title: 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.
abstract: 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 MS(n), 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 CH(2) group than acetildenafil, it was named nor-acetildenafil.
authors.affiliation: U.S. Food and Drug Administration, Division of Pharmaceutical Analysis, St. Louis, MO 63101, USA. john.reepmeyer@fda.hhs.gov
authors.forename: John C
authors.initials: JC
authors.lastname: Reepmeyer
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Woodruff
mesh_terms: D000588:Amines / Q000737:chemistry; D002853:Chromatography, Liquid; D019587:Dietary Supplements / Q000032:analysis*; D004340:Drug Contamination; D008401:Gas Chromatography-Mass Spectrometry; D013058:Mass Spectrometry; D010879:Piperazines / Q000032:analysis*; D011687:Purines / Q000032:analysis; D012015:Reference Standards; D000068677:Sildenafil Citrate; D013056:Spectrophotometry, Ultraviolet; D013449:Sulfonamides / Q000032:analysis; D013450:Sulfones / Q000032:analysis*
chemical_list: D000588:Amines; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D013450:Sulfones; D000068677:Sildenafil Citrate