CHARACTERIZATION 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 be en 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 t hat HPLC-NMR spectroscopy of the main drug peak in the 'time-slice' mo de of operation, in which the elution of the HPLC peak is sampled a sh ort time intervals, can be used to investigate the purity profile of t he single HPLC peak detected by UV absorption. These studies show that HPLC-NMR is of considerable value in rapidly assessing HPLC peak puri ty and hence will be of benefit in providing additional information to support submission for drug registration to regulatory agencies. (C) 1997 Elsevier Science B.V.