DMSO-enhanced MALDI MS imaging with normalization against a deuterated standard for relative quantification of dasatinib
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RESEARCH PAPER
DMSO-enhanced MALDI MS imaging with normalization against a deuterated standard for relative quantification of dasatinib in serial mouse pharmacology studies Sandra Schulz & Dimitri Gerhardt & Björn Meyer & Maic Seegel & Bernhard Schubach & Carsten Hopf & Katerina Matheis
Received: 9 July 2013 / Revised: 23 September 2013 / Accepted: 23 September 2013 / Published online: 13 October 2013 # Springer-Verlag Berlin Heidelberg 2013
Abstract Matrix-assisted laser desorption/ionization mass spectrometry imaging is an emerging powerful technique in drug metabolism and pharmacokinetics research. Despite recent progress in mass-spectrometry-based localization and relative quantification of small-molecule drugs and their metabolites in tissue, improved methods for drug extraction/ ionization are required. Furthermore, relative quantification of drugs by mass spectrometry imaging in larger rodent cohorts is a necessary proof-of-concept study to demonstrate the utility of such a workflow in an industrial setting. Using as an example the tyrosine kinase inhibitor dasatinib, a leukemia drug, we demonstrate that inclusion of dimethyl sulfoxide in
Sandra Schulz and Dimitri Gerhardt contributed equally to this publication Electronic supplementary material The online version of this article (doi:10.1007/s00216-013-7393-0) contains supplementary material, which is available to authorized users. S. Schulz : D. Gerhardt : B. Meyer : C. Hopf (*) Institute of Instrumental Analytics and Bioanalytics, Department of Biotechnology, Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163 Mannheim, Germany e-mail: [email protected] B. Meyer : C. Hopf Center for Applied Research in Biomedical Mass Spectrometry (ABIMAS), Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163 Mannheim, Germany B. Meyer : C. Hopf Institute of Medical Technology, Heidelberg University and Mannheim University of Applied Sciences, Paul-Wittsack-Str. 10, 68163 Mannheim, Germany D. Gerhardt : M. Seegel : B. Schubach : K. Matheis (*) Department of Bioanalytical Chemistry, Merck KGaA, Frankfurter Straße 250, 64293 Darmstadt, Germany e-mail: [email protected]
standard matrix solutions significantly improves ion intensity in mass spectrometry images and reveals enrichment of the drug in mouse kidney medulla. We furthermore show in a time-course study in multiple mice that normalization against a deuterated internal standard, dasatinib-D 8, which is applied together with the matrix, makes possible relative quantification of the drug that correlates well with canonical liquid chromatography–tandem mass spectrometry based drug quantification. Keywords Matrix-assisted laser desorption/ionization mass spectrometry imaging . Dasatinib . Internal standard . Quantification
Introduction Since its first application in drug distribution studies in 2003, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) imaging (MSI) has matured into an important analytical technology in drug metabolism and pharm
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