title: Impurity profiling in bulk pharmaceutical batches using 19F NMR spectroscopy and distinction between monomeric and dimeric impurities by NMR-based diffusion measurements.
abstract: The impurity profile of production batches of fluorine-containing drugs can be characterised efficiently using 19F NMR spectroscopy. This yields the number and proportions of impurities in the bulk drug to a level of approximately equal 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 dimeric species. Further distinction between the monomer and dimer impurities has been achieved through high resolution chemical shift-resolved NMR measurement of molecular diffusion coefficients on the intact mixture using 19F NMR spectroscopy. The ability of NMR-based diffusion coefficient determination to distinguish between monomeric and dimeric substances was validated using a standard mixture of authentic materials containing both monomers and dimers.
authors.affiliation: Chemical Analysis Department, Glaxo Wellcome Medicines Research Centre, Stevenage, UK.
authors.forename: N
authors.initials: N
authors.lastname: Mistry
authors.forename: I M
authors.initials: IM
authors.lastname: Ismail
authors.forename: R D
authors.initials: RD
authors.lastname: Farrant
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: J K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: J C
authors.initials: JC
authors.lastname: Lindon
mesh_terms: D000730:Androstadienes / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D019281:Dimerization; D004340:Drug Contamination; D005461:Fluorine / Q000032:analysis; D000068298:Fluticasone; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000730:Androstadienes; D005461:Fluorine; D000068298:Fluticasone