2010methyl\u2010benzonitrile (LY305) is a transdermal selective androgen receptor modulator (SARM) that has been under development as a potential therapeutic for conditions involving muscle wasting, osteoporosis, or hypogonadism. Due to its proven anabolic effects, its potential (and illicit) use in sport must be taken into consideration, necessitating information on its biotransformation for the implementation of adequate target analytes into routine doping control analytical procedures. In this study, the synthesis of LY305 and in\u00a0vitro\u2010derived metabolites of the SARM are described.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      LY305 was synthesized by a Buchwald\u2013Hartwig amination using 2\u2010chloro\u20104\u2010iodo\u20103\u2010methylbenzonitrile and (1\n                      <jats:italic>R<\/jats:italic>\n                      ,2\n                      <jats:italic>R<\/jats:italic>\n                      )\u20102\u2010amino\u20101\u2010methyl\u2010cyclopentanol. The in\u00a0vitro metabolism experiments were conducted using human liver microsomes (HLM) and the S9 fraction to allow for studying phase\u2010I and phase\u2010II biotransformations. For the detection and separation of LY305 and its metabolites, liquid chromatography\u2013high\u2010resolution tandem mass spectrometry was used.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, 18 metabolites were detected, nine of which were identified as phase\u2010I metabolites and an additional nine were attributed to phase\u2010II conjugates. Metabolic reactions were as follows: hydroxylation, dehydrogenation, oxidation, oxidation and hydroxylation,\n                      <jats:italic>O\u2010<\/jats:italic>\n                      glucuronidation, hydroxylation with subsequent glucuronidation, and bis\u2010hydroxylation with subsequent glucuronidation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The transdermal SARM LY305 was successfully synthesized and subjected to in\u00a0vitro metabolic studies, yielding chromatographic and mass spectral data that support improving comprehensive anti\u2010doping tests. To the best of our knowledge, no published experimental data exist that report on the in\u00a0vitro metabolic profile of LY305, a substance that might undergo further (pre)clinical evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.10124","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T08:18:43Z","timestamp":1755245923000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis and In\u00a0Vitro Metabolic Profiling of the Selective Androgen Receptor Modulator (SARM) LY305"],"prefix":"10.1002","volume":"39","author":[{"given":"Giorgi","family":"Kobidze","sequence":"first","affiliation":[{"name":"Department of Excellence\u2010Biomedical Sciences and Public Health Universit\u00e0 Politecnica Delle Marche  Ancona Italy"},{"name":"Center for Preventive Doping Research, Institute of Biochemistry German Sport University Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tristan","family":"M\u00f6ller","sequence":"additional","affiliation":[{"name":"Center for Preventive Doping Research, Institute of Biochemistry German Sport University Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui\u2010Chung","family":"Wen","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry University of Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco\u00a0Paolo","family":"Busard\u00f2","sequence":"additional","affiliation":[{"name":"Department of Excellence\u2010Biomedical Sciences and Public Health Universit\u00e0 Politecnica Delle Marche  Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Thevis","sequence":"additional","affiliation":[{"name":"Center for Preventive Doping Research, Institute of Biochemistry German Sport University Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.01.040"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.58.4.9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0b013e32832a3d79"},{"key":"e_1_2_9_5_1","unstructured":"World Anti\u2010Doping Agency \u201cProhibited List 2025 \u201d retrieved August 7 2025 https:\/\/www.wada\u2010ama.org\/sites\/default\/files\/2024\u201009\/2025list_en_final_clean_12_september_2024.pdf."},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.12479"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1055\/a\u20102638\u20106717"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01168"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol0265923"},{"key":"e_1_2_9_10_1","volume-title":"Introduction to Mass Spectrometry: Instrumentation, Applications, and Strategies for Data Interpretation","author":"Watson J. T.","year":"2009"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28145541"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.2951"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.3355"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.4146"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11094\u2010025\u201003419\u20108"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/d4lc01011f"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2024.101046"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2024.119688"}],"container-title":["Rapid Communications in Mass Spectrometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rcm.10124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T12:45:41Z","timestamp":1761482741000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/rcm.10124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,15]]},"references-count":17,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2025,11,30]]}},"alternative-id":["10.1002\/rcm.10124"],"URL":"https:\/\/doi.org\/10.1002\/rcm.10124","archive":["Portico"],"relation":{},"ISSN":["0951-4198","1097-0231"],"issn-type":[{"value":"0951-4198","type":"print"},{"value":"1097-0231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,15]]},"assertion":[{"value":"2025-06-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e10124"}}