High-performance liquid chromatographic determination of diltiazem and four of its metabolites in plasma. Application to pharmacokinetics.
A selective and very sensitive ion-pairing reversed-phase high-performance liquid chromatographic method has been developed for the simultaneous determination of diltiazem and four of its metabolites in plasma. The structurally related compound propionyl deacetyl-diltiazem was used as the internal standard and bromide was employed as the pairing ion. Plasma samples were extracted with methyl-tert.-butyl ether followed by back-extraction into 0.01 M hydrochloric acid and evaporation to dryness. High-performance liquid chromatographic analysis was carried out using C18-bonded silica and methanol-ammonium bromide-acetonitrile-triethylamine as the mobile phase. Using UV detection at 237 nm, the lower limit of detection in plasma was 0.1-0.2 ng/ml; calibration curves were linear between 1 and 800 ng/ml. The present assay procedure has been applied to monitoring plasma levels in intravenous and oral pharmacokinetic studies in several animal species and humans. The applicability of the new method could be confirmed by comparing plasma levels obtained by high-performance liquid chromatography with those obtained by gas chromatography.
D000818:Animals; D001552:Benzazepines / Q000097:blood*; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004110:Diltiazem / Q000097:blood*; D004285:Dogs; D006168:Guinea Pigs; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D011817:Rabbits; D013045:Species Specificity
D001552:Benzazepines; D004110:Diltiazem