pulsed NMR techniques were used to investigate the solid-state dynamics of porphine molecules in which the central protons have been replaced by deuterons. Changes observed in the line width of the *H NMR signal suggest that, as happened to be the case with the fully protonated derivative, molecules of deuterated porphine rotate in the crystal. Variable-temperature measurements of the proton relaxation times in the rotating frame provided the activation parameters for this motion, which were found to be slightly higher than those observed for the nondeuterated compound. This effect can be related to a combined motion that has been proposed for reconciling the CPMAS NMR and the X-ray results available for porphine, according to which the solid-state tautomerism of the central hydrogens might produce a reorientation of the molecules in the crystals about their main molecular axes. Upon replacement of the central protons by deuterons this model predicts that kinetic isotope effects known to characterize the N-H tautomerism of porphyrins will slow the rates of macrocycle reorientations in the crystal, a dynamic behavior which is reflected in the experimental results.
Introduction
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.
Aim
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.
Main Outcome Measure
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.