Studies on the Biotransformations and Biodistributions of Metal-Containing Drugs Using X-Ray Absorption Spectroscopy

Jade      B. Aitken; Aviva      Levina; Peter      A. Lay

Abstract

Most metal-based drugs are pro-drugs; therefore, it is essential that methods are developed to follow their speciation in biological fluids, cells and tissues. This will lead to both a better understanding of the factors that affect their efficacies and toxicities and, consequently, to the design of new and superior drugs. The use of X-ray absorption spectroscopy on bulk samples, and X-ray microprobe techniques on cells and tissues, provides unprecedented information on the biotransformations and biodistributions of metal-containing drugs that is required for a better understanding of their pharmacology. Here the methodologies that have been used on a range of metal- or metalloid-containing drugs and dietary supplements are reviewed, with an emphasis on research conducted within our group. In particular, applications of these techniques to anti-cancer, anti-diabetic, and anti-inflammatory drugs are discussed.

Keywords: Metal-containing drugs, anti-cancer drugs, anti-diabetic drugs and supplements, anti-inflammatory drugs, X-ray absorption spectroscopy, biotransformations, biodistributions, efficacy, complexes, glutathione complex, multiple-scattering contributions, ARSENIC, SELENIUM, XAS and SRIXE techniques