Comprehensive pharmaceutical preparation analysis is a term which aims to describe the complete characterisation of a pharmaceutical preparation, including active pharmaceutical ingredients (APIs), counter ions, degradents and excipients etc. However, obtaining this degree of component coverage using a chromatographic approach is far from a trivial challenge, due the wide variety of chemical species and their varied physio-chemical properties. In recent years, with the introduction of various commercial variants, mixed-mode chromatographic phases for LC have begun to attract more attention, particularly in the area of pharmaceutical analysis, as they can provde alternative selectivity to common single mode phases, typically reversed-phase ODS phases, for example. The inclusion of anion or cation exchange capacity, or indeed both, within a single phase which also possesses dominant reversed-phase character, can provide considerable space for greater selectivity control, and hence recent applications of simultaneous separation and quantitation of organic APIs and inorganic counter ions are numerous.

In the work to be presented here, we consider the true selectivity of a variety of mixed mode phases and attempt to utilise the full range of solute-solute interactions upon such phases to move closer to comprehensive analytical LC. The question as to whether such phases can be applied under so-called HILIC conditions will also be addressed, and the change of solute-sorbent interactions which take place during an applied mixed mode dual gradient (buffer concentration and % organic solvent) explored. Applications of these mixed-mode separations, both isocratic and gradient to complex mixtures of organic and inorganic solutes will be shown.