PHOTODEGRADATION OF IRINOTECAN (CPT-11) IN AQUEOUS-SOLUTIONS - IDENTIFICATION OF FLUORESCENT PRODUCTS AND INFLUENCE OF SOLUTION COMPOSITION

The photodegradation of irinotecan (CPT-11), the semisynthetic derivat ive of the antitumor alkaloid 20(S)-camptothecin, has been investigate d. The drug was exposed to laboratory light for up to 5 days in 0.9% s aline solution (pH 8.5). Five significant photodegradation products we re observed and a high-performance liquid chromatography (HPLC) assay was employed to isolate them from CPT-11 using gradient conditions. Th e structures were elucidated by nuclear magnetic resonance spectroscop y and tandem mass spectrometry and shown to be the result of extensive modifications of the lactone ring of CPT-11. Three of the compounds w ere found to belong to the mappicine group of alkaloids. In addition, the effect of light on the stability of CPT-11 in aqueous solutions an d biological fluids was also assessed, Potassium phosphate buffers (0. 05 M, pH 5.0-8.2) and saline, plasma, urine, and bile solutions contai ning 20 mu M CPT-11 were equilibrated in the dark for 24 h before bein g exposed to laboratory light for up to 171 h at ambient temperature. Four of the five identified photodegradation products were observed an d quantitated by isocratic HPLC, using a different detection mode (flu orescence) 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.