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- W1994589691 abstract "Amlodipine is a long acting dihydropyridine calcium antagonist recently introduced for the treatment of angina and hypertension. In order to document its stability in vitro and to develop a pharmacokinetic model in rabbits, a new reversed-phase liquid chromatography (LC) assay with UV detection was developed. The method utilized a C18 column (250 × 4.6 mm i.d.) with a mobile phase composed of a mixture of methanol 0.04 M ammonium acetate-acetonitrile (38:38:24, v/v/v) containing 0.02% triethylamine (final pH 7.1). Under these conditions, the retention times of amlodipine and the internal standard desipramine were 10.6 and 12.9 min, respectively. Using 1 ml of plasma, sensitivity of the assay was 2.5 ng ml−1 at which the RSD was 11%. The standard curve was linear from 2.5 to 100 ng ml−1 (r2 = 0.990), and the mean RSD at this concentration range was 6.8%. The pharmacokinetic model was developed in rabbits which provides results similar to those in dogs, but at less expense. The assay was also applied to a stability study comparing amlodipine and nifedipine in pH 3 and pH 7 ammonium acetate buffers and in methanol. Amlodipine was considerably more stable than nifedipine under all conditions. Finally the assay was applied to a pharmacokinetic study in rabbits (n = 6) after a single 1 mg kg−1 intravenous dose. The mean half-life (t12) of amlodipine was 6.5 h, the systemic clearance (CL) was 4.8 1 h−1 kg−1 and the apparent volume of distribution at steady state (Vdss) was 30.2 1 kg−1. In conclusion, the LC assay is simple and sensitive, and should be applicable to pharmaceutical analysis, pharmacokinetic studies and therapeutic drug monitoring although the latter requires validation." @default.
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- W1994589691 date "1991-01-01" @default.
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- W1994589691 title "Liquid chromatography assay for amlodipine: Chemical stability and pharmacokinetics in rabbits" @default.
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- W1994589691 doi "https://doi.org/10.1016/0731-7085(91)80178-c" @default.
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