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Localisation and quantitative analysis of moxifloxacin in hydrogel using time-of-flight secondary ion mass spectrometry: Application to drug diffusion profiling

(2024)

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Makadji_63951900_2024.pdf
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Abstract
Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS) is a promising analytical method in the biomedical sciences and pharmacology, enabling the simultaneous detection and localisation of organic compounds and biomolecules on the surface of tissue sections without the need for a labelling process that could affect the distribution of the analytes. By using a primary ion beam to probe the sample surface and generate secondary ions, this technique also enables depth profiling and 3D analysis to be carried out by eroding the sample with a cluster ion beam. However, TOF-SIMS encounters sensitivity problems when it comes to analysing organic compounds in biological samples. Tissue sections, being complex matrices, can adversely affect the detection of analytes. In addition, the probability of ionisation of the various compounds adds an additional complexity factor for quantification. This study explored the possibility of determining the quantity of moxifloxacin (MXF) in gelatin methacrylate (GelMA) hydrogels and corneal tissue using Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS). The main objective was to quantify the local presence of MXF in the GelMA matrix. Calibration curves for MXF showed that the F- ion is a reliable marker, although challenges remain in observing MXF cations. In response, solutions such as the incubation of hydrogels or the use of our new analysis beams were considered. The results also highlighted the importance of the choice of markers and experimental methods in guaranteeing the accuracy of the measurements. By integrating advanced imaging techniques and optimising existing protocols, this research paves the way for more detailed and precise studies in ocular pharmacokinetics, while highlighting the potential of GelMA hydrogels as model media for mimicking the corneal stroma.