Structural characterization of impurities in pioglitazone.

In the pioglitazone bulk drug three prominent impurities I-III were detected up to concentrations of 0.1% (ranging from 0.05-0.1%) by reversed phase HPLC. These impurities were isolated from enriched mother liquor samples and characterized as 5-(4-hydroxybenzyl)-1,3-thiazolidine-2,4-dione (I) 5-(4-fluorobenzyl)-1,3-thiazolidine-2,4-dione (II), 2-[2-(4-bromophenoxy) ethyl-5-ethyl pyridine (III) based on their 1H, and 13C NMR, DEPT, Mass and IR spectral data. Structure elucidation and synthesis of these impurities is discussed.