Towards a generic variable-length method development strategy for samples with a large variety in polarity.

The research proposal is focused on the development of a new chromatographic system for chemical analysis and is therefore situated in the field of analytical chemistry.  An increasing number of samples are emerging wherein the polarity of compounds varies between very hydrophilic and strongly hydrophobic. For these complex samples a method on a single column is no longer sufficient to separate all compounds. For separation problems with a  large variety in polarity, a parallel method development (MD) strategy on coupled columns with orthogonal stationary phases is proposed. The sample under consideration will first be split into polar and apolar compounds based on their retention on orthogonal phases. Subsequently, a  separate method will be developed for the apolar and polar compounds on orthogonal phases, using a strategy wherein the length of the column is varied according to the stage of the MD. To  llow an easy switching between column chemistries and lengths, each phase will be represented by columns of different lengths and with different stationary phases, comprised in an automated column coupler (ACC). An ACC consists of two switching valves that allow coupling columns in series and in this way change the length of a support in an automated way. The device also allows screening columns individually. Using two additional external valves, both ACCs can be used in parallel and series on a single LC system. The possibility to hyphenate the final obtained orthogonal separations will therefore also be investigated. The applicability of the proposed MD strategy will be demonstrated for the separation of pharmaceuticals in waste water.