RESUMO
HPLC coupled to UV diode array detection (DAD) is proposed for the determination of polycyclic aromatic hydrocarbons (PAHs) in pharmaceutical products for parenteral administration. Because rubber is a possible source of PAHs for these products, samples stored in containers with rubber parts were selected for the analysis. The basis for method optimization was EPA Method 8310, which determines 16 priority PAHs in ground water and wastewater by HPLC using both UV and fluorescence detection. Using DAD, two channels were selected for detection, with one operating at 254 nm for the detection of nine PAHs and the other at 225 nm for the detection of seven PAHs. This method allowed for the detection of PAHs using external calibration with LODs and LOQs ranging from 0.001 to 0.060 µg/mL and from 0.003 to 0.167 µg/mL, respectively. Within-day precision, expressed as RSD, varied from 1.24 to 7.76% for PAH concentrations from 0.05 to 0.50 µg/mL, and intraday precision varied from 3.10 to 9.40% for the same concentration range. Method accuracy was confirmed by recoveries of 75-120% of the spiked samples. This method was applied for the determination of PAHs in three commercial infusion solutions and in nine different medications stored in syringes prior to administration to patients. Twelve of 16 PAHs were found in these samples. Total PAH concentrations varied from 0.13 to 13.50 µg/mL. Pyrene was the most prevalent contaminant, being present in 11 of 12 samples in concentrations ranging from 0.17 to 4.80 µg/mL. This method presented good sensitivity for the measurement of PAH in the target samples, allowing for the determination of the 16 priority PAHs in one run and in 30 min.
Assuntos
Contaminação de Medicamentos , Soluções de Nutrição Parenteral/análise , Preparações Farmacêuticas/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Calibragem , Cromatografia Líquida de Alta Pressão , Limite de DetecçãoRESUMO
INTRODUCTION: Aluminum (Al) is a toxic element which may contaminate pharmaceutical products used as individual components to prepare total parenteral nutrition mixtures (TPN). OBJECTIVES: 1) to determine Al levels in the individual components used to prepare TPN mixtures; 2) to compare detected Al levels with those imposed by international regulations (FDA); 3) to calculate the total amount of Al administered to adult and children receiving those typical TPN mixtures. METHODS: Al was determined by Inductively Coupled Plasma- Atomic Emission Spectrometry (ICP-OES) (Perkin Elmer OPTIMA 5100 DV) in 44 individual products, from different labs and lots, belonging to 16 components available in Argentina: dextrose and amino acids for adult formulas and for pediatric formulas: lípids; potassium chloride; sodium chloride, magnesium sulfate; sodium phosphate; calcium gluconate; sodium glycerophosphate, zinc sulfate; multitrace elements; steril water (ampoules and great volume presentations). RESULTS: Al levels were detected in 43 of the 44 the studied components, except sterile water. The components of large volume presented between 249 y 1,580 µg Al/ L, between 4 and 180 times FDA established levels (25 µg Al/ L). Small volume components presented Al levels between 85 y 4,909 g/ L, not declared in labels. CONCLUSIONS: The highest amounts of Al were detected in calcium gluconate, sodium phosphate and multitrace elements. 2) Usually prescribed TPN mixtures would have higher Al levels than those accepted by FDA regulation; 3) The highest aluminum concentration was provided by dextrose, amino acids and lipids in adult TPN mixtures. In neonate TPN mixtures, Al highest amounts were provided by dextrose and calcium gluconate. The calculated concentration of Al in TPN mixtures was higher than those stipulated by international regulation (5 µg Al/kg (body weight)/ d). It would be advisable for manufacturers to declare the content of aluminum in the label, with the aim of avoiding toxicities which would compromise the critical patients' evolution.
Introducción: aluminio (Al) es un elemento tóxico que puede ser contaminante de productos farmacéuticos utilizados para preparar mezclas de nutrición parenteral (NP). Objetivos: 1) determinar la concentración de Al en componentes individuales utilizados para preparar mezclas de NP; 2) comparar las cantidades detectadas con los límites de la regulación internacional (FDA); 3) calcular la cantidad de Al administrada en fórmulas habituales de NP para neonatos, niños y adultos. Materiales y métodos: El Aluminio fue determinado por Espectroscopía de Emisión Atómica-Plasma-Inductivo de Argón (Perkin Elmer 5100 DV) en 44 productos comerciales, de diferentes laboratorios y lotes, correspondientes a 16 componentes individuales: dextrosa; aminoácidos para adultos y pediátricos; lípidos; cloruro de potasio; cloruro de sodio, sulfato de magnesio; fosfato de sodio; gluconato de calcio; glicerofosfato de sodio; sulfato de zinc; elementos multitraza; agua estéril en ampollas y de gran volumen. Resultados: Todos los componentes de gran volumen, excepto el agua, contenían entre 249 y 1.580 µg/L, superando entre 4 y 180 veces mas que los niveles establecidos por la FDA (25 µg/L). Los componentes de pequeño volumen contenían entre 85 y 4.909 µg/L, no declarados en los rótulos. Conclusiones: 1) La mayor cantidad de aluminio se encontró en el gluconato de calcio, fosfato de sodio y elementos multitraza. 2) Las mezclas de uso habitual para NP presentan niveles de Al mayores al límite de FDA. Los componentes que aportan mayor cantidad de aluminio en las mezclas de NP para adultos son: glucosa, aminoácidos y lípidos, pero en las de neonatos, el mayor aporte proviene de la dextrosa y gluconato de calcio. 3) En las mezclas de NP para neonatos, niños y adultos la cantidad de aluminio administrado por kg de peso supera la recomendación de FDA (5 µg/kg de peso /día). Los productos comerciales deberían declarar el contenido de Al para no comprometer la evolución de los pacientes graves.