title: Use of liquid chromatography-mass spectrometry and a hydrolytic technique for the detection and structure elucidation of a novel synthetic vardenafil designer drug added illegally to a "natural" herbal dietary supplement.
abstract: An herbal dietary supplement, marketed as a natural product for the enhancement of sexual function, was purchased covertly over the internet. The product was analyzed by LC-MS and found to contain a compound related to synthetic phosphodiesterase 5 (PDE-5) inhibitors. Based on LC with photodiode array and mass spectral detection, along with collision-induced dissociation-mass spectral analysis, the structure of the compound was tentatively identified as a designer drug of vardenafil in which the N-ethylpiperazine ring had been replaced by a piperidine ring. This structure was unambiguously confirmed by acid hydrolysis of both the unknown ("piperidenafil") and vardenafil and comparison of their hydrolysis products by LC-MS and GC-MS. The hydrolytic technique proved to be a useful tool for the structure elucidation of piperidenafil and may be a useful technique for the structure elucidation of other erectile dysfunction designer drugs in the future. The dosage level of piperidenafil in the herbal product was 41 mg per capsule when calculated as the free base.
authors.affiliation: US Food and Drug Administration, Division of Pharmaceutical Analysis, St. Louis, MO 63101, USA. reepmeyerj@cder.fda.gov
authors.forename: John C
authors.initials: JC
authors.lastname: Reepmeyer
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Woodruff
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D015198:Designer Drugs / Q000032:analysis* / Q000737:chemistry; D019587:Dietary Supplements / Q000032:analysis*; D006868:Hydrolysis; D007093:Imidazoles / Q000032:analysis* / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D010726:Phosphodiesterase Inhibitors / Q000032:analysis / Q000737:chemistry; D010879:Piperazines / Q000032:analysis* / Q000737:chemistry; D028321:Plant Preparations / Q000032:analysis / Q000737:chemistry; D011744:Pyrimidinones / Q000032:analysis* / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013450:Sulfones / Q000032:analysis* / Q000737:chemistry; D014227:Triazines / Q000032:analysis / Q000737:chemistry; D000069058:Vardenafil Dihydrochloride
chemical_list: D015198:Designer Drugs; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D028321:Plant Preparations; D011744:Pyrimidinones; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; C526115:piperidenafil