Transformation and Excretion of Drugs in Biological Systems. III. Separatory Determination of Metoclopramide and Its N⁴-Glucuronide and N⁴-Sulfonate in Rabbit Urine and Bile

The method of separatory determination of metoclopramide and its N4-glucuronide and N4-sulfonate, which are the major excrements in the urine and the bile of rabbits receiving metoclopramide, was established. Metoclopramide in the sample solution was extracted with chloroform under the condition of alkaline pH, and back-extracted with 1/15M KH2PO4 (pH 4.5). Metoclopramide in the aqueous layer was diazo-coupled in a brown test-tube which was used with a view to taking away the influence of light ; thus, a developed color was measured at 540 mμ. On the other hand, the separation of the glucuronide and the sulfonate from each other was carried out by utilizing the difference in stability between them, which are hydrolysed in an acid medium. Resulting metoclopramide was isolated and determined as above-mentioned. This method was applied to the urine and the bile of rabbits administered metoclopramide intravenously.