Métodos analíticos modernos para determinação de sildenafila e tadalafila em amostras de medicamentos e plasma humano.

Abstract

One of the highest incidences of illegal drug products is related to phosphodiesterase-5 inhibitors, used in the treatment of erectile dysfunction, including those containing sildenafil citrate (SLD) and tadalafil (TAD). In addition to being a criminal justice issue, the manufacturing and commercialization of illegal health products poses a serious threat to public health. SLD and TAD are also used in the treatment of pulmonary arterial hypertension (PAH), a rare but serious and progressive disease. In this context, the development of modern, simple, fast, environmentally friendly analytical methods, with high efficiency and applicability in the quantification of SLD and TAD in drug products and biological matrices, becomes relevant. Therefore, in the present study, a UHPLC-UV method for SLD and TAD in the presence of six degradation products was developed and validated. The drugs were submitted to a detailed forced degradation study. The separation of the analytes was possible in less than six minutes and the method was selective, linear, precise, accurate and robust. SLD was degraded in oxidative media, whereas TAD was degraded in acidic, alkaline and oxidative environment. The chemical structures and the mechanisms for the formation of the main degradation products were proposed by UHPLC-Q-TOF-MS. The UHPLC-UV method was applied in the pharmaceutical analysis of genuine and seized medicines and the lack of quality was evident in some of them. In addition, a bioanalytical method for the simultaneous quantification of TAD, SLD, N-desmethylsildenafil and six other drugs presents in the therapeutic protocol of PAH (amlodipine, bumetanide, digoxin, diltiazem, nifedipine and warfarin) in human plasma was developed by means of dispersive liquid-liquid microextraction (DLLME) and HPLC-MS/MS. Different factors that affected the DLLME procedure were investigated and optimized, obtaining an efficient and simple method, with reduced sample and solvents volumes. The method was validated and the results were satisfactory for selectivity, residual effect, matrix effect, linearity, precision, accuracy, recovery and stability of the analytes. Plasma samples from volunteers were analysed and the bioanalytical method proved to be suitable for the application.