Isolation and structural characterization of two tadalafil analogs found in dietary supplements

During routine screenings of two “libido enhancer” dietary supplements using LC–MSn, 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.

► Two new tadalafil analogs were detected in dietary supplements.
► LC–MSn, accurate mass and NMR were used to characterize the analogs.
► The analogs were named 2-hydroxypropylnortadalafil and n-butylnortadalafil.