Determination of the enantiomer and positional isomer impurities in atomoxetine hydrochloride with liquid chromatography using polysaccharide chiral stationary phases.

A normal-phase isocratic chiral liquid chromatographic method has been developed and validated for atomoxetine hydrochloride. In addition to the S-enantiomer of atomoxetine, the conditions separate both para and meta positional isomers and the phenyl des-methyl analog. Method development strategies included (a) evaluation of polysaccharide-based chiral stationary phases with nonaqueous mobile phases, (b) the use of an octyl stationary phase with a sulfated-beta-cyclodextrin mobile phase additive, and (c) capillary electrophoresis using a single isomer heptakis-6-sulfato-beta-cyclodextrin modifier.