title: Evaluation of sparfloxacin distribution by mass spectrometry imaging in a phototoxicity model.
abstract: Mass spectrometry imaging (MSI) was applied to samples from mouse skin and from a human in vitro 3D skin model in order to assess its suitability in the context of photosafety evaluation. MSI proved to be a suitable method for the detection of the model compound sparfloxacin in biological tissues following systemic administration (oral gavage, 100 mg/kg) and subsequent exposure to simulated sunlight. In the human in vitro 3D skin model, a concentration-dependent increase as well as an irradiation-dependent decrease of sparfloxacin was observed. The MSI data on samples from mouse skin showed high signals of sparfloxacin 8 h after dosing. In contrast, animals irradiated with simulated sunlight showed significantly lower signals for sparfloxacin starting already at 1 h postirradiation, with no measurable intensity at the later time points (3 h and 6 h), suggesting a time- and irradiation-dependent degradation of sparfloxacin. The acquisition resolution of 100 μm proved to be adequate for the visualization of the distribution of sparfloxacin in the gross ear tissue samples, but distinct skin compartments were unable to be resolved. The label-free detection of intact sparfloxacin was only the first step in an attempt to gain a deeper understanding of the phototoxic processes. Further work is needed to identify the degradation products of sparfloxacin implicated in the observed inflammatory processes in order to better understand the origin and the mechanism of the phototoxic reaction.
authors.affiliation: Novartis Institutes for BioMedical Research, Preclinical Safety, 4002, Basel, Switzerland.
authors.forename: Stéphanie Marie
authors.initials: SM
authors.lastname: Boudon
authors.forename: Grégory
authors.initials: G
authors.lastname: Morandi
authors.forename: Brendan
authors.initials: B
authors.lastname: Prideaux
authors.forename: Dieter
authors.initials: D
authors.lastname: Staab
authors.forename: Ursula
authors.initials: U
authors.lastname: Junker
authors.forename: Alex
authors.initials: A
authors.lastname: Odermatt
authors.forename: Markus
authors.initials: M
authors.lastname: Stoeckli
authors.forename: Daniel
authors.initials: D
authors.lastname: Bauer
mesh_terms: D000818:Animals; D017484:Dermatitis, Phototoxic / Q000378:metabolism*; D004195:Disease Models, Animal; D004423:Ear / Q000473:pathology; D004487:Edema / Q000378:metabolism / Q000473:pathology; D005260:Female; D024841:Fluoroquinolones / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008953:Models, Anatomic; D057054:Molecular Imaging / Q000379:methods*; D012867:Skin / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D014018:Tissue Distribution / Q000528:radiation effects
chemical_list: D024841:Fluoroquinolones; C061363:sparfloxacin