Use of dabsylation, column switching and chiral separation for the determination of a renin inhibitor in rat, marmoset and human plasma.

A high-performance liquid chromatographic method with column switching was developed for the determination of the renin inhibitor Ro 42-5892/001, (S)-alpha-(S)-alpha-(tert.-butylsulphonyl)methyl]hydrocinnama mido]-N- (1S,2R,3S)-1-(cyclohexylmethyl)-3-cylcopropyl-2, 3-dihydroxypropyl]imidazole-4-propionamide methanesulphonate (1:1), in rat, marmoset and human plasma, using a Nucleosil C8 120 (3 microns) stationary phase. Since the analyte and the internal standard are optical isomers, beta-cyclodextrin was used as a mobile phase constituent for their chiral separation. The method took advantage of the characteristics of dabsyl chloride derivatives, namely sensitivity, specificity and, particularly, stability, providing a quantification limit of 5 ng/ml. The accuracy (range of inaccuracy 1-13%) and the inter-assay precision (coefficient of variation range 1.8-9.1%) were acceptable. The method was successfully applied to toxicokinetic studies in rats and marmosets.