PMID- 26384683
OWN - NLM
STAT- MEDLINE
DCOM- 20160919
LR  - 20181113
IS  - 1879-1123 (Electronic)
IS  - 1044-0305 (Print)
IS  - 1044-0305 (Linking)
VI  - 27
IP  - 1
DP  - 2016 Jan
TI  - Mass Spectrometry Imaging of Drug Related Crystal-Like Structures in 
      Formalin-Fixed Frozen and Paraffin-Embedded Rabbit Kidney Tissue Sections.
PG  - 117-23
LID - 10.1007/s13361-015-1254-3 [doi]
AB  - 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.
FAU - Bruinen, Anne L
AU  - Bruinen AL
AD  - M4I, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The 
      Netherlands.
FAU - van Oevelen, Cateau
AU  - van Oevelen C
AD  - Preclinical Development and Safety, Janssen Research and Development, 
      Turnhoutseweg 30, 2340, Beerse, Belgium.
FAU - Eijkel, Gert B
AU  - Eijkel GB
AD  - M4I, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The 
      Netherlands.
FAU - Van Heerden, Marjolein
AU  - Van Heerden M
AD  - Preclinical Development and Safety, Janssen Research and Development, 
      Turnhoutseweg 30, 2340, Beerse, Belgium.
FAU - Cuyckens, Filip
AU  - Cuyckens F
AD  - Preclinical Development and Safety, Janssen Research and Development, 
      Turnhoutseweg 30, 2340, Beerse, Belgium.
FAU - Heeren, Ron M A
AU  - Heeren RM
AD  - M4I, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The 
      Netherlands. r.heeren@maastrichtuniversity.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150918
PL  - United States
TA  - J Am Soc Mass Spectrom
JT  - Journal of the American Society for Mass Spectrometry
JID - 9010412
RN  - 1HG84L3525 (Formaldehyde)
SB  - IM
MH  - Animals
MH  - Formaldehyde
MH  - Kidney/*chemistry
MH  - Male
MH  - Molecular Imaging/*methods
MH  - Paraffin Embedding
MH  - Rabbits
MH  - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods
PMC - PMC4686544
OTO - NOTNLM
OT  - DESI
OT  - Imaging mass spectrometry
OT  - MALDI
OT  - Metabolites
OT  - Multimodal
OT  - SIMS
EDAT- 2015/09/20 06:00
MHDA- 2016/09/20 06:00
PMCR- 2015/09/18
CRDT- 2015/09/20 06:00
PHST- 2015/05/31 00:00 [received]
PHST- 2015/08/12 00:00 [accepted]
PHST- 2015/08/09 00:00 [revised]
PHST- 2015/09/20 06:00 [entrez]
PHST- 2015/09/20 06:00 [pubmed]
PHST- 2016/09/20 06:00 [medline]
PHST- 2015/09/18 00:00 [pmc-release]
AID - 10.1007/s13361-015-1254-3 [pii]
AID - 1254 [pii]
AID - 10.1007/s13361-015-1254-3 [doi]
PST - ppublish
SO  - J Am Soc Mass Spectrom. 2016 Jan;27(1):117-23. doi: 10.1007/s13361-015-1254-3. 
      Epub 2015 Sep 18.