Separation and quantification of ropinirole and some impurities using capillary liquid chromatography

Ropinirole, 4-[2-(dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-one, is a pot ent anti-Parkinson's disease drug developed by SmithKline Beecham Pharmaceu ticals. Capillary liquid chromatography (CLC) was used for the separation a nd quantification of ropinirole and its five related impurities, potentiall y formed during its synthesis. A simultaneous optimization of three mobile phase parameters, i.e., pH, buffer concentration and acetonitrile content w as performed employing an experimental design approach which proved a power ful tool in method development. The retention factors of the investigated s ubstances in different mobile phases were determined. Baseline resolution o f the six substances on a C-18 reversed stationary phase was attained using a mobile phase with an optimized composition [acetonitrile-8.7 mM 2-(N-mor pholino)ethanesulfonic acid adjusted to pH 6.0 (55:45, v/v)]. It was shown that CLC, operated in the isocratic mode under the mobile phase flow-rate o f 4 mu l/min, can determine the level of these impurities, down to a level of 0.06% of the main component within 25 min. (C) 1999 Elsevier Science B.V . All rights reserved.