Determination of Sildenafil, Tadalafil, and Vardenafil in Tablets and Adulterated Herbal Products by ESI‐MS‐MS

Abstract

An electrospray tandem mass spectrometry (ESI‐MS‐MS) method was developed for the analysis of selected phosphodiesterase type 5 (PDE‐5) inhibitors, namely, sildenafil, tadalafil, and vardenafil in pharmaceutical preparations and adulterated herbal products. The method permits a fast (<3 min), selective detection and determination of these compounds in the presence of bulk powders of tablets or bulk herbal matrices of herbal products. Detection of sildenafil or tadalafil in adulterated herbal formulas was simply accomplished by recording the daughter scan of the product's extract and picking up significant fragment ions for the identification of PDE‐5 inhibitors. Quantification of sildenafil, tadalafil, and vardenafil, was achieved using multiple reaction monitoring (MRM) ion chromatograms at m/z 475>100, 390>268, 489>169, respectively. The concentration of each compound was determined from the calibration curve constructed by the internal standard calibration using phenylalanine (m/z 166>103) as an internal standard. Validation data showed that the developed tandem mass procedure was linear (r: 0.99), accurate (%DEVs±10%), and reproducible (RSD%.<7.5%) with a LLOQ of 20.0 ng mL⁻¹. Recovery studies of pre‐analyzed tablets spiked with known amounts of PDE‐5 inhibitors showed average percents of 100.4 (sildenafil), 101.5 (tadalafil), and 101.0 (vardenafil). Application of a tandem mass procedure to the analysis of three marketed herbal products with sexual enhancement properties, revealed the presence of undeclared sildenafil or tadalafil compounds at concentrations 43.5 and 33.9 mg of sildenafil and 7.7 mg of tadalafil. The derived data suggested that the developed tandem mass spectrometric method can be adopted for routine analysis of either dosage forms or herbal products adulterated with of PDE‐5 inhibitors.

Keywords:

• ESI‐MS‐MS
• PDE‐5 inhibitors
• Sildenafil
• Tadalafil
• Vardenafil
• Dosage forms
• Herbal products

Acknowledgments

The author wishes to thank the Faculty of Pharmacy, Kuwait University for providing the facility of the tandem mass spectrometer (Micromass, UK) used throughout this work. The author is also grateful to Dr. Mustafa Khalifa for his kind help and valuable discussions.