title: Development of an achiral supercritical fluid chromatography method with ultraviolet absorbance and mass spectrometric detection for impurity profiling of drug candidates. Part II. Selection of an orthogonal set of stationary phases.
abstract: Impurity profiling of organic products that are synthesized as possible drug candidates requires complementary analytical methods to ensure that all impurities are identified. Supercritical fluid chromatography (SFC) is a very useful tool to achieve this objective, as an adequate selection of stationary phases can provide orthogonal separations so as to maximize the chances to see all impurities. In this series of papers, we have developed a method for achiral SFC-MS profiling of drug candidates, based on a selection of 160 analytes issued from Servier Research Laboratories. In the first part of this study, focusing on mobile phase selection, a gradient elution with carbon dioxide and methanol comprising 2% water and 20mM ammonium acetate proved to be the best in terms of chromatographic performance, while also providing good MS response [1]. The objective of this second part was the selection of an orthogonal set of ultra-high performance stationary phases, that was carried out in two steps. Firstly, a reduced set of analytes (20) was used to screen 23 columns. The columns selected were all 1.7-2.5μm fully porous or 2.6-2.7μm superficially porous particles, with a variety of stationary phase chemistries. Derringer desirability functions were used to rank the columns according to retention window, column efficiency evaluated with peak width of selected analytes, and the proportion of analytes successfully eluted with good peak shapes. The columns providing the worst performances were thus eliminated and a shorter selection of columns (11) was obtained. Secondly, based on 160 tested analytes, the 11 columns were ranked again. The retention data obtained on these columns were then compared to define a reduced set of the best columns providing the greatest orthogonality, to maximize the chances to see all impurities within a limited number of runs. Two high-performance columns were thus selected: ACQUITY UPC(2) HSS C18 SB and Nucleoshell HILIC.
authors.affiliation: Université d'Orléans et CNRS, Institut de Chimie Organique et Analytique (ICOA), UMR 7311, Pôle de Chimie, rue de Chartres, B.P. 6759, 45067 Orléans, Cedex 2, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Lemasson
authors.affiliation: Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Bertin
authors.affiliation: Institut de Recherches Servier, 11 rue des Moulineaux, 92150 Suresnes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Hennig
authors.affiliation: Waters Corporation, 5 rue Jacques Monod, 78280 Guyancourt, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Boiteux
authors.affiliation: Université d'Orléans et CNRS, Institut de Chimie Organique et Analytique (ICOA), UMR 7311, Pôle de Chimie, rue de Chartres, B.P. 6759, 45067 Orléans, Cedex 2, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Lesellier
authors.affiliation: Université d'Orléans et CNRS, Institut de Chimie Organique et Analytique (ICOA), UMR 7311, Pôle de Chimie, rue de Chartres, B.P. 6759, 45067 Orléans, Cedex 2, France. Electronic address: caroline.west@univ-orleans.fr.
authors.forename: Caroline
authors.initials: C
authors.lastname: West
mesh_terms: D002245:Carbon Dioxide; D025924:Chromatography, Supercritical Fluid / Q000295:instrumentation / Q000379:methods*; D004340:Drug Contamination; D013058:Mass Spectrometry; D000432:Methanol; D004364:Pharmaceutical Preparations / Q000737:chemistry; D016062:Porosity; D012997:Solvents; D013237:Stereoisomerism
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents; D002245:Carbon Dioxide; D000432:Methanol
keywords: Derringer desirability functions; Mass detection; Pharmaceutical ingredients; Ranking; Screening process; Supercritical fluid chromatography