title: Mass Spectrometry Imaging of Drug Related Crystal-Like Structures in Formalin-Fixed Frozen and Paraffin-Embedded Rabbit Kidney Tissue Sections.
abstract: A multimodal mass spectrometry imaging (MSI) based approach was used to characterize the molecular content of crystal-like structures in a frozen and paraffin embedded piece of a formalin-fixed rabbit kidney. Matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) imaging and desorption electrospray ionization (DESI) mass spectrometry imaging were combined to analyze the frozen and paraffin embedded sample without further preparation steps to remove the paraffin. The investigated rabbit kidney was part of a study on a drug compound in development, in which severe renal toxicity was observed in dosed rabbits. Histological examination of the kidney showed tubular degeneration with precipitation of crystal-like structures in the cortex, which were assumed to cause the renal toxicity. The MS imaging approach was used to find out whether the crystal-like structures were composed of the drug compound, metabolites, or an endogenous compound as a reaction to the drug administration. The generated MALDI-MSI data were analyzed using principal component analysis. In combination with the MS/MS results, this way of data processing demonstrates that the crystal structures were mainly composed of metabolites and relatively little parent drug.
authors.affiliation: M4I, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Bruinen
authors.affiliation: Preclinical Development and Safety, Janssen Research and Development, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Cateau
authors.initials: C
authors.lastname: van Oevelen
authors.affiliation: M4I, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands.
authors.forename: Gert B
authors.initials: GB
authors.lastname: Eijkel
authors.affiliation: Preclinical Development and Safety, Janssen Research and Development, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Van Heerden
authors.affiliation: Preclinical Development and Safety, Janssen Research and Development, Turnhoutseweg 30, 2340, Beerse, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Cuyckens
authors.affiliation: M4I, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands. r.heeren@maastrichtuniversity.nl.
authors.forename: Ron M A
authors.initials: RM
authors.lastname: Heeren
mesh_terms: D000818:Animals; D005557:Formaldehyde; D007668:Kidney / Q000737:chemistry*; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D016612:Paraffin Embedding; D011817:Rabbits; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D005557:Formaldehyde
keywords: DESI; Imaging mass spectrometry; MALDI; Metabolites; Multimodal; SIMS