Thermal decomposition mechanism and kinetics of gemcitabine

Gemcitabine (GTB) is a nucleoside drug used in chemotherapy for various carcinomas. In order to know why does GTB have good thermal stability, and to further understand the relationship between thermal stability and molecular structure. The thermal decomposition of GTB was measured with various thermal analytical techniques, the gaseous products and the residues of thermal decomposition were determined and identified. The molecular bond orders were calculated. The thermal decomposition mechanism of GTB was discussed. The thermal decomposition kinetics and the prospective lifetime of GTB were studied using the ATSM method. The results indicated that two strong electronegative fluorine atoms on furan ring make the strong charge-transfer (CT) structure to be formed, this strong CT structure remarkably enhance the N-glycosidic bond and the weakest bond, and lead to higher thermal stability and distinctive thermal decomposition mechanism. The thermal decomposition of GTB is a three-stage process. The initial step of decomposition is likely due to the loss of a furan ring. Most of GTB decompose and carbonizes directly to form insoluble substance and small molecules and just part of GTB decompose by way of cytosine stage. The initial decomposition temperature in either nitrogen or air is 235 degrees C. For decomposition in nitrogen, the apparent activation energy Ea and pre-exponential factor A for the initial thermal decomposition are 123.4 kJ mol(-1) and 3.80 x 10(10) min(-1), respectively. For decomposition in air, the corresponding E-a and A are 126.3 kJ mol(-1) and 7.94 x 10(10) min(-1), respectively. GTB has very good thermal stability under routine temperature and dry air atmosphere.