SYNTHESIS OF A METABOLITE OF METOCLOPRAMIDE AND ITS DETECTION IN HUMAN URINE

The synthesis of 2-(4-amino-5-chloro-2-methoxybenzamido) acetic acid 2 , a metabolite of metoclopramide 1, has been accomplished through the coupling of 4-amino-5-chloro-2-methoxybenzoic acid 4 with glycine benz yl ester followed by a catalytic hydrogenation. Such a metabolite coul d not be detected directly in the human urines but only after its tran sformation into the corresponding methyl ester 6. Compound 6 was prepa red both by condensing acid 4 with glycine methyl ester and by reactin g acid 2 with diazomethane. HPLC analyses of biological samples were t herefore performed after treatment with diazomethane. In five healthy volunteers, the percentage of 6 spanned the range 0.6-1.2%.