Impurity profiling in bulk pharmaceutical batches using F-19 NMR spectroscopy and distinction between monomeric and dimeric impurities by NMR-based diffusion measurements

The impurity profile of production batches of fluorine-containing drugs can be characterised efficiently using F-19 NMR spectroscopy. This yields the number and proportions of impurities in the bulk drug to a level of approxi mate to 0.1 mole% in a few minutes of NMR experiment time. The approach has been exemplified using a partially purified batch of the steroidal product fluticasone propionate, the impurities in which include a number of dimeri c species. Further distinction between the monomer and dimer impurities has been achieved through high resolution chemical shift-resolved NMR measurem ent of molecular diffusion coefficients on the intact mixture using F-19 NM R spectroscopy. The ability of NMR-based diffusion coefficient determinatio n to distinguish between monomeric and dimeric substances was validated usi ng a standard mixture of authentic materials containing both monomers and d imers. (C) 1999 Elsevier Science B.V. All rights reserved.