title: Isolation and structural characterization of a new tadalafil analog (chloropropanoylpretadalafil) 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 chloropretadalafil, a known analog of 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 gas chromatography with Fourier Transform infrared detection and mass spectral detection (GC/FT-IR/MS), as well as high resolution mass spectrometry (HRMS). The analog had an accurate mass of m/z 441.1216 (error is 0.8706ppm) for the protonated species [M+H](+), corresponding to a molecular formula of C23H22ClN2O5. HRAM and GC/FT-IR/MS mass spectral fragmentation data suggested that the modification is a chloropropanoyl moiety extending from the nitrogen on the piperidine ring of chloropretadalafil. The proposed new analog has been named chloropropanoylpretadalafil.
authors.affiliation: U.S. Food and Drug Administration, Forensic Chemistry Center, Cincinnati, OH, United States. Electronic address: sara.kern@fda.hhs.gov.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Kern
authors.affiliation: U.S. Food and Drug Administration, Forensic Chemistry Center, Cincinnati, OH, United States.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Lorenz
authors.affiliation: U.S. Food and Drug Administration, Forensic Chemistry Center, Cincinnati, OH, United States.
authors.forename: Adam
authors.initials: A
authors.lastname: Lanzarotta
authors.affiliation: U.S. Food and Drug Administration, Forensic Chemistry Center, Cincinnati, OH, United States.
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Nickum
authors.affiliation: U.S. Food and Drug Administration, Forensic Chemistry Center, Cincinnati, OH, United States.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Litzau
mesh_terms: D002851:Chromatography, High Pressure Liquid; D019587:Dietary Supplements / Q000032:analysis*; D008401:Gas Chromatography-Mass Spectrometry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D000068581:Tadalafil / Q000031:analogs & derivatives* / Q000032:analysis / Q000302:isolation & purification
chemical_list: C000618692:chloropropanoylpretadalafil; D000068581:Tadalafil
keywords: GC/FT-IR/MS; LC-HRAM-MS; New tadalafil analog; Phosphodiesterase type-5 (PDE-5) inhibitors