اندازه‌گیری مبودیپین در مایعات بیولوژیک با روش HPLC و کاربرد این دارو در مطالعه فارماکوکینتیک در موش صحرایی An HPLC Method for Determination of Mebudipine in Biological Fluids in Rats and its Application in Pharmacokinetic Study

        Background & Aim: Mebudipine is a calcium antagonist drug which is used to treat blood pressure. A new high performance liquid chromatography(HPLC) system for the determination of a new 1, 4-dihydropyridine, mebudipine, in rat plasma and other biological fluids was developed in this study for the first time. Materials & Methods: To 1 ml of rat plasma and/or other biological fluids, 0.5 ml of internal standard(dibudipine) and 0.5 ml of 1 M NaOH was added. Mebudipine and internal standard were extracted to 5 ml ethyl acetate, evaporated under slow stream of nitrogen. The residue was reconstituted in 200µl mobile phase and 20µl of aliquots was injected into a HPLC system equipped with 4.6×250mm i.d.C18 analytical column. Mobile phase consisted of methanol(70%), water(25%) and acetonitril(5%) and its flow rate was 1 ml/min. Results: There were no interfering peaks from endogenous components in blank plasma chromatograms. Standard curves were linear(r(2)>0.99) over 10 to 500ng/ml. The extraction efficiency was above 90% and the minimum quantifiable concentration was 10ng/ml(CV<10%) which reveals that it is a suitable, convenient and simple HPLC assay for pharmacokinetic study of mebudipine in rat. Conclusion: By using this method, it was found out that while the oral bioavailability of mebudipine was low(<2%), it had a marked first-pass effect. The distribution of mebudipine into some tissues such as brain, heart, liver and kidney following intravenous administration(0.5 mg/kg) was studied and a rapid distribution of mebudipine into these tissues was found. It was concluded that brain, heart, liver and kidney are in the same compartment as plasma(central).