title: Analyzing complex mixtures of drug-like molecules: Ion mobility as an adjunct to existing liquid chromatography-(tandem) mass spectrometry methods.
abstract: The use of traveling wave ion mobility mass spectrometry (TWIMS) is evaluated in conjunction with, and as a possible alternative to, conventional LC-MS(/MS) methods for the separation and characterization of drug-like compounds and metabolites. As a model system we use an in vitro incubation mixture of the chemotherapeutic agent melphalan, which results in more than ten closely related hydrolysis products and chain-like oligomers. Ion mobility as a filtering tool results in the separation of ions of interest from interfering ions, based on charge state and shape/size. Different classes of chemical compounds often display different mobilities even if they show the same LC behavior - thereby providing an orthogonal separation dimension. Small molecules with identical or similar m/z that only differ in shape/size (e.g. isomers and isobars, monomers/dimers) can also be distinguished using ion mobility. Similar to retention times and mass-to-charge ratios, drift times are analyte-dependent and can be used as an additional identifier. We find that the compound melphalan shows two different drift times due to the formation of gas-phase charge isomers (protomers). The occurrence of protomers has important implications for ion mobility characterization of such analytes, and also for the interpretation of their fragmentation behavior (CID) in the gas phase.
authors.affiliation: Biomolecular & Analytical Mass Spectrometry, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium.
authors.forename: Jasper
authors.initials: J
authors.lastname: Boschmans
authors.affiliation: Biomolecular & Analytical Mass Spectrometry, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Lemière
authors.affiliation: Biomolecular & Analytical Mass Spectrometry, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom; School of Molecular and Cellular Biology, University of Leeds, LS2 9JT, United Kingdom. Electronic address: frank.sobott@uantwerp.be.
authors.forename: Frank
authors.initials: F
authors.lastname: Sobott
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D045424:Complex Mixtures / Q000032:analysis* / Q000737:chemistry; D007536:Isomerism; D008558:Melphalan / Q000032:analysis* / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D045424:Complex Mixtures; D008558:Melphalan
keywords: Ion mobility; Isomer separation; LC–MS; Melphalan; Protomers; Tandem MS