In this project I will develop new spectroscopy approaches that will allow one to obtain unprecedented structural information of drug molecules throughout the whole pharmaceutical process. High resolution structure determination ideally of unmodified drugs (i) in their free form, but also (ii) in complex dosage formulations, as well as (iii) during their delivery and target engagement in cells represents one of today’s major challenges in pharmaceutical industry, key to ensure productive drug uptake and improved efficacy. Current routine characterisation methods (such as detection of drugs in cells) often require sample modification (e.g. tagging with fluorescent labels) which may alter the behaviour of the drug. Here I will make use of the fact that a increasingly growing percentage (currently about 30%) of Active Pharmaceutical Ingredients (API) contain at least one fluorine atom, while hardly any excipients and no endogenous biomolecules in human cells do. By implementing innovative 19F solid state Nuclear Magnetic Resonance (NMR) approaches under fast Magic-Angle Spinning (MAS) and Dynamic Nuclear Polarisation (DNP) techniques, I will develop a new analytical tool with enhanced resolution and sensitivity, which will allow one to overcome the above mentioned challenges and to obtain structural information of unmodified drug molecules in complex and diverse formulation, in vitro and in cellular environments, as well as their interactions with various substrates (excipients, biological targets). The 19F NMR observables will be correlated with those of other nuclei (1H, 13C and 15N at natural abundance), using multidimensional 19F detected methods to distinguish between the drug molecule and excipients or cell background. The methods will be benchmarked on a variety of pharmaceutically relevant molecules and will concern both their pure constituents and their delivery systems.