Impurity profiling in bulk pharmaceutical batches using 19F 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 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.
Mistry
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N
Chemical Analysis Department, Glaxo Wellcome Medicines Research Centre, Stevenage, UK.
Ismail
I M
IM
Farrant
R D
RD
Liu
M
M
Nicholson
J K
JK
Lindon
J C
JC
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
D000730:Androstadienes; D005461:Fluorine; D000068298:Fluticasone