Effect of Metoclopramide on the Excretion Rate of Paracetamol Using HPLC-DAD

Abstract

A simple, precise, accurate and robust high-performance liquid chromatography assay was developed and validated for the simultaneous analysis of metoclopramide and paracetamol in human urine. The drugs were isolated from urine samples by solid-phase extraction using C8 cartridges, then analyzed on a C18 reversed-phase column using a mixture of aqueous phase (water containing 0.2% TEA adjusted to pH 3 using ortho-phosphoric acid) and methanol in a ratio of 80:20 (v/v). The method was found to be linear for both drugs in a concentration range of 0.5 to 160 µg/mL using a concentration of 10 µg/mL of internal standard (theophylline) in urine samples (r > 0.999). The accuracy of the method was higher than 91.73% (percentage of the grand mean of recoveries) and the precision was lower than 3.4% (overall percentage of relative standard deviation) for both metoclopramide and paracetamol. The method was applied to the determination of the drugs in urine samples obtained from male volunteers, following the administration of two formulations, one containing paracetamol alone (Paracetamol(®)) and the other containing a mixture of paracetamol and metoclopramide (Migracicid(®)). Determination of the drugs was conducted and the effect of increasing the rate of absorption, consequently increasing the mean urinary excretion of paracetamol due to the presence of metoclopramide in the pharmaceutical formulation, was recorded.