Boudon, Stephanie Marie, Morandi, Gregory, Prideaux, Brendan , Staab, Dieter, Junker Walker, Ursula, Odermatt, Alex, Stoeckli, Markus and Bauer, Daniel (2014) EVALUATION OF SPARFLOXACIN PHOTOTOXICITY USING MASS SPECTROMETRY IMAGING. Journal of the American Society for Mass Spectrometry, 25 (10). pp. 1803-1809. ISSN 1879-1123

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 the potential advantage of this technique 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) and subsequent exposure to simulated sun light. In the human in vitro 3D skin model, a concentration-dependent increase as well as an irradiation-dependent decrease of sparfloxacin in tissue samples was observed. The MSI data on samples from mouse skin showed high concentrations of sparfloxacin 8 hours after dosing. In contrast, animals irradiated with simulated sun light showed a significant lower tissue exposure starting already at 1 hour post-irradiation, with no measurable intensity at the later time points (3 hours and 6 hours), suggesting a time- and irradiation-dependent degradation of sparfloxacin. The resolution of 100 µm proved to be adequate for the resolution of a total tissue concentration, but higher resolutions beyond 10 µm would be required to resolve tissue structures. The detection of sparfloxacin parent compound was apparently 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.

Item Type:	Article
Keywords:	photosafety, phototoxicity, mass spectrometry imaging, sparfloxacin,
Date Deposited:	26 Apr 2016 23:46
Last Modified:	26 Apr 2016 23:46
URI:	https://oak.novartis.com/id/eprint/20301