title: Isolation and structural characterization of two tadalafil analogs found in dietary supplements.
abstract: During routine screenings of two "libido enhancer" dietary supplements using LC-MS(n), two compounds were detected that displayed structural similarities to tadalafil. These compounds were isolated from the supplements using high-performance liquid chromatography with fraction collection, and were characterized further using accurate mass determination and NMR. "Compound 1" had an m/z of 434 for the [M+H]⁺ ion, with a corresponding chemical formula of C₂₄H₂₄N₃O₅. "Compound 2" had an m/z of 432 for the [M+H]⁺ ion, with a corresponding chemical formula of C₂₅H₂₆N₃O₄. Although mass spectrometry indicated that these modifications occurred in place of the -CH₃ found on the pyrazinopyridoindole-1,4-dione of tadalafil, NMR was required to elucidate the correct configurations of these substitutions. The data obtained using NMR indicated that the structure of the -C₃H₇O moiety found in Compound 1 was 2-hydroxypropyl, and the -C₄H₉ in Compound 2 was n-butyl. These new analogs were given the names 2-hydroxypropylnortadalafil and n-butylnortadalafil, respectively.
authors: Forensic Chemistry Center, U.S. Food and Drug Administration, 6751 Steger Drive, Cincinnati, OH 45237, USA.
authors: Valerie M
authors: VM
authors: Toomey
authors: Jonathan J
authors: JJ
authors: Litzau
authors: Cheryl L
authors: CL
authors: Flurer
mesh_terms: D052117:Benzodioxoles / Q000737:chemistry / Q000302:isolation & purification*; D002243:Carbolines / Q000737:chemistry / Q000302:isolation & purification*; D002851:Chromatography, High Pressure Liquid; D019587:Dietary Supplements / Q000032:analysis* / Q000592:standards*; D004340:Drug Contamination / Q000331:legislation & jurisprudence; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D058986:Phosphodiesterase 5 Inhibitors / Q000737:chemistry / Q000302:isolation & purification*; D000068581:Tadalafil
chemical_list: D052117:Benzodioxoles; D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil; C572398:n-butylnortadalafil; C572397:2-hydroxypropylnortadalafil