Isolation and identification of ten new sildenafil derivatives in an alleged herbal supplement for sexual enhancement

Gaëtan Assemat; Stéphane Balayssac; Véronique Gilard; Nathalie Martins-Froment; Isabelle Fabing; Frédéric Rodriguez; Yves Génisson; Robert Martino; Myriam Malet-Martino

doi:10.1016/j.jpba.2020.113482

Isolation and identification of ten new sildenafil derivatives in an alleged herbal supplement for sexual enhancement

J Pharm Biomed Anal. 2020 Nov 30:191:113482. doi: 10.1016/j.jpba.2020.113482. Epub 2020 Aug 27.

Authors

Gaëtan Assemat¹, Stéphane Balayssac¹, Véronique Gilard¹, Nathalie Martins-Froment², Isabelle Fabing³, Frédéric Rodriguez⁴, Yves Génisson⁵, Robert Martino¹, Myriam Malet-Martino⁶

Affiliations

¹ Equipe RMN Biomédicale, Laboratoire SPCMIB (UMR CNRS 5068), Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse cedex, France.
² Service Commun de Spectrométrie de Masse, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse cedex, France.
³ Plate-forme Chromatographie, Laboratoire SPCMIB (UMR CNRS 5068), Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse cedex, France.
⁴ Bio-informatique, Laboratoire SPCMIB (UMR CNRS 5068), Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse cedex, France.
⁵ Equipe MoNALISA, Laboratoire SPCMIB (UMR CNRS 5068), Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse cedex, France.
⁶ Equipe RMN Biomédicale, Laboratoire SPCMIB (UMR CNRS 5068), Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse cedex, France. Electronic address: martino@chimie.ups-tlse.fr.

PMID: 32898728
DOI: 10.1016/j.jpba.2020.113482

Abstract

A sexual enhancer dietary supplement in pre-commercialization phase was analyzed. It contained the two phosphodiesterase-5 inhibitors (PDE-5i) sildenafil and methisosildenafil as major adulterants. Fourteen more sildenafil derivatives were detected and after isolation, their structures were elucidated thanks to NMR, high resolution and tandem mass spectrometry, and UV spectroscopy. Ten of them were never described. All these compounds are probably by-products of different reaction steps during the synthesis of the two PDE-5i that were not properly eliminated during the purification procedure. The total amount of sildenafil-related compounds was estimated at 68 mg per capsule, sildenafil and methisosildenafil accounting for 20 mg and 38 mg respectively.

Keywords: Adulteration; Dietary supplement; HPLC; Mass spectrometry; NMR; SFC.

MeSH terms

Dietary Supplements / analysis
Drug Contamination*
Phosphodiesterase 5 Inhibitors*
Sildenafil Citrate
Tandem Mass Spectrometry

Substances

Phosphodiesterase 5 Inhibitors
Sildenafil Citrate