title: DMSO-enhanced MALDI MS imaging with normalization against a deuterated standard for relative quantification of dasatinib in serial mouse pharmacology studies.
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 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-D8, 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.
authors.forename: Sandra
authors.initials: S
authors.lastname: Schulz
authors.forename: Dimitri
authors.initials: D
authors.lastname: Gerhardt
authors.forename: Björn
authors.initials: B
authors.lastname: Meyer
authors.forename: Maic
authors.initials: M
authors.lastname: Seegel
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schubach
authors.forename: Carsten
authors.initials: C
authors.lastname: Hopf
authors.forename: Katerina
authors.initials: K
authors.lastname: Matheis
mesh_terms: D000818:Animals; D000069439:Dasatinib; D003903:Deuterium / Q000737:chemistry; D005260:Female; D007553:Isotope Labeling; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011743:Pyrimidines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D013844:Thiazoles / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D011743:Pyrimidines; D013844:Thiazoles; D003903:Deuterium; D000069439:Dasatinib