To date, there are 80 synthetic PDE-5i found as adulterants in dietary supplements. Analogues of sildenafil remain as the top list with 50 (62%) and are followed by analogues of tadalafil, 21 (26%), analogues of vardenafil, 7 (9%) and others, 2 (3%). The sildenafil group can be sub-categorized into sulphonamide-bonded (24, 48%), acetyl-bonded (11, 22%), carbonyl or thiocarbonyl-bonded (8, 16%) and other types (7, 14%) based on the functional group linked to pyrazolopyrimidine-one moieties. Meanwhile, analogues of tadalafil have become popularly found as adulterants in dietary supplements like beverages and herbal extracts from 2015 to 2016. The uptrend has been observed with the increase in number and complexity with more trans-oriented and dimerized tadalafil analogues being reported. Interestingly, there is no much increase for analogues of vardenafil. About two thirds of analogues have been reported from the Asian countries (67%), followed by Europe (22%) and North America (11%). South Korea and Singapore have reported the most number of analogues with a total number of 40 (50%). One plausible contributing factor to this trend is the convenient purchase of sexual enhancement dietary supplements, especially the on-line purchase. In terms of analytical methodologies, high performance liquid chromatography (HPLC) hyphenated to ultra-violet (UV) and/or mass spectrometry (MS) detection have been preferred in the screening analysis, i.e. 70 out of 77 compounds have been analysed by HPLC-UV. In addition, the electrospray ionization multistage fragmentation experiments (ESI-MSn) for acquiring low- and high-resolution mass spectra have been successfully applied to detect and quantify PDE-5i in adulterated products simultaneously. Nuclear magnetic resonance (NMR) is another important technique in the structural elucidation of novel analogues.
Keywords: Mass Spectrometry; NMR; PDE-5i; dietary supplements; sildenafil; tadalafil; vardenafil.
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