Research in this laboratory has focused on the cytokinetic effect of t
axanes on nonmammalian systems. Taxanes are a class of natural product
s that includes the well-known anticancer compound, paclitaxel (Taxol)
. Our methodology for the study of fungal growth in liquid medium amen
ded with paclitaxel included membrane solid phase extraction (SPE) of
the fungal broth. This was followed try elution of paclitaxel from the
SPE membrane using methanol, The methanolic solution was evaporated u
nder relatively mild conditions, namely 41-43 degrees C and approximat
ely 85 kPag, Analysis of the concentrated solution indicated that it c
ontained a considerable quantity of 7-epi-taxol and smaller quantities
of 7-epi-10-deacetyl-taxol, 10-deacetyltaxol, and baccatin III, in ad
dition to paclitaxel, even in those cases where the medium had not bee
n inoculated with fungus, Obviously, fungal metabolism could not accou
nt for these observations. Although epimerization in solution at carbo
n 7 in the C ring of the taxane core has been observed and reported pr
eviously, no detailed study of the solution kinetics of paclitaxel deg
radation, including epimerization, is available, We report here our in
vestigation of the stability of paclitaxel in several solvent systems
at various temperatures and pressures. The investigations indicate tha
t the apparent activation energy barrier (E(a)) for paclitaxel degrada
tion is highly dependent on experimental conditions. These stability s
tudies emphasize the need to demonstrate explicitly that all taxane de
gradation, including epimerization, observed during in vitro studies i
s not an artifact of the analytical methodology employed.