Oxidative degradation peroxide-mediated

As mentioned previously, oxidative degradation pathways can be complex, and it is useful to consider the chemistry of oxidative degradation. The oxidative degradation of pharmaceuticals has been discussed in the literature,23-27 and we assert that there are three major pathways, (1) autoxidation or radical-mediated oxidation, (2) peroxide-mediated, and (3) photochemically induced (see Table 5). Traditionally, dilute aqueous peroxide solutions have been used for oxidative stress testing of pharmaceuticals. Landmark papers by Boccardi23 24 in 1992 and 1994 identified autoxidation as the major oxidative degradation pathway for pharmaceuticals. Boccardi showed that the use of radical initiators such as... 

For oxidation, different stressing schemes can be used, and this depends generally on the structure of the drug substance (active component) autooxidation, metals, peroxide-mediated, peroxy-mediated, bubbled oxygen, and pressurized oxygen. Auto-oxidation involves a free radical initiator such as AIBN (2,2 -azobisisobutyronitrile) or AMVN (2,2 -azobis(2,4-dimethylvaleronitrile) to initiate oxidation [37] and has been used to mimic long-term room temperature degradation related to oxidation. The concentration... 

There are no available data on the formation of hydroperoxides derived from DNA within cells. This is likely explained, at least partly, by the fact that DNA is a poorer target than proteins for OH radical as observed upon exposure of mouse myeloma cells to ionizing radiation . However, indirect evidence for DNA peroxidation within cells may be inferred from the measurement of final degradation products that may derive from thymine and guanine hydroperoxidation as the result of oxidation reactions mediated by OH radical and O2, respectively (Sections n.A.2 and n.E.2). It may be pointed out that the measurement of oxidized bases and nucleosides within DNA has been the subject of intense research during the last decade and accurate methods are now available . This includes DNA extraction that involves the chaotropic Nal precipitation step and the use of desferrioxamine to chelate transition metals in order to prevent spurious oxidation of overwhelming nucleobases to occur . HPLC coupled to electrospray ionization... 

---