Nov 21, 2019 – NMR Topical Group Meeting

Proton detected quantitative NMR (qHNMR) is a staple for the determination of analyte concentration in various stages of the drug discovery process. qHNMR remains unprecedented in its high precision, ease of use, non-destructive nature, and simultaneous detection of multiple analytes. Unfortunately, a major limitation results from the difficulty of suppressing protonated solvents thereby largely restricting qHNMR samples to those dissolved in favorable deuterated or biological aqueous solvents where more robust solvent suppression schemes exist. A method was developed that uses band selective optimized flip-angle short-transient (SOFAST) 1D experiments to measure analyte concentration of compounds dissolved in multi-component protonated solvents. When an external reference standard is used, selective excitation of the proton aromatic region (6-10) ppm is sufficient to measure analyte concentration while removing spectral contamination from a wide range of protonated solvents and excipients. Examples are provided which highlight key learnings from routine qHNMR investigations of solutions such as LC-MS/MS standards and animal dosing solutions. The findings presented illustrate how qHNMR can be used to improve the overall quality and reproducibility of experiments in the discovery setting.