title: HPLC & NMR-based forced degradation studies of ifosfamide: The potential of NMR in stability studies.
abstract: OBJECTIVE
  The aim of this study is to conduct a forced degradation study on ifosfamide under several stress conditions to investigate the robustness of the developed HPLC method. It also aims to provide further insight into the stability of ifosfamide and its degradation profile using both HPLC and NMR.
  
  
  METHODS
  Ifosfamide solutions (20mg/mL; n=15, 20mL) were stressed in triplicate by heating (70°C), under acidic (pH 1 & 4) and alkaline (pH 10 & 12) conditions. Samples were analysed periodically using HPLC and FT-NMR.
  
  
  CONCLUSIONS
  Ifosfamide was most stable under weakly acidic conditions (pH 4). NMR results suggested that the mechanism of ifosfamide degradation involves the cleavage of the PN bond. For all stress conditions, HPLC was not able to detect ifosfamide degradation products that were detected by NMR.
  
  
  CONCLUSIONS
  These results suggest that the developed HPLC method for ifosfamide did not detect the degradation products shown by NMR. It is possible that degradation products co-elute with ifosfamide, do not elute altogether or are not amenable to the detection method employed. Therefore, investigation of ifosfamide stability requires additional techniques that do not suffer from the aforementioned shortcomings.
authors.affiliation: School of Life Sciences, Pharmacy and Chemistry, Faculty of Science, Engineering and Computing, Kingston University-London, Kingston upon Thames, London KT1 2EE, UK. Electronic address: D.Salman@kingston.ac.uk.
authors.forename: D
authors.initials: D
authors.lastname: Salman
authors.affiliation: School of Life Sciences, Pharmacy and Chemistry, Faculty of Science, Engineering and Computing, Kingston University-London, Kingston upon Thames, London KT1 2EE, UK. Electronic address: jm.peron@kingston.ac.uk.
authors.forename: J-M R
authors.initials: JM
authors.lastname: Peron
authors.affiliation: School of Life Sciences, Pharmacy and Chemistry, Faculty of Science, Engineering and Computing, Kingston University-London, Kingston upon Thames, London KT1 2EE, UK. Electronic address: tgoronga@hotmail.co.uk.
authors.forename: T
authors.initials: T
authors.lastname: Goronga
authors.affiliation: School of Life Sciences, Pharmacy and Chemistry, Faculty of Science, Engineering and Computing, Kingston University-London, Kingston upon Thames, London KT1 2EE, UK. Electronic address: s.barton@kingston.ac.uk.
authors.forename: S
authors.initials: S
authors.lastname: Barton
authors.affiliation: School of Life Sciences, Pharmacy and Chemistry, Faculty of Science, Engineering and Computing, Kingston University-London, Kingston upon Thames, London KT1 2EE, UK. Electronic address: s.swinden@kingston.ac.uk.
authors.forename: J
authors.initials: J
authors.lastname: Swinden
authors.affiliation: School of Life Sciences, Pharmacy and Chemistry, Faculty of Science, Engineering and Computing, Kingston University-London, Kingston upon Thames, London KT1 2EE, UK. Electronic address: s.nabhani@kingston.ac.uk.
authors.forename: S
authors.initials: S
authors.lastname: Nabhani-Gebara
mesh_terms: D000143:Acids; D000468:Alkalies; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006358:Hot Temperature; D007069:Ifosfamide / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D019999:Pharmaceutical Solutions / Q000737:chemistry
chemical_list: D000143:Acids; D000468:Alkalies; D018906:Antineoplastic Agents, Alkylating; D019999:Pharmaceutical Solutions; D007069:Ifosfamide
keywords: Chemotherapy; Chimiothérapie; Degradation studies; Ifosfamide; Sarcoma; Sarcome; Stability; Stabilité; Études de dégradation