Is pain temporary and glory forever? Detection of tramadol using dried blood spot in cycling competitions.
Adult
Analgesics, Opioid
/ blood
Bicycling
/ physiology
Chromatography, High Pressure Liquid
/ methods
Doping in Sports
/ methods
Dried Blood Spot Testing
/ methods
Hematocrit
/ methods
Humans
Limit of Detection
Male
Pain
/ prevention & control
Substance Abuse Detection
/ methods
Time Factors
Tramadol
/ blood
DBS
UHPLC-MS/MS
cycling
metabolites
tramadol
Journal
Drug testing and analysis
ISSN: 1942-7611
Titre abrégé: Drug Test Anal
Pays: England
ID NLM: 101483449
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
received:
03
07
2020
revised:
21
08
2020
accepted:
21
08
2020
pubmed:
29
8
2020
medline:
1
10
2021
entrez:
29
8
2020
Statut:
ppublish
Résumé
Tramadol is a synthetic opioid drug used in the treatment of chronic and acute pain. An abnormal prevalence of its misuse in elite sport to overcome pain resulting from prolonged physical effort was recently reported. However, besides its antinociceptive effects, tramadol consumption is associated with negative effects such as numbness, confusion, and reduced alertness. This fact prompted the Union Cycliste Internationale to ban the use of tramadol in cycling competitions. Herein, we present the development of a dried blood spot (DBS) sample collection and preparation method followed by a liquid-chromatography mass spectrometry (LC-MS) analysis to rapidly determine the presence of tramadol and its two main metabolites in blood samples. The detection window of each analyte was evaluated and the analysis of performance on various MS platforms (HRMS and MS/MS) was assessed. Tramadol and its two main metabolites were detected up to 12 h after the intake of a single dose of 50 mg of tramadol in positive controls. In professional cycling competitions, 711 DBS samples collected from 361 different riders were analysed using the developed methodology, but all returned negative results (absence of parent and both metabolite compounds). In the context of professional cycling, we illustrate a valid method bringing together the easiness of collection and minimal sample preparation required by DBS, yet affording the performance standards of MS determination. The proposed method to detect tramadol and its metabolites was successfully implemented in cycling races with a probable strong deterrent effect.
Substances chimiques
Analgesics, Opioid
0
Tramadol
39J1LGJ30J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1649-1657Subventions
Organisme : Union Cycliste Internationale
Informations de copyright
© 2020 John Wiley & Sons, Ltd.
Références
Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923.
Lassen D, Damkier P, Brøsen K. The pharmacogenetics of tramadol. Clin Pharmacokinet. 2015;54(8):825-836.
Holgado D, Zandonai T, Zabala M, et al. Tramadol effects on physical performance and sustained attention during a 20-min indoor cycling time-trial: a randomised controlled trial. J Sci Med Sport. 2018;21(7):654-660.
Baltazar-Martins G, Plata MDM, Muñoz-Guerra J, Muñoz G, Carreras D, Del Coso J. Prevalence of tramadol findings in urine samples obtained in competition. Drug Test Anal. 2019;11(4):631-634.
Thiels CA, Habermann EB, Hooten WM, Jeffery MM. Chronic use of tramadol after acute pain episode: cohort study. BMJ. 2019;365:1849.
USADA. Tramadol: why some athletes and experts want it banned in sport|USADA. 2017. Available at: https://www.usada.org/spirit-of-sport/education/tramadol-why-some-athletes-and-anti-doping-experts-want-it-banned/
Díaz-Reval MI, Carrillo-Munguía N, Martínez-Casas M, González-Trujano ME. Tramadol and caffeine produce synergistic interactions on antinociception measured in a formalin model. Pharmacol Biochem Behav. 2010;97(2):357-362.
Baltazar-Martins G, Muñoz G, Carreras D, del Mar Plata M, Muñoz-Guerra J, Coso JD. The use of tramadol in combination with pseudoephedrine and caffeine in sports. Drug Test Anal. 2020;12:1203-1205.
Bejder J, Breenfeldt Andersen A, Bonne TC, et al. Tramadol does not improve performance or impair motor function in trained cyclists. Med Sci Sports Exerc. 2020;52(5):1169-1175.
UCI. Tramadol ban: all you need to know. 2019. Available at: https://www.uci.org/inside-uci/press-releases/tramadol-ban-all-you-need-to-know
UCI. Cycling Regulations Medical Rules Part 13. 2019.
Wagner M, Tonoli D, Varesio E, Hopfgartner G. The use of mass spectrometry to analyze dried blood spots. Mass Spectrom Rev. 2016;35(3):361-438.
Kaufmann A. High-resolution mass spectrometry for bioanalytical applications: is this the new gold standard? J Mass Spectrom JMS. 2020;55(9):e4533.
Allen KR. Interference by venlafaxine ingestion in the detection of tramadol by liquid chromatography linked to tandem mass spectrometry for the screening of illicit drugs in human urine. Clin Toxicol (Philadelphia, pa). 2006;44(2):147-153.
Ruta J, Boccard J, Cabooter D, et al. Method development for pharmaceutics: some solutions for tuning selectivity in reversed phase and hydrophilic interaction liquid chromatography. J Pharm Biomed Anal. 2012;63:95-105.
Haage P, Kronstrand R, Josefsson M, et al. Enantioselective pharmacokinetics of tramadol and its three main metabolites; impact of CYP2D6, CYP2B6, and CYP3A4 genotype. Pharmacol Res Perspect. 2018;6(4):e00419.
Velghe S, Delahaye L, Stove CP. Is the hematocrit still an issue in quantitative dried blood spot analysis? J Pharm Biomed Anal. 2019;163:188-196.
Bang I. Ein Verfahren zur Mikrobestimmung von Blutbestandteilen. Lund: C.W.K. Gleerup; 1913.
Lehmann S, Delaby C, Vialaret J, Ducos J, Hirtz C. Current and future use of “dried blood spot” analyses in clinical chemistry. Clin Chem Lab Med. 2013;51(10):1897-1909.
WADA. WADA leads exciting collaboration on dried-blood-spot testing (3 October 2019). 2019. Available at: https://www.wada-ama.org/en/media/news/2019-10/wada-leads-exciting-collaboration-on-dried-blood-spot-testing
Bach T. 5th World Conference on Doping in Sport Discourse. International Olympic Committee: Lausanne, Switzerland. 2019.