Biotransformation of urapidil: isolation and identification of metabolites in mouse, rat, dog and man.

The identification of biotransformation products of the new antihypertensive drug urapidil in mouse, rat, dog and man has been performed by means of high-performance liquid chromatographic and mass spectrometric techniques. In urine, three metabolites were found in addition to the unchanged drug. The para-hydroxylated product (1) (6-(3-[4-(o-methoxy-p-hydroxyphenyl)piperazinyl]-propylamino)-1, 3-dimethyl-uracil), the O-demethylated compound (2) (6-(3-[4-(o-hydroxyphenyl)piperazinyl]-propylamino)-1, 3-dimethyluracil) and the uracil-N-dealkylated compound (3) (6-(3-[4-(o-methoxyphenyl)piperazinyl]-propylamino)-1-methyluracil). In urine of dog, the metabolite with the N-oxide structure (5) was also identified, but only in trace amounts (6-(3-[4-(o-methoxyphenyl)piperazinyl-N-oxide]-propylamino)-1, 3-dimethyluracil).