Differentiation of 2-hydroxyglutarate enantiomers and its lactones by gas chromatography/electron ionization tandem mass spectrometry
© 2019 John Wiley & Sons, Ltd..
RATIONALE: 2-Hydroxyglutarate (2-hg) exists as enantiomers and can readily undergo cyclization to its lactone. Gas chromatography/electron ionization mass spectrometry (GC/EI-MS) has been used to separate 2-hg enantiomers in bodily fluids but the assay cannot simultaneously measure cyclic and acylic 2-hg enantiomers. Furthermore, the assignment of ion structures was not verified by complementary MS data.
METHODS: GC/EI-MS and product ion analysis were used to obtain MS and MS/MS spectra of 2-hg, deuterated and 13 C-labeled 2-hg, and 2-hg lactone. Ion structures and EI fragmentation mechanisms were determined by fragmentation pattern and isotopologue comparisons. Using the EI data, a GC/MS/MS assay was developed to separate and detect 2-hg enantiomers and 2-hg lactone enantiomers in blood and urine using a cyclodextrin capillary column.
RESULTS: A new ion structure was predicted for the 85 m/z fragment than what was previously hypothesized, and the 117 m/z ion was the only fragment unique to the linear 2-hg compound. MS/MS data suggested that the majority of the fragments were the result of secondary fragmentation. Finally, separation of serum and urine 2-hg and 2-hg lactone enantiomers was achieved, and the acyclic 2-hg compound was found to be the major compound detected, though the amount of lactone detected was considerable in a number of samples.
CONCLUSIONS: Unique EI fragmentation pathways for both 2-hg and the 2-hg lactone have been described. Subsequently, the GC/MS/MS assay presented herein has significant potential as a novel clinical assay as it separates and detects both 2-hg enantiomers and the 2-hg lactone enantiomers, a capability which has not been previously demonstrated by any other assay to date.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Rapid communications in mass spectrometry : RCM - 33(2019), 17 vom: 15. Sept., Seite 1401-1409 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Strain, Shinji K [VerfasserIn] |
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| Links: |
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| Themen: |
2889-31-8 |
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| Anmerkungen: |
Date Completed 06.03.2020 Date Revised 06.03.2020 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/rcm.8485 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM297660276 |
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| 100 | 1 | |a Strain, Shinji K |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Differentiation of 2-hydroxyglutarate enantiomers and its lactones by gas chromatography/electron ionization tandem mass spectrometry |
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| 500 | |a Date Revised 06.03.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2019 John Wiley & Sons, Ltd. | ||
| 520 | |a RATIONALE: 2-Hydroxyglutarate (2-hg) exists as enantiomers and can readily undergo cyclization to its lactone. Gas chromatography/electron ionization mass spectrometry (GC/EI-MS) has been used to separate 2-hg enantiomers in bodily fluids but the assay cannot simultaneously measure cyclic and acylic 2-hg enantiomers. Furthermore, the assignment of ion structures was not verified by complementary MS data | ||
| 520 | |a METHODS: GC/EI-MS and product ion analysis were used to obtain MS and MS/MS spectra of 2-hg, deuterated and 13 C-labeled 2-hg, and 2-hg lactone. Ion structures and EI fragmentation mechanisms were determined by fragmentation pattern and isotopologue comparisons. Using the EI data, a GC/MS/MS assay was developed to separate and detect 2-hg enantiomers and 2-hg lactone enantiomers in blood and urine using a cyclodextrin capillary column | ||
| 520 | |a RESULTS: A new ion structure was predicted for the 85 m/z fragment than what was previously hypothesized, and the 117 m/z ion was the only fragment unique to the linear 2-hg compound. MS/MS data suggested that the majority of the fragments were the result of secondary fragmentation. Finally, separation of serum and urine 2-hg and 2-hg lactone enantiomers was achieved, and the acyclic 2-hg compound was found to be the major compound detected, though the amount of lactone detected was considerable in a number of samples | ||
| 520 | |a CONCLUSIONS: Unique EI fragmentation pathways for both 2-hg and the 2-hg lactone have been described. Subsequently, the GC/MS/MS assay presented herein has significant potential as a novel clinical assay as it separates and detects both 2-hg enantiomers and the 2-hg lactone enantiomers, a capability which has not been previously demonstrated by any other assay to date | ||
| 650 | 4 | |a Evaluation Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Glutarates |2 NLM | |
| 650 | 7 | |a Lactones |2 NLM | |
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| 700 | 1 | |a Emmett, Mark R |e verfasserin |4 aut | |
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