Degradation Kinetics of Gonadorelin in Aqueous Solution

Abstract

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.

Degradation Kinetics of Methacrylated Dextrans in Aqueous Solution

“…The H0 values were calculated according to Hammett. 11,12 The initial concentrations were 40 µg/mL for dex-MA, 200 µg/mL for dex-HEMA, and 10 µg/mL for HEMA, except for the perchloric acid solutions, which contained 10-fold higher concentrations. Samples from the latter reaction mixtures were diluted 10 times, before mixing with 1 M acetate buffer pH 5.…”

Degradation Kinetics of Somatostatin in Aqueous Solution

“…Higher concentrations were not investigated, due to the limited amount of material that was available for the study. [5,6] Extrapolation of the Arrhenius plot to a temperature of 4 C gives a k obs of 3.3 Â 10 À4 d À1 and a t 90 of approximately 320 days at pH 7.4. At room temperature, the t 90 will be around 26 days under these solution conditions.…”

“…A nonlinear relationship between the buffer concentration and k obs was observed, which is probably due to the fact that the buffer concentrations used in our study are higher compared with other reports. [5,6,10,17] No attempts were made to identify the structure of the degradation products, however, oxidation of the disulfide bridge could be ruled out as a major degradation pathway, since incubating the peptide with dithiothreitol (60 C, 15 min, pH 7.4, somatostatin/DTT ratio 1/5) resulted in a shift of the single peak of nondegraded somatostatin from a retention time of 15.6 min to single peak at 18.3 min. This peak was never seen in any of the degradation experiments.…”

“…Despite the large number of reports dealing with the stability of peptide drugs such as ACTH, [3] calcitonin, [4] gonadorelin, [5,6] insulin, [7] (LH-RH), [8] nafarelin, [9] and secretin [10] to name just a few, very little is known about the stability of somatostatin. Analogs of this drug have been investigated before, [11][12][13] but, to our knowledge, no stability studies have been performed with the parent molecule somatostatin, except for one publication reporting the loss of peptide in solutions for total parenteral nutrition.…”

Degradation of Azaglycinamido Residues in Model Tripeptides Derived from Goserelin

“…The pK a value of the side chain of tyrosine in peptides was determined at 70°C in an earlier study and was found to be 9.5. 5 The macro constants of these fits are presented in Table II. The resulting fit of an one pK a model with a value fixed at 9.5 is not acceptable, the line does not include most points.…”