TY - JOUR
T1 - Quantitative mass spectrometry imaging of drugs and metabolites
T2 - a multiplatform comparison
AU - Lamont, Lieke
AU - Hadavi, Darya
AU - Viehmann, Brent
AU - Flinders, Bryn
AU - Heeren, Ron M. A.
AU - Vreeken, Rob J.
AU - Porta Siegel, Tiffany
N1 - Funding Information:
This research was part of the M4i research program. We are very grateful to Bart Verhoeven (IDEE) and Vasileios D. Trikalitis (ET, University of Twente) for 3D printing of the mold. The authors thank Gert B. Eijkel (M4i) and Klara Scupakova (M4i) for their support with data processing. We thank Marjolein van Heerden (Janssen Pharmaceutica) for her pathological expertise.
Funding Information:
This research received financially support from the Dutch Province of Limburg under the LINK program and the Integrated Technology Strategy (ITS) initiative program of Janssen Pharmaceutica NV.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/4
Y1 - 2021/4
N2 - Mass spectrometry imaging (MSI) provides insight into the molecular distribution of a broad range of compounds and, therefore, is frequently applied in the pharmaceutical industry. Pharmacokinetic and toxicological studies deploy MSI to localize potential drugs and their metabolites in biological tissues but currently require other analytical tools to quantify these pharmaceutical compounds in the same tissues. Quantitative mass spectrometry imaging (Q-MSI) is a field with challenges due to the high biological variability in samples combined with the limited sample cleanup and separation strategies available prior to MSI. In consequence, more selectivity in MSI instruments is required. This can be provided by multiple reaction monitoring (MRM) which uses specific precursor ion-product ion transitions. This targeted approach is in particular suitable for pharmaceutical compounds because their molecular identity is known prior to analysis. In this work, we compared different analytical platforms to assess the performance of MRM detection compared to other MS instruments/MS modes used in a Q-MSI workflow for two drug candidates (A and B). Limit of detection (LOD), linearity, and precision and accuracy of high and low quality control (QC) samples were compared between MS instruments/modes. MRM mode on a triple quadrupole mass spectrometer (QqQ) provided the best overall performance with the following results for compounds A and B: LOD 35.5 and 2.5 mu g/g tissue, R-2 0.97 and 0.98 linearity, relative standard deviation QC
AB - Mass spectrometry imaging (MSI) provides insight into the molecular distribution of a broad range of compounds and, therefore, is frequently applied in the pharmaceutical industry. Pharmacokinetic and toxicological studies deploy MSI to localize potential drugs and their metabolites in biological tissues but currently require other analytical tools to quantify these pharmaceutical compounds in the same tissues. Quantitative mass spectrometry imaging (Q-MSI) is a field with challenges due to the high biological variability in samples combined with the limited sample cleanup and separation strategies available prior to MSI. In consequence, more selectivity in MSI instruments is required. This can be provided by multiple reaction monitoring (MRM) which uses specific precursor ion-product ion transitions. This targeted approach is in particular suitable for pharmaceutical compounds because their molecular identity is known prior to analysis. In this work, we compared different analytical platforms to assess the performance of MRM detection compared to other MS instruments/MS modes used in a Q-MSI workflow for two drug candidates (A and B). Limit of detection (LOD), linearity, and precision and accuracy of high and low quality control (QC) samples were compared between MS instruments/modes. MRM mode on a triple quadrupole mass spectrometer (QqQ) provided the best overall performance with the following results for compounds A and B: LOD 35.5 and 2.5 mu g/g tissue, R-2 0.97 and 0.98 linearity, relative standard deviation QC
KW - Mimetic tissue model
KW - Desorption electrospray ionization
KW - MSI comparison
KW - MRM based drug imaging
KW - Absolute quantification
U2 - 10.1007/s00216-021-03210-0
DO - 10.1007/s00216-021-03210-0
M3 - Article
C2 - 33770207
SN - 1618-2642
VL - 413
SP - 2779
EP - 2791
JO - Analytical and Bioanalytical Chemistry
JF - Analytical and Bioanalytical Chemistry
IS - 10
ER -