Isolation and identification of hydroxythiohomosildenafil in herbal dietary supplements sold as sexual performance enhancement products

Abstract

An unknown compound is detected and isolated from two herbal dietary supplements bought on the internet. The structure of the unknown compound is elucidated using ESI-MS/MS, NMR, UV and IR. The compound, named hydroxythiohomosildenafil, is identified as an analogue of sildenafil in which the oxygen atom is substituted with a sulfur atom in the pyrazolopyrimidine moiety, and a hydroxyethyl group instead of a methyl group is attached to the piperazinyl nitrogen. It is the first report of this compound being detected in herbal dietary supplements. The UV, IR and completely assigned NMR data of hydroxythiohomosildenafil is recorded.

Use of near infrared spectroscopy and spectral databases to assess the quality of pharmaceutical products and aid characterization of unknown components

“…The inset is the expansion of the spectra between two dashed lines, and the arrows point to the peaks previously assigned to sildenafil citrate. in Pronoton are consistent with those of Li et al 31 The presence of H-29 and H-30 at 2.83 and 3.72 ppm, respectively, in the 1 H NMR spectra and the two carbon signals at 60.2 ppm (C-29) and 58.0 ppm (C-30) observed in 13 C NMR spectra and distortionless enhancement by polarization transfer (DEPT) spectra 32 were the markers of this compound and were used to differentiate it from sildenafil and its other derivatives. Based on these analyses, it was further confirmed that the product Pronoton was adulterated with hydroxythiohomosildenafil.…”

Rapid screening test for adulteration in raw materials of dietary supplements

“…By targeting the region of the spectra which will contain prominent features of the PDE-5 and PDE-5-like compounds, a single method can be used to ascertain the presence of multiple adulterants. Comparison of spectra obtained with the PDE-5 standards to literature spectra of PDE-5 inhibitors and their analogues not physically tested here confirms the presence of bands in this region [11][12][13][14][15]. KF31327, a PDE-5 like compound which does not share strong structural similarity to most PDE-5 inhibitors, also shows banding in this region, making this a highly effective method for detecting the presence of multiple PDE-5 inhibitors with a single test.…”

Sildenafil 4.0—Integrated Synthetic Chemistry, Formulation and Analytical Strategies Effecting Immense Therapeutic and Societal Impact in the Fourth Industrial Era

“…In the last decade, various bioanalytical methods have been reported in the literature dedicated to the analysis of sildenafil [ 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 ]. An overview is presented in Table 5 [ 30 , 123 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , ...…”

“…In these reports, liquid chromatography coupled with mass spectrometry has become the technique of choice offering highly selective and sensitive determinations. Moreover, the LC-MS/MS technique has been considered as the “gold standard” for the screening and identification of erectile dysfunction drugs and their illegal analogues in adulterated food supplements and sexual performance enhancement products [ 182 , 183 , 184 ].…”

“…Liquid extraction has been applied in two analytical LC-MS/MS protocols developed for the determination for the analyte in dried blood spot (DBS) [ 182 ] and human plasma [ 183 ]. In 2014, a DBS-based LC-MS method has been reported by the Jimenez and his co-workers [ 182 ].…”