RT Journal Article SR Electronic T1 SELECTIVE REDUCTION OF N-OXIDES TO AMINES: APPLICATION TO DRUG METABOLISM JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 966 OP 972 VO 32 IS 9 A1 Palaniappan Kulanthaivel A1 Robert J. Barbuch A1 Rita S. Davidson A1 Ping Yi A1 Gregory A. Rener A1 Edward L. Mattiuz A1 Chad E. Hadden A1 Lawrence A. Goodwin A1 William J. Ehlhardt YR 2004 UL http://dmd.aspetjournals.org/content/32/9/966.abstract AB Phase I oxidative metabolism of nitrogen-containing drug molecules to their corresponding N-oxides is a common occurrence. There are instances where liquid chromatography/tandem mass spectometry techniques are inadequate to distinguish this pathway from other oxidation processes, including C-hydroxylations and other heteroatom oxidations, such as sulfur to sulfoxide. Therefore, the purpose of the present study was to develop and optimize an efficient and practical chemical method to selectively convert N-oxides to their corresponding amines suitable for drug metabolism applications. Our results indicated that efficient conversion of N-oxides to amines could be achieved with TiCl3 and poly(methylhydrosiloxane). Among them, we found TiCl3 to be a facile and easy-to-use reagent, specifically applicable to drug metabolism. There are a few reports describing the use of TiCl3 to reduce N-O bonds in drug metabolism studies, but this methodology has not been widely used. Our results indicated that TiCl3 is nearly as efficient when the reductions were carried out in the presence of biological matrices, including plasma and urine. Finally, we have shown a number of examples where TiCl3 can be successfully used to selectively reduce N-oxides in the presence of sulfoxides and other labile groups. The American Society for Pharmacology and Experimental Therapeutics