Forensic Toxicology

, Volume 32, Issue 1, pp 148–153 | Cite as

Identification and quantitation of N,α-diethylphenethylamine in preworkout supplements sold via the Internet

  • Jaesin Lee
  • Bastiaan J. Venhuis
  • Sewoong Heo
  • Hyeyoung Choi
  • Ilung Seol
  • Eunmi Kim
Short Communication

Abstract

Shortly after we reported the seizure of the amphetamine derivative N,α-diethylphenethylamine (NADEP) as bulk powder, we have identified NADEP in preworkout supplements branded as “Craze” and sold via the Internet. A gas chromatography–mass spectrometry method was validated and used to quantitate NADEP in the supplements. The authentic NADEP sample of the previous study was used as the reference standard for quantitative analysis after purity assay using quantitative nuclear magnetic resonance spectroscopy. Using these methods, NADEP concentrations in two Craze supplements (Berry Lemonade Flavor and Candy Grape Flavor) were quantitated as 0.40 and 0.44 %, respectively. With the label suggesting a serving size of 5.3–5.8 g, this was equivalent to about 23 mg of NADEP. NADEP was patented in 1988 by Knoll Pharmaceuticals with claims of psychoactive effects (e.g., cognitive enhancement and pain tolerance). For unknown reasons, the compound was never developed into a medicine, and important data about its effects and risks are lacking. Nevertheless, the patent suggested an intended oral dose range of 10–150 mg with a target of 30 mg. Therefore, it could be assumed that NADEP was added to the supplements intentionally for its pharmacological effects without adequate labeling. Because NADEP is a structural analog of methamphetamine in which the two methyl groups are only replaced by ethyl groups, it is possible that the toxicity of NADEP is similar to that of methamphetamine. Thus, supplements containing NADEP should be removed from the market immediately. In countries where NADEP is not regulated as a controlled substance, it should be enforced under the Medicines Act.

Keywords

N,α-Diethylphenethylamine (NADEP) Preworkout supplement Craze Designer drug GC–MS NMR 

References

  1. 1.
    Lau G, Lo DST, Yao YJ, Leong HT, Chan CL, Chu SS (2004) A fatal case of hepatic failure possibly induced by nitrosofenfluramine: a case report. Med Sci Law 44:252–263PubMedCrossRefGoogle Scholar
  2. 2.
    WADA (2013) The 2013 prohibited list. World Anti-Doping Agency, MontrealGoogle Scholar
  3. 3.
    Zhang Y, Woods RM, Breitbach ZS, Armstrong DW (2012) 1,3-Dimethylamylamine (DMAA) in supplements and geranium products: natural or synthetic? Drug Test Anal 4:986–990PubMedCrossRefGoogle Scholar
  4. 4.
    Kelleher C, Christie R, Lalor K, Fox J, Bowden M, O’Donnell C (2011) An overview of new psychoactive substances and the outlets supplying them. National Advisory Committee on Drugs (NACD), DublinGoogle Scholar
  5. 5.
    Thomas JE, Munir JA, Mclntyre PZ, Ferguson MA (2009) STEMI in a 24-year-old man after use of a synephrine-containing dietary supplement: a case report and review of the literature. Tex Heart Inst J 36:586–590PubMedCentralPubMedGoogle Scholar
  6. 6.
    Lee J, Choe S, Choi H, Heo S, Kim E, Kim H, Bang E, Chung H (2013) Identification of N-ethyl-α-ethylphenethylamine in crystalline powder seized for suspected drug trafficking: a research chemical or a new designer drug? Forensic Toxicol 31:54–58CrossRefGoogle Scholar
  7. 7.
    Gadape HH, Parikh KS (2011) Quantitative determination and validation of metformin hydrochloride in pharmaceutical using quantitative nuclear magnetic resonance spectroscopy. E-J Chem 8: 767–781. http://dx.doi.org/10.1155/2011/46898
  8. 8.
    Gadape HH, Parikh KS (2011) Quantitative determination and validation of pioglitazone in pharmaceutical using quantitative nuclear magnetic resonance spectroscopy. J Chem Pharm Res 3:649–664Google Scholar
  9. 9.
    Miller JN, Miller JC (2005) Statistics and chemometrics for analytical chemistry, 5th edn. Pearson Education, HarlowGoogle Scholar
  10. 10.
    Peters FT, Drummer OH, Musshoff F (2007) Validation of new methods. Forensic Sci Int 165:216–224PubMedCrossRefGoogle Scholar
  11. 11.
    József K, Antal S, Éva S, Éva S, Zoltán T, Károly M, János B (1988) New psychostimulant agent. International application published under the patent cooperation treaty (PCT). World Intellectual Property Organization (WIPO), Publication No. WO 88/02254Google Scholar
  12. 12.
    Noggle FT, Clark CR, Pitts-Monk P, DeRuiter J (1991) Liquid chromatographic and mass spectral analysis of 1-phenyl-2-butanamines: homologues of the amphetamines. J Liq Chromatogr 14:1393–1408CrossRefGoogle Scholar
  13. 13.
    Ricaurte GA, DeLanney LE, Irwin I, Witkin JM, Katz JL, Langston JW (1989) Evaluation of the neurotoxic potential of N, N-dimethylamphetamine: an illicit analog of methamphetamine. Brain Res 490:301–306PubMedCrossRefGoogle Scholar
  14. 14.
    Junet R (1956) Ethylamphetamine in the treatment of obesity (in French). Praxis 45:986–988PubMedGoogle Scholar
  15. 15.
    Oberlender R, Nichols DE (1991) Structural variation and (+)-amphetamine like discriminative stimulus properties. Pharmacol Biochem Behav 38:581–586PubMedCrossRefGoogle Scholar
  16. 16.
    Nichols DE (1986) Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens. J Psychoact Drugs 18:305–313CrossRefGoogle Scholar
  17. 17.
    Suzuki O, Hattori H, Asano M, Oya M, Katsumata Y (1980) Inhibition of monoamine oxidase by d-methamphetamine. Biochem Pharmacol 29:2071–2073PubMedCrossRefGoogle Scholar
  18. 18.
    Nieddu M, Trignano C, Burrai L, Pirisi MA, Boatto G (2013) Cross-reactivities of 41 new amphetamine designer drugs to EMIT® immunoassays. Forensic Toxicol 31:133–137CrossRefGoogle Scholar
  19. 19.
    Pirisi MA, Nieddu M, Burrai L, Carta A, Briguglio I, Baralla E, Demontis MP, Varoni MV, Boatto G (2013) An LC–MS–MS method for quantitative analysis of six trimethoxyamphetamine designer drugs in rat plasma, and its application to a pharmacokinetic study. Forensic Toxicol 31:197–203CrossRefGoogle Scholar
  20. 20.
    Nakazono Y, Tsujikawa K, Kuwayama K, Kanamori T, Iwata YT, Miyamoto K, Kasuya F, Inoue H (2013) Differentiation of regioisomeric fluoroamphetamine analogs by gas chromatography–mass spectrometry and liquid chromatography–tandem mass spectrometry. Forensic Toxicol 31:241–250CrossRefGoogle Scholar
  21. 21.
    Zaitsu K, Miyagawa H, Sakamoto Y, Matsuta S, Tsuboi K, Nishioka H, Katagi M, Sato T, Tatsuno M, Tsuchihashi H, Suzuki K, Ishii A (2013) Mass spectrometric differentiation of the isomers of mono-methoxyethylamphetamines and mono-methoxydimethylamphetamines by GC–EI–MS–MS. Forensic Toxicol 31:292–300CrossRefGoogle Scholar

Copyright information

© Japanese Association of Forensic Toxicology and Springer Japan 2013

Authors and Affiliations

  • Jaesin Lee
    • 1
  • Bastiaan J. Venhuis
    • 2
  • Sewoong Heo
    • 1
  • Hyeyoung Choi
    • 1
  • Ilung Seol
    • 1
  • Eunmi Kim
    • 1
  1. 1.National Forensic ServiceSeoulSouth Korea
  2. 2.Health Protection CenterNational Institute for Public Health and the EnvironmentBilthovenThe Netherlands

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