Table 1.
Information of studies showing proof of analytical analysis of undeclared substances banned by WADA in dietary supplements.
| Number of analyzed dietary supplements | Number of dietary supplements that contain undeclared substances | Undeclared substances | Main results | Methods for detection | Country of origin | Ref. |
|---|---|---|---|---|---|---|
| 634 | 94 | Теstosterone, 4-norendionon, 4-аdendion, 5-adendiol, nandrolone, boldenone, dehydroepiandrosterone (DHEA) | 14.8% positive supplements showed anabolic steroid concentrations from 0.01 μg/g up to 190 μg/g | GC-MS | Germany | [36] |
| 75 | 7 | DHEA, 19-noranrostenedione, ephedrine | Seven products had hormones that were not listed on the labels, and two more products contained ephedrine and caffeine that were not clearly labeled | GC-MS | Switzerland | [23] |
| 103 | 3 | Nandrolone, testosterone, 4-androstenediol, androstenediol, androstenedione, bolasterone, boldenone, clostebol, DHEA, dihydrotestosterone (DHT), drostanolone, fluoxymesterone, mesterolone,4-norandrostenediol, 5-androstenedione, 5-norandrostenediol, 19-noranrostenedione, metandienone, metenolone, methyltestosterone, norethandrolone, oxandrolone, oxymesterone, stanozol, oxymetholone, testosterone propionate, 5-norandrostenedione | An amount of metandienone in three supplements in a range from 0.41 mg/g up to 17.30 mg/g was found | GC-MS | Switzerland | [37] |
| 12 | 11 | Testosterone, 5-androstenediol, 4-androstene-3,17-dione, 5-androstene-3,17-diol, 19-androstene-3b, 17b-diol | Supplements did not meet the labeling requirements. One supplement contained 10 mg of testosterone; another contained 77% more than the label stated; 11 of the 12 contained less than what was indicated | HPLC, GC-MS | USA | [38] |
| 64 | 8 | Nandrolone decanoate, testosterone decanoate, 4-androstendion, ephedrine, DHEA | Concentration range: 1–25 ng/g | LC-MS/MS GC-MS |
Italy | [39] |
| 19 | 15 | Тestosterone, beta-boldenone, alfa-boldenone, beta-nortestosterone | Concentrations between 0.01 mg/g and 2.5 mg/per capsule or tablet were found. Testosterone was in most samples (50%) | LC-MS/MS ESI |
Belgium | [40] |
| 16 | 9 | 1,3-Dimethylamylamine (DMAA) | Concentration range: 3.1 mg/g-415 mg/g | NMR | Germany | [28] |
| 112 | 6 | Dehydroepiandrosterone (DHEA) | Concentration range:1-500 ng/g | Androgen bioassay | New Zealand | [41] |
| 19 | 2 | Higenamine | Concentrations 6.42 ng/mL and 18.93 ng/mg were found in two samples | UHPLC-MS/MS | Serbia | [42] |
| 24 | 5 | Higenamine | Dosages of up to 62 ± 6.0 mg per serving were found | UHPLC-MS/MS | USA, Netherlands | [43] |
| 6 | 6 | D6-Methyltestosterone, methasterone, prostanozol | After positive doping samples, 6 dietary supplements were tested and all have undeclared substances | GC-MS | Germany | [44] |
| 10 | 2 | Sibutramine | More than 20 mg per tablet was found | Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) UHPLC-MS/MS |
Bulgaria | [31] |
| 20 | 14 | Andarine, ostarine, ibutamoren, arimistane | The amounts of these undeclared analytes ranged from 0.6 mg per capsule to 6.8 mg per capsule | UHPLC LC-HRAM (high-resolution accurate mass) |
UK | [26] |
| 188 | 29 | Sibutramine | Concentrations of detected sample range from 0.03 mg/g up to 132.40 mg/g | LC-MS/MS | South Korea | [32] |
| 123 | 24 | Sibutramine | Sibutramine contents in green coffee samples were 0.014–2 438 mg/kg; the highest content of sibutramine was found in one capsule sample (26 410 mg/kg) | LC-ESI-MS/MS | Croatia | [33] |
| 200 | 27 | Synephrine, yohimbine, 5-hydroxytryptophan, DHEA | The concentrations of detected samples ranged from 0.51 mg/g up to 226 mg/g | LC-MS/MS | South Korea | [35] |
| 13 | 13 | DMAA | Concentration range from 0.1 mg/g to 110 mg/g | HPLC-MS | USA | [29] |
| 8 | 7 | Sibutramine, phenolphthalein, bumetanide, phenytoin | Concentrations of sibutramine ranged from 6 mg up to 57 mg per capsule | LC-MS GC-MS |
Iran | [34] |
| 50 | 24 | Sibutramine, rimonabant, desmethylsibutramine, didesmethylsibutramine, sildenafil | Concentrations of sibutramine ranged from 0.1 mg up to 21 mg per capsule | HPLC-DAD-MS/MS | Netherlands | [45] |
| 52 | 11 | Theobromine, theophylline, pseudoephedrine, caffeine, hydrochlorothiazide, yohimbinе | Hydrochlorothiazide content found: 0.01 mg-0.37 mg Pseudoephedrine content found: 0.03 mg-11 mg |
UHPLC-DAD | Saudi Arabia | [48] |
| 5 | 5 | Sibutramine, 4-hydroxyamphetamine, caffeine, theophylline | Sibutramine content found: 15 and 26 mg/g Theophylline content found: 0.2-0.3 mg/g |
HRAM screening LC-MS/MS |
Italy | [49] |
| Dietary supplement Dexaprine | Synephrine, oxilofrine, deterenol, yohimbine, caffeine, theophylline | Oxilofrine content found: 1-5 mg | Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) | Netherlands | [50] | |
| 27 | 18 | Demelverine, hordenine, N, N-dimethyl-phenethylamine, synephrine, N-methyl-β-phenethylamine, methylsynephrine | Unlisted DMAA was identified in three products with concentrations ranging from 18 to 120.9 mg/daily dose, while unlisted DMBA was found in one product with a concentration of 108 mg/daily dose | LC-QTOF-MS | USA | [51] |
| 30 | 11 | 4-Androstenedione | 4-Androstenedione was found in a range of 1.04 ng/g-2.52 ng/g | UPLC-MS/MS | Iran | [53] |
| 108 | 53 | 1,3-Dimethylamylamine, sibutramine, methylphenidate, synephrine | DMAA was present in 20% of the dietary supplements. Out of the 108 samples, almost 50% were positive for sibutramine and 10% for methylphenidate | DART-MS/MS | Brazil, USA | [54] |
| 11 | 3 | Sibutramine | Concentrations of sibutramine ranged from 3.5 mg/g to 4.08 mg/g | Electrochemiluminescence (ECL) | China | [55] |
| 16 | 13 | Benfluorex, fluoxetine, pseudoephedrine, tiratricol | Pseudoephedrine 2.6-55.56 mg Fluoxetine 0.14-7.53 Benfluorex 0.01-0.07 Tiratricol 0.01-0.67 |
LC-UV | Italy | [57] |
| 120 | 29 | Sibutramine, fluoxertine | Sibutramine 0.26-113.22 mg per capsule Fluoxetine 1.80-101.08 mg per capsule |
UHLPC-LTQ-Orbitrap MS | China | [58] |
| 17 | 8 | 1,3-Dimethylamylamine (1,3-DMAA), 1,4-dimethylamylamine (1,4-DMAA), 1,3-dimethylbutylamine (1,3-DMBA), higenamine, deterenol, phenpromethamine, oxilofrine, octodrine, beta-methylphenylethylamine | Concentration range for detected stimulants were 2.7-17 mg of deterenol, 1.3-20 mg of phenpromethamine, 5.7-92 mg of beta-methylphenylethylamine, 18-73 mg of octodrine, 48 mg of higenamine, 18-55 mg of oxilofrine, 17 mg of 1,3-dimethylamylamine, 1.8 mg to 6.6 of 1,3-dimethylbutylamine, and 5.3 mg of 1,4-dimethylamylamine | UHPLC quadrupole-Orbitrap MS | Netherlands | [59] |
| 32 | 16 | Phenethylamine, synephrine, oxilofrine, hordenine, beta-methylphenethylamine, N-methyltyramine, octopamine, deterenol | High concentrations of phenethylamine were found in two products (29.9 and 26.8%, respectively). Synephrine was detected in 15 products with various contents ranging from 0.5 to 5.7%. The concentration of oxilofrine in these products ranged from 0.2 to 11.6%; deterenol with a content of 4.1%. The potential intake of the compound was estimated to be 28.7 mg | NMR | USA | [60] |
| 40 | 32 | Тestosterone propionate, testosterone phenylpropionate, testosterone isocaproate, testosterone decanoate, testosterone cypionate, testosterone undecanoate, stanozolol, drostanolone propionate, trenbolone acetate, oxymetholone, methandrostenolone | Eight of the 40 samples analyzed lacked all or some of the components listed on the label | NMR | Brazil | [61] |
| 160 | 89 | Sibutramine, fluoxetine, phenolphthalein, orlistat | Sibutramine was detected in 26% of the capsules, with sibutramine concentration ranging from 0.1 to 22 mg per dosage unit (capsule). The dosages found in this study varied from 0.05 to 56 mg per capsule, with phenolphthalein 0.8 mg-29 mg per capsule fluoxetine | NMR | France | [62] |
| 48 | 3 | Nandrolone, testosterone, dehydroepiandrosterone (DHEA), 5α-androstan-3,17-dione, 19-norandrostendione, progesterone | Positive tests included substances at values ranging from 0.022 to 0.398 mg/kg | Two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC–TOF-MS) | Czech Republic | [63] |
| 20 | 5 | Phenethylamine, N, N-diethyl phenethylamine, N-ethyl-α-ethyl-phenethylamine | N-Ethyl-α-ethyl-phenethylamine was found in a range of 6.48-23.4 mg per capsule Phenethylamine in a range of 1.39-24.7 mg |
LC-MS-MS | USA | [64] |
| 9 | 6 | Ephedrine | Ephedrine range: 1.08-3.54 mg per capsule | HPLC | USA | [65] |
| 7 | 7 | 1,3-Dimethylamylamine | DMAA range from 1.1 mg/g to 32 mg/g was found | UPLC-MS/MS | USA | [66] |
| 2 | 2 | Sibutramine, phenolphthalein | 24.71 mg sibutramine and 48.20 mg phenolphthalein were found | HPLC | Romania | [67] |
| 10 | 3 | Sibutramine, fluoxetine | All three adulterate supplements were manufactured in China and labeled as food supplements containing only plants—“100% natural products” | Fourier-transform infrared spectroscopy (FTIR) GC-MS |
Romania | [68] |
| 20 | 3 | Ephedrine, caffeine | Ephedrine range: 31–90 mg/dose | HLPC | Romania | [69] |
| 26 | 18 | Sildenafil, tadalafil, vardenafil | 69% of the analyzed products that are found on the Romanian market turned out to be adulterated | LC-MS | Romania | [70] |
| 80 | 76 | Diphenoxylate, tramadol, codeine, sertraline, fluoxetine | Diphenoxylate and tramadol are found at concentrations of 1.4–4 mg/capsule and 67–150 mg/capsule, respectively | GC-MS | Iran | [72] |
| 138 | 74 | Fluoxetine | In comparison to supplements produced and purchased in South Africa (5194 ng/g), supplements imported and purchased in South Africa showed a greater amount of fluoxetine contamination (20052 ng/g) | LC-MS | South Africa | [73] |
| 24 | 16 | 13 anabolic steroids | Amount of found substances per capsule: DHEA: 16 mg-28 mg Androstenedione: 1 mg-9 mg Methasterone: 2.4 mg-8 mg Testosterone: 7 mg Furazabol: 31 mg Androst-4-ene-3,11,17-trione: 61 mg |
GC-MS HPLC DAD UV-VIS NMR |
UK | [74] |
| 198 | 5 | Testosterone, stanozolol, 5α-hydroxylaxogenin | According to the detected concentration and daily serving size, it was found that 0.34 μg of stanozolol would be consumed per day. | LC-MS/MS | Korea | [75] |
| 36 | 8 | Ephedrine, pseudoephedrine | Ephedrine at a concentration ranging from 370 ng/g to 1000 ng/g (in one case, ephedrine was not declared in the label) pseudoephedrine in 540 ng/g | LC–HRMS | Italy | [76] |
| 52 | 26 | Sibutramine | Half of the supplements included sibutramine in levels as high as 35 mg per capsule | HPLC-UV | Switzerland | [77] |
| 124 | 6 | Diuretics | Nearly 5% of the samples were found to be contaminated with diuretics at values ranging from 0.051 to 162 mg/g | UHPLC-Q-Orbitrap | Republic of Korea | [78] |
| 3 | 3 | Sibutramine | A new method was developed for the identification and quantification of the sibutramine by HPTLC | HPLC HPTLC |
Turkey | [79] |
| 18 | 8 | 4-Androstene-3β,17β-diol, 5α-androstane-3β,17β-diol | Concentration that was around or above 0.01 mg per capsule or tablet was found | LC-MS/MS | Netherlands | [80] |
| 2 | 2 | Мetandienone, Stanozolol | Metandienone with a concentration of 16.8 mg/tablet and stanozolol 14.5 mg/tablet were identified. Norandrostenedione was also found in both products, along with small levels of numerous additional steroids | GC-MS HPLC-DAD |
Germany | [81] |