Abstract

A sensitive analytical procedure is described for reserpine and methyl reserpate. The compounds are separated by solvent extraction and fluorescence is developed in ethylene dichloride solutions following addition of trichloracetic acid and sodium nitroprusside. Fluorescence is also produced under the same conditions by yohimbine and other tetrahydroharman derivatives.

These methods were applied to the determination of reserpine and methyl reserpate levels in animal tissues. High levels of methyl reserpate were found in the rat after oral administration of reserpine, but not after parenteral administration. Relatively low levels of methyl reserpate were found in the dog and monkey. The dog showed higher levels of reserpine-like compounds than either the rat or monkey. Approximately sixty-five per cent of the dose of reserpine given orally to rats was accounted for as methyl reserpate in the urine and feces, while only small amounts were excreted following paretiteral administration. Methyl reserpate was detected in rat urine by paper chromatography. It was also isolated by countercurrent extraction procedures and identified as methyl reserpate by its ultraviolet and infra-red absorption characteristics.

Reserpine was hydrolyzed in vitro by preparations from the intestinal mucosa of the rat, methyl reserpate being identified by paper chromatography as one of the hydrolysis products. No significant amounts of hydrolysis were found with similar preparations from the dog and monkey. The metabolism of reserpine in the rat therefore is modified considerably by the oral route of administration, since methyl reserpate appears to be formed in the intestinal tract.