| dc.description |
Paclitaxel is a very important anticancer drug commonly called Taxol®.
We know from previous work (Hoffman, et al., 1998) that Taxol exists in filbert, Corylus avellana L. material. Quantification of Taxol in filbert plant material is painstaking and hitherto was accomplished by rapidly processing single batches in a complicated procedure (Hoffman, et al., 1998), which seemingly unavoidably, was accompanied by some degradation.
However for extraction, testing, plant physiological and horticultural purposes a simplified method of determining Taxol yield is required. All simplified methods tested were found limited by rapid degradation of Taxol. Under these conditions not only is the sought product broken down, but we were unable to distinguish Taxol precursors from degradation products. Thus it was decided to go back to first principles and study the degradation of Taxol in vitro.
Degradation kinetics of Taxol was studied using electrospray ionization mass spectrometry (ESIMS) to identify possible Taxol adducts and degradation products.
Our preparation for ESIMS analysis by experimental necessity involved various other components. Since some of these components interacted with the degradation products, we developed a program to distinguish these putative adducts from spurious components found in the system and we were able to plot the pH dependence of Taxol degradation in this system at room temperature (approximately 25oC). The results of the mass spectrometric analysis of these degradants were found dependent on pH and time.
Our results show major degradation at pH 9 and beyond, plus minor degradation at pH 5. Two optimum pHs for stability were found at pH 4 and pH 7. This data varies slightly from the published results Dordunoo and Burt (1996). Our smoother curves define two pHs events in this pH range which to our knowledge, have not been reported and our temperature was lower.
We hope that this information will help us extract Taxol more efficiently with greater yield from novel plant sources, e.g. hazel (filbert) tree, Corylus avellana L. The possibility of Taxol dimer formation in solution and perhaps in vivo can be inferred, but not proven, in this work. This dimer, may exist, in dynamic equilibrium with parent compound, Taxol. |
|