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Evaluation of Sparfloxacin Distribution by Mass Spectrometry Imaging in a Phototoxicity Model

  • Research Article
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Journal of The American Society for Mass Spectrometry

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.

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Acknowledgments

The authors thank Mr. Martin Schneider and Dr. Ulla Plappert-Helbig for their expertise and support with the animal experiments; Dr. Hans-Joerg Martus and Dr. Willi Suter for their scientific support (all Novartis Pharma AG).

This work was supported by Novartis Institute for BioMedical Research, Novartis Pharma AG, Switzerland. The authors are grateful for the support by COST action BM1104.

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Author notes

  1. Stéphanie Marie Boudon

    Present address: DSM Nutritional Products, R&D Personal Care, 4002, Basel, Switzerland

Authors and Affiliations

  1. Novartis Institutes for BioMedical Research, Preclinical Safety, 4002, Basel, Switzerland

    Stéphanie Marie Boudon, Ursula Junker & Daniel Bauer

  2. Novartis Institutes for BioMedical Research, Analytical Sciences, 4002, Basel, Switzerland

    Grégory Morandi, Dieter Staab & Markus Stoeckli

  3. Rutgers New Jersey Medical School, Public Health Research Institute, Newark, NJ, USA

    Brendan Prideaux

  4. Swiss Center for Applied Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, 4056, Basel, Switzerland

    Alex Odermatt

Authors
  1. Stéphanie Marie Boudon
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  2. Grégory Morandi
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  4. Dieter Staab
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  5. Ursula Junker
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  7. Markus Stoeckli
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  8. Daniel Bauer
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Correspondence to Daniel Bauer.

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Boudon, S.M., Morandi, G., Prideaux, B. et al. Evaluation of Sparfloxacin Distribution by Mass Spectrometry Imaging in a Phototoxicity Model. J. Am. Soc. Mass Spectrom. 25, 1803–1809 (2014). https://doi.org/10.1007/s13361-014-0947-3

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  • DOI: https://doi.org/10.1007/s13361-014-0947-3

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