Bindra D S, Williams T D, Stella V J
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66405.
Pharm Res. 1994 Jul;11(7):1060-4. doi: 10.1023/a:1018903908385.
The degradation of O6-benzylguanine (BG) in aqueous polyethylene glycol (PEG) 400 solution at room temperature had been investigated using chromatographic and spectrometric methods. The degradation of BG in this solvent appeared to arise from a reaction between BG and formaldehyde. The formaldehyde was present as an impurity in PEG 400 and probably formed through air oxidation of PEG 400. The major product of this reaction was believed to be a methylene-bridged compound containing two BG molecules. This was probably produced via an intermediate imine, a schiff base between one BG molecule and formaldehyde. This degradation reaction was the only observable reaction in the 40% PEG/water solvent (pH 8.0) i.e. degradation of the drug via hydrolysis was minimal under these conditions.
采用色谱和光谱法研究了室温下O6-苄基鸟嘌呤（BG）在聚乙二醇（PEG）400水溶液中的降解情况。BG在该溶剂中的降解似乎源于BG与甲醛之间的反应。甲醛作为PEG 400中的杂质存在，可能是通过PEG 400的空气氧化形成的。该反应的主要产物被认为是一种含有两个BG分子的亚甲基桥连化合物。这可能是通过一种中间体亚胺生成的，即一个BG分子与甲醛之间的席夫碱。在40%PEG/水溶剂（pH 8.0）中，这种降解反应是唯一可观察到的反应，即在这些条件下，药物通过水解的降解最小。
