IDENTIFICATION OF THE DEGRADATION PRODUCTS OF GONADORELIN AND 3 ANALOGS IN AQUEOUS-SOLUTION

Degradation products of the peptides gonadorelin and its analogues bus erelin, goserelin, and triptorelin were characterized with LC/MS, chir al amino acid analysis, and FAB-MS(-MS). Differences in chemical struc tures of gonadorelin, its analogues, and their respective decompositio n products were evaluated in relation to the putative degradation mech anisms, In acidic solution, gonadorelin and triptorelin are deamidated , whereas buserelin and goserelin undergo debutylation. En the pH rang e 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 az aglycinamide residue, which is also subject to degradation in the neut ral pH region. At pH > 7, (4)serine epimerization is the main pathway of degradation of all four peptides, Parallel to the epimersation, hyd rolysis of gonadorelin, goserelin, and triptorelin occurs.