Determinação de impurezas elementares em amostras autênticas e apreendidas de comprimidos contendo sildenafila e tadalafila.

Abstract

Drug counterfeiting is an illegal activity in expansion worldwide. In this regard, the main targets are those medicines with high costs, or the ones sought after by the population, among which stand out those intended for sexual impotence, particularly drugs containing sildenafil and tadalafil. Elemental impurities determination in pharmaceuticals has become an emerging topic due to the regulatory changes about the permissible limits, the analytical techniques applied for this determination and also because of the toxicity of some elements even at trace levels. The inductively coupled plasma mass spectrometry (ICP-MS) is the technique that presents the highest sensitivity for elemental impurities analysis. Based on the above considerations, in this study six authentic samples and ten samples seized by the Federal Police and the Civil Police of the state of Minas Gerais of tablets containing sildenafil and tadalafil were analyzed in accordance with chapter 232 and 233 of the United States Pharmacopeia (USP). The main goal of this study was to establish a comparison between the levels of elemental impurities determined in the authentic and seized samples. For this, a new method using a microwave assisted acid digestion and ICP-MS was developed and validated aiming at the simultaneous determination of the elements Ag, As, Au, Ba, Cd, Co, Cr, Cu, Hg, Ir, Li, Mo, Ni, Os, Pb, Pd, Pt, Rh, Ru, Sb, Se, Sn, Tl e V. The sample preparation procedure was optimized through a 22 factorial design with central point, evaluating the reverse aqua regia concentration and the volume of H2O2. In optimal conditions 0.1 g of the samples were submitted to a microwave-assisted digestion using 5 mL of 3HNO3:1HCl 20% v v-1 and 2 mL de H2O2 30% v v-1. The precision and accuracy were evaluated by addition and recovery experiments at three levels (0.5; 1.0 e 5.0 µg L-1) in two authentic samples. Recoveries ranged from 70 to 127% except for Ag, Cu and Ni. The limits of quantification were calculated from 10 independent blanks and ranged from 0.005 (Tl) to 1.3 µg g-1 (Se). The levels determined ranged from 0.006 (Cd) to 6.0 µg g-1 (Ni) and the highest concentrations were determined in the seized samples. The levels determined in authentic and seized samples are below their respective maximum allowable limits, as established in chapter 232 of USP, although, this study shows the risk people are submitted when exposed to counterfeit drug products.