title: Enhanced selectivity and search speed for method development using one-segment-per-component optimization strategies.
abstract: Linear gradient programs are very frequently used in reversed phase liquid chromatography to enhance the selectivity compared to isocratic separations. Multi-linear gradient programs on the other hand are only scarcely used, despite their intrinsically larger separation power. Because the gradient-conformity of the latest generation of instruments has greatly improved, a renewed interest in more complex multi-segment gradient liquid chromatography can be expected in the future, raising the need for better performing gradient design algorithms. We explored the possibilities of a new type of multi-segment gradient optimization algorithm, the so-called "one-segment-per-group-of-components" optimization strategy. In this gradient design strategy, the slope is adjusted after the elution of each individual component of the sample, letting the retention properties of the different analytes auto-guide the course of the gradient profile. Applying this method experimentally to four randomly selected test samples, the separation time could on average be reduced with about 40% compared to the best single linear gradient. Moreover, the newly proposed approach performed equally well or better than the multi-segment optimization mode of a commercial software package. Carrying out an extensive in silico study, the experimentally observed advantage could also be generalized over a statistically significant amount of different 10 and 20 component samples. In addition, the newly proposed gradient optimization approach enables much faster searches than the traditional multi-step gradient design methods.
authors.affiliation: Department of Chemical Engineering (CHIS-IR), Vrije Universiteit Brussel, Belgium. Electronic address: Eva.Tyteca@vub.ac.be.
authors.forename: Eva
authors.initials: E
authors.lastname: Tyteca
authors.affiliation: Department of Chemical Engineering (CHIS-IR), Vrije Universiteit Brussel, Belgium.
authors.forename: Kim
authors.initials: K
authors.lastname: Vanderlinden
authors.affiliation: UCB Pharma, Belgium.
authors.forename: Maxime
authors.initials: M
authors.lastname: Favier
authors.affiliation: UCB Pharma, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Clicq
authors.affiliation: Department of Pharmaceutical Analysis, Katholieke Universiteit Leuven, Belgium.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Cabooter
authors.affiliation: Department of Chemical Engineering (CHIS-IR), Vrije Universiteit Brussel, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Desmet
mesh_terms: D000465:Algorithms; D056148:Chromatography, Reverse-Phase / Q000379:methods; D003198:Computer Simulation; D015233:Models, Statistical; D010578:Petroleum / Q000032:analysis; D062065:Wastewater / Q000032:analysis
chemical_list: D010578:Petroleum; D062065:Wastewater
keywords: Gradient optimization; LSS model; Method development; Multi-segment gradients; Non-linear retention model; Retention modeling