Boschmans, J, Lemière, F and Sobott, F (2017) Analyzing complex mixtures of drug-like molecules: ion mobility as an adjunct to existing liquid chromatography-(tandem) mass spectrometry methods. Journal of Chromatography A, 1490. pp. 80-88. ISSN 0021-9673
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Elsevier B.V. This is an author produced version of a paper published in Journal of Chromatography A. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | LC-MS; Tandem MS; Ion mobility; Isomer separation; Protomers; Melphalan |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 Feb 2017 12:03 |
Last Modified: | 14 Feb 2018 01:38 |
Published Version: | https://doi.org/10.1016/j.chroma.2017.02.015 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.chroma.2017.02.015 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:112424 |