Evaluations about the physico-chemical stability of docetaxel and irinotecan pre-diluted and diluted solutions: pharmaco-economic perspectives

Abstract

Several clinically used anticancer drugs are well-known as far as their pharmacologic properties are concerned, but scarcely ever the interest towards their physico-chemical characteristics in solution led to practical acknowledgement in their management. Thanks to the Units for Centralized Anticancer Drug Handling, the importance to evaluate the concentration of saturation (physical stability) or the possible transformations undergone by a drug in solution (chemical stability) has become the starting point for avoiding useless wasting drugs and economic resources. By HPLC experiments we have demonstrated that the solutions of two drugs, docetaxel and irinotecan, are particularly stable at different concentrations and times of analyses in our experimental conditions. The best mobile phase for docetaxel was water/methanol/acetonitrile in 42/32/26 volumetric ratio: for halving concentrations (0.72-0.36-0.18-0.09 mg/mL) in NaCl 0.9%, the highest value gave a six-day and the three lower concentrations a fourteen-day stability, when storage occurred at room temperature and light protected. Elution of irinotecan was possible through an analysis in mobile phase gradient: at t0 a 20% ammonium acetate 10 mM and 80% methanol mixture, and after 5 min, a 80% ammonium acetate 10 mM and 20% methanol mixture. The physico-chemical stability was showed for five days, for any concentration of analysis when storage occurred at 2-8°C and light protected.