Analytical and Bioanalytical Chemistry

, Volume 411, Issue 27, pp 7087–7094 | Cite as

Quantitative evaluation of liposomal doxorubicin and its metabolites in spheroids

  • Jessica K. Lukowski
  • Amanda B. HummonEmail author
Research Paper


Accurate measurement and understanding of therapeutic uptake and metabolism is key in the drug development process. This work examines the amount of doxorubicin that can penetrate into spheroids after being encapsulated in a liposomal configuration in comparison with free drug. Through a process known as serial trypsinization, three distinct cellular populations of a spheroid were successfully separated and a small molecule extraction was used to isolate the chemotherapeutic. Doxorubicin showed a time-dependent permeability into spheroids with the most drug accumulating in the core at 24 h of treatment. Entrapment of the chemotherapeutic delayed the permeability of the drug and resulted in reduced amounts quantified at the earlier time points. These findings validate the claim that liposomal therapeutics have the ability to alter the pharmacokinetics and pharmacodynamics profiles of a drug while also demonstrating the combined power of mass spectrometry and three-dimensional cell cultures to evaluate drug penetration and metabolism.

Graphical abstract


nLC-MS/MS 3D cell cultures Doxorubicin Liposomal drug delivery 



The authors thank Matt Bernier and the Campus Chemical Instrument Center at Ohio State University for help with the analysis of the samples. A.H. and J.L. were supported by the National Science Foundation (CAREER Award, No. CHE-1351595).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2019_2084_MOESM1_ESM.pdf (631 kb)
ESM 1 (PDF 631 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Chemistry and BiochemistryUniversity of Notre DameNotre DameUSA
  2. 2.Department of Chemistry and Biochemistry and the Comprehensive Cancer CenterThe Ohio State UniversityColumbusUSA

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