{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T10:46:25Z","timestamp":1761648385191,"version":"build-2065373602"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,11,4]],"date-time":"2016-11-04T00:00:00Z","timestamp":1478217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"German Equestrian Federation (FN)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Testing and Analysis"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>Methylxanthines positives in competition samples have challenged doping control laboratories and racing jurisdictions since methylxanthines are naturally occurring prohibited substances and often constituents of feed. For theobromine, an international threshold (renamed in International Residue Limit, IRL) of 2\u2009\u00b5g\/mL in urine has been established. On the basis of the data presented herein, a threshold or rather an IRL for theobromine in plasma of 0.3\u2009\u00b5g\/mL was proposed and was thereupon approved by the International Federation of Horseracing Authorities (IFHA). Official recommendations for reporting caffeine and theophylline are still lacking. The aim of the study was to investigate IRLs for theobromine in blood and for caffeine and theophylline in blood and urine. Therefore, a set of six administrations were carried out including both single i.v. and single oral administrations of caffeine, theobromine and theophylline. Plasma and urine concentrations were determined using a validated liquid chromatography\u2010tandem mass spectrometry (LC\u2010MS\/MS). Applying the Toutain model approach an effective plasma concentration (EPC) of caffeine was estimated at 3.05\u2009\u00b5g\/mL, irrelevant concentrations in blood (IPC) and urine (IUC) approached 6 and 12\u2009ng\/mL, respectively. EPC of theobromine was calculated with 3.80\u2009\u00b5g\/mL, and irrelevant concentrations of theobromine were determined at 8\u2009ng\/mL in plasma and at 142\u2009ng\/mL in urine. Toutain modelling of the theophylline data produced an EPC, IPC, and IUC of 3.20\u2009\u00b5g\/mL, 6\u2009ng\/mL, and 75\u2009ng\/mL, respectively. The obtained irrelevant concentrations were used to postulate IRLs for theobromine in plasma and for caffeine and theophylline in plasma and urine. Copyright \u00a9 2016 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/dta.2097","type":"journal-article","created":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T10:07:05Z","timestamp":1474625225000},"page":"1372-1384","source":"Crossref","is-referenced-by-count":11,"title":["Control of methylxanthines in the competition horse: pharmacokinetic\/pharmacodynamic studies on caffeine, theobromine and theophylline for the assessment of irrelevant concentrations"],"prefix":"10.1002","volume":"9","author":[{"given":"Marc","family":"Machnik","sequence":"first","affiliation":[{"name":"Center for Preventive Doping Research \u2013 Institute of Biochemistry German Sport University Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Pharmacy University of Veterinary Medicine Hannover  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Koppe","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Pharmacy University of Veterinary Medicine Hannover  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Kietzmann","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Pharmacy University of Veterinary Medicine Hannover  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ina","family":"Schenk","sequence":"additional","affiliation":[{"name":"Center for Preventive Doping Research \u2013 Institute of Biochemistry German Sport University Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"D\u00fce","sequence":"additional","affiliation":[{"name":"German Equestrian Federation  Warendorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Thevis","sequence":"additional","affiliation":[{"name":"Center for Preventive Doping Research \u2013 Institute of Biochemistry German Sport University Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilhelm","family":"Sch\u00e4nzer","sequence":"additional","affiliation":[{"name":"Center for Preventive Doping Research \u2013 Institute of Biochemistry German Sport University Cologne  Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre\u2010Louis","family":"Toutain","sequence":"additional","affiliation":[{"name":"Department of Experimental Physiopathology and Toxicology National Veterinary School of Toulouse  Toulouse France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,11,4]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_5_2_1","DOI":"10.1111\/j.1439-0442.1981.tb01241.x"},{"doi-asserted-by":"publisher","key":"e_1_2_5_3_1","DOI":"10.1016\/S0065-2296(08)60228-1"},{"doi-asserted-by":"publisher","key":"e_1_2_5_4_1","DOI":"10.2741\/1367"},{"doi-asserted-by":"publisher","key":"e_1_2_5_5_1","DOI":"10.1007\/BF00734999"},{"doi-asserted-by":"publisher","key":"e_1_2_5_6_1","DOI":"10.1111\/j.1600-0773.1995.tb00111.x"},{"key":"e_1_2_5_7_1","first-page":"101","volume-title":"Pharmakotherapie bei Haus\u2010 und Nutztieren","author":"L\u00f6scher W.","year":"2003"},{"key":"e_1_2_5_8_1","first-page":"1244","article-title":"Adenosine 3\u2019,5\u2019\u2010phosphate in biological materials. 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