Evaluation of orthogonal/dissimilar RP-HPLC systems sets for their suitability as method-development starting points for drug impurity profiles.

Orthogonal or dissimilar separation systems provide different selectivities and their application can facilitate the development of methods to identify and quantify impurities in a drug substance. Two sets of chromatographic systems potentially applicable for method development were evaluated using four drug/impurity profiles. The sets consist of orthogonal or dissimilar systems and systems with good overall separation properties, selected in earlier studies. The aim of this study is to evaluate these systems for selectivity differences in the impurity profiles. These differences should allow determining the number of compounds occurring in an impurity profile. Then, one or a very limited number of systems is to be proposed for further method development. To examine the selectivity changes and separation quality for each impurity profile, both the normalized retention times tau and the resolutions between pairs of consecutively eluting peaks were plotted on parallel axes, representing the systems. For each profile, several systems of the studied sets can serve as potential starting points for further method development. All impurities could be separated from the active substance and from each other on at least one system. However, for the different profiles, different systems were selected as best, which makes that each system in a given set has its importance, depending on the properties of the profile.