Determination of Metallic Contaminants in Human Recombinant Erythropoietin (EPO) Formulations by Adsorptive Cathodic Stripping Voltammetry and UV Photo-Decomposition of Samples

摘要

A contaminacao de pacientes corn insuficiencia renal por especies metalicas pode estar associada a presenca destes na medicacao empregada durante o tratamento. Dentre os possiveis contaminantes estao metais nefrotoxicos tail como aluminio, cromo e niquel. No presente trabalho, a presenca de Al, Cr e Ni como contaminantes em formulacoes de eritropoetina (EPO)foi investigada atraves da otimizacao de metodos analiticos empregando a voltametria adsortiva de redissolucao catodica (AdCSV) associada a foto-decomposicao de amostras com radiacao UV. A irradiacao UV de amostras acidificadas de EPO pelo periodo de 2 a 3 horas na presenca de H_20_2 possibilitou a decomposicao eficiente da amostra e a determinacao dos contaminantes por AdCSV sem a interferencia da matriz. 0 metodo otimizado foi aplicado na determinacao dos metais em formulae-6es comerciais de EPO utilizadas rotineiramente no tratamento da anemia em pacientes com insuficiencia renal cronica. Os niveis de contaminacao encontrados nas amostras estudadas variaram de 420,2 a 840,5 ng mL~(-1) (RSD 2-5%) para o Al, de 12,0 a 40,0 ng mL~(-1) (RSD 2-6%) para o Cr e de 4,1 a 8,2 ng mL~(-1) (RSD 3-8%) para o Ni. Os resultados obtidos por AdCSV foram comparaveis aos obtidos por espectrometria de absoreao atomica com atomizacao em forno de grafite (GFAAS). A contaminacao de formulae-6es EPO com Al, Cr e Ni mostrou ser uma fonte de contaminacao importante para pacientes anemicos com insuficiencia renal cronica.The contamination of renal failure patients by metals can be associated to the presence of toxic metals in the medication, since they can be absorbed by the organism. Among the possible contaminants, there are nephrotoxic metals such as aluminum, chromium and nickel. In the present work, the presence of Al, Cr and Ni as contaminants in erythropoietin formulations (EPO) was investigated by optimizing the adsorptive cathodic stripping voltammetric (AdCSV) method and the photo-decomposition of samples by UV irradiation. The UV irradiation of acidified EPO samples from 2 to 3 h in the presence of H_20_2 allowed the efficient sample decomposition and the determination of the contaminants by AdCSV without matrix interferences. The method was applied for the determination of the metals in commercial EPO formulations used routinely in the treatment of anemia in patients undergoing chronic renal failure. The contamination levels determined in the samples ranged from 420.2 to 840.5 ng mL~(-1) (RSD 2-5%) for Al, 12.0 to 40.0 ng mL~(-1) (RSD 2-6%) for Cr and 4.1 to 8.2 ng (RSD 3-8%). The results obtained by AdCSV were in good agreement with those obtained by the comparative GFAAS measurements.The contamination of EPO formulations with Al, Cr and Ni was shown to be a serious contamination source for anemic patients undergoing chronic renal failure.