High performance liquid chromatography of mebudipine: application to pharmacokinetic study.

Purpose: To develop a high performance liquid chromatography system for the determination of a new 1,4-dihydropyridine, mebudipine, in rabbit plasma.
Methods: To 1 ml of rabbit plasma was added internal standard (dibudipine) and 0.5 ml of 1 M NaOH. Mebudipine and internal standard were extracted to 5 ml ethyl acetate, evaporated under slow stream of nitrogen. The residue was reconstituted in 200 microl mobile phase and 20 microl of aliquots were injected into a HPLC system equipped with 4.6 x 250 mm 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 500 ng/ml. The extraction efficiency was >90% and the minimum quantifiable concentration was 10 ng/ml (CV<10%).
Conclusion: A suitable, convenient and simple HPLC assay for pharmacokinetic study of mebudipine in rabbits was developed.