title: Investigation of the effect of mobile phase composition on selectivity using a solvent-triangle based approach in achiral SFC.
abstract: Defining a method development methodology for achiral drug impurity profiling in SFC requires a number of steps. Initially, diverse stationary phases are characterized and a small number of orthogonal or dissimilar phases are selected for further method development. In this paper, we focus on a next step which is the investigation of the modifier composition on chromatographic selectivity. A solvent-triangle based approach is used in which blends of organic solvents, mainly ethanol (EtOH), propanol (PrOH), acetonitrile (ACN) and tetrahydrofuran (THF) mixed with methanol (MeOH) are tested as modifiers on six dissimilar stationary phases. The tested modifier blends were composed to have equal eluotropic strengths as calculated on bare silica. The modifier leads to minor changes in terms of elution order, retention and mixture resolution. However, varying only the modifier composition on a given stationary phase does not lead to the creation of dissimilar systems. Therefore the modifier composition is an optimization parameter, with the stationary phase being the factor determining most the selectivity of a given mixture in achiral SFC.
authors: Vrije Universiteit Brussel (VUB), Center for Pharmaceutical Research (CePhaR), Department of Analytical Chemistry and Pharmaceutical Technology (FABI), Laarbeeklaan 103, B-1090 Brussels, Belgium. Electronic address: charlene.galea@vub.ac.be.
authors: Charlene
authors: C
authors: Muscat Galea
authors: Vrije Universiteit Brussel (VUB), Center for Pharmaceutical Research (CePhaR), Department of Analytical Chemistry and Pharmaceutical Technology (FABI), Laarbeeklaan 103, B-1090 Brussels, Belgium. Electronic address: debby.mangelings@vub.ac.be.
authors: Debby
authors: D
authors: Mangelings
authors: Vrije Universiteit Brussel (VUB), Center for Pharmaceutical Research (CePhaR), Department of Analytical Chemistry and Pharmaceutical Technology (FABI), Laarbeeklaan 103, B-1090 Brussels, Belgium. Electronic address: yvanvdh@vub.ac.be.
authors: Yvan
authors: Y
authors: Vander Heyden
mesh_terms: D000433:1-Propanol / Q000737:chemistry; D000097:Acetonitriles / Q000737:chemistry; D001569:Benzodiazepines / Q000032:analysis; D025924:Chromatography, Supercritical Fluid / Q000295:instrumentation* / Q000379:methods; D003975:Diazepam / Q000032:analysis; D004340:Drug Contamination; D000431:Ethanol / Q000737:chemistry; D005663:Furans / Q000737:chemistry; D006860:Hydrogen Bonding; D008140:Lorazepam / Q000032:analysis; D000432:Methanol / Q000737:chemistry; D015999:Multivariate Analysis; D009930:Organic Chemicals; D010076:Oxazepam / Q000032:analysis; D025341:Principal Component Analysis; D015203:Reproducibility of Results; D012822:Silicon Dioxide; D012997:Solvents / Q000737:chemistry; D013693:Temazepam / Q000032:analysis
chemical_list: D000097:Acetonitriles; D005663:Furans; D009930:Organic Chemicals; D012997:Solvents; D001569:Benzodiazepines; D000431:Ethanol; C018674:tetrahydrofuran; D010076:Oxazepam; D012822:Silicon Dioxide; D000433:1-Propanol; D013693:Temazepam; D008140:Lorazepam; D003975:Diazepam; D000432:Methanol; C032159:acetonitrile
keywords: Achiral SFC; Drug impurity profiling; Eluotropic strength; Modifiers; Separation optimization