Characterisation of impurities in bulk drug batches of fluticasone propionate using directly coupled HPLC-NMR spectroscopy and HPLC-MS.
Directly coupled HPLC NMR spectroscopic and HPLC-MS approaches have been used to confirm the identity of four known dimeric impurities in a partially purified batch of fluticasone propionate each at levels of 0.06-0.9% of parent compound based on UV absorption. It is also shown that HPLC NMR spectroscopy of the main drug peak in the 'time-slice' mode of operation, in which the elution of the HPLC peak is sampled a short time intervals, can be used to investigate the purity profile of the single HPLC peak detected by UV absorption. These studies show that HPLC-NMR is of considerable value in rapidly assessing HPLC peak purity and hence will be of benefit in providing additional information to support submission for drug registration to regulatory agencies.
Mistry
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N
Chemical Analysis Department, GlaxoWellcome Medicines Research Centre, Stevenage, UK.
Ismail
I M
IM
Smith
M S
MS
Nicholson
J K
JK
Lindon
J C
JC
D000730:Androstadienes / Q000032:analysis* / Q000302:isolation & purification; D018927:Anti-Asthmatic Agents / Q000032:analysis*; D000893:Anti-Inflammatory Agents / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D019281:Dimerization; D004220:Disulfides; D004340:Drug Contamination; D000068298:Fluticasone; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013056:Spectrophotometry, Ultraviolet
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D004220:Disulfides; D000068298:Fluticasone