Strategies for characterizing sildenafil, vardenafil, tadalafil and their analogues in herbal dietary supplements, and detecting counterfeit products containing these drugs Saranjit Singh, Bhagwat Prasad, Akash A. Savaliya, Ravi P. Shah, Vikrantsinh M. Gohil, Amandeep Kaur The success of synthetic phosphodiesterase type-5 (PDE-5)-inhibitor drugs (viz sildenafil, vardenafil and tadalafil), which are constituents of popular brands (viz Viagra, Levitra and Cialis, respectively) for the treatment of erectile dysfunction in males, has led to their widespread use as adulterants in herbal dietary supplements (HDSs). There have been reports that not only these three approved drugs but also their unapproved analogues have been found in HDSs. The problem is becoming more complex, as concealed, structurally modified analogues are increasingly being used. Also, counterfeits of the popular brands have emerged. Fortunately, it has become possible to detect these drugs and their derivatives as adulterants and counterfeits by using modern sensitive and selective analytical techniques [e.g., liquid chromatography with tandem mass spectrometry, Fourier transform (FT) with near infrared spectrometry, and FT with Raman spectroscopy], although some conventional approaches have also been employed. We critically review the literature, and present generalized strategies, including flow charts, for characterizing adulteration of PDE-5 inhibitors in HDSs, and detecting and categorizing counterfeit products. ª 2008 Elsevier Ltd. All rights reserved. Keywords: Adulteration; Analogue; Counterfeit; Detection; Herbal dietary supplement; PDE-5 inhibitor; Sildenafil; Tadalafil; Vardenafil 1. Introduction Sildenafil citrate (Viagra, Pfizer), varde- nafil hydrochloride (Levitra, Bayer) and tadalafil (Cialis, Elli Lilly) (Fig. 1) are marketed as approved drugs for the treat- ment of erectile dysfunction (ED) in males. The physiological process of erection involves the release of nitric oxide (NO) in the corpus cavernosum of the penis, mediated by the parasympathetic nervous system. NO binds to the receptors of the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to Saranjit Singh*, Bhagwat Prasad, Akash A. Savaliya, Ravi P. Shah Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar 160 062, India Vikrantsinh M. Gohil, Amandeep Kaur Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar 160 062, India * Corresponding author. Tel.: +91 172-2214682; Fax: +91 172-2214692; E-mail: ssingh@niper.ac.in Trends in Analytical Chemistry, Vol. 28, No. 1, 2009 Trends 0165-9936/$ - see front matter ª 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.trac.2008.09.004 13 0165-9936/$ - see front matter ª 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.trac.2008.09.004 13