title: "Dark" Singlet Oxygen and Electron Paramagnetic Resonance Spin Trapping as Convenient Tools to Assess Photolytic Drug Degradation.
abstract: Forced degradation studies are an important tool for a systematic assessment of decomposition pathways and identification of reactive sites in active pharmaceutical ingredients (APIs). Two methodologies have been combined in order to provide a deeper understanding of singlet oxygen-related degradation pathways of APIs under light irradiation. First, we report that a "dark" singlet oxygen test enables the investigation of drug reactivity toward singlet oxygen independently of photolytic irradiation processes. Second, the photosensitizing properties of the API producing the singlet oxygen was proven and quantified by spin trapping and electron paramagnetic resonance analysis. A combination of these techniques is an interesting addition to the forced degradation portfolio as it can be used for (1) revealing unexpected degradation pathways of APIs due to singlet oxygen, (2) clarifying photolytic drug-drug interactions in fixed-dose combinations, and (3) synthesizing larger quantities of hardly accessible oxidative drug degradants.
authors.affiliation: Janssen R&D Pharmaceutical Development and Manufacturing Sciences, Beerse, Belgium. Electronic address: ppersich@its.jnj.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Persich
authors.affiliation: Janssen R&D Pharmaceutical Development and Manufacturing Sciences, Beerse, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Hostyn
authors.affiliation: Janssen R&D Pharmaceutical Development and Manufacturing Sciences, Beerse, Belgium; Department of Chemistry-Organic Synthesis, University of Antwerp, Antwerp, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Joie
authors.affiliation: Janssen R&D Pharmaceutical Development and Manufacturing Sciences, Beerse, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Winderickx
authors.affiliation: Janssen R&D Pharmaceutical Development and Manufacturing Sciences, Beerse, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Pikkemaat
authors.affiliation: Janssen R&D Pharmaceutical Development and Manufacturing Sciences, Beerse, Belgium.
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Romijn
authors.affiliation: Department of Chemistry-Organic Synthesis, University of Antwerp, Antwerp, Belgium.
authors.forename: Bert U W
authors.initials: BU
authors.lastname: Maes
mesh_terms: D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D008027:Light / Q000009:adverse effects; D010083:Oxidants, Photochemical / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D010782:Photolysis; D026082:Singlet Oxygen / Q000737:chemistry* / Q000378:metabolism; D019097:Spin Trapping / Q000379:methods*
chemical_list: D010083:Oxidants, Photochemical; D004364:Pharmaceutical Preparations; D026082:Singlet Oxygen
keywords: chemical stability; degradation products; oxidation; photodegradation; photolysis