Fine mapping the spatial distribution and concentration of unlabeled drugs within tissue micro-compartments using imaging mass spectrometry.

PloS One
Anna NilssonPer E Andrén

Abstract

Readouts that define the physiological distributions of drugs in tissues are an unmet challenge and at best imprecise, but are needed in order to understand both the pharmacokinetic and pharmacodynamic properties associated with efficacy. Here we demonstrate that it is feasible to follow the in vivo transport of unlabeled drugs within specific organ and tissue compartments on a platform that applies MALDI imaging mass spectrometry to tissue sections characterized with high definition histology. We have tracked and quantified the distribution of an inhaled reference compound, tiotropium, within the lungs of dosed rats, using systematic point by point MS and MS/MS sampling at 200 microm intervals. By comparing drug ion distribution patterns in adjacent tissue sections, we observed that within 15 min following exposure, tiotropium parent MS ions (mass-to-charge; m/z 392.1) and fragmented daughter MS/MS ions (m/z 170.1 and 152.1) were dispersed in a concentration gradient (80 fmol-5 pmol) away from the central airways into the lung parenchyma and pleura. These drug levels agreed well with amounts detected in lung compartments by chemical extraction. Moreover, the simultaneous global definition of molecular ion signatures localized ...Continue Reading

References

Jun 28, 2003·Analytical and Bioanalytical Chemistry·Detlev SuckauArmin Holle
Nov 5, 2003·Journal of Mass Spectrometry : JMS·Michelle L ReyzerRichard M Caprioli
Dec 22, 2004·Mechanisms of Ageing and Development·Tatiana C RohnerMarkus Stoeckli
Oct 29, 2005·Journal of the American Society for Mass Spectrometry·Shelley N JacksonAmina S Woods
Feb 8, 2006·Mass Spectrometry Reviews·Melanie HilarioMarkus Müller
Jun 22, 2006·Current Drug Metabolism·Bradley L AckermannKevin L Duffin
Aug 22, 2006·Journal of Pharmacological and Toxicological Methods·Yunsheng HsiehWalter A Korfmacher
Sep 15, 2006·Analytical Chemistry·Sheerin Khatib-ShahidiRichard M Caprioli
Dec 23, 2006·Current Opinion in Chemical Biology·Michelle L Reyzer, Richard M Caprioli
Mar 1, 2007·Journal of Mass Spectrometry : JMS·Pierre ChaurandRichard M Caprioli
May 31, 2007·Journal of Mass Spectrometry : JMS·Luca SignorGérard Hopfgartner
Jun 2, 2007·International Journal of Mass Spectrometry·Jeremy L NorrisRichard M Caprioli
Jun 30, 2007·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Bradford C Dickerson
Oct 9, 2007·Nuclear Medicine and Biology·Floris P Jansen, Jean-Luc Vanderheyden
Jan 1, 2008·Nature Methods·Malin AnderssonRichard M Caprioli

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Citations

Dec 24, 2011·Bioanalysis·Stacey R Oppenheimer, Dieter M Drexler
Nov 28, 2013·Analytical and Bioanalytical Chemistry·Shane R EllisRon M A Heeren
Dec 6, 2011·Bioanalysis·Ákos Végvári, Balázs Döme
Oct 20, 2012·Clinica Chimica Acta; International Journal of Clinical Chemistry·Hui YeLingjun Li
May 20, 2014·Analytical Chemistry·Mélanie LagarrigueCharles Pineau
Jun 8, 2014·Analytical and Bioanalytical Chemistry·Min ShenBaohua Shen
May 9, 2014·Bioanalysis·Aurélien Thomas, Pierre Chaurand
Apr 20, 2014·Journal of the American Society for Mass Spectrometry·Jeremy A BarryDavid C Muddiman
Apr 26, 2011·Journal of Proteomics·Tyler GreerLingjun Li
Jan 24, 2014·Natural Product Reports·Nanna BjarnholtChristian Janfelt
Jun 3, 2011·The Journal of Biological Chemistry·Erin H SeeleyRichard M Caprioli
Oct 21, 2011·Nature Protocols·Rita Casadonte, Richard M Caprioli
Feb 10, 2012·American Journal of Physiology. Endocrinology and Metabolism·Nadja GrobeMariana Morris
Jun 16, 2012·The Journal of Biological Chemistry·Aaron G PothDavid J Craik
Oct 19, 2013·Journal of Proteome Research·Ákos VégváriGyörgy Marko-Varga
Aug 24, 2013·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Mohammadreza ShariatgorjiPer E Andrén
Mar 8, 2011·Analytical and Bioanalytical Chemistry·Christopher D CerrutiAlain Brunelle
Jan 28, 2016·Analytical Chemistry·Chad W ChumbleyRichard M Caprioli
Feb 19, 2013·Expert Review of Proteomics·Hassan DihaziAbdul R Asif
Apr 23, 2013·Advanced Drug Delivery Reviews·Christopher B LietzLingjun Li
Jul 31, 2012·Journal of Proteomics·Brendan Prideaux, Markus Stoeckli
May 29, 2012·Journal of Proteomics·Liam A McDonnellGarry L Corthals
Jun 30, 2012·Journal of Proteomics·Emrys A JonesLiam A McDonnell
May 29, 2012·Journal of Proteomics·H M Santos, J L Capelo
Jul 6, 2012·Trends in Biotechnology·Rima Ait-BelkacemDaniel Lafitte
Dec 20, 2014·Analytical Chemistry·Anna NilssonPer E Andrén
Mar 29, 2011·Journal of Proteomics·György Marko-VargaAkos Végvári
Feb 27, 2016·Bioanalysis·Yutaka SugiharaÁkos Végvári

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Methods Mentioned

BETA
chemical

Software Mentioned

Flex Imaging
ImagePrep
Image Prep
BioMap
FlexImaging

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