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Semiempirical rules to determine drug sensitivity and ionization efficiency in secondary ion mass spectrometry using a model tissue sample

Semiempirical rules to determine drug sensitivity and ionization efficiency in secondary ion mass spectrometry using a model tissue sample
Semiempirical rules to determine drug sensitivity and ionization efficiency in secondary ion mass spectrometry using a model tissue sample
There is an increasing need in the pharmaceutical industry to reduce drug failure at late stage and thus reduce the cost of developing a new medicine. Since most drug targets are intracellular, this requires a better understanding of the drug disposition within a cell. Secondary ion mass spectrometry has been identified as a potentially important technique to do this, as it is label-free and allows imaging in 3D with subcellular resolution and recent studies have shown promise for amiodarone. An important analytical parameter is sensitivity, and we measure this in a bovine liver homogenate reference sample for 20 drugs representing important class types relevant to the pharmaceutical industry. We also measure the sensitivity for pure drug and show, for the first time, that the secondary ion mass spectrometry (SIMS) positive ionization efficiency for small molecules is a simple power-law relationship to the log P value. This discovery will be important for advancing the understanding of the SIMS ionization process in small molecules that has, until now, been elusive. This simple relationship is found to hold true for drug doped in the bovine liver homogenate reference sample, except for fluticasone, nicardipine, and sorafenib which suffer from severe matrix suppression. This relationship provides a simple semiempirical method to determine drug sensitivity for positive secondary ions. Furthermore, we show, on chosen models, how the use of different solvents during sample preparation can affect the ionization of analytes.
0003-2700
11028-11036
Vorng, Jean-Luc
a0342d67-3015-4da5-b029-3690f614be27
Kotowska, Anna M.
aa939e30-cff7-47ef-9def-503386755335
Passarelli, Melissa K.
655899fd-514a-44c5-bb7b-9cb4302f9f2f
West, Andrew
fa95ae31-5789-4368-af47-55f4ca8c281a
Marshall, Peter S.
d3b2585d-26d2-4099-808a-688e3e523940
Havelund, Rasmus
4c5492a9-b204-402c-9d26-aeacffc2e0d2
Seah, Martin P.
09ff937f-dfbe-4680-9a5e-e098d4b3aa32
Dollery, Colin T.
e8e1cee1-e678-426e-a0a8-064ebc9160bf
Rakowska, Paulina D.
73bf2145-e2fa-46ee-9ad9-f74c80d5a369
Gilmore, Ian S.
f864335b-9cb0-4f44-b80f-30809227212b
Vorng, Jean-Luc
a0342d67-3015-4da5-b029-3690f614be27
Kotowska, Anna M.
aa939e30-cff7-47ef-9def-503386755335
Passarelli, Melissa K.
655899fd-514a-44c5-bb7b-9cb4302f9f2f
West, Andrew
fa95ae31-5789-4368-af47-55f4ca8c281a
Marshall, Peter S.
d3b2585d-26d2-4099-808a-688e3e523940
Havelund, Rasmus
4c5492a9-b204-402c-9d26-aeacffc2e0d2
Seah, Martin P.
09ff937f-dfbe-4680-9a5e-e098d4b3aa32
Dollery, Colin T.
e8e1cee1-e678-426e-a0a8-064ebc9160bf
Rakowska, Paulina D.
73bf2145-e2fa-46ee-9ad9-f74c80d5a369
Gilmore, Ian S.
f864335b-9cb0-4f44-b80f-30809227212b

Vorng, Jean-Luc, Kotowska, Anna M., Passarelli, Melissa K., West, Andrew, Marshall, Peter S., Havelund, Rasmus, Seah, Martin P., Dollery, Colin T., Rakowska, Paulina D. and Gilmore, Ian S. (2016) Semiempirical rules to determine drug sensitivity and ionization efficiency in secondary ion mass spectrometry using a model tissue sample. Analytical Chemistry, 88 (22), 11028-11036. (doi:10.1021/acs.analchem.6b02894).

Record type: Article

Abstract

There is an increasing need in the pharmaceutical industry to reduce drug failure at late stage and thus reduce the cost of developing a new medicine. Since most drug targets are intracellular, this requires a better understanding of the drug disposition within a cell. Secondary ion mass spectrometry has been identified as a potentially important technique to do this, as it is label-free and allows imaging in 3D with subcellular resolution and recent studies have shown promise for amiodarone. An important analytical parameter is sensitivity, and we measure this in a bovine liver homogenate reference sample for 20 drugs representing important class types relevant to the pharmaceutical industry. We also measure the sensitivity for pure drug and show, for the first time, that the secondary ion mass spectrometry (SIMS) positive ionization efficiency for small molecules is a simple power-law relationship to the log P value. This discovery will be important for advancing the understanding of the SIMS ionization process in small molecules that has, until now, been elusive. This simple relationship is found to hold true for drug doped in the bovine liver homogenate reference sample, except for fluticasone, nicardipine, and sorafenib which suffer from severe matrix suppression. This relationship provides a simple semiempirical method to determine drug sensitivity for positive secondary ions. Furthermore, we show, on chosen models, how the use of different solvents during sample preparation can affect the ionization of analytes.

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More information

Published date: 11 October 2016

Identifiers

Local EPrints ID: 445185
URI: http://eprints.soton.ac.uk/id/eprint/445185
ISSN: 0003-2700
PURE UUID: 1d589bbd-9fd5-4d27-9ba2-64f268eff5aa
ORCID for Paulina D. Rakowska: ORCID iD orcid.org/0000-0002-3710-8395

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Date deposited: 24 Nov 2020 17:34
Last modified: 28 Apr 2022 02:31

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Contributors

Author: Jean-Luc Vorng
Author: Anna M. Kotowska
Author: Melissa K. Passarelli
Author: Andrew West
Author: Peter S. Marshall
Author: Rasmus Havelund
Author: Martin P. Seah
Author: Colin T. Dollery
Author: Ian S. Gilmore

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