Use of liquid chromatography–mass spectrometry and a chemical cleavage reaction for the structure elucidation of a new sildenafil analogue detected as an adulterant in an herbal dietary supplement

An herbal dietary supplement, marketed as a natural product for the enhancement of sexual function, was analyzed by HPLC with photodiode array and mass spectral detection and found to contain a compound related to the synthetic phosphodiesterase-5 (PDE-5) inhibitors. Based on UV spectra, mass spectra and direct infusion MSn, the structure of the compound was tentatively identified as a sildenafil analogue in which the sulfonyl group had been replaced with an acetyl group. This new analogue is similar to acetildenafil, a previously reported sildenafil analogue, but differs in that it contains an N-methyl group where acetildenafil contains an N-ethyl group. The structure of the unknown was unequivocally established by chemical cleavage of the phenacylamine group of the molecule to generate N-methylpiperazine; other cleavage products matched those generated from acetildenafil. Since the new compound has one less CH2 group than acetildenafil, it was named nor-acetildenafil.