{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:03:03Z","timestamp":1789945383166,"version":"4.0.1"},"reference-count":21,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Testing and Analysis"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The study investigates the metabolic profiles of 4\u2010chlorotestosterone (clostebol, 4\u2010CT) and 6\u03b1\u2010chlorotestosterone (6\u2010CT), highlighting how the chlorine atom's position may potentially influence the metabolism. In 4\u2010CT, the chlorine atom is at C4, forming a stable vinyl halide; conversely, in 6\u2010CT, the chlorine at C6 is an allylic halide, a much more reactive position. A single oral dose of 10\u2009mg of 4\u2010CT (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092) and 25\u2009mg of 6\u2010CT (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092) was administered, and urine samples were collected before and after the administration for 4\u2009days. Samples were extracted with tert\u2010butyl methyl ether at basic pH after enzymatic hydrolysis with \u03b2\u2010glucuronidase. Trimethylsilyl derivatives were analyzed by mass spectrometry coupled to gas chromatography. Although apparently minor the difference between 4\u2010CT and 6\u2010CT was observed notable differences in the metabolic profiles due to the position of the chlorine atom that seems to define the metabolic route. Although the formation of the metabolite 4\u2010chloro\u2010androst\u20104\u2010ene\u20103\u03b1\u2010hydroxy\u201017\u2010one (M1) was the main metabolic product for 4\u2010CT, this is not the result for 6\u2010CT. The \u03944\u20105 reduced metabolites for both 4\u2010CT and 6\u2010CT, identified as chlorinated androsterone and etiocholanolone, showed different excretion patterns, which may be linked to the inhibition degree of 5\u2010reductases provoked by the chloride position. In the doping field, if the usual chromatographic conditions are used to detect steroids, special attention should be paid to the presence of a signal at the retention time of 4\u2010CT M1 in a sample due to the similarities in transition relative ratio and elution time with the homologous 6\u2010CT metabolite.\n                  <\/jats:p>","DOI":"10.1002\/dta.70153","type":"journal-article","created":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T22:30:24Z","timestamp":1789943424000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Consequences of Chlorine Position in Testosterone Analogs: A GC\u2013MS Study of C4\u2010 Versus C6\u2010Chlorotestosterone Biotransformation"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7066-4916","authenticated-orcid":false,"given":"Dayamin","family":"Mart\u00ednez_Brito","sequence":"first","affiliation":[{"name":"Laboratorio Antidoping FMSI Federazione Medico Sportiva Italiana  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Colamonici","sequence":"additional","affiliation":[{"name":"Laboratorio Antidoping FMSI Federazione Medico Sportiva Italiana  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4534-0370","authenticated-orcid":false,"given":"Rodny Montes","family":"de Oca Porto","sequence":"additional","affiliation":[{"name":"Laboratorio Antidoping of Havana Ministry of Public Health  La Habana Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8037-6750","authenticated-orcid":false,"given":"Xavier","family":"de la Torre","sequence":"additional","affiliation":[{"name":"Laboratorio Antidoping FMSI Federazione Medico Sportiva Italiana  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5296-8126","authenticated-orcid":false,"given":"Francesco","family":"Botr\u00e8","sequence":"additional","affiliation":[{"name":"Laboratorio Antidoping FMSI Federazione Medico Sportiva Italiana  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"issue":"12","key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1002\/dta.3953","article-title":"Clostebol Metabolism by Different Routes of Administration: Selection of Diagnostic Urinary Markers","volume":"17","author":"Torre X.","year":"2025","journal-title":"Drug Testing and Analysis"},{"key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/jms.3517","article-title":"New Clostebol Metabolites in Human Urine by Liquid Chromatography Time\u2010of\u2010Flight Tandem Mass Spectrometry and Their Application for Doping Control","volume":"50","author":"Lu J.","year":"2015","journal-title":"Journal of Mass Spectrometry"},{"key":"e_1_2_8_4_1","first-page":"43","volume-title":"Recent Advances in Doping Analysis","author":"Thieme D.","year":"1997"},{"key":"e_1_2_8_5_1","first-page":"23","article-title":"Studies on Anabolic Steroids. I. Integrated Methodological Approach to the Gas Chromatographic\u2010Mass Spectrometric Analysis of Steroids Metabolites in Urine","volume":"489","author":"Mass\u00e9 R.","year":"1989","journal-title":"Journal of Chromatography. Biomedical Applications"},{"key":"e_1_2_8_6_1","volume-title":"Martindale. The Complete Drug Reference","author":"Sweetman S. C.","year":"2009"},{"key":"e_1_2_8_7_1","unstructured":"World Anti\u2010Doping Agency (WADA) \u201cInternational Standard Prohibited List 2025 \u201d Montreal Quebec Canada 2025."},{"key":"e_1_2_8_8_1","unstructured":"World Anti\u2010Doping Agency (WADA) \u201c2023 Anti\u2010Doping Testing Figures \u201d2023."},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1021\/jm00338a025","article-title":"CCXIII. Synthesis of Some 6\u2010Chlorotestosterone Derivatives","volume":"6","author":"Cross A. D.","year":"1963","journal-title":"Journal of Medicinal Chemistry"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11102698"},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/dta.2510","article-title":"Identification of the Anabolic Steroid 6\u03b2\u2010Chlorotestosterone in a Dietary Supplement","volume":"11","author":"Falconer T. M.","year":"2019","journal-title":"Drug Testing and Analysis"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2025.109720"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2024.110869"},{"key":"e_1_2_8_14_1","first-page":"14","article-title":"Ethical Principles for Medical Research Involving Human Subjects. General Principles","volume":"81","author":"World Medical Association Declaration of Helsinki","year":"2014","journal-title":"Journal of the American College of Dentists"},{"key":"e_1_2_8_15_1","unstructured":"World Anti\u2010Doping Agency (WADA) \u201cWADA Technical Document\u2014TD2022DL Decision Limits for the Confirmatory Quantification of Exogenous Threshold Substances by Chromatography\u2010Based \u201d2022."},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1093\/clinchem\/42.7.1001","article-title":"Metabolism of Anabolic Androgenic Steroids","volume":"42","author":"Schanzer W.","year":"1996","journal-title":"Clinical Chemistry"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1002\/dta.2951","article-title":"Detection of Clostebol in Sports: Accidental Doping?","volume":"12","author":"Torre X.","year":"2020","journal-title":"Drug Testing and Analysis"},{"key":"e_1_2_8_18_1","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1002\/dta.70092","article-title":"Comprehensive Profiling of 6\u03b1\u2010Chloro\u2010Testosterone Metabolism in Human Urine Using Gas Chromatography\u2010Mass Spectrometry","volume":"18","author":"Mart\u00ednez_Brito D.","year":"2026","journal-title":"Drug Testing and Analysis"},{"key":"e_1_2_8_19_1","unstructured":"World Anti\u2010Doping Agency \u201cTechnical Document TD2022MRPL. Minimum Required Performance Levels and Applicable Minimum Reporting Levels for Non\u2010Threshold Substances Analyzed by Chromatographic\u2014Mass Spectrometric Analytical Methods \u201d2022."},{"key":"e_1_2_8_20_1","unstructured":"World Anti\u2010Doping Agency (WADA) \u201cTechnical Document\u2010TD2023IDCR. Minimum Criteria for Chromatographic\u2010Mass Spectrometric Confirmation of the Identity of Analytes for Doping Control Purposes \u201d2023."},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","DOI":"10.1002\/9780470727140","volume-title":"Trace Quantitative Analysis by Mass Spectrometry","author":"Boyd R. K.","year":"2008"},{"key":"e_1_2_8_22_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/B978-0-08-091906-5.00002-1","volume-title":"Hormones","author":"Norman A. 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