@inproceedings{8678313,
  abstract     = {{Due to the increasing complexity of pharmaceutical drug formulations, as e.g. used in combination therapies, assessment of the active ingredients and of the thereby related impurities is becoming an ever more challenging task by conventional 1-dimensional chromatographic separation techniques. This because baseline separation of all solutes in complex samples can thereby not be obtained anymore, while the impurities typically arising at very low concentrations require also sensitive detection to enable their identification and quantification following current regulations.1 In order to address limited peak capacities, comprehensive 2-dimensional LCxLC approaches are increasingly used to analyse natural and synthetic samples of high complexity. Although the possibilities of LCxLC have been incrementally improving, overall many of the current approaches are limited in their robustness, characterized by modulation problems, too low orthogonality and undersampling.2
Especially the modulation issue often becomes visible in form of solvent immiscibility and excessive eluting strength issues, leading to e.g. peak broadening, decreased sensitivity and repeatability issues. Only a few comprehensive LCxLC modes, all using purely aqueous separation modes in the first dimension, are today exempted from these concerns. One of those is the recently introduced combination of temperature-responsive chromatography with reversed phase liquid chromatography (TRLCxRPLC).3 
Such temperature responsive phases thereby depict an adaptable hydrophobicity and hence retention characteristics as a function of temperature. A main benefit of the approach is that it forgoes the need for the addition of organic solvents to the mobile phase. This new separation technique inherently reduces the methodical complexity of multidimensional LC, by allowing problem free modulation when using a conventional loop based 10-port valve and a purely aqueous mobile phase in the first dimension. This on the one hand allows for the transfer of high sample volumes from the first to the second dimension with near perfect peak refocussing, and on the other hand can facilitate more sensitive detection compared to conventional LCxLC approaches, which often require miniaturization of the first dimension.  The possibilities offered by TRLCxRPLC in terms of selectivity, sensitivity, peak capacities and quantitative potential are assessed for improved separation of pharmaceutical mixtures. Therefore, synthetic mixtures of structurally similar pharmaceutical compounds are investigated, while optimizing the first and second dimension to optimally use the given separation space and the added selectivity. Additionally, several column (core-shell) chemistries are assessed in the second dimension.}},
  author       = {{Wicht, Kristina and Baert, Mathijs and Krieger, Sonja and von Doehren, Norwin and de Villiers, André and Lynen, Frederic}},
  booktitle    = {{High-Performance Liquid Phase Separations and Related Techniques, 48th International Symposium, Abstracts}},
  keywords     = {{2D-LC,TRLC,RPLC}},
  language     = {{eng}},
  location     = {{Milan, Italy}},
  pages        = {{1}},
  title        = {{Improved pharmaceutical impurity determination via comprehensive 2D-LC temperature-responsive x reversed phase liquid chromatography}},
  year         = {{2019}},
}