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

The scale at which erectile dysfunction (ED) medicines are obtained outside of the official health system rivals and possibly exceeds legitimate sales. According to literature a high-risk segment of this market is occupied by adulterated food supplements. The principle adulterants identified were structural analogues of the registered ED drugs sildenafil, tadalafil, and vardenafil. Currently, at least 46 different analogues have been reported and still more are expected.The intellectual origin of analogues was found in patent literature which described the drug discovery process. Patent literature offers a flexible approach to synthesize hundreds of analogues. Most of the analogues currently known had long been disclosed in patent literature. Screening for (new) analogues is best carried out by using advanced LC–MS/MS techniques that focus on marker fragment ions.Analogues are experimental drugs in essence because most have no known efficacy or safety profile. Their use in seemingly harmless food supplements is expected to cause serious adverse effects. However, few reports have emerged in literature on actual harm. Considering the exposure to analogues and their adverse effects being unknown a gross underreporting of complaints is expected.

► Analogues of sildenafil, tadalafil, and vardenafil are predominantly found as adulterants in food supplements.
► Analogues are essentially experimental drugs which were discarded from the drug discovery process for having deficiencies.
► The number of analogues of ED drugs identified increased from 1 in 2003 to at least 46 in 2011.
► Most analogues were described in patent literature or were derived from the disclosed information.
► Food supplements adulterated with analogues pose a high health risk but little is known about the actual harm caused.