title: Development of generic liquid chromatography-mass spectrometry methods using experimental design.
abstract: Standard approaches to development of liquid chromatography-mass spectrometry (LC-MS) methods, either ion-pairing or reversed-phase liquid chromatography, have been through trial and error or intentional variation of experimental factors. These approaches to method optimization fail to take into account interactions between experimental factors and therefore the results may not be optimal for the combination of experimental factors. Another approach to optimization is through the use of chemometrics. Chemometric approaches can be more efficient than trial and error or intentional variation because chemometrics make use of multivariate designs; experimental factors are varied simultaneously at the various levels. Therefore chemometrics can take into account interactions between factors. The goal of this study was to develop a generic ion-pair LC-MS method for the analysis of acidic compounds using a chemometric approach called design of experiments (DOE). Four acidic compounds which cover three classes of acidic functional groups: 1-naphthyl phosphate (1), 1-naphthalenesulfonic acid (2), 2-naphthalenesulfonic acid (3), and (1-naphthoxy)acetic acid (4) were used as model compounds to develop the generic method. This study illustrates that LC-MS conditions can be optimized efficiently with minimal amount of experimentation using a chemometric approach to experimental design.
authors.affiliation: Merck Frosst Canada and Company, Kirkland, Quebec. carmai_seto@merck.com
authors.forename: Carmai
authors.initials: C
authors.lastname: Seto
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Bateman
authors.forename: Berton
authors.initials: B
authors.lastname: Gunter
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D015233:Models, Statistical; D012107:Research Design