Drug impurity profiling: Method optimization on dissimilar chromatographic systems: Part I: pH optimization of the aqueous phase.

The use of dissimilar chromatographic systems in drug impurity profiling can be very advantageous. Screening a new-drug impurity mixture on those systems not only enhances the chance that all impurities are revealed, but also allows choosing a suited system for further method development. In this paper several strategies were evaluated to predict the optimal pH (of the buffer used in the mobile phase) from the screening results.

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.

Stationary phases in the screening of drug/impurity profiles and in their separation method development: identification of columns with different and similar selectivities.

The classification or characterization of stationary phases based on chromatographic parameters, in general, requires different test solutes/mixtures and several mobile phases. To simplify the classification/characterization of reversed-phase liquid chromatographic columns, to be used in separating drug/impurity profiles, a new test procedure was proposed. It consists of injecting two mixtures of relatively similar active substances applying a standard gradient.

Orthogonality and similarity within silica-based reversed-phased chromatographic systems.

The starting point of this study was a current set of 32 chromatographic systems used to select initial conditions for method development to determine the impurity profile of a drug. The system exhibiting the best selectivity is then selected for further method development. In this current set eight silica-based phases are applied in conjunction with four mobile phases at different pH.

Selection of reversed-phase liquid chromatographic columns with diverse selectivity towards the potential separation of impurities in drugs.

To select appropriate stationary phases from the continuously expanding supply of potentially suitable HPLC columns, the properties of 28 frequently applied stationary phases were determined by measuring several chromatographic parameters. From these results, based on chromatographic expertise, eight stationary phases with different properties and selectivities were selected. The aim of this study is to apply chemometric tools to evaluate the initially selected set of columns, i.