Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging
Detecting metabolites and parent compound within a cell type is now a priority for pharmaceutical development. In this context, three-dimensional secondary ion mass spectrometry (SIMS) imaging was used to investigate the cellular uptake of the antiarrhythmic agent amiodarone, a phospholipidosis-indu...
| Main Authors: | , , , , , , , |
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| Format: | Article |
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American Chemical Society
2015
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| Online Access: | https://eprints.nottingham.ac.uk/37559/ |
| _version_ | 1848795484091580416 |
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| author | Passarelli, Melissa K. Newman, Carla F. Marshall, Peter S. West, Andrew Gilmore, Ian S. Bunch, Josephine Alexander, Morgan R. Dollery, Colin T. |
| author_facet | Passarelli, Melissa K. Newman, Carla F. Marshall, Peter S. West, Andrew Gilmore, Ian S. Bunch, Josephine Alexander, Morgan R. Dollery, Colin T. |
| author_sort | Passarelli, Melissa K. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Detecting metabolites and parent compound within a cell type is now a priority for pharmaceutical development. In this context, three-dimensional secondary ion mass spectrometry (SIMS) imaging was used to investigate the cellular uptake of the antiarrhythmic agent amiodarone, a phospholipidosis-inducing pharmaceutical compound. The high lateral resolution and 3D imaging capabilities of SIMS combined with the multiplex capabilities of ToF mass spectrometric detection allows for the visualization of pharmaceutical compound and metabolites in single cells. The intact, unlabeled drug compound was successfully detected at therapeutic dosages in macrophages (cell line: NR8383). Chemical information from endogenous biomolecules was used to correlate drug distributions with morphological features. From this spatial analysis, amiodarone was detected throughout the cell with the majority of the compound found in the membrane and subsurface regions and absent in the nuclear regions. Similar results were obtained when the macrophages were doped with amiodarone metabolite, desethylamiodarone. The FWHM lateral resolution measured across an intracellular interface in a high lateral resolution ion images was approximately 550 nm. Overall, this approach provides the basis for studying cellular uptake of pharmaceutical compounds and their metabolites on the single cell level. |
| first_indexed | 2025-11-14T19:32:49Z |
| format | Article |
| id | nottingham-37559 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:32:49Z |
| publishDate | 2015 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-375592020-05-04T17:13:36Z https://eprints.nottingham.ac.uk/37559/ Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging Passarelli, Melissa K. Newman, Carla F. Marshall, Peter S. West, Andrew Gilmore, Ian S. Bunch, Josephine Alexander, Morgan R. Dollery, Colin T. Detecting metabolites and parent compound within a cell type is now a priority for pharmaceutical development. In this context, three-dimensional secondary ion mass spectrometry (SIMS) imaging was used to investigate the cellular uptake of the antiarrhythmic agent amiodarone, a phospholipidosis-inducing pharmaceutical compound. The high lateral resolution and 3D imaging capabilities of SIMS combined with the multiplex capabilities of ToF mass spectrometric detection allows for the visualization of pharmaceutical compound and metabolites in single cells. The intact, unlabeled drug compound was successfully detected at therapeutic dosages in macrophages (cell line: NR8383). Chemical information from endogenous biomolecules was used to correlate drug distributions with morphological features. From this spatial analysis, amiodarone was detected throughout the cell with the majority of the compound found in the membrane and subsurface regions and absent in the nuclear regions. Similar results were obtained when the macrophages were doped with amiodarone metabolite, desethylamiodarone. The FWHM lateral resolution measured across an intracellular interface in a high lateral resolution ion images was approximately 550 nm. Overall, this approach provides the basis for studying cellular uptake of pharmaceutical compounds and their metabolites on the single cell level. American Chemical Society 2015-07-07 Article PeerReviewed Passarelli, Melissa K., Newman, Carla F., Marshall, Peter S., West, Andrew, Gilmore, Ian S., Bunch, Josephine, Alexander, Morgan R. and Dollery, Colin T. (2015) Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging. Analytical Chemistry, 87 (13). pp. 6696-6702. ISSN 1520-6882 http://pubs.acs.org/doi/abs/10.1021/acs.analchem.5b00842 doi:10.1021/acs.analchem.5b00842 doi:10.1021/acs.analchem.5b00842 |
| spellingShingle | Passarelli, Melissa K. Newman, Carla F. Marshall, Peter S. West, Andrew Gilmore, Ian S. Bunch, Josephine Alexander, Morgan R. Dollery, Colin T. Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging |
| title | Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging |
| title_full | Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging |
| title_fullStr | Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging |
| title_full_unstemmed | Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging |
| title_short | Single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3D mass spectrometry imaging |
| title_sort | single-cell analysis: visualizing pharmaceutical and metabolite uptake in cells with label-free 3d mass spectrometry imaging |
| url | https://eprints.nottingham.ac.uk/37559/ https://eprints.nottingham.ac.uk/37559/ https://eprints.nottingham.ac.uk/37559/ |