Abstract
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 language | English |
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Pages (from-to) | 1113-1125 |
Number of pages | 13 |
Journal | Journal of Pharmaceutical and Biomedical Analysis |
Volume | 35 |
Issue number | 5 |
DOIs | |
State | Published - 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.
Keywords
- CPT
- CPT-20(S)-acetate
- CPT-20(S)-glycinate
- LC/ESI/MS
- PBS
- RP-HPLC
- 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