The hydrolytic stability of poly(2-(dimethylamino)ethyl methacrylate) was investigated and compared with the stability of its monomer 2-(dimethylamino)ethyl methacrylate (DMAEMA), with 2-(dimethylamino)ethyl isobutyrate (DMAEIB), representing the repeating unit in the polymer, and with the related 3-(dimethylamino)propyl methacrylate (DMAPMA) (H 0/pH range −0.5 to +12, at 37 °C, in aqueous solution). At pH < 3, the unsaturated DMAEMA and DMAPMA were more stable than the saturated DMAEIB. At pH 4−8, DMAEMA and DMAEIB were equally stable, but less stable than DMAPMA. This has been ascribed to a coordination of the protonated dimethylamino group and the ester carbonyl, rendering the ester more susceptible to nucleophilic attack of a hydroxyl ion. At alkaline pH (>pK a) no differences in stability between the compounds were found. P(DMAEMA), either in its free form or complexed to DNA, was substantially more stable to hydrolytic degradation than DMAEMA and DMAEIB. Fluorescence measurements performed with a copolymer of DMAEMA and dansyl ethyl methacrylamide showed that the dielectric constant (εr) experienced in the environment of the polymer backbone, was low (about 7). This microenvironment might be the reason for the hydrolytic stability of the polymer, since the hydrolysis of the monomer decreased substantially with decreasing εr of the medium. Accelerated degradation (80 °C, pH 1 and 7) of p(DMAEMA) and poly(2-(dimethylamino)ethyl acrylate), p(DMAEA), showed that p(DMAEA) was more sensitive to hydrolysis. This can be explained by the assumption that, due to the lack of the methyl group, the εr in the environment of the acrylate backbone is higher than the εr in the environment of the p(DMAEMA) backbone.

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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 Kobs 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, borate, and carbonate buffer have no influence on the decomposition rate of the analyte. Increasing ionic strength led to higher Kobs at pH 2 and lower Kobs at pH 9, but influences were relatively small.

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