Identification of the degradation products of gonadorelin and three analogues in aqueous solution

Degradation products of the peptides gonadorelin and its analogues buserelin, goserelin, and triptorelin were characterized with LC/MS, chiral amino acid analysis, and FAB-MS(-MS). Differences in chemical structures of gonadorelin, its analogues, and their respective decomposition products were evaluated in relation to the putative degradation mechanisms, In acidic solution, gonadorelin and triptorelin are deamidated, whereas buserelin and goserelin undergo debutylation. En the pH range 5-6, the peptide backbone of all four analogues is hydrolyzed at the N-terminal side of the (4)serine residue, The hydroxyl moiety of the (4)serine residue catalyzes this hydrolysis. Goserelin possesses an azaglycinamide residue, which is also subject to degradation in the neutral pH region. At pH > 7, (4)serine epimerization is the main pathway of degradation of all four peptides, Parallel to the epimersation, hydrolysis of gonadorelin, goserelin, and triptorelin occurs.