The identification of a nitrosated prodrug of the PDE-5 inhibitor aildenafil in a dietary supplement: a Viagra with a pop

B J Venhuis; G Zomer; M Hamzink; H D Meiring; Y Aubin; D de Kaste

doi:10.1016/j.jpba.2010.11.020

The identification of a nitrosated prodrug of the PDE-5 inhibitor aildenafil in a dietary supplement: a Viagra with a pop

J Pharm Biomed Anal. 2011 Mar 25;54(4):735-41. doi: 10.1016/j.jpba.2010.11.020. Epub 2010 Nov 21.

Authors

B J Venhuis¹, G Zomer, M Hamzink, H D Meiring, Y Aubin, D de Kaste

Affiliation

¹ National Institute for Public Health and the Environment, Center for Quality of Chemical-Pharmaceutical Products, Anthonie van Leeuwenhoeklaan 9, Bilthoven, The Netherlands. Bastiaan.Venhuis@rivm.nl

PMID: 21145686
DOI: 10.1016/j.jpba.2010.11.020

Abstract

A new unapproved analogue of sildenafil was detected in capsules of a herbal dietary supplement promoted as a libido enhancing product. Using LC-DAD-MS, MS-MS, HRMS, IR and NMR the analogue was shown to be a derivative of the PDE-5 inhibitor aildenafil with a nitrosamine moiety. A hydrolysis experiment showed that the new analogue was a prodrug of aildenafil and was therefore named nitroso-prodenafil. A capsule contained 108 mg of nitroso-prodenafil which is equivalent to 84 mg of aildenafil and 5.1 mg of nitrogen monoxide (NO). Although it is unknown how much NO can be usefully generated there is 3-fold more NO present than in a 10 mg isorbide nitrate tablet. Both PDE-5 inhibitors and nitrosamines cause vasodilatation by increasing levels of NO. To their coincidental use is warned against because it may cause a fatal drop in blood pressure. In addition, nitrosamines are known carcinogens. This is the first time a PDE-5 inhibitor and a potential NO donor were identified in one molecule. The findings indicate the dangerous level of advancement in medicinal chemistry by producers of unapproved drugs.

MeSH terms

Designer Drugs / analysis
Designer Drugs / chemistry
Designer Drugs / isolation & purification
Dietary Supplements / analysis*
Erectile Dysfunction / diet therapy
Humans
Hydrolysis
Magnetic Resonance Spectroscopy
Male
Molecular Structure
Nitric Oxide Donors / analysis*
Nitric Oxide Donors / chemistry
Nitrosamines / analysis*
Nitrosamines / chemistry
Nitrosation
Phosphodiesterase 5 Inhibitors / analysis*
Phosphodiesterase 5 Inhibitors / chemistry
Phosphodiesterase 5 Inhibitors / isolation & purification
Piperazines / analysis*
Piperazines / chemistry
Piperazines / isolation & purification
Prodrugs / analysis*
Prodrugs / chemistry
Prodrugs / isolation & purification
Spectrometry, Mass, Electrospray Ionization
Spectroscopy, Fourier Transform Infrared
Sulfones / analysis*
Sulfones / chemistry
Sulfones / isolation & purification
Tandem Mass Spectrometry

Substances

Designer Drugs
Nitric Oxide Donors
Nitrosamines
Phosphodiesterase 5 Inhibitors
Piperazines
Prodrugs
Sulfones
aildenafil
2-((5-(5-(3,5-dimethylpiperazine-1-sulfonyl)-2-ethoxyphenyl)-1-methyl-3-propyl-1H-pyrazolo(4,3-d)pyrimidin-7-yl)oxy)-N-methyl-N-nitroso-1,3-thiazol-5-amine