title: "Orthogonal" separations for reversed-phase liquid chromatography.
abstract: A general procedure is proposed for the rapid development of a reversed-phase liquid chromatographic (RP-LC) separation that is "orthogonal" to a pre-existing ("primary") method for the RP-LC separation of a given sample. The procedure involves a change of the mobile-phase organic solvent (B-solvent), the replacement of the primary column by one of very different selectivity, and (only if necessary) a change in mobile phase pH or the use of a third column. Following the selection of the "orthogonal" B-solvent, column and mobile phase pH, further optimization of peak spacing and resolution can be achieved by varying separation temperature and either isocratic %B or gradient time. The relative "orthogonality" of the primary and "orthogonal" RP-LC methods is then evaluated from plots of retention for one method versus the other. The present procedure was used to develop "orthogonal" methods for nine routine RP-LC methods from six pharmaceutical analysis laboratories. The relative success of this approach can be judged from the results reported here.
authors.affiliation: Pfizer Global Research & Development, Pharmaceutical Sciences, Analytical R&D, Michigan Laboratories, Ann Arbor, MI, USA.
authors.forename: Jackson
authors.initials: J
authors.lastname: Pellett
authors.forename: Patrick
authors.initials: P
authors.lastname: Lukulay
authors.forename: Yun
authors.initials: Y
authors.lastname: Mao
authors.forename: William
authors.initials: W
authors.lastname: Bowen
authors.forename: Robert
authors.initials: R
authors.lastname: Reed
authors.forename: M
authors.initials: M
authors.lastname: Ma
authors.forename: R C
authors.initials: RC
authors.lastname: Munger
authors.forename: J W
authors.initials: JW
authors.lastname: Dolan
authors.forename: Loren
authors.initials: L
authors.lastname: Wrisley
authors.forename: K
authors.initials: K
authors.lastname: Medwid
authors.forename: N P
authors.initials: NP
authors.lastname: Toltl
authors.forename: C C
authors.initials: CC
authors.lastname: Chan
authors.forename: M
authors.initials: M
authors.lastname: Skibic
authors.forename: Kallol
authors.initials: K
authors.lastname: Biswas
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Wells
authors.forename: L R
authors.initials: LR
authors.lastname: Snyder
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D003198:Computer Simulation; D004340:Drug Contamination; D008433:Mathematics; D004364:Pharmaceutical Preparations / Q000302:isolation & purification; D012680:Sensitivity and Specificity; D012997:Solvents / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents