Degradation kinetics of gonadorelin in aqueous solution

被引:16
作者
Hoitink, MA
Beijnen, JH
Bult, A
vanderHouwen, OAGJ
Nijholt, J
Underberg, WJM
机构
[1] Dept. of Pharmaceutical Analysis, Faculty of Pharmacy, Utrecht University, NL-3584 CA, Utrecht
关键词
D O I
10.1021/js9601187
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The degradation kinetics of gonadorelin were investigated systematically with reversed-phase high-performance liquid chromatography. The stability-indicating properties of this system were checked with photodiode array detection and by comparison with capillary zone electrophoretic analysis. Influences of gonadorelin concentration, pH, temperature, buffer ions, and ionic strength on the degradation kinetics were studied. The pH-log k(obs) profile can be divided into three parts, a proton, a solvent, and a hydroxyl-catalyzed section, with different degradation products. These degradation products were characterized by mass using LC-MS. Gonadorelin is most stable at pH 5-5.5 with a half-life of 70 days at 70 degrees C. The overall degradation rate constant as a function of the temperature under acidic and alkaline conditions obeys the Arrhenius equation. The gonadorelin concentration and the concentrations of acetate, phosphate, berate, and carbonate buffer have no influence on the decomposition rate of the analyte. Increasing ionic strength led to higher k(obs) at pH 2 and lower k(obs) at pH 9, but influences were relatively small.
引用
收藏
页码:1053 / 1059
页数:7
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