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

Abstract

Minor impurities of (R)-1-acetoxymethy 1-3-(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 high-performance 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 μg/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-μm Zorbax Rx C-8 packing.