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

摘要

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. All three approaches yielded acceptable conditions for the separation of atomoxetine from related molecules with the former fully validated and the latter two held as alternatives if needed. The final method conditions employing a Chiralcel OD-H column and mobile phase of hexane/IPA/DEA/TFA (85/15/0.15/0.2, v/v/v/v) at 1.0 mL/min have been fully validated with acceptable specificity, linearity, accuracy, repeatability, intermediate precision and quantitation limit.