Gas Chromatography-Mass Spectrometric Analysis of a Counterfeit Sildenafil product and its Potential Hepatotoxicity in Mice

Abstract

The market of illicit erection/potency enhancers has grown significantly in the last decade. Some of those products lack any data about active ingredients, have dosage mislabeling or claim to contain only natural substances. The aim of this study is to elucidate the various contents and concentration of sildenafil in a cheap illicit erection enhancer tablets available in local markets and to evaluate its potential toxic effects on the liver. An illicit oral preparation (tablet form), sold in local market as an erection enhancer and claim to contain 130 mg of sildenafil citrate/ tablet, was analyzed by Gas Chromatography-Mass Spectrometry (GCMS). The same preparation was dissolved in distilled water and administered per oral route in two doses (8.13 mg/Kg/ day and 50 mg/kg/day) for 8 weeks to male mice to investigate its effects on hepatic tissue. A control group was given distilled water only. Analysis of the tablets demonstrated several ingredients including the potential hepatotoxic 1-Bromo-2,4-dimethoxyanthrquinone, and NTrichloroacetyl-tryptamine with no traces for sildenafil citrate. The study showed that the preparation caused dose dependent histopathologic changes in liver of mice. These changes included lobular inflammation, kupffer cell hyperplasia, nuclear alterations (nuclear vesiculation, anisonucleosis, binucleation), hydropic degeneration and large areas of necrosis. Vascular congestion and fibrosis were also observed. The study has confirmed the phenomenon of counterfeit preparation for treatment of erectile dysfunction as the investigated product has been shown to lack active sildenafil despite being marketed as a sildenafil product. In addition, the study has pointed out the potential hepatotoxicity of anthraquinone derivatives.