title: Use of a hydrolytic procedure and spectrometric methods in the structure elucidation of a thiocarbonyl analogue of sildenafil detected as an adulterant in an over-the-counter herbal aphrodisiac.
abstract: A sildenafil-related compound was detected in an herbal dietary supplement marketed as an aphrodisiac. The compound was identified as an analogue of sildenafil in which the carbonyl group in the pyrimidine ring of sildenafil was substituted with a thiocarbonyl group, and the methyl group on the piperazine ring was substituted with a hydroxyethyl group. Based on this structure, the compound was named thiohydroxyhomosildenafil. The structure of the compound was established using HPLCIMS, UV spectrometry, electrospray ionization-MS/MS, NMR spectrometry, and a hydrolytic process. One key product of hydrolysis was 1-(2-hydroxyethyl)-piperazine; the identification of this product defined the amine portion of the compound. Another key product of hydrolysis was hydroxyhomosildenafil, generated by hydrolysis of the thiocarbonyl group to a carbonyl group (C = S --> C = O). Hydroxyhomosildenafil was detected as a minor component in the dietary supplement.
authors.affiliation: U.S. Food and Drug Administration, Division of Pharmaceutical Analysis, St. Louis, MO 63101, USA. reepmeyer@gmail.com
authors.forename: John C
authors.initials: JC
authors.lastname: Reepmeyer
authors.forename: D André
authors.initials: DA
authors.lastname: D'Avignon
mesh_terms: D001046:Aphrodisiacs / Q000032:analysis*; D002244:Carbon / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002855:Chromatography, Thin Layer / Q000379:methods; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D008956:Models, Chemical; D010879:Piperazines / Q000032:analysis* / Q000737:chemistry; D028321:Plant Preparations / Q000032:analysis*; D011687:Purines / Q000032:analysis / Q000737:chemistry; D000068677:Sildenafil Citrate; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013053:Spectrophotometry / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013450:Sulfones / Q000032:analysis* / Q000737:chemistry
chemical_list: D001046:Aphrodisiacs; D010879:Piperazines; D028321:Plant Preparations; D011687:Purines; D013450:Sulfones; D002244:Carbon; D000068677:Sildenafil Citrate