Abstract
A radioreceptor assay (RRA) for the quantitative determination of a new antiallergic agent, 1- (2-ethoxyethyl) -2- (4-methyl-1-homopiperazinyl) benzimidazole difumarate (KB-2413), has been developed. This RRA method, based upon competitive binding of [3H] mepyramine and KB-2413 to histamine H1 receptors in guinea pig cerebellum, allows the simple, sensitive and reproducible determination of KB-2413 in plasma. The determination limit was 0.1 ng (as free base) /ml and the standard curve was linear over the range of 0.1 to 5.0 ng/ml. The intra-and inter-assay coefficients of variation for the determination of KB-2413 were 5.2-11.1 % and 3.4-5.6%, respectively. The active metabolites, 1- (2-ethoxyethyl) -2- (1-homopiperazinyl) benzimidazole and 1- (2-ethoxyethyl) -5-hydroxy-2- (4-methyl-1-homopiperazinyl) benzimidazole, cross-reacted to the extents of 28.6 and 21.1 %, respectively. However, plasma levels obtained by the RRA method and the gas chromatographic method for the intact drug were well correlated in guinea pigs after oral administration of KB-2413.
