{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T08:07:08Z","timestamp":1769501228062,"version":"3.49.0"},"reference-count":21,"publisher":"Wiley","issue":"11-12","license":[{"start":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T00:00:00Z","timestamp":1539734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Testing and Analysis"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In sports drugs testing, the differentiation between the abuse of the prohibited substance trimetazidine and that of the permitted drug lomerizine is required because trimetazidine is one of the metabolites of lomerizine. Therefore, it is important to identify a lomerizine\u2010specific metabolite in urine that allows making the distinction. In this study, a simple dilute\u2010and\u2010shoot method employing liquid chromatography\u2013high resolution\u2013tandem mass spectrometry for the quantification of trimetazidine, lomerizine and the specific metabolite bis\u2010(4\u2010fluorophenyl)\u2010methylpiperazine (M6) in urine was developed. An oral dose of 15\u00a0mg was administered to 10 male volunteers, after which urine samples collected during the following 276\u00a0hours were analyzed using the developed method, allowing for examination of the target analytes' excretion profile. The limit of detection of all target analytes was &lt;0.02\u00a0ng\/mL. In all volunteers, the metabolite M6 was detected up to 276\u00a0hours after administration. After more than 12\u00a0hours, all volunteers were found to have higher concentrations of the metabolite M6 than of trimetazidine. The concentrations of trimetazidine, lomerizine, M6, and the M6\/trimetazidine ratio in the final sample collected after 276\u00a0hours were 0.2\u20130.9\u00a0ng\/mL, &lt;0.05\u20130.1\u00a0ng\/mL, 14.1\u201338.3\u00a0ng\/mL, and 28.8\u2013122.9, respectively. The urinary excretion of trimetazidine, unchanged lomerizine, and the metabolite M6 within the first 276\u00a0hours was 0.64%, 0.006%, and 6.1%, respectively. Consequently, the absence of the metabolite M6 in doping control urine samples corroborates the conclusion that lomerizine is unlikely to be the source of trimetazidine. The results confirm that the M6 metabolite is the longest\u2010lasting urinary metabolite of lomerizine currently known.<\/jats:p>","DOI":"10.1002\/dta.2504","type":"journal-article","created":{"date-parts":[[2018,9,21]],"date-time":"2018-09-21T21:50:38Z","timestamp":1537566638000},"page":"1689-1697","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Lomerizine, trimetazidine and bis\u2010(4\u2010fluorophenyl)\u2010methylpiperazine in human urine after oral administration of lomerizine dihydrochloride: analysis by liquid chromatography\u2010high resolution\u2010tandem mass spectrometry"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3614-4121","authenticated-orcid":false,"given":"Masato","family":"Okano","sequence":"first","affiliation":[{"name":"Anti\u2010Doping Laboratory, LSI Medience Corporation  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuhiko","family":"Sato","sequence":"additional","affiliation":[{"name":"Anti\u2010Doping Laboratory, LSI Medience Corporation  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Kageyama","sequence":"additional","affiliation":[{"name":"Anti\u2010Doping Laboratory, LSI Medience Corporation  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3458.1995.tb00284.x"},{"key":"e_1_2_6_3_1","unstructured":"World Anti\u2010Doping Agency.The World Anti\u2010Doping Code. The 2018 Prohibited List. International Standard Montreal. Montreal Canada. Available at:https:\/\/www.wada\u2010ama.org\/sites\/default\/files\/prohibited_list_2018_en.pdf[Accessed 31 July 2018]."},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1248\/yakushi1947.115.2_120"},{"key":"e_1_2_6_5_1","first-page":"4663","article-title":"Metabolism of lomerizine hydrochloride in human","volume":"22","author":"Awata N","year":"1994","journal-title":"Jpn Pharmacol Ther"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.1893"},{"key":"e_1_2_6_7_1","first-page":"1597","article-title":"Identification of human cytochrome P450 isoforms involved in the metabolism of lomerizine hydrochloride","volume":"27","author":"Miyanaga H","year":"1999","journal-title":"Jpn. Pharmacol. 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