A RAPID AND SENSITIVE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC METHOD FOR THE DETERMINATION OF METOCLOPRAMIDE IN PLASMA AND ITS USE IN PHARMACOKINETIC STUDIES

A rapid and sensitive high-performance liquid chromatographic (HPLC) assay has been developed for the determination of metoclopramide in plasma. The assay is performed after single extraction of metoclopramide and diazepam (internal standard) from alkalinized plasma into ether and eluted from a Nova Pak C-18-column with a mobile phase composed of acetonitrile:water (55:45%, v/v) adjusted to pH 3. The column eluent was monitored at 273 nm. Measurement was achieved by taking the peak-height ratios of the drug to the internal standard. The detection limit for metoclopramide in plasma is 5 ng/ml. Within-day coefficients of variation (CVs) ranged from 3.05 to 4.43% and between-day (CVs) from 4.1 to 5.7% at three different concentrations. Preliminary stability tests showed that metoclopramide is stable for at least 3 weeks in plasma after freezing. The method is applied for the determination of the pharmacokinetic parameters of metoclopramide after administration of two tablet formulations, to 4 healthy male volunteers.