Correlative Optical Spectroscopy and Mass Spectrometry Imaging Methodology to Visualise Drug Distribution in a Soft Tissue Section.

A new correlative imaging methodology combining sub-micron spatial resolution with sensitive drug detection by optical spectroscopy and mass spectrometry imaging has been developed to visualise chemical distribution upon drug application in soft tissue. In this example, the method has been tested on excised skin tissue after in vitro topical application of a commercial nonsteroidal anti-inflammatory drug product for 16 hours. Non-destructive optical spectroscopic methods, including stimulated Raman scattering, second harmonic generation, and two-photon fluorescence microscopies, were first employed to map the skin structure and morphology. Subsequently, the same skin tissue samples were analysed via time-of-flight secondary ion mass spectrometry (ToF-SIMS), which enabled enhanced sensitivity for the detection of diclofenac across the outermost skin layers - epidermis and dermis. Image registration methods were devised to integrate the optical and mass spectrometric data. This approach combines label-free, high-resolution visualisation of tissue structure with sensitive chemical detection, and represents a valuable tool for investigating drug distribution in skin and potentially, in other soft biological tissues.