Abstract
This paper reviews the prevalence of legal and illegal stimulants in relation to doping-control analysis. Stimulants are among the oldest classes of doping agents, having been used since ancient times. Despite the ease with which they can be detected and the availability of sensitive detection methods, stimulants are still popular among athletes. Indeed, they remain one of the top three most popular classes of prohibited substances. Because the list of legal and illegal stimulants is extensive only a selection is discussed in detail. The compounds selected are caffeine, ephedrines, amphetamine and related compounds, methylphenidate, cocaine, strychnine, modafinil, adrafinil, 4-methyl-2-hexaneamine, and sibutramine. These compounds are mainly prevalent in sport or are of therapeutic importance. Because stimulants are the oldest doping class the first detection methods were for this group. Several early detection techniques including GC–NPD, GC–ECD, and TLC are highlighted. The more novel detection techniques GC–MS and LC–MS are also discussed in detail. In particular, the last technique has been shown to enable successful detection of stimulants difficult to detect by GC–MS or for stimulants previously undetectable. Because stimulants are also regularly detected in nutritional (food) supplements a section on this topic is also included.
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References
Delbeke FT (2000) Biol Sport 17(2):81–86
Van Wimersa Greidanus TB, Stoele F, Hartgens F (2000) In: Hartgens F, Kuipers H (eds) Bohn Stafleu–Van Loghum. België, Houten, p 3
Donohoe T, Johnson N (1986) Drug abuse in sports. Blackwell, Oxford
Verroken M (2000) Best Pract Res Clin Endocrinol Metab 14(1):1–23
The 2010 Prohibited List, International Standard (2010) World Anti-Doping Agency. http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/WADA_Prohibited_List_2010_EN.pdf. Accessed 13.01.2011
Docherty JR (2008) Br J Pharmacol 154(3):606–622
Jones G (2008) Drugs and ergogenic aids to improve sport performance, vol 44. Essays in biochemistry. Portland Press Ltd, London, pp 109–123
Avois L, Robinson N, Saudan C, Baume N, Mangin P, Saugy M (2006) Br J Sports Med 40:16–20
Van Eenoo P, Delbeke FT (2010) In: Thieme D, Hemmersbach P (eds) Handbook of experimental pharmacology. Springer-Verlag, Berlin, pp 227–249
Thevis M, Sigmund G, Geyer H, Schanzer W (2010) Endocrinol Metab Clin N Am 39(1):89–105
Hemmersbach P, de la Torre R (1996) J Chromatogr B 687(1):221–238
2010 Prohibited List, Summary of Major Modifications (2010) World Anti-Doping Agency. http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/WADA_Summary_of_Modifications_2010_EN.pdf. Accessed 13.01.2011
WADA (2009) 2009 adverse analytical findings and atypical findings reported by accredited laboratories. World Anti-Doping Agency, Montreal
2009 Adverse Analytical Findings and Atypical Findings Reported by Accredited Laboratories (2009) World Anti-Doping Agency. http://www.wada-ama.org/Documents/Science_Medicine/Anti-Doping_Laboratories/Lab_Statistics/WADA_2009_LaboratoryStatisticsReport_Final.pdf. Accessed 13.01.2011
2008 Adverse Analytical Findings and Atypical Findings Reported by Accredited Laboratories (2008) World Anti-Doping Agency. http://www.wada-ama.org/Documents/Science_Medicine/Anti-Doping_Laboratories/WADA_LaboStatistics_2008.pdf. Accessed 13.01.2011
Deventer K, Van Eenoo P, Baele G, Pozo OJ, Van Thuyne W, Delbeke FT (2009) Drug Test Anal 1(5–6):209–213
Graham T (1998) News on sport nutrition: insider 6(2):1–7
Anselme F, Collomp K, Mercier B, Ahmaidi S, Prefaut C (1992) Eur J Appl Physiol Occup Physiol 65(2):188–191
Collomp K, Ahmaidi S, Chatard JC, Audran M, Prefaut C (1992) Eur J Appl Physiol Occup Physiol 64(4):377–380
Graham TE, Rush JWE, Vansoeren MH (1994) Can J Appl Physiol 19(2):111–138
Greer F, McLean C, Graham TE (1998) J Appl Physiol 85(4):1502–1508
Sinclair CJD, Geiger JD (2000) J Sport Med Phys Fit 40(1):71–79
Tarnopolsky MA (1994) Sports Med 18(2):109–125
Graham TE, Spriet LL (1995) J Appl Physiol 78(3):867–874
Kovacs EMR, Stegen JHCH, Brouns F (1998) J Appl Physiol 85(2):709–715
Van Thuyne W, Delbeke FT (2006) Int J Sports Med 27(9):745–750
Van Thuyne W, Roels K, Delbeke FT (2005) Int J Sports Med 26(9):714–718
Bell DG, McLellan TM, Sabiston CM (2002) Med Sci Sports Exerc 34(2):344–349
Bouchard R, Weber AR, Geiger JD (2002) Clin J Sport Med 12(4):209–224
Jacobs I, Pasternak H, Bell DG (2003) Med Sci Sports Exerc 35(6):987–994
Gill ND, Shield A, Blazevich AJ, Zhou S, Weatherby RP (2000) Br J Clin Pharmacol 50(3):205–213
Chester N, Reilly T, Mottram DR (2003) Int J Sports Med 24(1):3–8
Hodges K, Hancock S, Currell K, Hamilton B, Jeukendrup AE (2006) Med Sci Sports Exerc 38(2):329–333
Chu KS, Doherty TJ, Parise G, Milheiro JS, Tarnopolsky MA (2002) Clin J Sport Med 12(6):387–390
Gillies H, Derman WE, Noakes TD, Smith P, Evans A, Gabriels G (1996) J Appl Physiol 81(6):2611–2617
Jones G (2008) In: Cooper CE, Beneke R (eds) Essays in biochemistry, volume 44: drugs and ergogenic aids to improve sport performance, vol 44. Portland Press, London, pp 109–123
Pokrywka A, Tszyrsznic W, Kwiatkowska DJ (2009) Int J Sports Med 30(8):569–572
Strano-Rossi S, Leone D, de la Torre X, Botre F (2009) Ther Drug Monit 31(4):520–526
van der Merwe PJ, Brown LW, Hendrikz SE (1994) J Chromatogr 661(2):357–361
Van Eenoo P, Delbeke FT, Roels K, De Backer P (2001) J Chromatogr B 760(2):255–261
Spyridaki MHE, Tsitsimpikou CJ, Siskos PA, Georgakopoulos CG (2001) J Chromatogr B 758(2):311–314
Gmeiner G, Geisendorfer T, Kainzbauer J, Nikolajevic M, Tausch H (2002) J Chromatogr B 768(2):215–221
Thevis M, Schanzer W (2005) J Chromatogr Sci 43(1):22–31
Spyridaki M-H, Kiousi P, Vonaparti A, Valavani P, Zonaras V, Zahariou M, Sianos E, Tsoupras G, Georgakopoulos C (2006) Anal Chim Acta 573:242–249
Deventer K, Pozo OJ, Van Eenoo P, Delbeke FT (2009) J Chromatogr B 877:369–374
Edeleano L (1887) Ber Deutsch Chem Ges 20(1):616–622
Rang HP, Dale MM, Ritter JM (1995) Pharmacology, 3e Edition edn. Churchill Livingstone, New York
Kraemer T, Maurer HH (2002) Ther Drug Monit 24(2):277–289
Polgar M, Vereczkey L, Szporny L, Czira G, Tamas J, Gacsbaitz E, Holly S (1979) Xenobiotica 9(8):511–519
Gomez C, Segura J, Monfort N, Suominen T, Leinonen A, Vahermo M, Yli-Kauhaluoma J, Ventura R (2010) Anal Bioanal Chem 397(7):2903–2916
Appolonova SA, Shpak AV, Semenov VA (2004) J Chromatogr B 800(1–2):281–289
Logan B (2002) Forensic Sci Rev 14:410–416
Delbeke FT, Debackere M (1975) J Chromatogr 106(2):412–417
Redalieu E (1982) Drug Metab Dispos 10(6):708–709
Deventer K, Pozo OJ, Van Eenoo P, Delbeke FT (2009) J Chromatogr A 1216(31):5819–5827
Solans A, Carnicero M, Delatorre R, Segura J (1994) J Chromatogr B 658(2):380–384
Ventura R, Roig M, Monfort N, Saez P, Berges R, Segura J (2008) Eur J Mass Spectrom 14(3):191–200
Mazzarino M, de la Torre X, Botre F (2008) Anal Bioanal Chem 392(4):681–698
Eichhorst J, Etter M, Lepage J, Lehotay DC (2004) Clin Biochem 37(3):175–183
Badoud F, Grata E, Perrenoud L, Avois L, Saugy M, Rudaz S, Veuthey JL (2009) J Chromatogr A 1216(20):4423–4433
Badoud F, Grata E, Perrenoud L, Saugy M, Rudaz S, Veuthey JL (2009) J Chromatogr A 1217(25):4109–4119
Thorngren JO, Ostervall F, Garle M (2008) J Mass Spectrom 43(7):980–992
Technical Document: Minimum Required Performance Limits for Detection of Prohibited Substances: TD2010MRPL (2010) WADA (World Anti-Doping Agency). http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-IS-Laboratories/WADA_TD2010MRPLv1.0_Minimum%20Required%20Performance%20Levels_Sept%2001%202010_EN.pdf. Accessed 13.01.2011
Ramcharitar V, Levine B, Smialek JE (1995) J Forensic Sci 40(1):99–101
Van Eenoo P, Deventer K, Roels K, Delbeke FT (2006) Forensic Sci Int 164(2–3):159–163
Strano-Rossi S, Molaioni F, Rossi F, Botre F (2005) Rapid Commun Mass Spectrom 19(11):1529–1535
Van Thuyne W, Van Eenoo P, Delbeke FT (2007) J Chromatogr B 857(2):259–265
Tseng YL, Uralets V, Lin CT, Kuo FH (2005) J Pharm Biomed Anal 39(5):1042–1045
Lopez FA (2006) J Dev Behav Pediatr 27(5):410–416
Kaufman KR, Gerner R (2005) Br J Sports Med 39(4):241–244
Hatton CK (2007) Pediatr Clin N Am 54 (4):713–733
Rao RN, Shinde DD, Talluri M, Agawane SB (2008) J Chromatogr B 873(1):119–123
Lu JH, Wang XB, Yang SM, Liu X, Qin Y, Shen L, Wu Y, Xu YX, Wu MT, Ouyang GF (2009) Rapid Commun Mass Spectrom 23(11):1592–1600
Deventer K, Pozo OJ, Van Eenoo P, Delbeke FT (2008) LC–GC N Am 26 (4):376–389
The 2007 Prohibited List, International Standard (2007) World Anti-Doping Agency. http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/WADA_Prohibited_List_2007_EN.pdf. Accessed 13.01.2011
Perrenoud L, Saugy M, Saudan C (2009) J Chromatogr B 877(29):3767–3770
Geyer H, Parr MK, Koehler K, Mareck U, Schanzer W, Thevis M (2008) J Mass Spectrom 43(7):892–902
Heal DJ, Aspley S, Prow MR, Jackson HC, Martin KF, Cheetham SC (1998) Int J Obes 22:S18–S28
McNeely W, Goa KL (1998) Drugs 56(6):1093–1124
King DJ, Devaney N (1988) Br J Clin Pharmacol 26(5):607–611
Glick SD, Haskew RE, Maisonneuve IM, Carlson JN, Jerussi TP (2000) Eur J Pharmacol 397(1):93–102
Sardela VF, Motta MTR, Padilha MC, Pereira HMG, Neto FRA (2009) J Chromatogr B 877(27):3003–3011
Strano-Rossi S, Colamonici C, Botre F (2007) Rapid Commun Mass Spectrom 21(2):79–88
Thevis M, Sigmund G, Schiffer AK, Schnazer W (2006) Eur J Mass Spectrom 12(2):129–136
Meyer MR, Maurer HH (2010) Curr Drug Metab 11(5):468–482
Gibbons S, Zloh M Bioorg Med Chem Lett 20 (14):4135–4139
Archer RP (2009) Forensic Sci Int 185(1–3):10–20
Rosner P, Quednow B, Girreser U, Junge T (2005) Forensic Sci Int 148(2–3):143–156
Torrance H, Cooper G (2010) Forensic Sci Int 202(1–3):E62–E63
Mephedrone report (2009) Institute of Psychiatry, King's College, London. http://194.83.136.209/documents/reports/Mephedrone.pdf. Accessed 17.01.2011
de la Torre R, Farre M, Navarro M, Pacifici R, Zuccaro P, Pichini S (2004) Clin Pharmacokinet 43(3):157–185
Beckett AH, Moffat AC (1968) J Pharm Pharmacol S 20:S48–S50
Beckett AH, Tucker GT, Moffat AC (1967) J Pharm Pharmacol 19(5):273–294
Donike M, Jaenicke L, Stratman.D, Hollmann W (1970) J Chromatogr 52(2):237–250
Donike M (1973) J Chromatogr 78(2):273–279
Delbeke FT, Debackere M (1978) J Chromatogr 161(NOV):360–365
Delbeke FT, Debackere M (1977) J Chromatogr 133(1):214–217
Delbeke FT, Debackere M (1977) J Chromatogr 136(3):385–390
Kraemer T, Maurer HH (1998) J Chromatogr B 713(1):163–187
Rossi SS, de la Torre X, Botre F (2010) Rapid Commun Mass Spectrom 24(10):1475–1480
Maurer HH (1998) J Chromatogr B 713(1):3–25
Thieme D, Sachs H (2003) Anal Chim Acta 492(1–2):171–186
Goebel C, Trout GJ, Kazlauskas R (2004) Anal Chim Acta 502(1):65–74
Deventer K, Van Eenoo P, Delbeke FT (2005) Rapid Commun Mass Spectrom 19(2):90–98
Maurer HH (2006) J Mass Spectrom 41(11):1399–1413
Thevis M, Schanzer W (2007) Anal Bioanal Chem 388(7):1351–1358
Hemmersbach P (2008) J Mass Spectrom 43(7):839–853
Bowers LD (2009) Ann Rev Anal Chem 2:485–507
Deventer K, Van Eenoo P, Delbeke FT (2006) Rapid Commun Mass Spectrom 20(5):877–882
Lu JH, Wang S, Dong Y, Wang XB, Yang SM, Zhang JL, Deng J, Qin Y, Xu YX, Wu M, Ouyang GF (2010) Anal Chim Acta 657(1):45–52
Thomas A, Sigmund G, Guddat S, Schanzer W, Thevis M (2008) Eur J Mass Spectrom 14(3):135–143
Peters RJB, Oosterink JE, Stolker AAM, Georgakopoulos C, Nielen MWF (2010) Anal Bioanal Chem 396(7):2583–2598
Vonaparti A, Lyris E, Angelis YS, Panderi I, Koupparis M, Tsantili-Kakoulidou A, Peters RJB, Nielen MWF, Georgakopoulos C (2010) Rapid Commun Mass Spectrom 24(11):1595–1609
Dikunets MA, Appolonova SA, Rodchenkov GM (2009) J Anal Chem 64(8):832–842
Kolmonen M, Leinonen A, Kuuranne T, Pelander A, Ojanpera I (2009) Drug Test Anal 1(5–6):250–266
Murray GJ, Danaceau JP (2009) J Chromatogr B 877(30):3857–3864
Kolmonen M, Leinonen A, Pelander A, Ojanpera I (2007) Anal Chim Acta 585(1):94–102
Davies AM (1997) Food Surveill 103:1–18
Abourashed EA, El-Alfy AT, Khan IA, Walker L (2003) Phytother Res 17(7):703–712
Gurley BJ, Wang P, Gardner SF (1998) J Pharm Sci 87(12):1547–1553
Delbeke FT (2001) In: Peters C, Schulz T, Michna H (eds) Biomedical Side Effects of Doping, vol 13. Sport & Buch Strauß, Cologne (Germany), pp 155–161
de Hon O, Coumans B (2007) Br J Sports Med 41(11):800–805, discussion 805
Turner M, McCrory P, Johnston A (2005) Br J Pharmacol 39 (10):e37
Parr MK, Geyer H, Sigmund G, Köhler K, Schänzer W (2003) In: Schänzer W, Geyer H, Gotzmann A, Mareck U (eds) Recent advances in doping analysis, vol 11. Sport & Buch Strauß, Cologne (Germany), pp 67–75
Nederlands Zekerheidssysteem Voedingssupplementen Topsport—NZVT (2003) http://www.necedo.nl/nzvt/thenetherlandssecuritysystemnutritionalsupplements. Accessed 13.01.2011
Deventer K, Van Thuyne W, Mikulcikova P, Van Eenoo P, Delbeke FT (2007) 103(4):1508–1513
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The authors would like to thank Lance Brooker for correcting the language in the manuscript.
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Published in the special issue Anti-Doping Analysis with Guest Editor Mario Thevis.
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Deventer, K., Roels, K., Delbeke, F.T. et al. Prevalence of legal and illegal stimulating agents in sports. Anal Bioanal Chem 401, 421–432 (2011). https://doi.org/10.1007/s00216-011-4863-0
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DOI: https://doi.org/10.1007/s00216-011-4863-0