title: Isolation and structural characterization of a new tadalafil analog (2-hydroxyethylnortadalafil) found in a dietary supplement.
abstract: A screen for known PDE-5 inhibitors in a dietary supplement product marketed for "enhanced sexual performance" detected a compound that structurally resembled tadalafil. The compound was isolated from the supplement matrix using high-performance liquid chromatography with ultraviolet detection (HPLC-UV) and a fraction collector, and was further characterized using nuclear magnetic resonance (NMR), liquid chromatography-mass spectrometry (LC-MS), as well as high-resolution accurate mass mass spectrometry (HRAM-MS). The analog had an accurate mass of m/z 420.15614 (error is 1.77235ppm) for the protonated species [M+H](+), corresponding to a molecular formula of C23H22N3O5. Mass spectral fragmentation data suggested that the modification occurred in place of the CH3 located on the pyrazinopyridoindole-1,4-dione of tadalafil. NMR was utilized to further elucidate the configuration of the substitution. The analysis indicated that the moiety is a CH2CH2OH, hydroxyethyl group. The new analog has been named 2-hydroxyethylnortadalafil.
authors.affiliation: United States Food and Drug Administration, Forensic Chemistry Center, 6751 Steger Drive, Cincinnati, OH, 45237, USA. Electronic address: sara.kern@fda.hhs.gov.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Kern
authors.affiliation: United States Food and Drug Administration, Forensic Chemistry Center, 6751 Steger Drive, Cincinnati, OH, 45237, USA.
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Nickum
authors.affiliation: United States Food and Drug Administration, Forensic Chemistry Center, 6751 Steger Drive, Cincinnati, OH, 45237, USA.
authors.forename: Rick A
authors.initials: RA
authors.lastname: Flurer
authors.affiliation: United States Food and Drug Administration, Forensic Chemistry Center, 6751 Steger Drive, Cincinnati, OH, 45237, USA.
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Toomey
authors.affiliation: United States Food and Drug Administration, Forensic Chemistry Center, 6751 Steger Drive, Cincinnati, OH, 45237, USA.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Litzau
mesh_terms: D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002851:Chromatography, High Pressure Liquid; D019587:Dietary Supplements; D013058:Mass Spectrometry; D058986:Phosphodiesterase 5 Inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D066244:Proton Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet; D000068581:Tadalafil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil; C000618187:2-hydroxyethylnortadalafil
keywords: LC/MS; PDE-5 inhibitor; Tadalafil analog