title: Development of a LC-LC-MS complete heart-cut approach for the characterization of pharmaceutical compounds using standard instrumentation.
abstract: A total heart-cut LC-LC-MS technique is described for the analysis of pharmaceutical compounds. Utilizing ordinary LC-MS equipment, a standardized multi-dimensional, highly selective approach was developed. The system was developed on synthetic mixtures containing ten active pharmaceutical compounds. The methodology would be further deployed for the impurity characterization of batches of active chemical, process intermediates, and reference standards. Column-switching was employed to heart-cut sequential fractions from one set of LC conditions to another set of LC conditions. Two high efficiency columns, including the Merck Chromolith C18, for fast LC-LC analysis were used. The system provides a highly automated, turnkey, multi-dimensional approach applicable to a variety of complex mixtures with little user intervention. It is envisioned that this idea could be viewed as a platform for other types of LC-LC analyses including peptide and achiral-chiral analyses.
authors.affiliation: Chemical Science Analytical Department, Pharmacia, Monsanto Searle, Global, 4901 Searle Parkway, Skokie, IL 60077, USA. edward.m.sheldon@pharmacia.com
authors.forename: Edward M
authors.initials: EM
authors.lastname: Sheldon
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods / Q000639:trends; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation / Q000379:methods / Q000639:trends; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods* / Q000639:trends
chemical_list: D004364:Pharmaceutical Preparations