Chapter 3 - Fluorine-19 or Phosphorus-31 NMR Spectroscopy: A Powerful Technique for Biofluid Metabolic Studies and Pharmaceutical Formulation Analysis of Fluorinated or Phosphorylated Drugs

Abstract

This chapter presents an overview of the advantages and limitations of NMR spectroscopy along with a review of fluorinated drugs such as anti-bacterials, neuroleptics, analgesics, anti-inflammatory agents, anesthetics, anti-cancer agents, and anti-fungals. Pharmaceutical formulation analysis of fluorinated or phosphorylated drugs using fluorine-19 NMR or phosphorus-31 NMR as the analytical technique are also discussed. Fluorine-19 orphosphorus-31 nuclear magnetic resonance spectroscopy provides a highly specific tool for detection, identification, and quantification, in a single run, of all the fluorine- or phosphorus-containing species, including unexpected substances in the bulk solutions analyzed. Fluorine-19 and phosphorus-31 nuclei have NMR characteristics of nuclear spin of 1/2, relatively narrow lines, 100% natural abundance, high sensitivity for fluorine-19 nucleus and correct sensitivity for phosphorus-31 nucleus, and large chemical shift range, which minimizes signal overlap. An important advantage specific to 19F NMR is that the negligible level of endogenous mobile fluorinated metabolites of low molecular mass eliminates interfering background signals. Moreover, F and P NMR of biological matrices are not hampered by dynamic range problems as encountered in proton NMR due to the intense signal of water protons that must be suppressed. Despite their limited sensitivity, F and P NMR can be considered as concurrent to, even in some cases, chromatographic techniques for the analysis of biofluids or pharmaceutical formulations.