N,N-dimethyl-2-phenylpropan-1-amine quantification in urine: application to excretion study following single oral dietary supplement dose

Abstract

N,N-dimethyl-2-phenylpropan-1-amine (NN-DMPPA) is a new designer stimulant prohibited in sport in-competition according to the List of Prohibited Substances and Methods published by the World Anti-Doping Agency (WADA). The first published data on the excretion study of NN-DMPPA to support the knowledge of NN-DMPPA in routine anti-doping control have been presented. The reliable gas chromatography-mass spectrometry quantitative method (GC-MS) has been validated and applied to the excretion study of NN-DMPPA. The validation parameters of the GC-MS method for determination of NN-DMPPA in human urine were the linear calibration range of 100 to 7500 ng/mL, the LOD of 13.9 ng/mL and the LOQ of 42.2 ng/mL. According to the obtained repeatability, intermediate precision, and trueness, the applied GC-MS method was precise and accurate. Urine samples from three volunteers in the excretion study were collected for 5 days after single oral administration of the supplement NOXPUMP containing NN-DMPPA. The obtained results showed the maximum concentration of NN-DMPPA (189-303 ng/mL) in urine samples at a time of 2-3 h post-administration. The NN-DMPPA concentration in urine samples was higher than 50 ng/mL until 22-23 h after the dietary supplement ingestion. This means that according to the WADA rules the use of a supplement containing NN-DMPPA may be related to a positive case when athletes took this supplement in-competition. Moreover, excretion results demonstrate also that NN-DMPPA may be detected in urine samples by the applied GC-MS method till 46 h after supplement administration. Additionally, the excretion study of β-methylphenethylamine as the second prohibited substance present in the supplement NOXPUMP has been investigated. Graphical Abstract Excretion study of new designer stimulant, N,N-dimethyl-2-phenylpropan-1-amine, and β-methylphenethylamine following single oral NOXPUMP supplement dose.

Analysis for higenamine in urine by means of ultra‐high‐performance liquid chromatography–tandem mass spectrometry: Interpretation of results

“…21 Therefore, it is important to develop methods for the identification and estimation of concentrations of compounds which are similar to known prohibited substances. 16,[22][23][24] Thus, the interpretation of estimated concentration of higenamine should be further discussed.…”

Dietary Supplement and Food Contaminations and Their Implications for Doping Controls

“…The concentration was 122 µg/g, and BMPEA was also detected at an amount of 18 mg/g. The administration of a 3 g single-dose to three healthy volunteers (recommended daily dose by the manufacturer: 1 sachet containing 15 g of powder) resulted in urinary concentrations of more than 50 ng/mL (50% of the MRPL) for 22-23 h (NN-DMPPA) and 3-12 h (BMPEA) [85]. As the MRPL was installed to harmonize the analytical performance of the doping control laboratories and is not a threshold or detection limit, AAFs can also result from lower urinary concentrations [68].…”

“…Dietary supplements contaminated with prohormones of nandrolone (e.g., 19-norandrostenedione) Supplement consumption n/a [42,43,47,50] Dietary supplement contaminated with prohormones of testosterone (e.g., 4-androstenedione) Supplement consumption n/a [43] Musk pod formulations naturally containing different anabolic-androgenic steroids Treatment with traditional Asian medicine yes [103] Meat contaminated with clenbuterol Food intake yes [106,109,110] no [111,116] Meat contaminated with clostebol Food intake yes [118] Meat contaminated with nandrolone Food intake yes [118] Meat contaminated with metenolone Food intake yes [119] Offal and meat from non-castrated pigs/boars naturally enriched with different steroid hormones Food intake yes [121,122] Dietary supplement contaminated or adulterated with stanozolol Supplement consumption yes [54] Dietary supplements contaminated or adulterated with ostarine Supplement consumption yes [58][59][60][61][62][63][64] Dietary supplements contaminated with hydrochlorothiazide Supplement consumption yes [90] NSAID contaminated with hydrochlorothiazide Administration of an analgesic yes [97] Malaria chemoprophylaxis drug containing proguanil In vesica conversion of proguanil metabolite yes [98] Dietary supplement containing N,N-dimethyl-2-phenylpropan-1-amine & β-methylphenethylamine Supplement consumption no [85] Dietary supplement containing N-ethyl-α-ethyl-phenylethylamine Supplement consumption yes [87] Dietary supplement containing octodrine Supplement consumption no [88] Poppy seeds naturally containing high amounts of morphine Food intake no [123,125]…”

Annual banned‐substance review: analytical approaches in human sports drug testing

“…By means of administration studies and urine sample analysis by GC‐MS, elimination curves for the intact drug and one of its metabolites (2‐amino‐1‐phenylbutane) were obtained to support the interpretation of urinary concentrations occurring in the context of AAFs in doping controls. Similarly, the properties of the designer stimulant N , N ‐dimethyl‐2‐phenyl‐propan‐1‐amine (NN‐DMPPA) as an illicit ingredient in a nutritional supplement were studied . Also here, GC‐MS was used to generate unequivocal analytical data, enabling the quantification of the administered drug in human urine.…”

“…Similarly, the properties of the designer stimulant N,N-dimethyl-2-phenyl-propan-1-amine (NN-DMPPA) as an illicit ingredient in a nutritional supplement were studied. [142] Also here, GC-MS was used to generate unequivocal analytical data, enabling the quantification of the administered drug in human urine. Following the oral administration of 365 μg of NN-DMPPA, urinary concentrations of up to 300 ng/mL were monitored within 2-3 h post application, and concentrations above 50 ng/mL were still observed after 24 h, outlining the difficulty of assigning the time of drug use to in-vs. out-of-competition periods.…”