Synthesis of deuterated analogs, reference standards and metabolites of pharmaceuticals

The aim of the work was the synthesis of deuterated analogs of pharmaceuticals in order to provide an internal analytical standard suitable for LC/MS/MS analysis of very low concentrations of these drugs in body fluids. In this part of the work deuterated formoterol-d6, deuterated tolperison-d7 and deuterated analog of BY-170424 were prepared. Tandutinib, Erlotinib and Gefitinib were prepared with substantial improvement and full characterization of the intermediates to be used as reference compounds for the Drug Matrix Chemogenomics program. In order to provide the analytical standards necessary for NDA submission, the by-products of phenazopyridines (were synthesized and fully characterized as API (active pharmaceutical ingredient). The main metabolites of sulphapyridine, N-acetylsulfapyridin and 5-hydroxy-sulfapyridine as well as both isomers of oxygenated butorphanol metabolite, trans- and cis-hydroxybutorphanol, were synthesized. 8-Fluoro-galanthamine was prepared and separated into the stereoisomers and the structure confirmed by x-ray analysis in order to be able to study the pharmacological and physical properties of this compound as acetylcholin esterase inhibitor. (author)