Mechanistic explanation to the variable degradation behaviour of stavudine and zidovudine under hydrolytic, oxidative and photolytic conditions

The kinetics of decomposition of zidovudine and stavudine was studied under ICH recommended stress conditions of hydrolysis, oxidation and photolysis. The two drugs, which are closely related in structure, showed the same order of sensitivity under hydrolytic conditions, viz. acid > water > alkali. But stavudine was found to hydrolyse overall much faster than zidovudine. Both drugs were almost stable under basic conditions. Stavudine showed decomposition on exposure to peroxide while zidovudine was stable. On the contrary, zidovudine showed more sensitivity to light than stavudine, which was almost photostable. Thymine was formed as a major decomposition product of both the drugs under all the three stress conditions. The observed behaviour is explained mechanistically. (C) 2004 Elsevier B.V. All rights reserved.