thiomethisosildenafil and Erectile-Dysfunction

Unapproved ingredients included in herbal medicines and dietary supplements have been detected as adulterated synthetic drugs used for erectile dysfunction. Extraction from a dietary supplement was performed to isolate the compounds by HPLC analysis. The structural characterization was confirmed using mass spectrometry (ESI-TOF/MS and LC-MS/MS),

Topics: Chromatography, High Pressure Liquid; Cyclic Nucleotide Phosphodiesterases, Type 5; Dietary Supplements; Erectile Dysfunction; Gene Expression Regulation, Enzymologic; Herbal Medicine; Humans; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Models, Molecular; Molecular Structure; Phosphodiesterase 5 Inhibitors; Piperazines; Sildenafil Citrate; Sulfones

Two analogues of sildenafil were detected in herbal dietary supplements marketed as aphrodisiacs. Both compounds were identified as thioketone analogues of sildenafil in which the carbonyl group in the pyrimidine ring of sildenafil was substituted with a thiocarbonyl group. The first compound was identified as thiosildenafil, a compound that has recently been reported as an adulterant in health supplements. The structure of the second compound was established using LC-MS, UV spectroscopy, ESI-MS(n), NMR and a hydrolytic process. A detailed study of the hydrolysis products of sildenafil, thiosildenafil, and the second unknown compound proved that the second compound, named thiomethisosildenafil, had a structure analogous to sildenafil in which the N-methylpiperazine moiety had been replaced with 2,6-dimethylpiperazine and the oxygen atom of the carbonyl group in the heterocyclic ring had been replaced with a sulfur atom. Under the hydrolytic reaction conditions employed in this study, thioketones hydrolyze to ketones (e.g., thiosildenafil-->sildenafil), making this a valuable technique for the structure elucidation of thiosildenafil analogues. Ten herbal dietary supplements, each as a capsule dosage form, were found to contain 8-151 mg of thiomethisosildenafil per capsule, and one herbal dietary supplement was found to contain 35 mg of thiosildenafil per capsule.

Topics: Aphrodisiacs; Chromatography, Liquid; Dietary Supplements; Drug Contamination; Erectile Dysfunction; Food Contamination; Humans; Hydrolysis; Ketones; Male; Mass Spectrometry; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Phosphodiesterase Inhibitors; Piperazines; Purines; Pyrimidines; Sildenafil Citrate; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Ultraviolet; Sulfones

Seventeen herbal dietary supplements, marketed as natural substances for the enhancement of sexual function, were analyzed by diffusion ordered spectroscopy (DOSY) (1)H NMR. The method allowed a global analysis of the samples with detection of both active and inactive ingredients present in these complex matrixes. Eight formulations contained compounds related to the synthetic phosphodiesterase-5 inhibitors. Sildenafil, tadalafil, vardenafil, hydroxyhomosildenafil, thiosildenafil, and the newly identified adulterant thiomethisosildenafil were detected. Quantification of these active ingredients was carried out by HPLC or NMR. In addition to these actives, about 30 compounds or excipients were characterized. This study ended up with a three-dimensional DOSY-COSY (1)H NMR experiment on a herbal formulation which provided both virtual separation and structural information.

Topics: Chromatography, High Pressure Liquid; Dietary Supplements; Drug Contamination; Erectile Dysfunction; Excipients; Humans; Magnetic Resonance Spectroscopy; Male; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Phytotherapy; Plants, Medicinal; Pyrimidines; Sulfones