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

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.