Degradation kinetics of gonadorelin in aqueous solution.
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.
Department of Pharmaceutical Analysis, Faculty of Pharmacy, Utrecht University, The Netherlands.
M A
MA
Hoitink
J H
JH
Beijnen
A
A
Bult
O A
OA
van der Houwen
J
J
Nijholt
W J
WJ
Underberg
D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D013058:Mass Spectrometry; D012996:Solutions; D013696:Temperature; D014867:Water
D002021:Buffers; D012996:Solutions; D014867:Water; D007987:Gonadotropin-Releasing Hormone