Structure determination of new analogues of vardenafil and sildenafil in dietary supplements

Abstract

New analogues of vardenafil and sildenafil illegally added to dietary supplements were detected by high-performance liquid chromatography (HPLC) analysis with a photodiode array detector (PDA). These compounds were isolated and their structures elucidated by mass spectrometry (MS), infrared (IR) spectroscopy, one- and two-dimensional nuclear magnetic resonance (NMR). One of the new analogues given the trivial name pseudovardenafil (compound 1) was structurally elucidated and shown to be 1-[[3-(1,4-dihydro-5-methyl-4-oxo-7-propylimidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxyphenyl]sulfonyl]-piperidine. It was a vardenafil analogue isolated from a dietary supplement capsule. Compared with vardenafil, the piperidine ring was substituted for the ethylpiperazine group. The second new analogue, trivially named hydroxyhongdenafil (compound 2), was separated from bulk powder used as a raw material for a dietary supplement. The piperazine and phenyl groups were connected through an acetyl group instead of a sulfonyl group, and hydroxyethylpiperazine was substituted for the methylpiperazine of sildenafil. It was structurally elucidated as 5-[2-ethoxy-5-[[4-(2-hydroxyethyl)-1-piperazinyl]acetyl]phenyl]-1,4-dihydro-1-methyl-3-propyl-7H-pyrazolo[4,3-d]pyrimidin-7-one.

Adulteration of herbal sexual enhancers and slimmers: The wish for better sexual well-being and perfect body can be risky

“…The detection limit was set to be 3.0% (w/w). piperazine and phenyl groups connected through an acetyl group instead of a sulfonyl group, and hydroxyethylpiperazine substituted for the methylpiperazine of sildenafil, were detected (Park et al, 2007).…”

Towards a decade of detecting new analogues of sildenafil, tadalafil and vardenafil in food supplements: A history, analytical aspects and health risks

“…Hydroxy-acetildenafil Hydroxy-hongdenafil [18,19,111] Homosildenafil [11,24,109] Nitroso-prodenafil (top) Muta-prodenafil (below) [55,56] [75] increased sensitivity and specificity [8]. In searching for unknowns MS/MS screening techniques are very suitable.…”

Structural characterization of sulfoaildenafil, an analog of sildenafil

“…Numerous analogs of sildenafil, tadalafil and vardenafil have been reported in the literature [2,[11][12][13][14][15][16][17][18][19][20][21]. In general, analogs of sildenafil, such as homosildenafil [2,11], hydroxyhomosildenafil [11,12] and aildenafil (dimethylsildenafil, methisosildenafil) [18,19], incorporate structural changes in the piperazine portion of the molecule.…”