The goal of the research program is directed toward the development of analytical methodology to determine the quantitative, qualitative, and/or structural identification of inorganic chemical constituents and impurities in drug and biological products through spectrometric means. Depending on the type of product, and particular inorganic constituent/impurity, method development may involve spectrometric techniques such as flame atomic absorption spectrometry (FAAS), graphite furnace atomic absorption spectrometry (GFAAS), flame emission spectrometry (FES), inductively coupled argon plasma-emission spectrometry (ICP-AES) and inductively coupled plasma-mass spectrometry (ICP-MS). The primary objective of the current project focuses on the development of methodology for the quantitative analysis of low level aluminum concentrations in injectable biological products that contain aluminum, either, as a result of inadvertent contamination (5%, 20% and 25% Albumin [Human], or through intentional addition (Antihemophilic Factor [Human], Immune Globulin Intravenous [Human]). The current project utilizes the instrumental technique of graphite furnace atomic absorption spectrometry (GFAAS). Prior studies involving electrothermal atomization have shown that earlier atomizer designs in use had limitations in that the temperature distribution along the atomizer was not always uniform due to contact of atomizer tube ends with water cooled contact cylinders. This often would cause memory effects as a result of sample matrix condensation at the cooler ends of the atomizer tube. However, as a result of more recent advances in graphite furnace technology, there have been several improvements in the basic design of electrothermal atomizers. The current project utilizes an improved atomizer design, which consists of a transversally heated graphite tube as opposed to the earlier longitudinally heated one. This new design theoretically provides a more uniform temperature distribution over the entire tube length, i.e., the atomizer tube ends will reach the same temperature as the tube center during the atomization stage. Under these conditions, the formation of free atoms will be optimal, molecular formation from atoms will be decreased, the loss of atoms will be minimized, and condensation at the cooler tube ends, which can often produce memory effects, will be substantially eliminated. In order to evaluate efficacy of the improved atomizer design, analytical method development in the current project will focus on three main areas of experimental investigation: 1) sample preparation (digestive vs non-digestive techniques), 2) optimization of drying, thermal pretreatment and atomization times and temperatures, and 3) matrix modification, which is a technique that aids better separation of the analyte from matrix components by making the matrix more volatile and/ or stabilizing the analyte. Validation of the method will be accomplished by determining the accuracy, precision, specificity, detection and quantitation limits, linearity, and range when determining the aluminum content of various inter-laboratory and intra-laboratory reference materials as well as various low level aluminum containing biological products.
