title: The application of electrochemistry to pharmaceutical stability testing--comparison with in silico prediction and chemical forced degradation approaches.
abstract: The aim of this study was to evaluate the use of electrochemistry to generate oxidative degradation products of a model pharmaceutical compound. The compound was oxidized at different potentials using an electrochemical flow-cell fitted with a glassy carbon working electrode, a Pd/H2 reference electrode and a titanium auxiliary electrode. The oxidative products formed were identified and structurally characterized by LC-ESI-MS/MS using a high resolution Q-TOF mass spectrometer. Results from electrochemical oxidation using electrolytes of different pH were compared to those from chemical oxidation and from accelerated stability studies. Additionally, oxidative degradation products predicted using an in silico commercially available software were compared to those obtained from the various experimental methods. The electrochemical approach proved to be useful as an oxidative stress test as all of the final oxidation products observed under accelerated stability studies could be generated; previously reported reactive intermediate species were not observed most likely because the electrochemical mechanism differs from the oxidative pathway followed under accelerated stability conditions. In comparison to chemical degradation tests electrochemical degradation has the advantage of being much faster and does not require the use of strong oxidizing agents. Moreover, it enables the study of different operating parameters in short periods of time and optimisation of the reaction conditions (pH and applied potential) to achieve different oxidative products mixtures. This technique may prove useful as a stress test condition for the generation of oxidative degradation products and may help accelerate structure elucidation and development of stability indicating analytical methods.
authors: Pfizer Worldwide R+D, Ramsgate Road, Sandwich, Kent, CT139NJ, United Kingdom. Electronic address: susana.dasilvatorres@pfizer.com.
authors: Susana
authors: S
authors: Torres
authors: Pfizer Worldwide R+D, Ramsgate Road, Sandwich, Kent, CT139NJ, United Kingdom.
authors: Roland
authors: R
authors: Brown
authors: Pfizer Worldwide R+D, Ramsgate Road, Sandwich, Kent, CT139NJ, United Kingdom.
authors: Roman
authors: R
authors: Szucs
authors: Pfizer Worldwide R+D, Eastern Point Road, Groton, CT, United States.
authors: Joel M
authors: JM
authors: Hawkins
authors: Pfizer Worldwide R+D, Eastern Point Road, Groton, CT, United States.
authors: Todd
authors: T
authors: Zelesky
authors: Pfizer Worldwide R+D, Ramsgate Road, Sandwich, Kent, CT139NJ, United Kingdom.
authors: Garry
authors: G
authors: Scrivens
authors: Pfizer Worldwide R+D, Ramsgate Road, Sandwich, Kent, CT139NJ, United Kingdom.
authors: Alan
authors: A
authors: Pettman
authors: Pfizer Worldwide R+D, Ramsgate Road, Sandwich, Kent, CT139NJ, United Kingdom.
authors: Mark R
authors: MR
authors: Taylor
mesh_terms: D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D004355:Drug Stability; D055664:Electrochemical Techniques / Q000295:instrumentation; D004566:Electrodes; D004867:Equipment Design; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D015394:Molecular Structure; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012984:Software; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations
keywords: Electrochemistry; Forced degradation; In silico methods; Oxidation; Stability