Monitoring subcellular biotransformation of N-l-leucyldoxorubicin by micellar electrokinetic capillary chromatography coupled to laser-induced fluorescence detection

Chad P. Satori, Brandon Meyer, Edgar A. Arriaga

Research output: Contribution to journalArticlepeer-review

Abstract

Development of prodrugs is a promising alternative to address cytotoxicity and nonspecificity of common anticancer agents. N-l-leucyldoxorubicin (LeuDox) is a prodrug that is biotransformed to the anticancer drug doxorubicin (Dox) in the extracellular space; however, its biotransformation may also occur intracellularly in endocytic organelles. Such organelle-specific biotransformation is yet to be determined. In this study, magnetically enriched endocytic organelle fractions from human uterine sarcoma cells were treated with LeuDox. Micellar electrokinetic chromatography with laser-induced fluorescence detection (MEKC-LIF) was used to determine that 10 % of LeuDox was biotransformed to Dox, accounting for 43 % of the biotransformation occurring in the post-nuclear fraction. This finding suggests that endocytic organelles also participate in the intracellular biotransformation of LeuDox to Dox. [Figure not available: see fulltext.]

Original languageEnglish (US)
Pages (from-to)2389-2397
Number of pages9
JournalAnalytical and Bioanalytical Chemistry
Volume406
Issue number9-10
DOIs
StatePublished - Jan 1 2014

Keywords

  • Biotransformation
  • Doxorubicin
  • Endocytic organelles
  • Micellar electrokinetic chromatography
  • N-l-leucyldoxorubicin
  • Prodrugs

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