Identification, synthesis and characterization of new impurities in tenofovir.

A detailed impurity study was conducted on tenofovir, (R)-({[1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid (1), which is the key starting material of manufacturing the active pharmaceutical ingredient (API) tenofovir disoproxil fumarate (2) based on a recently reported procedure. The major impurities generated in the production of tenofovir (1) have been synthesized, characterized and confirmed. The possible formation mechanisms of these impurities were elucidated herein, which would help to understand the process. In addition, this work will also improve the quality control during manufacturing tenofovir and tenofovir disoproxil fumarate (2).