Characterization of Sildenafil analogs by MS/MS and NMR: A guidance for detection and structure elucidation of phosphodiesterase-5 inhibitors

• Synthetic pathway for preparation of sixteen analogs of Sildenafil is proposed.
• A list of key MS/MS and NMR signals of these analogs is provided.
• This list will help to ascertain if a supplement is adulterated by an analog.
• This list of signals will help to determine the structure of novel analogs.
• A discussion and systematic analyses are reported on mass fragmentation patterns.

Novel synthetic analogs of Sildenafil are constantly detected as adulterants in counterfeit drugs and dietary supplements. Their intake constitutes a serious health hazard as side effects are unknown. In this paper an investigation is carried out on NMR and MS/MS spectra of Sildenafil, Thiosildenafil, Acetildenafil and thirteen of their analogs: a list of key signals is reported and discussed with the intent to provide a tool that can help in detecting adulteration and in elucidating the structure of novel analogs. In this view extensive spectral data were reported, discussed and summarized in tables.A discussion on mass fragmentation and NMR chemical shifts is also provided to rationalize assignation. Moreover, a comprehensive information on the route of synthesis is provided for the benefit of those medicines control laboratories that need to synthesize analogs reference standards in-house.

By a detailed analysis of the characteristic MS/MS fragments and NMR signals of the analogues belonging to the class of Sildenafil, Acetyldenafil and Thio-Sildenafil, the article gives an instrument to easily point out the presence of new analogues in a sample and to determine their structure.Figure optionsDownload as PowerPoint slide