Paclitaxel Stability in Solution

Research in this laboratory has focused on the cytokinetic effect of taxanes on nonmammalian systems. Taxanes are a class of natural products that includes the well-known anticancer compound, paclitaxel (Taxol). Our methodology for the study of fungal growth in liquid medium amended with paclitaxel included membrane solid phase extraction (SPE) of the fungal broth. This was followed by elution of paclitaxel from the SPE membrane using methanol. The methanolic solution was evaporated under relatively mild conditions, namely 41−43 °C and approximately 85 kPag. Analysis of the concentrated solution indicated that it contained a considerable quantity of 7-epi-taxol and smaller quantities of 7-epi-10-deacetyltaxol, 10-deacetyltaxol, and baccatin III, in addition to paclitaxel, even in those cases where the medium had not been inoculated with fungus. Obviously, fungal metabolism could not account for these observations. Although epimerization in solution at carbon 7 in the C ring of the taxane core has been observed and reported previously, no detailed study of the solution kinetics of paclitaxel degradation, including epimerization, is available. We report here our investigation of the stability of paclitaxel in several solvent systems at various temperatures and pressures. The investigations indicate that the apparent activation energy barrier (E a) for paclitaxel degradation is highly dependent on experimental conditions. These stability studies emphasize the need to demonstrate explicitly that all taxane degradation, including epimerization, observed during in vitro studies is not an artifact of the analytical methodology employed.