The usefulness of 2D DOSY and 3D DOSY‐COSY ¹H NMR for mixture analysis: application to genuine and fake formulations of sildenafil (Viagra)

Abstract

Two-dimensional diffusion ordered spectroscopy (DOSY) (1)H NMR is proposed to analyze drugs that are complex mixtures in order to discriminate genuine from fake formulations. The method was applied to the analysis of 17 formulations of sildenafil, one being genuine Viagra and the others illegally manufactured formulations of this drug coming from India, Syria and China. It enabled (i) distinguishing imitations or counterfeit from the authentic formulation, (ii) detecting the presence of sildenafil or adulterants, (iii) gaining information on the formulation process by detection of various excipients, thus giving a precise and global 'signature' of the manufacturer. Even though some samples are slightly overdosed, the quality of products manufactured in India and Syria was better than that of Chinese formulations which were adulterated with vardenafil and homosildenafil. This study also presents a three-dimensional DOSY-COSY (1)H NMR experiment that provides both virtual separation and structural information.

Identification of Thiosildenafil in a Health Supplement

“…Thiosildenafil: The ethyl acetate extract was evaporated and the residue directly examined by NMR. 1 H NMR (400 MHz, CDCl 3 ) and ITMS data were in accordance with reported ones [7].…”

“…The reason of this proliferation is mainly due to the intention to escape analytical controls. Therefore, several efforts were focused on the best analytical tool to catch the adulterant, since first HPLC determination [4], followed by NMR [5], LC/MS and LC/MS/MS [6], until the recent 2D and 3D DOSY 1 H NMR [7]. In this paper we report a further case of adulteration and propose the use of HPTLC as simple, direct and low cost method to detect such and other adulterants, also in case of their presence in complex herbal mixtures.…”

Facing Counterfeit Medications in Sexual Medicine. A Systematic Scoping Review on Social Strategies and Technological Solutions

“…26 Another potential risk comes from the use of different APIs in the preparation of the counterfeited product, either voluntarily, in order to increase efficacy, 59 or involuntarily, following inadequate quality control. For treatments used in sexual medicine, agents voluntarily added to increase efficacy include different drugs belonging to the same family (eg, vardenafil being added to sildenafil tablets 40 ), or drugs potentially "synergistic" to the main product (eg, sildenafil being added to dapoxetine tablets 57 ). While in theory the effects of the combined drugs might lead to increased efficacy, the risk of developing side effects is similarly increased; additionally, the association of these drugs is not recommended by any of the regulatory agencies or guidelines.…”

An Evaluation of Prevalence of Low Quality of Medicines in Saudi Arabia and Factors Associated an Analytical Comparative Study

“…In contrast, the security authority in Jazan region, the south region in Saudi Arabia, had managed, in coordination with the health affairs in Jazan, to thwart the smuggling of the biggest prohibited shipment of sexual medicines introduced to the Saudi border from Yemen. The experts estimate this case to be the largest shipment of drugs smuggled into Saudi Arabia (worth more than half a million Saudi riyal) [51][52][53][54][55][56][57][58][59][60].…”