Analysis of the stability and degradation products of triptolide

Triptolide is the major active ingredient of the Chinese herbal remedy Trip terygium wilfordii Hook F. (TwHF). As triptolide content is used to estimat e the potency of preparations of TwHF, assessment of its stability is warra nted. The accelerated stability of triptolide was investigated in 5% ethanol solu tion in a light-protected environment at pH 6.9, within a temperature range of 60-90 degrees C. The observed degradation rate followed first-order kin etics. The degradation rate constant (K(25)degrees C) obtained by trending line analysis of Arrhenius plots of triptolide was 1.4125 x 10(-4) h(-1). T he times to degrade 10% (t(1/10)) and 50% (t(1/2)) at 25 degrees C were 31 and 204 days, respectively. Stability tests of triptolide in different solv ents and different pH conditions (pH 4-10) in a light-protected environment at room temperature demonstrated that basic medium and a hydrophilic solve nt were the major factors that accelerated the degradation of triptolide. T riptolide exhibited the fastest degradation rate at pH 10 and the slowest r ate at pH 6. In a solvent comparison, triptolide was found to be very stabl e in chloroform. The stability of triptolide in organic polar solvents test ed at Both 100% and 90% concentration was greater in ethanol than in methan ol than in dimethylsulphoxide. Stability was also greater in a mixture of s olvent:pH 6 buffer (9:1) than in 100% solvent alone. An exception was ethyl acetate, which is less polar than the other solvents tested, but permitted more rapid degradation of triptolide. Two of the degradation products of t riptolide were isolated and identified by HPLC and mass spectroscopy as tri ptriolide and triptonide. This suggested that the decomposition of triptoli de occurred at the C12 and C13 epoxy group and the C14 hydroxyl. The openin g of the C12 and C13 epoxy is an irreversible reaction, but the reaction oc curring on the C14 hydroxyl is reversible. These results show that the major degradation pathway of triptolide involve s decomposition of the C12 and C13 epoxy group. Since this reaction is very slow at 4 degrees C at pH 6, stability is enhanced under these conditions.