title: Comprehensive determination of the cyclic FEE peptide chemical stability in solution.
abstract: 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.
authors.affiliation: Department of Quality Control and Analytical Development, General Equipments and Health Products Agency, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Rotival
authors.affiliation: Department of Quality Control and Analytical Development, General Equipments and Health Products Agency, Assistance Publique - Hôpitaux de Paris, Paris, France. Electronic address: melisande.bernard@eps.aphp.fr.
authors.forename: M
authors.initials: M
authors.lastname: Bernard
authors.affiliation: Department of Quality Control and Analytical Development, General Equipments and Health Products Agency, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Henriet
authors.affiliation: Department of Quality Control and Analytical Development, General Equipments and Health Products Agency, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Fourgeaud
authors.affiliation: Department of Quality Control and Analytical Development, General Equipments and Health Products Agency, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: J R
authors.initials: JR
authors.lastname: Fabreguettes
authors.affiliation: Department of Quality Control and Analytical Development, General Equipments and Health Products Agency, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Surget
authors.affiliation: Department of Quality Control and Analytical Development, General Equipments and Health Products Agency, Assistance Publique - Hôpitaux de Paris, Paris, France; Department of Physical Chemistry of Drug, Faculty of Pharmaceutical and Biological Sciences, Paris-Descartes University, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Guyon
authors.affiliation: Department of Quality Control and Analytical Development, General Equipments and Health Products Agency, Assistance Publique - Hôpitaux de Paris, Paris, France; Department of Physical Chemistry of Drug, Faculty of Pharmaceutical and Biological Sciences, Paris-Descartes University, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Do
mesh_terms: D020134:Catalytic Domain; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004355:Drug Stability; D006868:Hydrolysis; D013058:Mass Spectrometry / Q000379:methods; D010456:Peptides, Cyclic / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry*
chemical_list: D010456:Peptides, Cyclic; D012996:Solutions
keywords: CID; Chemical stability; Cyclic peptide; Degradation pathway; HPLC; Low-energy CID; MS; Mass spectrometry; cFEE; collision-induced dissociation; cyclic protein with a sequence of 6 amino acids (Cys-Ser-Phe-Glu-Glu-Cys); high performance liquid chromatography; mass spectrometry