Detection of a tadalafil analogue as an adulterant in a dietary supplement for erectile dysfunction.
BACKGROUND
Several cases of adulteration of dietary supplements with tadalafil, sildenafil, and vardenafil, or their unapproved analogues have been reported worldwide. Mainly, the presence of the latter represents a serious health risk to consumers as their efficacy and toxic effects have not been assessed and may result in unpredictable adverse effects.


OBJECTIVE
To investigate the suspected adulteration with synthetic phosphodiesterase type 5 (PDE-5) inhibitors in a dietary supplement marketed in Argentina for the treatment of erectile dysfunction (ED).


METHODS
The content of the capsules of the dietary supplement (sample A) was analyzed by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) diode-array detection. From the organic extract of sample A, a major compound was purified by column chromatography (CC). The isolated compound was identified by proton nuclear magnetic resonance (1H NMR) and carbon NMR (13C NMR), heteronuclear single quantum coherence, distortionless enhancement by polarization transfer (DEPT 135), electrospray ionization mass spectrometry, and ultraviolet, and infrared (Fourier transform infrared spectroscopy) spectroscopy.


METHODS
Proof of adulteration of herbal products with synthetic PDE-5 inhibitors.


RESULTS
By TLC and HPLC analysis, a major compound was detected in sample A organic extract. The purification of this extract by CC led to the isolation of a pure compound which was identified according to its spectral data as (6R,12aR)-2-amino-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydropyrazino [1',2':1,6] pyrido [3,4-b] indole-1,4-dione or aminotadalafil.


CONCLUSIONS
An unapproved PDE-5 inhibitor analogue, which was identified as aminotadalafil, has been detected in a dietary supplement. This study represents the first report in Latin America and one of the few independent studies of an adulteration with an unapproved PDE-5 inhibitor of an herbal product for ED treatment.
Cátedra de Farmacognosia, Facultad de Farmacia y Bioquímica (UBA), IQUIMEFA (UBA-CONICET), Buenos Aires, Argentina.
Jeronimo
J
Ulloa
Luis
L
Sambrotta
Flavia
F
Redko
Osvaldo Nestor
ON
Mazza
Gustavo
G
Garrido
Edgardo F
EF
Becher
Liliana
L
Muschietti
D001118:Argentina; D052117:Benzodioxoles; D002243:Carbolines / Q000008:administration & dosage / Q000009:adverse effects*; D002851:Chromatography, High Pressure Liquid; D019587:Dietary Supplements / Q000009:adverse effects* / Q000032:analysis; D004340:Drug Contamination / Q000517:prevention & control; D007172:Erectile Dysfunction / Q000188:drug therapy*; D006801:Humans; D008297:Male; D004364:Pharmaceutical Preparations / Q000032:analysis*; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D028321:Plant Preparations / Q000009:adverse effects* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D000068581:Tadalafil
D052117:Benzodioxoles; D002243:Carbolines; D004364:Pharmaceutical Preparations; D058986:Phosphodiesterase 5 Inhibitors; D028321:Plant Preparations; D000068581:Tadalafil; C551065:aminotadalafil
Adulteration; Aminotadalafil; Dietary Supplements; Erectile Dysfunction; PDE-5 Inhibitor Analogues