Study of the electrospray ionization tandem mass spectrometry of sildenafil derivatives

Abstract

A detailed analysis of the product ion spectrum generated from the protonated molecule of sildenafil (Viagra(R)) under multiple tandem mass spectrometry (ESI-MS(n)) conditions using an ion-trap mass spectrometer is reported. Molecular composition data of the fragment ions were obtained with the aid of comparisons of the multiple tandem mass spectra of eight sildenafil derivatives in two series, the structures of which are identical except for some substituted alkyl groups. Attempts have been made to provide rational pathways for the formation of the fragment ions from these protonated sildenafil derivatives. The structure-fragmentation relationships will facilitate the characterization of the structures of other sildenafil analogs.

Direct intramolecular gas‐phase transfer reactions during fragmentation of sildenafil and thiosildenafil analogs in electrospray ionization mass spectrometry

“…Zhong 10 has defined the structures of four product ions from fragmentation of product ion m/z 377 in sildenafil, which correspond in mass to those listed here. Each structure is a result of fragmentation of the sulfinic acid group or ethoxy group on the benzene ring.…”

“…[1][2][3][4][5][6][7][8][9] Electrospray ionization mass spectrometry (ESI-MS) has been used extensively in the characterization of ED drug analogs, and has been the primary tool, along with nuclear magnetic resonance (NMR), in the structural elucidation of these designer drugs. The ESI-MS fragmentation pathways for sildenafil were initially studied by Zhong et al 10 by comparison of the MS n fragmentation patterns of sildenafil and eight sildenafil derivatives. Many of these fragmentation pathways were further supported by mass spectral analysis of the sildenafil designer drugs.…”

Structure elucidation of thioketone analogues of sildenafil detected as adulterants in herbal aphrodisiacs

“…The sildenafil product ion at m/z 377 results from fragmentation of the S-N sulfonamide bond with a hydrogen transfer, and the other sildenafil product ions listed in Table 1 are also devoid of the piperazine ring moiety [3,9,15,18]. Major product ions from compound 1 (thiosildenafil) are 30 Da higher than those seen in sildenafil (Table 1), 16 mass units attributed to the presence of a thioketone instead of a ketone and 14 mass units resulting from migration of the methyl group on the piperazine nitrogen atom to the thiocarbonyl sulfur atom, a phenomenon that has been previously reported [19].…”

Low‐energy collision‐induced dissociation of sildenafil thiono analogues: gas‐phase intramolecular nucleophilic substitution through ion‐neutral complexes between a cationic substrate and a thione‐containing neutral nucleophile

“…Representative fragment ions of sildenafil were observed at m/z 377, 313, 311, 299, 283, 163, 100 and 99, and this fragmentation has been well described previously. 6,7 Among these product ions, we were especially interested in the ions at m/z 377, 313 and 311. Compound 1 is a structural analogue of sildenafil in which the oxygen atom is substituted with a sulfur atom in the pyrazolopyrimidine moiety.…”