Photodegradation of irinotecan (CPT-11) in aqueous solutions: identification of fluorescent products and influence of solution composition

Journal of Pharmaceutical Sciences
H M DoddsL P Rivory

Abstract

The photodegradation of irinotecan (CPT-11), the semi-synthetic derivative of the antitumor alkaloid 20(S)-camptothecin, has been investigated. The drug was exposed to laboratory light for up to 5 days in 0.9% saline solution (pH 8.5). Five significant photodegradation products were observed and a high-performance liquid chromatography (HPLC) assay was employed to isolate them from CPT-11 using gradient conditions. The structures were elucidated by nuclear magnetic resonance spectroscopy and tandem mass spectrometry and shown to be the result of extensive modifications of the lactone ring of CPT-11. Three of the compounds were found to belong to the mappicine group of alkaloids. In addition, the effect of light on the stability of CPT-11 in aqueous solutions and biological fluids was also assessed. Potassium phosphate buffers (0.05 M, pH 5.0-8.2) and saline, plasma, urine, and bile solutions containing 20 microM CPT-11 were equilibrated in the dark for 24 h before being exposed to laboratory light for up to 171 h at ambient temperature. Four of the five identified photodegradation products were observed and quantitated by isocratic HPLC, using a different detection mode (fluorescence) than the one used for gradient elution. In ...Continue Reading

References

Jul 1, 1992·Journal of Pharmaceutical Sciences·J Fassberg, V J Stella
Jan 1, 1990·Progress in Medicinal Chemistry·J V Greenhill, M A McLelland
Dec 16, 1983·Biochemical and Biophysical Research Communications·M RanceK Wüthrich

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Citations

Jan 31, 2002·Journal of Chromatography. B, Biomedical Sciences and Applications·M PalumboG Zagotto
Oct 12, 2004·Phytotherapy Research : PTR·Vlasta BrezováDaniela Kost'álová
Feb 2, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yiqing TangAndrew L Lewis
Nov 28, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Jim Siderov
Jul 21, 2009·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Jeanette KaiserIrene Krämer
Oct 22, 2002·The Journal of Pharmacology and Experimental Therapeutics·Helen M DoddsLaurent P Rivory
Feb 24, 2001·Annals of the New York Academy of Sciences·L P Rivory

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