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.
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Pharma Division, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Eckert
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Leube
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D000818:Animals; D000959:Antihypertensive Agents / Q000097:blood*; D002144:Callithrix; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007093:Imidazoles; D051381:Rats; D012015:Reference Standards; D012083:Renin / Q000097:blood; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D004124:p-Dimethylaminoazobenzene / Q000031:analogs & derivatives* / Q000737:chemistry; D000092502:Renin Inhibitors
D000959:Antihypertensive Agents; D007093:Imidazoles; D012083:Renin; D004124:p-Dimethylaminoazobenzene; D000092502:Renin Inhibitors; C010572:4-N,N-dimethylaminoazobenzene-4'-sulfonyl chloride; C065581:remikiren