Comprehensive determination of the cyclic FEE peptide chemical stability in solution

•cFEE is a cyclic hexapeptide used to enhance in vitro fertilization rate.•A stability study allowed to access degradation profile of cFEE by HPLC-MS/MS.•Main degradation pathway involved rupture of FEE sequence with loss of efficacy.•Potential antagonists were at negligible relative amounts.

The FEE cyclic hexapeptide (cFEE) is an investigational new drug added to the insemination medium in order to improve the in vitro fertilization rate. The pharmacological activity of small peptides is highly dependent on the conservation of the amino acid sequence and of the structural conformation of the active site. To enhance the scientific knowledge required for the clinical use of cFEE, a comprehensive determination of its chemical stability in solution was realized in accelerated conditions. Degradation products have been detected and identified by liquid chromatography/Qtrap® mass spectrometry. The main degradation products highlighted during the product shelf life were produced by hydrolysis and only certain sites were involved. In most cases, the cyclic conformation was lost and regarding the major degradation pathway, the sequence representing the active site was affected.

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