Structural characterization of sulfoaildenafil, an analog of sildenafil

Abstract

Phosphodiesterase type 5 (PDE-5) inhibitors represent a class of drugs used primarily in the treatment of erectile dysfunction. Currently, three PDE-5 inhibitors have been approved by the U.S. Food and Drug Administration (FDA) for use in the United States: sildenafil citrate, tadalafil, and vardenafil hydrochloride trihydrate. A bulk material, labeled as an ingredient for a dietary supplement, was analyzed for the presence of PDE-5 inhibitors. The compound that was detected displayed structural similarities to sildenafil, and was characterized further using LC-MS(n), FTICRMS, X-ray crystallography and NMR. The compound was given the name sulfoaildenafil. When compared to sildenafil, sulfoaildenafil contains a sulfur atom substitution for the oxygen atom in the pyrazolopyrimidine portion of the molecule, and a 3,5-dimethyl substitution on the piperazine ring, rather than the 4-methyl moiety. The X-ray crystallographic data indicate that the material in this sample is comprised of two polymorphs, which may affect the chemical and/or biological properties of any product formulated with this compound.

A multidisciplinary approach for the analysis of an adulterated dietary supplement where the active pharmaceutical ingredient was embedded in the capsule shell

“…Although effective for providing an initial assessment of the sample, a reduced spectral resolution and number of scans may reduce ones ability to differentiate closely related compounds/structures, such as analogs. Since a current trend in the male enhancement dietary supplement market has involved the use of PDE-5 analogs [5][6][7][8][9][10], a more selective approach was required. While it is possible to collect higher spectral resolution/higher sensitivity/smaller area ATR-FT-IR images in a short timeframe, this approach would be much less representative of the sample.…”

“…Over the past several years many products have been adulterated with phosphodiesterase type 5 (PDE-5) inhibitors, such as sildenafil citrate, tadalafil and vardenafil HCl·3H 2 O, which are only approved in the prescription pharmaceuticals Viagra ® , Cialis ® and Levitra ® to treat erectile dysfunction [1][2][3][4]. A more current trend involves the use of PDE-5 analogs [5][6][7][8][9][10], which provide similar physiological effects [11][12][13] but have structural modifications to the approved parent compounds.…”

Spectroscopic and Spectrometric Methods Used for the Screening of Certain Herbal Food Supplements Suspected of Adulteration

“…These blood pressure falls are often accompanied by other specific symptoms among which: headache, flushing, dyspepsia, nasal congestion, dizziness, myalgia, back pain, and abnormal vision,are but a few to be mentioned. 7-9 …”

A novel approach to simultaneous screening and confirmation of regulated pharmaceutical compounds in dietary supplements by LC/MS/MS with an information-dependent acquisition method

“…Thus, the recent regulations require confirmatory techniques, such as liquid chromatography/tandem mass spectrometry (LC/MS/MS). Highly sensitive and selective analysis for known structures using transitions can be achieved by MRM experiments using a triple quadrupole instrument (Hernando et al 2007;Wang et al 2007;Gratz et al 2009). For analysis, many methods have employed the MRM ion ratio in a complex matrix.…”