A quality by design approach to impurity method development for atomoxetine hydrochloride (LY139603)

The development of an ion-pairing HPLC method and associated system suitability parameters for the analysis of atomoxetine hydrochloride (LY139603 HCl) using a quality by design approach is described. Potential method conditions were evaluated for their ability to meet design requirements and statistically designed experiments were used to optimize conditions and demonstrate method robustness for the separation of atomoxetine and impurities. The separation of two early eluting impurities, phenyl methylaminopropanol (PMAP (±)3-methylamino-1-phenylpropanol) and mandelic acid is correlated to the separation of other impurities that elute near the main sample component and the resolution of this peak pair is used as a system suitability test without the need for impurity reference standards.