Degradation of camptothecin-20(S)-glycinate ester prodrug under physiological conditions

Xinli Liu, Junhong Zhang, Lin Song, Bert C. Lynn, Thomas G. Burke

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


We have compared the strikingly different decomposition pathways for camptothecin-20(S)-acetate -acetate and camptothecin-20(S)-glycinate in phosphate buffered saline, human plasma and blood. The aliphatic ester analog camptothecin-20(S)-acetate demonstrated excellent stability in the above fluids for many hours with minimal hydrolysis, while the camptothecin-20(S)-glycinate analog (differing solely by the presence of an amino group) underwent rapid and essentially complete decomposition. Reversed-phase high performance liquid chromatography (RP-HPLC) with electrospray ionization-mass spectral (ESI-MS) detection was then used to correlate structural information for camptothecin-20(S)-glycinate decomposition products. ESI-MS detection indicated the ring-opened carboxylate form of camptothecin and the ring-opened degradation product co-elute near the solvent front, while the latest eluting decomposition product was the closed-ring lactone form of camptothecin. A novel decomposition product with intermediate retention time displayed an identical mass-to-charge ratio as camptothecin-20(S)-glycinate ester but a strikingly different fragmentation pattern. The LC-ESI-MS evidence of a novel camptothecin prodrug degradation pathway is provided in this report.

Original languageEnglish
Pages (from-to)1113-1125
Number of pages13
JournalJournal of Pharmaceutical and Biomedical Analysis
Issue number5
StatePublished - Sep 3 2004

Bibliographical note

Funding Information:
This work was supported by NIH CA 63653 grant (to T.G.B). We also acknowledge University of Kentucky Mass Spectrometry Facility.


  • CPT
  • CPT-20(S)-acetate
  • CPT-20(S)-glycinate
  • PBS
  • camptothecin
  • camptothecin-20(S)-acetate
  • camptothecin-20(S)-glycinate
  • liquid chromatography electrospray ionization-mass spectrometry
  • phosphate buffered saline

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry


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