کاربرد روش جدید کروماتوگرافی مایع با کارکرد عالی برای فارماکوکینتیک دیبودیپین در موش بزرگ آزمایشگاهی

عنوان انگليسی

Application of a new high performance liquid chromatography method to the pharmacokinetics of dibudipine in rats

خلاصه انگلیسی

Purpose: To develop a HPLC method for assay of dibudipine in biological fluids and to study its pharmacokinetics in the rat. Methods. HPLC: 2 μl (20 μg/ml) mebudipine as internal standard, 0.2 ml NaOH 1 M and 2 ml ethyl acetate were added to 0.2 ml of rat plasma. The mixture was shaken for 10 min, centrifuged, and the supernatant was dried under nitrogen. The dissolved residue was injected to a C18 analytical column. Mobile phase flowed at 1 ml/min with a composition of methanol - water-acetonitrile (70-25-5). The eluent was monitored at 238 nm. Pharmacokinetic study: plasma samples were collected periodically after intravenous (0.5 mg/kg) or oral (10 mg/ kg) administration of dibudipine to rats (n = 4/group). In addition, separate groups of animals were administered 0.5 mg/kg doses of the drug for serial collection of brain, heart, kidney and liver (n = 4/time). The concentration of the drug in tissue or plasma was assayed using the above HPLC method. Results. Calibration curves were linear over a concent ration of 10-1000 ng/ml and CV was less than 10%. Dibudipine showed a bi-exponential decline after IV injection in the rats with a t1/2 beta of 2.5 ± 0.5(mean ± SE) hr. Oral bioavailability was low. Distribution of dibudipine to the examined tissues was rapid, and with the exception of the brain, the concentrations of the drug in all tissues were higher than the plasma levels Conclusions. The HPLC method was simple and convenient. Moreover, it could be applied to investigations of the pharmacokinetics of dibudipine in the rat.

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