Application of 19F quantitative NMR to pharmaceutical analysis

The presence of fluorine in an active pharmaceutical ingredient (API) can impart important pharmacological attributes with regards to metabolism, stability, and selectivity. As such, nearly one-third of newly approved small molecule drugs contain at least one fluorine atom. F-19 is 100% naturally abundant lending to virtually unimpeded detection of fluorine-containing molecules, even in complex mixtures. Despite these promising characteristics, the thorough evaluation of a method for F-19 qNMR (quantitative NMR) has been lacking. Herein we present experimental methodology and optimized parameters for uniform quantitative sampling of fluorine-containing drugs and we compare results obtained using both gravimetric and absolute concentration methods for data reduction.