{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:39:14Z","timestamp":1786977554795,"version":"build-2736575974"},"reference-count":12,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,9,11]],"date-time":"2015-09-11T00:00:00Z","timestamp":1441929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"World Anti-Doping Agency (WADA)"},{"name":"GlaxoSmithKline (GSK)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Testing and Analysis"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:p>\n                    Drug candidates, which have the potential of enhancing athletic performance represent a risk of being misused in elite sport. Therefore, there is a need for early consideration by anti\u2010doping authorities and implementation into sports drug testing programmes. The hypoxia\u2010inducible factor (HIF) or prolyl hydroxylase inhibitor (PHI) GSK1278863 represents an advanced candidate of an emerging class of therapeutics that possess substantial potential for abuse in sport due to their capability to stimulate the biogenesis of erythrocytes and, consequently, the individual's oxygen transport capacity. A thorough characterization of such analytes by technologies predominantly used for doping control purposes and the subsequent implementation of the active drug and\/or its main urinary metabolite(s) are vital for comprehensive, preventive, and efficient anti\u2010doping work. In the present study, the HIF PHI drug candidate GSK1278863 (comprising a 6\u2010hydroxypyrimidine\u20102,4\u2010dione nucleus) and its bishydroxylated metabolite M2 (GSK2391220A) were studied regarding their mass spectrometric behaviour under electrospray ionization (ESI\u2010MS\/MS) conditions. Synthesized reference materials were used to elucidate dissociation pathways by means of quadrupole\/time\u2010of\u2010flight high resolution\/high accuracy tandem mass spectrometry, and their detection from spiked urine and elimination study urine samples under routine doping control conditions was established using liquid chromatography\u2010electrospray ionization\u2010tandem mass spectrometry with direct injection. Dissociation pathways to diagnostic product ions of GSK1278863 (e.g.\n                    <jats:italic>m<\/jats:italic>\n                    \/\n                    <jats:italic>z<\/jats:italic>\n                    291, 223, and 122) were proposed as substantiated by determined elemental compositions and MS\n                    <jats:sup>n<\/jats:sup>\n                    experiments as well as comparison to spectra of the bishydroxylated analogue M2. An analytical assay based on direct urine injection using liquid chromatography coupled with tandem mass spectrometry (LC\u2010MS\/MS) was developed for the simultaneous determination of GSK1278863 in combination with its bishydroxylated metabolite M2. Validation parameters including limit of detection (0.5\u20131\u2009ng\/mL), linearity, specificity, ion suppression\/enhancement (&lt;10%), intra\u2010 and inter\u2010day precision (6\u201322%) were determined, demonstrating the fitness\u2010for\u2010purpose of the assay for doping control screening of urine samples for the presence of the drug candidate and its main metabolite and for expanding current anti\u2010doping efforts to this new class of therapeutics. However, administration study urine sample analysis suggested the use of M2 rather than the intact drug due to extensive metabolic conversion. Copyright \u00a9 2015 John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/dta.1870","type":"journal-article","created":{"date-parts":[[2015,9,11]],"date-time":"2015-09-11T02:04:45Z","timestamp":1441937085000},"page":"858-863","source":"Crossref","is-referenced-by-count":18,"title":["Mass spectrometric characterization of a prolyl hydroxylase inhibitor GSK1278863, its bishydroxylated metabolite, and its implementation into routine doping controls"],"prefix":"10.1002","volume":"8","author":[{"given":"Mario","family":"Thevis","sequence":"first","affiliation":[{"name":"Center for Preventive Doping Research \u2010 Institute of Biochemistry German Sport University Cologne  Am Sportpark M\u00fcngersdorf 6 50933 Cologne Germany"},{"name":"European Monitoring Center for Emerging Doping Agents  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Milosovich","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  King of Prussia PA 19406 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermes","family":"Licea\u2010Perez","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  King of Prussia PA 19406 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Knecht","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  King of Prussia PA 19406 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Cavalier","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline  King of Prussia PA 19406 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Sch\u00e4nzer","sequence":"additional","affiliation":[{"name":"Center for Preventive Doping Research \u2010 Institute of Biochemistry German Sport University Cologne  Am Sportpark M\u00fcngersdorf 6 50933 Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,9,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2006.05.008"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69120-4"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2011.566861"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.2010.510836"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.390"},{"key":"e_1_2_6_7_1","unstructured":"World Anti\u2010Doping Agency The 2015 Prohibited List. 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