Application of Flow NMR to an Open-Access Pharmaceutical Environment

We present the application of flow NMR in an automated, open-access environment. The adjustment of parameters affecting the selection of the correct sample size, the elimination of carry-over, and the optimization of sample recovery are addressed. Advantages of this method include ease of use, elimination of NMR tubes, and elimination of handling errors that can result in the contamination of the probe. Sample throughput is similar to instruments using a conventional autosampler (for Bruker instruments, a BACS) although the time used for shimming the sample can be eliminated when the sample solvent does not change. The key feature of our methodology is that only one push solvent is used. This has major advantages over methods that switch solvents because there is no extensive flushing required between solvents and the deuterated push solvent, deuterium oxide, is economical. The disadvantage is the need to maintain the push and transfer solvents and usually the loss of the exchangeable protons that the sample may have. The protocol we present, using a single push solvent, contributes to the application of flow NMR in hands-on medicinal chemistry environments.