title: Electrochemical oxidation coupled with liquid chromatography and mass spectrometry to study the oxidative stability of active pharmaceutical ingredients in solution: A comparison of off-line and on-line approaches.
abstract: Stability studies of pharmaceutical drug products and pharmaceutical active substances are important to research and development in order to fully understand and maintain product quality and safety throughout its shelf-life. Oxidative forced degradation studies are among the different types of stability studies performed by the pharmaceutical industry in order to understand the intrinsic stability of drug molecules. We have been comparing the use of electrochemistry as an alternative oxidative forced degradation method to traditional forced degradation and accelerated stability studies. Using the electrochemical degradation approach the substrate oxidation takes place in a commercially available electrochemical cell and the effluent of the cell can be either a) directly infused into the mass spectrometer or b) injected in a chromatographic column for separation of the different products formed prior to the mass spectrometry analysis. To enable the study of large numbers of different experimental conditions and molecules we developed a new dual pump automated electrochemical screening platform. This system used a HPLC pump and autosampler to load and wash the electrochemical cell and deliver the oxidized sample plug to a second injection loop. This system enabled the automatic sequential analyses of large numbers of different solutions under varied experimental conditions without need for operator intervention during the run sequence. Here we describe the system and evaluate its performance using a test molecule with well characterized stability and compare results to those obtained using an off-line electrochemistry approach.
authors.affiliation: Pfizer Worldwide R+D, Ramsgate Road, Sandwich, Kent CT139NJ, United Kingdom. Electronic address: susana.dasilvatorres@pfizer.com.
authors.forename: Susana
authors.initials: S
authors.lastname: Torres
authors.affiliation: Pfizer Worldwide R+D, Ramsgate Road, Sandwich, Kent CT139NJ, United Kingdom.
authors.forename: Roland
authors.initials: R
authors.lastname: Brown
authors.affiliation: Pfizer Worldwide R+D, Eastern Point Road, Groton, CT, United States.
authors.forename: Todd
authors.initials: T
authors.lastname: Zelesky
authors.affiliation: Pfizer Worldwide R+D, Ramsgate Road, Sandwich, Kent CT139NJ, United Kingdom.
authors.forename: Garry
authors.initials: G
authors.lastname: Scrivens
authors.affiliation: Pfizer Worldwide R+D, Ramsgate Road, Sandwich, Kent CT139NJ, United Kingdom.
authors.forename: Roman
authors.initials: R
authors.lastname: Szucs
authors.affiliation: Pfizer Worldwide R+D, Eastern Point Road, Groton, CT, United States.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Hawkins
authors.affiliation: Pfizer Worldwide R+D, Ramsgate Road, Sandwich, Kent CT139NJ, United Kingdom.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Taylor
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods; D004355:Drug Stability; D055664:Electrochemical Techniques / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods; D010084:Oxidation-Reduction; D019999:Pharmaceutical Solutions / Q000032:analysis* / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D019999:Pharmaceutical Solutions
keywords: Chromatography; Degradation; Electrochemistry; Mass spectrometry; Oxidation; Stability