Mechanistic explanation to the variable degradation behaviour of stavudine and zidovudine under hydrolytic, oxidative and photolytic conditions
Mechanistic explanation to the variable degradation behaviour of stavudine and zidovudine under hydrolytic, oxidative and photolytic conditions
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DOI：
10.1016/j.jpba.2004.03.007
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发表时间：
2004-06-29
影响因子：
3.4
通讯作者：
Singh, S
中科院分区：
文献类型：
--
作者：
Dunge, A;Chakraborti, AK;Singh, S
在ICH推荐的水解、氧化和光解强制降解条件下，研究了齐多夫定和司他夫定的分解动力学。这两种药物在结构上密切相关，在水解条件下表现出相同的敏感性顺序，即酸>水>碱。但司他夫定的水解速度比齐多夫定快得多。两种药物在碱性条件下几乎稳定。司他夫定在暴露于过氧化物时显示分解，而齐多夫定是稳定的。相反，齐多夫定比司他夫定对光更敏感，司他夫定几乎是光稳定的。在所有三种强制降解条件下，胸腺嘧啶均作为两种药物的主要分解产物形成。观察到的行为是机械解释。(C)2004 Elsevier B.V.保留所有权利。
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.