Isolation and structural characterization of a new tadalafil analog (2-hydroxyethylnortadalafil) found in a dietary supplement

• A new synthetic phosphodiesterase type-5 (PDE-5) inhibitor analog has been isolated and characterized.
• The new analog was detected in an “all-natural” dietary supplement marketed for “enhanced sexual performance”.
• The analog was characterized by HPLC-UV, LC–MSn, high-resolution accurate mass MS, and NMR.
• The analog is structurally similar to tadalafil.

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 1.77235 ppm) 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.

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