title: Characterization of Sildenafil analogs by MS/MS and NMR: a guidance for detection and structure elucidation of phosphodiesterase-5 inhibitors.
abstract: 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.
authors.affiliation: Dipartimento del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Mustazza
authors.affiliation: Dipartimento del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Borioni
authors.affiliation: Dipartimento del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Electronic address: andrea.rodomonte@iss.it.
authors.forename: Andrea Luca
authors.initials: AL
authors.lastname: Rodomonte
authors.affiliation: Dipartimento del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Bartolomei
authors.affiliation: Dipartimento del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Antoniella
authors.affiliation: Scuola in Scienze del Farmaco e dei Prodotti della Salute, Università di Camerino, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: Di Martino
authors.affiliation: Dipartimento del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Valvo
authors.affiliation: Dipartimento del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Sestili
authors.affiliation: Scuola in Scienze del Farmaco e dei Prodotti della Salute, Università di Camerino, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Costantini
authors.affiliation: Dipartimento del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Gaudiano
mesh_terms: D058110:Counterfeit Drugs / Q000032:analysis; D019587:Dietary Supplements / Q000032:analysis; D004340:Drug Contamination; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D058986:Phosphodiesterase 5 Inhibitors / Q000032:analysis / Q000737:chemistry; D010879:Piperazines / Q000032:analysis* / Q000737:chemistry; D011687:Purines / Q000032:analysis / Q000737:chemistry; D011743:Pyrimidines / Q000032:analysis* / Q000737:chemistry; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000032:analysis* / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D058110:Counterfeit Drugs; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D011743:Pyrimidines; D013450:Sulfones; D000068677:Sildenafil Citrate; C539492:thiosildenafil
keywords: Acetildenafil; MS/MS; NMR; Phosphodiesterase-5 inhibitors; Sildenafil analogs