Determination of minor impurities of (R)-1-acetoxymethyl-3-(7-[(1-N,N-dimethylcarbamoyl)-6-(4-fluorophenyl)-indol-3-oyl]-1H,3H-pyrrolo[1,2-c]thiazol-3-yl)pyridinium chloride by high performance liquid chromatography

Minor impurities of (R)-1-acetoxymethyl-3-(7-[(1-N,N-dimethylcarbamoyl)-6-(4-fluorophenyl)-indol-3-oyl]-1H,3H-pyrrolo[1,2-c]thiazol-3-yl)pyridinium chloride (I), a pro-drug, were determined using highperformance liquid chromatography. Manufacturing impurities, degradation products, and active drug, (R)-7-[(1-N,N-dimethylcarbamoyl)-6-(4-fluorophenyl)-indol-3-oyl] -1H,3H-pyrrolo[1,2-c]thiazole (II) were separated using a reversed-phase system with gradient elution. Detector response was linear for II to approximately 470 mu g/mL which represents 47% of the drug concentration. The procedure provides relative standard deviations of 3.0% to 13.2% in typical bulk drug lots. A variety of reversed-phased columns were evaluated for the assay method with the optimum resolution achieved using a 5-mu m Zorbax Rx C-8 packing.