title: Photodegradation of irinotecan (CPT-11) in aqueous solutions: identification of fluorescent products and influence of solution composition.
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 general, CPT-11 was found to be unstable under neutral and alkaline conditions for all solutions investigated, with the exception of bile. We conclude that CPT-11 is photolabile and that care should be taken to protect samples, particularly those intended for the isolation and identification of novel metabolites of CPT-11.
authors.affiliation: University of Queensland Department of Medicine, Princess Alexandra Hospital, Woolloongabba, Australia.
authors.forename: H M
authors.initials: HM
authors.lastname: Dodds
authors.forename: D J
authors.initials: DJ
authors.lastname: Craik
authors.forename: L P
authors.initials: LP
authors.lastname: Rivory
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics / Q000652:urine; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D000077146:Irinotecan; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010782:Photolysis; D012996:Solutions; D014867:Water
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012996:Solutions; D014867:Water; D000077146:Irinotecan; D002166:Camptothecin