Determinação de impurezas elementares em fármacos e estudo de interferências em ICP-MS após decomposição em sistema de alta pressão e por combustão iniciada por micro-ondas

• Ano de defesa: 2014
• Autor(a) principal: Müller, Aline Lima Hermes
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; BR; Química; UFSM; Programa de Pós-Graduação em Química
• Palavras-chave em Português: Controle de qualidade em fármacos; Elementos tóxicos; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/4290

In this work a wet microwave assisted digestion procedure using Multiwave® and UltraWave® systems, microwave induced combustion (MIC) and dry ashing decomposition method were evaluated for the digestion of levodope (LEVO), propranolol hydrochloride (PROP), sodium diclofenac (DICL), primaquine diphosphate (PRIM) and sulfamethoxazole (SULF). The proposed decomposition methods were evaluated based on the sample mass, oxidant mixtures, temperature, time of decomposition, residual acidity, residual carbon content (RCC) and recovery of elemental impurities. Only wet decomposition methods with UltraWave® system and MIC provided suitable digests for all active pharmaceutical ingredients (APIs) and recovery values between 91 and 109% were obtained for all elemental impurities (As, Cd, Cr, Cu, Ir, Hg, Mn, Mo, Ni, Pb, Pd, Pt, Rh, Ru and V) determined by inductively coupled plasma with mass spectrometry (ICP-MS), with the exception of Os. Decomposition with UltraWave® system was carried out using masses up to 500 mg of APIs, 6 mL of HNO3 and maximum temperature and pressure of 270 ° C and 199 bar, respectively, for further determination of As, Cd, Cr, Cu, Hg, Mn, Mo, Ni, Pb e V. For the determination of other elemental impurities (Ir, Os, Pd, Pt, Rh and Ru) masses of 250 mg of the APIs were digested with 4.5 mL HNO3 and 1.5 mL HCl. Digests obtained using UltraWave® system have shown RCC values lower than 250 mg L-1 and residual acidity equivalent to 25% of the initial amount of HNO3 which allowed solving the spectral interferences on ICP-MS determination. MIC digests were performed using pellets of APIs with 500 mg and 7 mol L-1 HNO3 as absorbing solution for subsequent determination of all elemental impurities, with the exception of Ir, Os, Pd, Pt, Rh and Ru. On the other hand, for the determination of Ir, Os, Pd , Pt, Rh and Ru a mixture of 300 mg of APIs and 200 mg NH4Cl and 6 mL of aqua regia as absorbing solution and were used for MIC digestion. RCC values provided by MIC were lower than 60 mg L-1 for all APIs. Polyatomic interferences caused by S, P and Cl (present in APIs chemical structure) in the determination of 51V , 52Cr , 53Cr , 63Cu and 65Cu were solved using dynamic reaction cell ( DRC ) with ammonia as reaction gas. Determination of As was carried out using flow injection analysis with chemical vapor generation (FI-VG) combined with ICP-MS to solve the polyatomic interference caused by APIs matrices containing Cl. The decomposition methods using Ultrawave® and MIC were validated according to the recommendations of pharmacopoeial compendia. The limits of detection and quantification obtained by the proposed methods meet the requirements outlined in the USP Pharmaceutical Forum.