Determination of the imidazo quinazoline derivative Ro 13-6438 in biological fluids by high-performance liquid...

A high-performance liquid chromatographic assay has been developed for the imidazo quinazoline derivative Ro 13-6438 [D-(-)-6-chloro-1,5-dihydro-3-methylimidazo(2,1-b)-quinazolin++ +-2(3H)-one], which is under clinical investigation as a cardioactive drug. The drug is extracted from biological fluids into 1-chlorobutane--1-hexanol (90:10) and back-extracted into perchloric acid. This extract is chromatographed directly, using a reversed-phase high-performance liquid chromatographic system with ultraviolet detection at 254 nm. The detection limit in plasma is about 1 ng ml-1, using a 1-ml sample. The assay is rapid, accurate and sufficiently sensitive for the study of the single-dose kinetics of Ro 13-6438 in man following a 7.5-mg intravenous dose. No instability of the unchanged substance was observed in plasma during storage for one day at room temperature and for five months at --20 degrees C.