The potentials for the ML3"/ML3 couple of MnL3, FeL3, and CoL3 complexes (L = acetylacetonate, 8-quinolinate, picolinate, 2,2'-bipyridyl, 1,10-phenanthroline) occur at substantially less positive values than those for their zinc analogues and are clearly ligand-centered. The negative shift in potential for these ligand oxidations is proportional to their metal-ligand covalent-bond energies. The reductions for the bipyridyl and phenanthroline complexes of these transition metals also are ligand-centered. Electrochemical characterization of tetrakis(2,6-dichlorophenyl)porphine and of its neutral porphinato complexes with Zn, Mn, Fe, and Co indicates that electron transfer occurs within the porphyrin ring and that the metal-porphyrin bonding involves covalent a bonds between d"sp valence electrons of the neutral metal (or hydrogen atoms of porphine) and two pyrrole p electrons of the uncharged porphyrin.

The purpose of this study was to identify a degradation product in a tablet formulation of raloxifene hydrochloride (R-HCl), delineate the role of excipients in its formation, and develop a rational strategy for its control. The degradant was identified as an N-oxide derivative of the drug substance based upon spectroscopic characterization and chromatographic comparison to the synthetic N-oxide. To identify the factors contributing to the formation of N-oxide, binary mixtures of each excipient with R-HCl were exposed to 125 degrees C in open containers. Raloxifene hydrochloride underwent an order of magnitude increase in conversion to the N-oxide in the presence of two excipients, povidone and crospovidone, as compared with its conversion in the presence of other excipients. To confirm a hypothesis that peroxide impurities in these two excipients contributed to the oxidation of the drug substance, tablet lots were spiked with quantities of H2O2 equivalent to 200, 400, 600, and 800 ppm peroxide over the intrinsic levels present in povidone and crospovidone. A strong correlation was observed between the total peroxide level and the quantity of the N-oxide formed upon accelerated storage. From these experiments a rational limit test for peroxide content in povidone and crospovidone was adopted as part of a control strategy to limit formation of the degradation product.

No abstract

No abstract

The oxidation of hydroxide ion and phenoxide ion in acetonitrile has been characterized by cyclic voltammetry at glassy-carbon electrodes. In the presence of transition-metal complexes MnL2+ [M = Mn, Fe, Co, Ni; L = (OPPh3)4, (2,2'-bipyridine)3] and metalloporphyrins M(por) [M = Mn(III), Fe(III), Co(II); por = 5,10,15,20-tetraphenylporphinato(2-), 5,10,15,20-tetrakis-(2,6-dichlorophenyl)porphinato(2-)] the oxidation potentials for "OH and PhO" are shifted to less positive potentials. This is due to the stabilization of the oxy radical products ("OH and PhO") via formation of a d-p (d"-"OR) covalent bond. With excess "OH relative to the metal complex, oxidation of "OH is facilitated by an ECE mechanism [ML("OH) ML('OH) -22,