Skip to main content

Development and Application of DropletProbe Mass Spectrometry for Examining Biodistribution of Therapeutics

  • Protocol
  • First Online:
Mass Spectrometry Imaging of Small Molecules

Abstract

dropletProbe mass spectrometry is a novel technique for molecular characterization of surfaces. It can be used for rapid ex vivo analysis of therapeutics from thin animal tissue sections and has been shown to improve understanding of a drug’s absorption, distribution, metabolism and excretion (ADME) properties. Here, we describe the tissue distribution analysis of diclofenac from a dosed whole-body mouse thin tissue section using a dropletProbe mass spectrometry system.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Solon EG (2015) Autoradiography techniques and quantification of drug distribution. Cell Tissue Res 360(1):87–107. https://doi.org/10.1007/s00441-014-2093-4

    Article  PubMed  Google Scholar 

  2. Solon EG, Schweitzer A, Stoeckli M, Prideaux B (2010) Autoradiography, MALDI-MS, and SIMS-MS imaging in pharmaceutical discovery and development. AAPS J 12(1):11–26. https://doi.org/10.1208/s12248-009-9158-4

    Article  CAS  PubMed  Google Scholar 

  3. Buchberger AR, DeLaney K, Johnson J, Li L (2018) Mass spectrometry imaging: a review of emerging advancements and future insights. Anal Chem 90(1):240–265. https://doi.org/10.1021/acs.analchem.7b04733

    Article  CAS  PubMed  Google Scholar 

  4. Duenas ME, Essner JJ, Lee YJ (2017) 3D MALDI mass spectrometry imaging of a single cell: spatial mapping of lipids in the embryonic development of zebrafish. Sci Rep 7(1):14946. https://doi.org/10.1038/s41598-017-14949-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Norris JL, Caprioli RM (2013) Analysis of tissue specimens by matrix-assisted laser desorption/ionization imaging mass spectrometry in biological and clinical research. Chem Rev 113(4):2309–2342. https://doi.org/10.1021/cr3004295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Aichler M, Walch A (2015) MALDI imaging mass spectrometry: current frontiers and perspectives in pathology research and practice. Lab Investig 95(4):422–431. https://doi.org/10.1038/labinvest.2014.156

    Article  CAS  PubMed  Google Scholar 

  7. Eikel D, Vavrek M, Smith S, Bason C, Yeh S, Korfmacher WA, Henion JD (2011) Liquid extraction surface analysis mass spectrometry (LESA-MS) as a novel profiling tool for drug distribution and metabolism analysis: the terfenadine example. Rapid Commun Mass Spectrom 25(23):3587–3596. https://doi.org/10.1002/rcm.5274

    Article  CAS  PubMed  Google Scholar 

  8. Wu Q, Huang Z, Wang Y, Zhang Z, Lu H (2020) Absolute quantitative imaging of sphingolipids in brain tissue by exhaustive liquid microjunction surface sampling-liquid chromatography-mass spectrometry. J Chromatogr A 1609:460436. https://doi.org/10.1016/j.chroma.2019.460436

    Article  CAS  PubMed  Google Scholar 

  9. Kertesz V, Van Berkel GJ (2010) Liquid microjunction surface sampling coupled with high-pressure liquid chromatography-electrospray ionization-mass spectrometry for analysis of drugs and metabolites in whole-body thin tissue sections. Anal Chem 82(14):5917–5921. https://doi.org/10.1021/ac100954p

    Article  CAS  PubMed  Google Scholar 

  10. Kertesz V, Cahill JF, Srijanto BR, Collier CP, Vavrek M, Chen B (2020) Absolute quantitation of propranolol from 200-mum regions of mouse brain and liver thin tissues using laser ablation-dropletProbe-mass spectrometry. Rapid Commun Mass Spectrom 35:e9010. https://doi.org/10.1002/rcm.9010

    Article  CAS  Google Scholar 

  11. Pan N, Rao W, Kothapalli NR, Liu R, Burgett AW, Yang Z (2014) The single-probe: a miniaturized multifunctional device for single cell mass spectrometry analysis. Anal Chem 86(19):9376–9380. https://doi.org/10.1021/ac5029038

    Article  CAS  PubMed  Google Scholar 

  12. Yin R, Burnum-Johnson KE, Sun X, Dey SK, Laskin J (2019) High spatial resolution imaging of biological tissues using nanospray desorption electrospray ionization mass spectrometry. Nat Protoc 14(12):3445–3470. https://doi.org/10.1038/s41596-019-0237-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Chen B, Vavrek M, Cancilla MT (2020) Optimization of dropletProbe-mass spectrometry for whole-body tissue distribution analysis of drug-like molecules. J Am Soc Mass Spectrom 31(12):2558–2562. https://doi.org/10.1021/jasms.0c00168

    Article  CAS  PubMed  Google Scholar 

  14. Chen B, Vavrek M, Gundersdorf R, Zhong W, Cancilla MT (2020) Combining MALDI mass spectrometry imaging and droplet-base surface sampling analysis for tissue distribution, metabolite profiling, and relative quantification of cyclic peptide melanotan II. Anal Chim Acta 1125:279–287. https://doi.org/10.1016/j.aca.2020.05.050

    Article  CAS  PubMed  Google Scholar 

  15. Kertesz V, Weiskittel TM, Van Berkel GJ (2015) An enhanced droplet-based liquid microjunction surface sampling system coupled with HPLC-ESI-MS/MS for spatially resolved analysis. Anal Bioanal Chem 407(8):2117–2125. https://doi.org/10.1007/s00216-014-8287-5

    Article  CAS  PubMed  Google Scholar 

  16. Kertesz V, Van Berkel GJ (2014) Sampling reliability, spatial resolution, spatial precision, and extraction efficiency in droplet-based liquid microjunction surface sampling. Rapid Commun Mass Spectrom 28(13):1553–1560. https://doi.org/10.1002/rcm.6931

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The work of V.K. was supported by the US Department of Energy, Office of Science, Biological and Environmental Research, Bioimaging Science Program. The authors acknowledge Alain Creissen and Sloan Tilley (HTX Technology) and Matt Orcutt (Resolution Labs) for providing technical support of dropletProbe MS. We acknowledge Scott Fauty (Merck & Co., Inc., Kenilworth, NJ, USA) for performing animal experiments.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bingming Chen .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Chen, B., Vavrek, M., Cancilla, M.T., Kertesz, V. (2022). Development and Application of DropletProbe Mass Spectrometry for Examining Biodistribution of Therapeutics. In: Lee, YJ. (eds) Mass Spectrometry Imaging of Small Molecules. Methods in Molecular Biology, vol 2437. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2030-4_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-2030-4_12

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2029-8

  • Online ISBN: 978-1-0716-2030-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics