High-Performance Liquid Chromatographic (HPLC) and HPLC-Mass Spectrometric (MS) Analysis of the Degradation of the Luteinizing Hormone-Releasing Hormone (LH-RH) Antagonist RS-26306 in Aqueous Solution
- 1 January 1990
- journal article
- research article
- Published by Springer Nature in Pharmaceutical Research
- Vol. 07 (5) , 530-536
- https://doi.org/10.1023/a:1015829119270
Abstract
The kinetics of the degradation of an LH-RH antagonist, RS-26306,1, in aqueous solution from pH 1 to pH 11 were studied by reverse-phase HPLC. The pH–rate profiles at 50, 60, and 80°C were U-shaped with the rate law of kobs = kHaH + kw + kOHaOH. The predicted 25°C shelf life at the pH of maximum stability, pH ∼5, is greater than 10 years. The products from the degradation were analyzed by HPLC-MS using thermospray ionization. Below pH 3, the primary product, 2, forms from the acid-catalyzed deamidation of the C-terminal amide. Above pH 7, epimerization of the individual amino acids is the principal reaction. Between pH 4 and pH 6, intramolecular serine-catalyzed peptide hydrolysis becomes important, yielding a tripeptide, 3, and a heptapeptide, 4. At the pH of maximum stability all three pathways for degradation are observed.This publication has 4 references indexed in Scilit:
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