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Hybrid x-ray luminescence and optical imaging
Published in Yi-Hwa Liu, Albert J. Sinusas, Hybrid Imaging in Cardiovascular Medicine, 2017
Raiyan T. Zaman, Michael V. McConnell, Lei Xing
Metals and other trace elements play an important role in many physiological processes in all biological systems. Characterization of precise metal concentrations, their spatial distribution, and chemical speciation in individual cells and cell compartments will provide much needed information to explore the metallome in health and disease. Ralle et al. described in their review article synchrotron-based x-ray fluorescent microscopy (SXRF) to be the ideal tool to quantitatively measure trace elements with high sensitivity at high resolution (Ralle and Lutsenko 2009). SXRF is based on the intrinsic fluorescent properties of each element and is therefore element specific. Recent advances in synchrotron technology and optimization of sample preparation have made it possible to image metals in mammalian tissue with submicron resolution.
Profiling extractable and leachable inorganic impurities in ophthalmic drug containers by ICP-MS
Published in Pharmaceutical Development and Technology, 2018
Each permutation of experimental conditions produced a unique set of elemental concentrations. Table 2 reports concentrations for the elements tested, in reference to United States Pharmacopeia inhalation daily exposure limits. While the measured levels for all elements passed USP guidelines, it is not clear that instilled eye drops should not be held to more stringent limits (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, 2015). As discussed in the introduction, the ocular cavity sustains a local metal ion equilibrium, and even trace level contaminations to a small, compartmentalized volume can have an amplified impact on the microenvironmental metallome. Heavy metals like Cd and Pb were extracted under at least one set of experimental conditions. Results also suggested that with improper storage, a consumer may be exposed to raised levels of Zn and Fe in the eye drops; both of these elements have been reported to play a role in lens protein degradation and cataract development (Bush and Goldstein 2001; Hori et al. 2009). Other metals, including redox-active Ni and Mn, were additionally detected at elevated concentrations, which could potentially also contribute to MCO reactions that lead in part to cataract disease. In fact, experiments report that Mn in the presence of bicarbonate catalyzes H2O2-dependent oxidation of amino acids (Stadtman 1993). These findings warrant future study to determine explicit and appropriate levels of USP-regulated elements that can be safely administered into the eye. The data also demonstrate the need for elemental extractable and leachable testing, and perhaps expanded research on metal contamination mitigation strategies, such as addition of nontoxic pharmacological chelators to the drug formulation (Stadtman 1993; Bush and Goldstein 2001).